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Conserved domains on  [gi|1907161909|ref|XP_036020872|]
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arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 isoform X4 [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
1112-1291 7.05e-95

RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


:

Pssm-ID: 239850  Cd Length: 184  Bit Score: 303.85  E-value: 7.05e-95
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1112 DGNALQDQQLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLEDVTGVLKSFL 1191
Cdd:cd04385      1 DGPALEDQQLTDNDIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARSVQLREGEYTVHDVADVLKRFL 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1192 SDIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLF 1271
Cdd:cd04385     81 RDLPDPLLTSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLF 160
                          170       180
                   ....*....|....*....|....
gi 1907161909 1272 QTK----GQTSEEVNVIEDLINNY 1291
Cdd:cd04385    161 QTDehsvGQTSHEVKVIEDLIDNY 184
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
678-798 1.26e-77

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP2 localizes to the cell periphery and on focal adhesions composed of paxillin and vinculin, and functions downstream of RhoA to regulate focal adhesion dynamics. ARAP2 is a PI(3,4,5)P3-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RhoGAP domain and does not have RhoGAP activity. ARAP2 reduces Rac1oGTP levels by reducing Arf6oGTP levels through GAP activity. AGAP2 also binds to and regulates focal adhesion kinase (FAK). Thus, ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology.


:

Pssm-ID: 350081 [Multi-domain]  Cd Length: 121  Bit Score: 252.14  E-value: 1.26e-77
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  678 ETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVIG 757
Cdd:cd08856      1 ETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVVG 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1907161909  758 NKRANDFWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFR 798
Cdd:cd08856     81 NKPANLFWAANLFSEEDLHMDSDVEQRTPFITQKYKEGKFR 121
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
1378-1489 5.83e-56

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13259:

Pssm-ID: 473070  Cd Length: 121  Bit Score: 189.95  E-value: 5.83e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1378 REKSIKEGILKLKEEPSKILSGNKFQDRCVVLRDGHLFIYKDPKSSKHDKMFPLRAMKFYLGVKKKMKPPTSWGLTVYSE 1457
Cdd:cd13259     10 KVGSTKHGMLKFREEPSKLLSGNKFQDRYFILNDECLLLYKDVKSSKPEKEWPLKSLKVYLGIKKKLKPPTSWGFTVLLE 89
                           90       100       110
                   ....*....|....*....|....*....|..
gi 1907161909 1458 KHHWHLCCDSLQAQMEWMASIFIAQHENDIWP 1489
Cdd:cd13259     90 KQQWYLCCDSQMEQREWMATILSAQHDGDIWP 121
PH3_ARAP cd13256
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
890-1000 4.46e-52

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 3; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the third PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270076  Cd Length: 110  Bit Score: 178.42  E-value: 4.46e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  890 SSFLCDFLYQTAAAASRVSsEKKLLEDTNKKWCVLEGGFLSYYENDRCTTPNGTINISEVICLAVHKEDFYLNTGPIFVF 969
Cdd:cd13256      1 SVFHSGFLYKSPSAAKPTL-ERRAREEFSRRWCVLEDGFLSYYESERSPEPNGEIDVSEIVCLAVSPPDTHPGDGFPFTF 79
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1907161909  970 EIYLPSERVFLFGAETSQIQRKWTETIAKRF 1000
Cdd:cd13256     80 ELYLESERLYLFGLETAEALHEWVKAIAKAF 110
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
482-573 8.31e-49

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270073  Cd Length: 94  Bit Score: 168.33  E-value: 8.31e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  482 EKCGWLDKLSPQG-KRMFQKRWVKFDGLSISYYNNDREMYSKGIIPLTAISTVRAQGDNKFEIVTTQRTFVFRVEKEEER 560
Cdd:cd13253      1 IKSGYLDKQGGQGnNKGFQKRWVVFDGLSLRYFDSEKDAYSKRIIPLSAISTVRAVGDNKFELVTTNRTFVFRAESDDER 80
                           90
                   ....*....|...
gi 1907161909  561 NDWISILLSALKS 573
Cdd:cd13253     81 NLWCSTLQAAISE 93
PH2_ARAP cd13254
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
583-673 3.48e-47

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 2; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the second PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270074  Cd Length: 90  Bit Score: 163.74  E-value: 3.48e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  583 AVAPEKCGYLELRGYKAKIFTVLRGNSVWLCKNEQDFKSGLGITIIPMNVANVKQVDRavkQSFEIITPYRSFSFTADSE 662
Cdd:cd13254      3 KPNPDKCGYLELRGYKAKVYAALMGDEVWLYKNEQDFRLGIGITVIEMNGANVKDVDR---RSFDLTTPYRSFSFTAESE 79
                           90
                   ....*....|.
gi 1907161909  663 REKQEWIEAVQ 673
Cdd:cd13254     80 HEKQEWIEAVQ 90
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
1013-1108 1.76e-45

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13257:

Pssm-ID: 473070  Cd Length: 91  Bit Score: 158.86  E-value: 1.76e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1013 YDLIGQLFYKDCHALDQWRKGWFAMDKSSLCFCLQTQEAqEERMNLRRLQELTISTMVQNgekvDVLLLVEKGRTLYIHG 1092
Cdd:cd13257      1 FERLGRLFYKDGLALDRAREGWFALDKSSLHACLQMQEV-EERMHLRKLQELSIQGDVQL----DVLVLVERRRTLYIQG 75
                           90
                   ....*....|....*.
gi 1907161909 1093 HTKLDFTVWHTAIEKA 1108
Cdd:cd13257     76 ERKLDFTGWHTAIQKA 91
Ubl1_cv_Nsp3_N-like super family cl28922
first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV ...
1287-1372 2.21e-44

first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model.


The actual alignment was detected with superfamily member cd17227:

Pssm-ID: 475130  Cd Length: 98  Bit Score: 155.82  E-value: 2.21e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1287 LINNYVE--------IFEISPVMEAEELTNDILAIKNIIPMKGDIWATFEVIENEELERPLHYTENVLEQVLQWSSLAEP 1358
Cdd:cd17227      5 LIEVYLEkkepdcsiIIRVSPTMEAEELTNDVLEIKNIIPDKKDIWATFEVIENGELERPLHYKENVLEQVLQWSSLSEP 84
                           90
                   ....*....|....
gi 1907161909 1359 GSAYLVVKRFLTID 1372
Cdd:cd17227     85 GSAYLIVKRFQAAD 98
SAM_Arap1,2,3 cd09490
SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) ...
6-68 7.30e-32

SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) domain of Arap1,2,3 subfamily proteins (angiotensin receptor-associated) is a protein-protein interaction domain. Arap1,2,3 proteins are phosphatidylinositol-3,4,5-trisphosphate-dependent GTPase-activating proteins. They are involved in phosphatidylinositol-3 kinase (PI3K) signaling pathways. In addition to SAM domain, Arap1,2,3 proteins contain ArfGap, PH-like, RhoGAP and UBQ domains. SAM domain of Arap3 protein was shown to interact with SAM domain of Ship2 phosphatidylinositol-trisphosphate phosphatase proteins. Such interaction apparently plays a role in inhibition of PI3K regulated pathways since Ship2 converts PI(3,4,5)P3 into PI(3,4)P2. Proteins of this subfamily participate in regulation of signaling and trafficking associated with a number of different receptors (including EGFR, TRAIL-R1/DR4, TRAIL-R2/DR5) in normal and cancer cells; they are involved in regulation of actin cytoskeleton remodeling, cell spreading and formation of lamellipodia.


:

Pssm-ID: 188889  Cd Length: 63  Bit Score: 118.94  E-value: 7.30e-32
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907161909    6 EVNADIRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMIF 68
Cdd:cd09490      1 EADLDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGHRRRILKQLPIIT 63
 
Name Accession Description Interval E-value
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
1112-1291 7.05e-95

RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239850  Cd Length: 184  Bit Score: 303.85  E-value: 7.05e-95
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1112 DGNALQDQQLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLEDVTGVLKSFL 1191
Cdd:cd04385      1 DGPALEDQQLTDNDIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARSVQLREGEYTVHDVADVLKRFL 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1192 SDIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLF 1271
Cdd:cd04385     81 RDLPDPLLTSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLF 160
                          170       180
                   ....*....|....*....|....
gi 1907161909 1272 QTK----GQTSEEVNVIEDLINNY 1291
Cdd:cd04385    161 QTDehsvGQTSHEVKVIEDLIDNY 184
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
678-798 1.26e-77

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP2 localizes to the cell periphery and on focal adhesions composed of paxillin and vinculin, and functions downstream of RhoA to regulate focal adhesion dynamics. ARAP2 is a PI(3,4,5)P3-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RhoGAP domain and does not have RhoGAP activity. ARAP2 reduces Rac1oGTP levels by reducing Arf6oGTP levels through GAP activity. AGAP2 also binds to and regulates focal adhesion kinase (FAK). Thus, ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology.


Pssm-ID: 350081 [Multi-domain]  Cd Length: 121  Bit Score: 252.14  E-value: 1.26e-77
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  678 ETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVIG 757
Cdd:cd08856      1 ETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVVG 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1907161909  758 NKRANDFWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFR 798
Cdd:cd08856     81 NKPANLFWAANLFSEEDLHMDSDVEQRTPFITQKYKEGKFR 121
PH5_ARAP cd13259
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
1378-1489 5.83e-56

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 5; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the five PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270079  Cd Length: 121  Bit Score: 189.95  E-value: 5.83e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1378 REKSIKEGILKLKEEPSKILSGNKFQDRCVVLRDGHLFIYKDPKSSKHDKMFPLRAMKFYLGVKKKMKPPTSWGLTVYSE 1457
Cdd:cd13259     10 KVGSTKHGMLKFREEPSKLLSGNKFQDRYFILNDECLLLYKDVKSSKPEKEWPLKSLKVYLGIKKKLKPPTSWGFTVLLE 89
                           90       100       110
                   ....*....|....*....|....*....|..
gi 1907161909 1458 KHHWHLCCDSLQAQMEWMASIFIAQHENDIWP 1489
Cdd:cd13259     90 KQQWYLCCDSQMEQREWMATILSAQHDGDIWP 121
PH3_ARAP cd13256
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
890-1000 4.46e-52

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 3; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the third PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270076  Cd Length: 110  Bit Score: 178.42  E-value: 4.46e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  890 SSFLCDFLYQTAAAASRVSsEKKLLEDTNKKWCVLEGGFLSYYENDRCTTPNGTINISEVICLAVHKEDFYLNTGPIFVF 969
Cdd:cd13256      1 SVFHSGFLYKSPSAAKPTL-ERRAREEFSRRWCVLEDGFLSYYESERSPEPNGEIDVSEIVCLAVSPPDTHPGDGFPFTF 79
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1907161909  970 EIYLPSERVFLFGAETSQIQRKWTETIAKRF 1000
Cdd:cd13256     80 ELYLESERLYLFGLETAEALHEWVKAIAKAF 110
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
482-573 8.31e-49

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270073  Cd Length: 94  Bit Score: 168.33  E-value: 8.31e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  482 EKCGWLDKLSPQG-KRMFQKRWVKFDGLSISYYNNDREMYSKGIIPLTAISTVRAQGDNKFEIVTTQRTFVFRVEKEEER 560
Cdd:cd13253      1 IKSGYLDKQGGQGnNKGFQKRWVVFDGLSLRYFDSEKDAYSKRIIPLSAISTVRAVGDNKFELVTTNRTFVFRAESDDER 80
                           90
                   ....*....|...
gi 1907161909  561 NDWISILLSALKS 573
Cdd:cd13253     81 NLWCSTLQAAISE 93
PH2_ARAP cd13254
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
583-673 3.48e-47

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 2; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the second PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270074  Cd Length: 90  Bit Score: 163.74  E-value: 3.48e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  583 AVAPEKCGYLELRGYKAKIFTVLRGNSVWLCKNEQDFKSGLGITIIPMNVANVKQVDRavkQSFEIITPYRSFSFTADSE 662
Cdd:cd13254      3 KPNPDKCGYLELRGYKAKVYAALMGDEVWLYKNEQDFRLGIGITVIEMNGANVKDVDR---RSFDLTTPYRSFSFTAESE 79
                           90
                   ....*....|.
gi 1907161909  663 REKQEWIEAVQ 673
Cdd:cd13254     80 HEKQEWIEAVQ 90
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
1127-1274 1.54e-46

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.


Pssm-ID: 459875  Cd Length: 148  Bit Score: 164.26  E-value: 1.54e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1127 PIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVkLRAGKHQLEDVTGVLKSFLSDIDDALLTKELYPY 1206
Cdd:pfam00620    1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVD-LDLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907161909 1207 WVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTK 1274
Cdd:pfam00620   80 FIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPP 147
PH4_ARAP cd13257
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
1013-1108 1.76e-45

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 4; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the fourth PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270077  Cd Length: 91  Bit Score: 158.86  E-value: 1.76e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1013 YDLIGQLFYKDCHALDQWRKGWFAMDKSSLCFCLQTQEAqEERMNLRRLQELTISTMVQNgekvDVLLLVEKGRTLYIHG 1092
Cdd:cd13257      1 FERLGRLFYKDGLALDRAREGWFALDKSSLHACLQMQEV-EERMHLRKLQELSIQGDVQL----DVLVLVERRRTLYIQG 75
                           90
                   ....*....|....*.
gi 1907161909 1093 HTKLDFTVWHTAIEKA 1108
Cdd:cd13257     76 ERKLDFTGWHTAIQKA 91
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
1125-1291 5.34e-45

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.


Pssm-ID: 214618  Cd Length: 174  Bit Score: 160.89  E-value: 5.34e-45
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  1125 DVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVkLRAGKHQLEDVTGVLKSFLSDIDDALLTKELY 1204
Cdd:smart00324    2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPD-LDLSEYDVHDVAGLLKLFLRELPEPLITYELY 80
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  1205 PYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKGQTSEEV--- 1281
Cdd:smart00324   81 EEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLkdi 160
                           170
                    ....*....|....
gi 1907161909  1282 ----NVIEDLINNY 1291
Cdd:smart00324  161 rhqnTVIEFLIENA 174
RA_ARAP2 cd17227
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1287-1372 2.21e-44

Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2); ARAP2, also termed Centaurin-delta-1 (Cnt-d1), or Protein PARX, is a phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3))-dependent Arf Rap-activated guanosine triphosphatase (GTPase)-activating protein (GAP), which promotes GLUT1-mediated basal glucose uptake by modifying sphingolipid metabolism through glucosylceramide synthase (GCS). ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology. ARAP2 contains multiple functional domains, including ArfGAP and RhoGAP domains, as well as a sterile alpha motif (Sam) domain, five PH domains, and a RA domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes.


Pssm-ID: 340747  Cd Length: 98  Bit Score: 155.82  E-value: 2.21e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1287 LINNYVE--------IFEISPVMEAEELTNDILAIKNIIPMKGDIWATFEVIENEELERPLHYTENVLEQVLQWSSLAEP 1358
Cdd:cd17227      5 LIEVYLEkkepdcsiIIRVSPTMEAEELTNDVLEIKNIIPDKKDIWATFEVIENGELERPLHYKENVLEQVLQWSSLSEP 84
                           90
                   ....*....|....
gi 1907161909 1359 GSAYLVVKRFLTID 1372
Cdd:cd17227     85 GSAYLIVKRFQAAD 98
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
684-799 9.99e-44

Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 460200 [Multi-domain]  Cd Length: 117  Bit Score: 154.69  E-value: 9.99e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  684 EVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRAND 763
Cdd:pfam01412    2 RVLRELLKLPGNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLD--TWTDEQLELMKAGGNDRANE 79
                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1907161909  764 FWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFRK 799
Cdd:pfam01412   80 FWEANLPPSYKPPPSSDREKRESFIRAKYVEKKFAK 115
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
692-797 2.11e-32

Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 214518 [Multi-domain]  Cd Length: 119  Bit Score: 122.45  E-value: 2.11e-32
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909   692 NESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQK 771
Cdd:smart00105    7 IPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDT--WTEEELRLLQKGGNENANSIWESNLDD 84
                            90       100
                    ....*....|....*....|....*..
gi 1907161909   772 DEELQVDSPV-EKRKNFITQKYKEGKF 797
Cdd:smart00105   85 FSLKPPDDDDqQKYESFIAAKYEEKLF 111
SAM_Arap1,2,3 cd09490
SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) ...
6-68 7.30e-32

SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) domain of Arap1,2,3 subfamily proteins (angiotensin receptor-associated) is a protein-protein interaction domain. Arap1,2,3 proteins are phosphatidylinositol-3,4,5-trisphosphate-dependent GTPase-activating proteins. They are involved in phosphatidylinositol-3 kinase (PI3K) signaling pathways. In addition to SAM domain, Arap1,2,3 proteins contain ArfGap, PH-like, RhoGAP and UBQ domains. SAM domain of Arap3 protein was shown to interact with SAM domain of Ship2 phosphatidylinositol-trisphosphate phosphatase proteins. Such interaction apparently plays a role in inhibition of PI3K regulated pathways since Ship2 converts PI(3,4,5)P3 into PI(3,4)P2. Proteins of this subfamily participate in regulation of signaling and trafficking associated with a number of different receptors (including EGFR, TRAIL-R1/DR4, TRAIL-R2/DR5) in normal and cancer cells; they are involved in regulation of actin cytoskeleton remodeling, cell spreading and formation of lamellipodia.


Pssm-ID: 188889  Cd Length: 63  Bit Score: 118.94  E-value: 7.30e-32
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907161909    6 EVNADIRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMIF 68
Cdd:cd09490      1 EADLDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGHRRRILKQLPIIT 63
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
692-799 9.15e-27

GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ARF-mediated vesicular transport [Intracellular trafficking and secretion];


Pssm-ID: 227651 [Multi-domain]  Cd Length: 319  Bit Score: 112.95  E-value: 9.15e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  692 NESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRANDFWAGNLQK 771
Cdd:COG5347     17 DSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLD--NWTEEELRRMEVGGNSNANRFYEKNLLD 94
                           90       100       110
                   ....*....|....*....|....*....|..
gi 1907161909  772 DEELQV----DSPVekRKNFITQKYKEGKFRK 799
Cdd:COG5347     95 QLLLPIkakyDSSV--AKKYIRKKYELKKFID 124
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
483-572 1.66e-12

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 65.26  E-value: 1.66e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909   483 KCGWLDKLSPQGKRMFQKRWVKFDGLSISYYNNDREMYS---KGIIPLTAIS------TVRAQGDNKFEIVTTQR-TFVF 552
Cdd:smart00233    3 KEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSykpKGSIDLSGCTvreapdPDSSKKPHCFEIKTSDRkTLLL 82
                            90       100
                    ....*....|....*....|
gi 1907161909   553 RVEKEEERNDWISILLSALK 572
Cdd:smart00233   83 QAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
482-572 7.51e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 63.35  E-value: 7.51e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  482 EKCGWLDKLSPQGKRMFQKRWVKFDGLSISYYNNDREMYS---KGIIPLTAISTVRA------QGDNKFEIVTTQ----R 548
Cdd:pfam00169    2 VKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDDKSGKSkepKGSISLSGCEVVEVvasdspKRKFCFELRTGErtgkR 81
                           90       100
                   ....*....|....*....|....
gi 1907161909  549 TFVFRVEKEEERNDWISILLSALK 572
Cdd:pfam00169   82 TYLLQAESEEERKDWIKAIQSAIR 105
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
677-765 6.59e-11

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 66.42  E-value: 6.59e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  677 AETLSD-YEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIV 755
Cdd:PLN03114     3 SENLNDkISVFKKLKAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDS--WSSEQLKMMIY 80
                           90
                   ....*....|
gi 1907161909  756 IGNKRANDFW 765
Cdd:PLN03114    81 GGNNRAQVFF 90
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
1382-1483 5.48e-10

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 57.94  E-value: 5.48e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  1382 IKEGILKLKEEPSKilsgNKFQDRCVVLRDGHLFIYKDPK---SSKHDKMFPLRAMKFYLGVKKKMKpPTSWGLTV-YSE 1457
Cdd:smart00233    2 IKEGWLYKKSGGGK----KSWKKRYFVLFNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREAPDPDSS-KKPHCFEIkTSD 76
                            90       100
                    ....*....|....*....|....*.
gi 1907161909  1458 KHHWHLCCDSLQAQMEWMASIFIAQH 1483
Cdd:smart00233   77 RKTLLLQAESEEEREKWVEALRKAIA 102
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
586-677 5.45e-09

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 55.25  E-value: 5.45e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909   586 PEKCGYLELRGYKA-----KIFTVLRGNSVWLCKNEQDFKSGLGITIIPMNVANVKQVDRA----VKQSFEIITPYR-SF 655
Cdd:smart00233    1 VIKEGWLYKKSGGGkkswkKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPdsskKPHCFEIKTSDRkTL 80
                            90       100
                    ....*....|....*....|..
gi 1907161909   656 SFTADSEREKQEWIEAVQQSIA 677
Cdd:smart00233   81 LLQAESEEEREKWVEALRKAIA 102
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
919-996 5.95e-09

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 55.25  E-value: 5.95e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909   919 KKWCVLEGGFLSYYEND---RCTTPNGTINISEVICLAVHKEDfylNTGPIFVFEIYLPSERVFLFGAETSQIQRKWTET 995
Cdd:smart00233   20 KRYFVLFNSTLLYYKSKkdkKSYKPKGSIDLSGCTVREAPDPD---SSKKPHCFEIKTSDRKTLLLQAESEEEREKWVEA 96

                    .
gi 1907161909   996 I 996
Cdd:smart00233   97 L 97
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
10-67 9.64e-09

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.


Pssm-ID: 425739  Cd Length: 64  Bit Score: 53.04  E-value: 9.64e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907161909   10 DIRDFLMSINLEQYLLHFREfGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMI 67
Cdd:pfam00536    7 DVGEWLESIGLGQYIDSFRA-GYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRL 63
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
10-67 7.91e-08

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 50.76  E-value: 7.91e-08
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907161909    10 DIRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMI 67
Cdd:smart00454    8 SVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKL 65
PH pfam00169
PH domain; PH stands for pleckstrin homology.
919-996 1.64e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 45.25  E-value: 1.64e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  919 KKWCVLEGGFLSYYENDRCT---TPNGTINISEVICLAVHKEDfylNTGPIFVFEIYLPS---ERVFLFGAETSQIQRKW 992
Cdd:pfam00169   20 KRYFVLFDGSLLYYKDDKSGkskEPKGSISLSGCEVVEVVASD---SPKRKFCFELRTGErtgKRTYLLQAESEEERKDW 96

                   ....
gi 1907161909  993 TETI 996
Cdd:pfam00169   97 IKAI 100
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
1289-1367 1.77e-05

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.


Pssm-ID: 425871  Cd Length: 93  Bit Score: 45.02  E-value: 1.77e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907161909 1289 NNYVEIfEISPVMEAEELTNDILAIKNIIPMKGDiWATFEVIENEELERPLHYTENVLEQVLQWSSlaEPGSAYLVVKR 1367
Cdd:pfam00788   16 TTYKTI-LVSSSTTAEEVIEALLEKFGLEDDPRD-YVLVEVLERGGGERRLPDDECPLQIQLQWPR--DASDSRFLLRK 90
PH pfam00169
PH domain; PH stands for pleckstrin homology.
1382-1483 3.14e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 44.48  E-value: 3.14e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1382 IKEGILKLKEEPSKilsgNKFQDRCVVLRDGHLFIYKDPKSSKHDK---MFPLRAMKFYLGVKKKMKP-PTSWGLTVY-- 1455
Cdd:pfam00169    2 VKEGWLLKKGGGKK----KSWKKRYFVLFDGSLLYYKDDKSGKSKEpkgSISLSGCEVVEVVASDSPKrKFCFELRTGer 77
                           90       100
                   ....*....|....*....|....*...
gi 1907161909 1456 SEKHHWHLCCDSLQAQMEWMASIFIAQH 1483
Cdd:pfam00169   78 TGKRTYLLQAESEEERKDWIKAIQSAIR 105
PH pfam00169
PH domain; PH stands for pleckstrin homology.
586-677 1.62e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 42.55  E-value: 1.62e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  586 PEKCGYLELRGYKAKI-----FTVLRGNSVWLCKNEQDFKSGLGITIIPMN----VANVKQVDRAVKQSFEIIT----PY 652
Cdd:pfam00169    1 VVKEGWLLKKGGGKKKswkkrYFVLFDGSLLYYKDDKSGKSKEPKGSISLSgcevVEVVASDSPKRKFCFELRTgertGK 80
                           90       100
                   ....*....|....*....|....*
gi 1907161909  653 RSFSFTADSEREKQEWIEAVQQSIA 677
Cdd:pfam00169   81 RTYLLQAESEEERKDWIKAIQSAIR 105
 
Name Accession Description Interval E-value
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
1112-1291 7.05e-95

RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239850  Cd Length: 184  Bit Score: 303.85  E-value: 7.05e-95
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1112 DGNALQDQQLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLEDVTGVLKSFL 1191
Cdd:cd04385      1 DGPALEDQQLTDNDIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARSVQLREGEYTVHDVADVLKRFL 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1192 SDIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLF 1271
Cdd:cd04385     81 RDLPDPLLTSELHAEWIEAAELENKDERIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLF 160
                          170       180
                   ....*....|....*....|....
gi 1907161909 1272 QTK----GQTSEEVNVIEDLINNY 1291
Cdd:cd04385    161 QTDehsvGQTSHEVKVIEDLIDNY 184
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
678-798 1.26e-77

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP2 localizes to the cell periphery and on focal adhesions composed of paxillin and vinculin, and functions downstream of RhoA to regulate focal adhesion dynamics. ARAP2 is a PI(3,4,5)P3-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RhoGAP domain and does not have RhoGAP activity. ARAP2 reduces Rac1oGTP levels by reducing Arf6oGTP levels through GAP activity. AGAP2 also binds to and regulates focal adhesion kinase (FAK). Thus, ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology.


Pssm-ID: 350081 [Multi-domain]  Cd Length: 121  Bit Score: 252.14  E-value: 1.26e-77
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  678 ETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVIG 757
Cdd:cd08856      1 ETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVVG 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1907161909  758 NKRANDFWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFR 798
Cdd:cd08856     81 NKPANLFWAANLFSEEDLHMDSDVEQRTPFITQKYKEGKFR 121
ArfGap_ARAP cd08837
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; The ARAP subfamily ...
683-798 1.66e-73

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics.


Pssm-ID: 350066 [Multi-domain]  Cd Length: 116  Bit Score: 239.97  E-value: 1.66e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  683 YEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVIGNKRAN 762
Cdd:cd08837      1 YEVAEKIWSNPANRFCADCGAPDPDWASINLCVVICKQCAGEHRSLGSNISKVRSLKMDTKVWTEELVELFLKLGNDRAN 80
                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1907161909  763 DFWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFR 798
Cdd:cd08837     81 RFWAANLPPSEALHPDADSEQRREFITAKYREGKYR 116
ArfGap_ARAP3 cd17902
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily ...
683-798 3.51e-57

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP3 possesses a unique dual-specificity GAP activity for Arf6 and RhoA regulated by PI(3,4,5)P3 and a small GTPase Rap1-GTP. The RhoGAP activity of ARAP3 is enhanced by direct binding of Rap1-GTP to the Ras-association (RA) domain. ARAP3 is involved in regulation of cell shape and adhesion.


Pssm-ID: 350089 [Multi-domain]  Cd Length: 116  Bit Score: 193.20  E-value: 3.51e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  683 YEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVIGNKRAN 762
Cdd:cd17902      1 YEVAEKIWSNKANRFCADCHASSPDWASINLCVVICKQCAGQHRSLGSGISKVQSLKLDTSVWSNEIVQLFIVLGNDRAN 80
                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1907161909  763 DFWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFR 798
Cdd:cd17902     81 RFWAARLPASEALHPDATPEQRREFISRKYREGRFR 116
PH5_ARAP cd13259
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
1378-1489 5.83e-56

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 5; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the five PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270079  Cd Length: 121  Bit Score: 189.95  E-value: 5.83e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1378 REKSIKEGILKLKEEPSKILSGNKFQDRCVVLRDGHLFIYKDPKSSKHDKMFPLRAMKFYLGVKKKMKPPTSWGLTVYSE 1457
Cdd:cd13259     10 KVGSTKHGMLKFREEPSKLLSGNKFQDRYFILNDECLLLYKDVKSSKPEKEWPLKSLKVYLGIKKKLKPPTSWGFTVLLE 89
                           90       100       110
                   ....*....|....*....|....*....|..
gi 1907161909 1458 KHHWHLCCDSLQAQMEWMASIFIAQHENDIWP 1489
Cdd:cd13259     90 KQQWYLCCDSQMEQREWMATILSAQHDGDIWP 121
ArfGap_ARAP1 cd17901
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily ...
684-798 7.38e-53

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP1 localizes to the plasma membrane, the Golgi complex, and endosomal compartments. It displays PI(3,4,5)P3-dependent ArfGAP activity that regulates Arf-, RhoA-, and Cdc42-dependent cellular events. For example, ARAP1 inhibits the trafficking of epidermal growth factor receptor (EGFR) to the early endosome.


Pssm-ID: 350088 [Multi-domain]  Cd Length: 116  Bit Score: 180.78  E-value: 7.38e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  684 EVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVIGNKRAND 763
Cdd:cd17901      2 EVAEKIWSVESNRFCADCGSPKPDWASVNLCVVICKRCAGEHRGLGPSVSKVRSLKMDRKVWTEELIELFLLLGNGKANQ 81
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1907161909  764 FWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFR 798
Cdd:cd17901     82 FWAANVPPSEALCPSSSSEERRHFITAKYKEGKYR 116
PH3_ARAP cd13256
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
890-1000 4.46e-52

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 3; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the third PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270076  Cd Length: 110  Bit Score: 178.42  E-value: 4.46e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  890 SSFLCDFLYQTAAAASRVSsEKKLLEDTNKKWCVLEGGFLSYYENDRCTTPNGTINISEVICLAVHKEDFYLNTGPIFVF 969
Cdd:cd13256      1 SVFHSGFLYKSPSAAKPTL-ERRAREEFSRRWCVLEDGFLSYYESERSPEPNGEIDVSEIVCLAVSPPDTHPGDGFPFTF 79
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1907161909  970 EIYLPSERVFLFGAETSQIQRKWTETIAKRF 1000
Cdd:cd13256     80 ELYLESERLYLFGLETAEALHEWVKAIAKAF 110
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
482-573 8.31e-49

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270073  Cd Length: 94  Bit Score: 168.33  E-value: 8.31e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  482 EKCGWLDKLSPQG-KRMFQKRWVKFDGLSISYYNNDREMYSKGIIPLTAISTVRAQGDNKFEIVTTQRTFVFRVEKEEER 560
Cdd:cd13253      1 IKSGYLDKQGGQGnNKGFQKRWVVFDGLSLRYFDSEKDAYSKRIIPLSAISTVRAVGDNKFELVTTNRTFVFRAESDDER 80
                           90
                   ....*....|...
gi 1907161909  561 NDWISILLSALKS 573
Cdd:cd13253     81 NLWCSTLQAAISE 93
PH2_ARAP cd13254
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
583-673 3.48e-47

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 2; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the second PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270074  Cd Length: 90  Bit Score: 163.74  E-value: 3.48e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  583 AVAPEKCGYLELRGYKAKIFTVLRGNSVWLCKNEQDFKSGLGITIIPMNVANVKQVDRavkQSFEIITPYRSFSFTADSE 662
Cdd:cd13254      3 KPNPDKCGYLELRGYKAKVYAALMGDEVWLYKNEQDFRLGIGITVIEMNGANVKDVDR---RSFDLTTPYRSFSFTAESE 79
                           90
                   ....*....|.
gi 1907161909  663 REKQEWIEAVQ 673
Cdd:cd13254     80 HEKQEWIEAVQ 90
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
1127-1274 1.54e-46

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.


Pssm-ID: 459875  Cd Length: 148  Bit Score: 164.26  E-value: 1.54e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1127 PIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVkLRAGKHQLEDVTGVLKSFLSDIDDALLTKELYPY 1206
Cdd:pfam00620    1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVD-LDLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907161909 1207 WVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTK 1274
Cdd:pfam00620   80 FIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPP 147
PH4_ARAP cd13257
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
1013-1108 1.76e-45

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 4; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the fourth PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270077  Cd Length: 91  Bit Score: 158.86  E-value: 1.76e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1013 YDLIGQLFYKDCHALDQWRKGWFAMDKSSLCFCLQTQEAqEERMNLRRLQELTISTMVQNgekvDVLLLVEKGRTLYIHG 1092
Cdd:cd13257      1 FERLGRLFYKDGLALDRAREGWFALDKSSLHACLQMQEV-EERMHLRKLQELSIQGDVQL----DVLVLVERRRTLYIQG 75
                           90
                   ....*....|....*.
gi 1907161909 1093 HTKLDFTVWHTAIEKA 1108
Cdd:cd13257     76 ERKLDFTGWHTAIQKA 91
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
1125-1291 5.34e-45

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.


Pssm-ID: 214618  Cd Length: 174  Bit Score: 160.89  E-value: 5.34e-45
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  1125 DVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVkLRAGKHQLEDVTGVLKSFLSDIDDALLTKELY 1204
Cdd:smart00324    2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPD-LDLSEYDVHDVAGLLKLFLRELPEPLITYELY 80
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  1205 PYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKGQTSEEV--- 1281
Cdd:smart00324   81 EEFIEAAKLEDETERLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLkdi 160
                           170
                    ....*....|....
gi 1907161909  1282 ----NVIEDLINNY 1291
Cdd:smart00324  161 rhqnTVIEFLIENA 174
RA_ARAP2 cd17227
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1287-1372 2.21e-44

Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2); ARAP2, also termed Centaurin-delta-1 (Cnt-d1), or Protein PARX, is a phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3))-dependent Arf Rap-activated guanosine triphosphatase (GTPase)-activating protein (GAP), which promotes GLUT1-mediated basal glucose uptake by modifying sphingolipid metabolism through glucosylceramide synthase (GCS). ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology. ARAP2 contains multiple functional domains, including ArfGAP and RhoGAP domains, as well as a sterile alpha motif (Sam) domain, five PH domains, and a RA domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes.


Pssm-ID: 340747  Cd Length: 98  Bit Score: 155.82  E-value: 2.21e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1287 LINNYVE--------IFEISPVMEAEELTNDILAIKNIIPMKGDIWATFEVIENEELERPLHYTENVLEQVLQWSSLAEP 1358
Cdd:cd17227      5 LIEVYLEkkepdcsiIIRVSPTMEAEELTNDVLEIKNIIPDKKDIWATFEVIENGELERPLHYKENVLEQVLQWSSLSEP 84
                           90
                   ....*....|....
gi 1907161909 1359 GSAYLVVKRFLTID 1372
Cdd:cd17227     85 GSAYLIVKRFQAAD 98
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
684-799 9.99e-44

Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 460200 [Multi-domain]  Cd Length: 117  Bit Score: 154.69  E-value: 9.99e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  684 EVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRAND 763
Cdd:pfam01412    2 RVLRELLKLPGNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLD--TWTDEQLELMKAGGNDRANE 79
                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1907161909  764 FWAGNLQKDEELQVDSPVEKRKNFITQKYKEGKFRK 799
Cdd:pfam01412   80 FWEANLPPSYKPPPSSDREKRESFIRAKYVEKKFAK 115
ArfGap cd08204
GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family ...
687-792 2.97e-39

GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family of proteins containing an ArfGAP catalytic domain that induces the hydrolysis of GTP bound to the small guanine nucleotide-binding protein Arf, a member of the Ras superfamily of GTPases. Like all GTP-binding proteins, Arf proteins function as molecular switches, cycling between GTP (active-membrane bound) and GDP (inactive-cytosolic) form. Conversion to the GTP-bound form requires a guanine nucleotide exchange factor (GEF), whereas conversion to the GDP-bound form is catalyzed by a GTPase activating protein (GAP). In that sense, ArfGAPs were originally proposed to function as terminators of Arf signaling, which is mediated by regulating Arf family GTP-binding proteins. However, recent studies suggest that ArfGAPs can also function as Arf effectors, independently of their GAP enzymatic activity to transduce signals in cells. The ArfGAP domain contains a C4-type zinc finger motif and a conserved arginine that is required for activity, within a specific spacing (CX2CX16CX2CX4R). ArfGAPs, which have multiple functional domains, regulate the membrane trafficking and actin cytoskeleton remodeling via specific interactions with signaling lipids such as phosphoinositides and trafficking proteins, which consequently affect cellular events such as cell growth, migration, and cancer invasion. The ArfGAP family, which includes 31 human ArfGAP-domain containing proteins, is divided into 10 subfamilies based on domain structure and sequence similarity. The ArfGAP nomenclature is mainly based on the protein domain structure. For example, ASAP1 contains ArfGAP, SH3, ANK repeat and PH domains; ARAPs contain ArfGAP, Rho GAP, ANK repeat and PH domains; ACAPs contain ArfGAP, BAR (coiled coil), ANK repeat and PH domains; and AGAPs contain Arf GAP, GTP-binding protein-like, ANK repeat and PH domains. Furthermore, the ArfGAPs can be classified into two major types of subfamilies, according to the overall domain structure: the ArfGAP1 type includes 6 subfamilies (ArfGAP1, ArfGAP2/3, ADAP, SMAP, AGFG, and GIT), which contain the ArfGAP domain at the N-terminus of the protein; and the AZAP type includes 4 subfamilies (ASAP, ACAP, AGAP, and ARAP), which contain an ArfGAP domain between the PH and ANK repeat domains.


Pssm-ID: 350058 [Multi-domain]  Cd Length: 106  Bit Score: 141.48  E-value: 2.97e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  687 EKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWA 766
Cdd:cd08204      2 EELLKLPGNKVCADCGAPDPRWASINLGVFICIRCSGIHRSLGVHISKVRSLTLDS--WTPEQVELMKAIGNARANAYYE 79
                           90       100
                   ....*....|....*....|....*..
gi 1907161909  767 GNLQKDEELQ-VDSPVEKRKNFITQKY 792
Cdd:cd08204     80 ANLPPGFKKPtPDSSDEEREQFIRAKY 106
RhoGAP cd00159
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ...
1127-1290 1.85e-35

RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. The RhoGAPs are one of the major classes of regulators of Rho G proteins.


Pssm-ID: 238090 [Multi-domain]  Cd Length: 169  Bit Score: 133.20  E-value: 1.85e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1127 PIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRagKHQLEDVTGVLKSFLSDIDDALLTKELYPY 1206
Cdd:cd00159      1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLE--DYDVHDVASLLKLYLRELPEPLIPFELYDE 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1207 WVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLF-------QTKGQTSE 1279
Cdd:cd00159     79 FIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLrppdsddELLEDIKK 158
                          170
                   ....*....|.
gi 1907161909 1280 EVNVIEDLINN 1290
Cdd:cd00159    159 LNEIVEFLIEN 169
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
692-797 2.11e-32

Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 214518 [Multi-domain]  Cd Length: 119  Bit Score: 122.45  E-value: 2.11e-32
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909   692 NESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQK 771
Cdd:smart00105    7 IPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDT--WTEEELRLLQKGGNENANSIWESNLDD 84
                            90       100
                    ....*....|....*....|....*..
gi 1907161909   772 DEELQVDSPV-EKRKNFITQKYKEGKF 797
Cdd:smart00105   85 FSLKPPDDDDqQKYESFIAAKYEEKLF 111
SAM_Arap1,2,3 cd09490
SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) ...
6-68 7.30e-32

SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) domain of Arap1,2,3 subfamily proteins (angiotensin receptor-associated) is a protein-protein interaction domain. Arap1,2,3 proteins are phosphatidylinositol-3,4,5-trisphosphate-dependent GTPase-activating proteins. They are involved in phosphatidylinositol-3 kinase (PI3K) signaling pathways. In addition to SAM domain, Arap1,2,3 proteins contain ArfGap, PH-like, RhoGAP and UBQ domains. SAM domain of Arap3 protein was shown to interact with SAM domain of Ship2 phosphatidylinositol-trisphosphate phosphatase proteins. Such interaction apparently plays a role in inhibition of PI3K regulated pathways since Ship2 converts PI(3,4,5)P3 into PI(3,4)P2. Proteins of this subfamily participate in regulation of signaling and trafficking associated with a number of different receptors (including EGFR, TRAIL-R1/DR4, TRAIL-R2/DR5) in normal and cancer cells; they are involved in regulation of actin cytoskeleton remodeling, cell spreading and formation of lamellipodia.


Pssm-ID: 188889  Cd Length: 63  Bit Score: 118.94  E-value: 7.30e-32
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907161909    6 EVNADIRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMIF 68
Cdd:cd09490      1 EADLDIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGHRRRILKQLPIIT 63
RhoGAP_fRGD1 cd04398
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1126-1295 8.86e-32

RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD1-like proteins. Yeast Rgd1 is a GAP protein for Rho3 and Rho4 and plays a role in low-pH response. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239863  Cd Length: 192  Bit Score: 123.67  E-value: 8.86e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLED---VTGVLKSFLSDIDDALLTKE 1202
Cdd:cd04398     16 VPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLLISPEDYESDihsVASLLKLFFRELPEPLLTKA 95
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1203 LYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKGQTSEEVN 1282
Cdd:cd04398     96 LSREFIEAAKIEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWGPTLMNAAPDNAADMS 175
                          170
                   ....*....|....*..
gi 1907161909 1283 ----VIEDLINNYVEIF 1295
Cdd:cd04398    176 fqsrVIETLLDNAYQIF 192
ArfGap_AGAP cd08836
ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation ...
695-792 5.46e-29

ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.


Pssm-ID: 350065 [Multi-domain]  Cd Length: 108  Bit Score: 112.38  E-value: 5.46e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQKDEE 774
Cdd:cd08836     12 NDHCVDCGAPNPDWASLNLGALMCIECSGIHRNLGTHISRVRSLDLDD--WPVELLKVMSAIGNDLANSVWEGNTQGRTK 89
                           90
                   ....*....|....*...
gi 1907161909  775 LQVDSPVEKRKNFITQKY 792
Cdd:cd08836     90 PTPDSSREEKERWIRAKY 107
ArfGap_ACAP cd08835
ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP ...
695-797 1.45e-28

ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP domain is an essential part of ACAP proteins that play important role in endocytosis, actin remodeling and receptor tyrosine kinase-dependent cell movement. ACAP subfamily of ArfGAPs are composed of coiled coils (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. In addition, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.


Pssm-ID: 350064 [Multi-domain]  Cd Length: 116  Bit Score: 111.58  E-value: 1.45e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQKDEE 774
Cdd:cd08835     13 NAQCCDCGSPDPRWASINLGVTLCIECSGIHRSLGVHVSKVRSLTLDS--WEPELLKVMLELGNDVVNRIYEANVPDDGS 90
                           90       100
                   ....*....|....*....|....*
gi 1907161909  775 LQ--VDSPVEKRKNFITQKYKEGKF 797
Cdd:cd08835     91 VKptPDSSRQEREAWIRAKYVEKKF 115
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
692-799 9.15e-27

GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ARF-mediated vesicular transport [Intracellular trafficking and secretion];


Pssm-ID: 227651 [Multi-domain]  Cd Length: 319  Bit Score: 112.95  E-value: 9.15e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  692 NESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRANDFWAGNLQK 771
Cdd:COG5347     17 DSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLD--NWTEEELRRMEVGGNSNANRFYEKNLLD 94
                           90       100       110
                   ....*....|....*....|....*....|..
gi 1907161909  772 DEELQV----DSPVekRKNFITQKYKEGKFRK 799
Cdd:COG5347     95 QLLLPIkakyDSSV--AKKYIRKKYELKKFID 124
RA_ARAP3 cd17228
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1296-1368 1.62e-26

Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3 (ARAP3); ARAP3, also termed Centaurin-delta-3 (Cnt-d3), is a phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3))-dependent Arf Rap-activated guanosine triphosphatase (GTPase)-activating protein (GAP) that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members, ADP-ribosylation factor 6 (Arf6) and Ras homolog gene family member A (RhoA). It is regulated by phosphatidylinositol 3,4,5-trisphosphate and a small GTPase Rap1-GTP, and has been implicated in the regulation of cell shape and adhesion. ARAP3 contains multiple functional domains, including ArfGAP and RhoGAP domains, as well as a sterile alpha motif (Sam) domain, five PH domains, and a RA domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes.


Pssm-ID: 340748  Cd Length: 99  Bit Score: 104.96  E-value: 1.62e-26
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907161909 1296 EISPVMEAEELTNDILAIKNIIPMKGDIWATFEVIENEELERPLHYTENVLEQVLQWSSLAEPGSAYLVVKRF 1368
Cdd:cd17228     22 KVSPTMTAEELTNQVLDMRNIAAASKDVWLTFEVIENGELERPLHPKEKVLEQALQWCKLPEPSSAYLLVKKV 94
ArfGap_GIT cd08833
The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein ...
694-792 2.49e-26

The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350062 [Multi-domain]  Cd Length: 109  Bit Score: 104.69  E-value: 2.49e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  694 SNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRANDFWAGNL---- 769
Cdd:cd08833      7 NARVCADCSAPDPEWASINRGVLICDECCSIHRSLGRHISQVKSLRKD--QWPPSLLEMVQTLGNNGANSIWEHSLldps 84
                           90       100
                   ....*....|....*....|....*
gi 1907161909  770 --QKDEELQVDSPVEKRKNFITQKY 792
Cdd:cd08833     85 qsGKRKPIPPDPVHPTKEEFIKAKY 109
ArfGap_SMAP cd08839
Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of ...
693-792 9.36e-25

Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of Arf GTPase-activating proteins consists of the two structurally-related members, SMAP1 and SMAP2. Each SMAP member exhibits common and distinct functions in vesicle trafficking. They both bind to clathrin heavy chain molecules and are involved in the trafficking of clathrin-coated vesicles. SMAP1 preferentially exhibits GAP toward Arf6, while SMAP2 prefers Arf1 as a substrate. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin. SMAP2 regulates Arf1-dependent retrograde transport of TGN38/46 from the early endosome to the trans-Golgi network (TGN). SMAP2 has the Clathrin Assembly Lymphoid Myeloid (CALM)-binding domain, but SMAP1 does not.


Pssm-ID: 350068 [Multi-domain]  Cd Length: 103  Bit Score: 100.04  E-value: 9.36e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  693 ESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQKD 772
Cdd:cd08839      8 EDNKYCADCGAKGPRWASWNLGVFICIRCAGIHRNLGVHISKVKSVNLDS--WTPEQVQSMQEMGNARANAYYEANLPDG 85
                           90       100
                   ....*....|....*....|.
gi 1907161909  773 -EELQVDSPVEkrkNFITQKY 792
Cdd:cd08839     86 fRRPQTDSALE---NFIRDKY 103
ArfGap_ADAP cd08832
ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) ...
693-765 2.71e-24

ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350061 [Multi-domain]  Cd Length: 113  Bit Score: 99.26  E-value: 2.71e-24
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907161909  693 ESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFW 765
Cdd:cd08832     15 PGNNTCADCGAPDPEWASYNLGVFICLDCSGIHRSLGTHISKVKSLRLDN--WDDSQVEFMEENGNEKAKAKY 85
ArfGap_AGAP2 cd08853
ArfGAP with GTPase domain, ANK repeat and PH domain 2; The AGAP subfamily of ADP-ribosylation ...
695-793 6.39e-24

ArfGAP with GTPase domain, ANK repeat and PH domain 2; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.


Pssm-ID: 350078 [Multi-domain]  Cd Length: 109  Bit Score: 98.16  E-value: 6.39e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQKDEE 774
Cdd:cd08853     13 NSHCVDCETQNPKWASLNLGVLMCIECSGIHRNLGTHLSRVRSLDLDD--WPVELRKVMSSIGNELANSIWEGSSQGQTK 90
                           90
                   ....*....|....*....
gi 1907161909  775 LQVDSPVEKRKNFITQKYK 793
Cdd:cd08853     91 PSSDSTREEKERWIRAKYE 109
ArfGap_AGAP3 cd08855
ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation ...
695-793 1.34e-23

ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion.


Pssm-ID: 350080 [Multi-domain]  Cd Length: 110  Bit Score: 97.05  E-value: 1.34e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQKDEE 774
Cdd:cd08855     14 NSFCIDCDAPNPDWASLNLGALMCIECSGIHRNLGTHLSRVRSLDLDD--WPVELSMVMTAIGNAMANSVWEGALDGYSK 91
                           90
                   ....*....|....*....
gi 1907161909  775 LQVDSPVEKRKNFITQKYK 793
Cdd:cd08855     92 PGPDSTREEKERWIRAKYE 110
ArfGap_AGAP1 cd08854
ArfGAP with GTPase domain, ANK repeat and PH domain 1; The AGAP subfamily of ADP-ribosylation ...
695-793 2.01e-23

ArfGAP with GTPase domain, ANK repeat and PH domain 1; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.


Pssm-ID: 350079 [Multi-domain]  Cd Length: 109  Bit Score: 96.62  E-value: 2.01e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRANDFWAGNLQKDEE 774
Cdd:cd08854     13 NSLCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLD--DWPRELTLVLTAIGNHMANSIWESCTQGRTK 90
                           90
                   ....*....|....*....
gi 1907161909  775 LQVDSPVEKRKNFITQKYK 793
Cdd:cd08854     91 PAPDSSREERESWIRAKYE 109
RhoGAP_ARHGAP21 cd04395
RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1126-1295 3.07e-23

RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP21-like proteins. ArhGAP21 is a multi-domain protein, containing RhoGAP, PH and PDZ domains, and is believed to play a role in the organization of the cell-cell junction complex. It has been shown to function as a GAP of Cdc42 and RhoA, and to interact with alpha-catenin and Arf6. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239860  Cd Length: 196  Bit Score: 99.01  E-value: 3.07e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQ-LEDVTGVLKSFLSDIDDALLTKELY 1204
Cdd:cd04395     18 VPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRdVNVVSSLLKSFFRKLPEPLFTNELY 97
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1205 PYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKGQT------- 1277
Cdd:cd04395     98 PDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTSDDNmetmvth 177
                          170
                   ....*....|....*....
gi 1907161909 1278 -SEEVNVIEDLINNYVEIF 1295
Cdd:cd04395    178 mPDQCKIVETLIQHYDWFF 196
RhoGAP_myosin_IX cd04377
RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1123-1273 9.55e-23

RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in class IX myosins. Class IX myosins contain a characteristic head domain, a neck domain, a tail domain which contains a C6H2-zinc binding motif and a RhoGAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239842  Cd Length: 186  Bit Score: 97.51  E-value: 9.55e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1123 KNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRagKHQLEDVTGVLKSFLSDIDDALLTKE 1202
Cdd:cd04377     12 DRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDPDSVNLE--DYPIHVITSVLKQWLRELPEPLMTFE 89
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907161909 1203 LYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQT 1273
Cdd:cd04377     90 LYENFLRAMELEEKQERVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRC 160
ArfGap_ASAP cd08834
ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation ...
695-797 1.27e-22

ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation factor GTPase-activating proteins; The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. Both ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350063 [Multi-domain]  Cd Length: 117  Bit Score: 94.59  E-value: 1.27e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRANDFWAGNLQKDEE 774
Cdd:cd08834     15 NDVCCDCGSPDPTWLSTNLGILTCIECSGVHRELGVHVSRIQSLTLD--NLGTSELLLARNLGNEGFNEIMEANLPPGYK 92
                           90       100
                   ....*....|....*....|...
gi 1907161909  775 LQVDSPVEKRKNFITQKYKEGKF 797
Cdd:cd08834     93 PTPNSDMEERKDFIRAKYVEKKF 115
ArfGap_ArfGap1 cd08830
Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
693-793 2.50e-22

Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350059 [Multi-domain]  Cd Length: 115  Bit Score: 93.72  E-value: 2.50e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  693 ESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNlqkd 772
Cdd:cd08830     12 PGNNRCFDCGAPNPQWASVSYGIFICLECSGVHRGLGVHISFVRSITMDS--WSEKQLKKMELGGNAKLREFFESY---- 85
                           90       100
                   ....*....|....*....|.
gi 1907161909  773 eELQVDSPvekrknfITQKYK 793
Cdd:cd08830     86 -GISPDLP-------IREKYN 98
ArfGap_ACAP1 cd08852
ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs ...
684-797 7.53e-22

ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.


Pssm-ID: 350077 [Multi-domain]  Cd Length: 120  Bit Score: 92.33  E-value: 7.53e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  684 EVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRAND 763
Cdd:cd08852      2 HAVAQVQSVDGNAQCCDCREPAPEWASINLGVTLCIQCSGIHRSLGVHFSKVRSLTLDS--WEPELVKLMCELGNVIINQ 79
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1907161909  764 FWAGNLqkdEELQV-----DSPVEKRKNFITQKYKEGKF 797
Cdd:cd08852     80 IYEARI---EAMAIkkpgpSSSRQEKEAWIRAKYVEKKF 115
ArfGap_ACAP2 cd08851
ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs ...
695-797 3.74e-21

ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.


Pssm-ID: 350076 [Multi-domain]  Cd Length: 116  Bit Score: 90.43  E-value: 3.74e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDasIWSNELIELFIVIGNKRANDFWAGNLQK--D 772
Cdd:cd08851     13 NASCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLD--TWEPELLKLMCELGNDVINRIYEARVEKmgA 90
                           90       100
                   ....*....|....*....|....*
gi 1907161909  773 EELQVDSPVEKRKNFITQKYKEGKF 797
Cdd:cd08851     91 KKPQPGGQRQEKEAYIRAKYVERKF 115
RA_ARAPs cd17113
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1295-1368 5.70e-21

Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing proteins ARAP1, ARAP2, ARAP3, and similar proteins; ARAPs are phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3))-dependent Arf Rap-activated guanosine triphosphatase (GTPase)-activating proteins (GAPs). They contain multiple functional domains, including ArfGAP and RhoGAP domains, as well as a sterile alpha motif (Sam) domain, five PH domains, and a RA domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes.


Pssm-ID: 340633  Cd Length: 95  Bit Score: 88.84  E-value: 5.70e-21
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907161909 1295 FEISPVMEAEELTNDILAIKNIIPMKGDiWATFEVIENEELERPLHYTENVLEQVLQWSSLaEPGSAYLVVKRF 1368
Cdd:cd17113     20 IKVTPTMTAEEVVEQALNKKNLGGPEGN-WALFEVIEDGGLERPLHESEKVLDVVLRWSQW-PRKSNYLCVKKN 91
ArfGap_ACAP3 cd08850
ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 belongs ...
695-797 2.93e-20

ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. It has been shown that ACAP3 positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) also have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages.


Pssm-ID: 350075 [Multi-domain]  Cd Length: 116  Bit Score: 87.69  E-value: 2.93e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGnlqKDEE 774
Cdd:cd08850     13 NDQCCDCGQPDPRWASINLGILLCIECSGIHRSLGVHCSKVRSLTLDS--WEPELLKLMCELGNSTVNQIYEA---QCEE 87
                           90       100
                   ....*....|....*....|....*...
gi 1907161909  775 LQVDSPV-----EKRKNFITQKYKEGKF 797
Cdd:cd08850     88 LGLKKPTasssrQDKEAWIKAKYVEKKF 115
RhoGAP_ARHGAP27_15_12_9 cd04403
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
1121-1278 5.69e-20

RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP27 (also called CAMGAP1), ARHGAP15, 12 and 9-like proteins; This subgroup of ARHGAPs are multidomain proteins that contain RhoGAP, PH, SH3 and WW domains. Most members that are studied show GAP activity towards Rac1, some additionally show activity towards Cdc42. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239868 [Multi-domain]  Cd Length: 187  Bit Score: 89.37  E-value: 5.69e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1121 LC---KNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELleSFKKDaRSVKLRAGKHQLED---VTGVLKSFLSDI 1194
Cdd:cd04403      8 LCqreNSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKL--RFAVD-HDEKLDLDDSKWEDihvITGALKLFFREL 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1195 DDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTK 1274
Cdd:cd04403     85 PEPLFPYSLFNDFVAAIKLSDYEQRVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTLLRPE 164

                   ....
gi 1907161909 1275 GQTS 1278
Cdd:cd04403    165 QETG 168
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1127-1295 6.39e-20

RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239837 [Multi-domain]  Cd Length: 194  Bit Score: 89.50  E-value: 6.39e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1127 PIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKH-QLEDVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04372     17 PMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRDGEKADISATVYpDINVITGALKLYFRDLPIPVITYDTYP 96
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1206 YWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKGQTS------- 1278
Cdd:cd04372     97 KFIDAAKISNPDERLEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPPEDSAlttlndm 176
                          170
                   ....*....|....*...
gi 1907161909 1279 -EEVNVIEDLINNYVEIF 1295
Cdd:cd04372    177 rYQILIVQLLITNEDVLF 194
RhoGAP_myosin_IXB cd04407
RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1123-1272 2.87e-19

RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXB. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239872 [Multi-domain]  Cd Length: 186  Bit Score: 87.35  E-value: 2.87e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1123 KNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRagKHQLEDVTGVLKSFLSDIDDALLTKE 1202
Cdd:cd04407     12 KTSVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKLE--NYPIHAITGLLKQWLRELPEPLMTFA 89
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1203 LYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQ 1272
Cdd:cd04407     90 QYNDFLRAVELPEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLR 159
RhoGAP_p190 cd04373
RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1113-1271 4.54e-19

RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p190-like proteins. p190, also named RhoGAP5, plays a role in neuritogenesis and axon branch stability. p190 shows a preference for Rho, over Rac and Cdc42, and consists of an N-terminal GTPase domain and a C-terminal GAP domain. The central portion of p190 contains important regulatory phosphorylation sites. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239838  Cd Length: 185  Bit Score: 86.74  E-value: 4.54e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1113 GNALQDQQLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDaRSVKLRAGKHQLEDVTGVLKSFLS 1192
Cdd:cd04373      2 GVPLANVVTSEKPIPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQD-HNLDLVSKDFTVNAVAGALKSFFS 80
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907161909 1193 DIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLF 1271
Cdd:cd04373     81 ELPDPLIPYSMHLELVEAAKINDREQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLM 159
ArfGap_SMAP2 cd08859
Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of ...
693-796 1.32e-18

Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of Arf GTPase-activating proteins consists of the two structurally-related members, SMAP1 and SMAP2. Each SMAP member exhibits common and distinct functions in vesicle trafficking. They both bind to clathrin heavy chain molecules and are involved in the trafficking of clathrin-coated vesicles. SMAP1 preferentially exhibits GAP toward Arf6, while SMAP2 prefers Arf1 as a substrate. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin. SMAP2 regulates Arf1-dependent retrograde transport of TGN38/46 from the early endosome to the trans-Golgi network (TGN). SMAP2 has the Clathrin Assembly Lymphoid Myeloid (CALM)-binding domain, but SMAP1 does not.


Pssm-ID: 350083 [Multi-domain]  Cd Length: 107  Bit Score: 82.73  E-value: 1.32e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  693 ESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNLQKD 772
Cdd:cd08859      8 EENKFCADCQSKGPRWASWNIGVFICIRCAGIHRNLGVHISRVKSVNLDQ--WTQEQIQCMQEMGNGKANRLYEAFLPEN 85
                           90       100
                   ....*....|....*....|....*
gi 1907161909  773 -EELQVDSPVEkrkNFITQKYKEGK 796
Cdd:cd08859     86 fRRPQTDQAVE---GFIRDKYEKKK 107
RhoGAP_ARHGAP20 cd04402
RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1113-1295 1.39e-18

RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP20-like proteins. ArhGAP20, also known as KIAA1391 and RA-RhoGAP, contains a RhoGAP, a RA, and a PH domain, and ANXL repeats. ArhGAP20 is activated by Rap1 and induces inactivation of Rho, which in turn leads to neurite outgrowth. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239867  Cd Length: 192  Bit Score: 85.43  E-value: 1.39e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1113 GNALQDqqLCKND-VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLEsfkkdarsvKLRAGKHQLED------VTG 1185
Cdd:cd04402      3 GQPLSN--ICEDDnLPKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKE---------KLNSGVEVDLKaepvllLAS 71
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1186 VLKSFLSDIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMV 1265
Cdd:cd04402     72 VLKDFLRNIPGSLLSSDLYEEWMSALDQENEEEKIAELQRLLDKLPRPNVLLLKHLICVLHNISQNSETNKMDAFNLAVC 151
                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1907161909 1266 FSSCLFQTKGQTSEEVNV-------IEDLINNYVEIF 1295
Cdd:cd04402    152 IAPSLLWPPASSELQNEDlkkvtslVQFLIENCQEIF 188
RhoGAP_Bcr cd04387
RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr ...
1126-1272 3.51e-18

RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr (breakpoint cluster region protein)-like proteins. Bcr is a multidomain protein with a variety of enzymatic functions. It contains a RhoGAP and a Rho GEF domain, a Ser/Thr kinase domain, an N-terminal oligomerization domain, and a C-terminal PDZ binding domain, in addition to PH and C2 domains. Bcr is a negative regulator of: i) RacGTPase, via the Rho GAP domain, ii) the Ras-Raf-MEK-ERK pathway, via phosphorylation of the Ras binding protein AF-6, and iii) the Wnt signaling pathway through binding beta-catenin. Bcr can form a complex with beta-catenin and Tcf1. The Wnt signaling pathway is involved in cell proliferation, differentiation, and cell renewal. Bcr was discovered as a fusion partner of Abl. The Bcr-Abl fusion is characteristic for a large majority of chronic myelogenous leukemias (CML). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239852 [Multi-domain]  Cd Length: 196  Bit Score: 84.59  E-value: 3.51e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLEDVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04387     16 VPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEMDVNAIAGTLKLYFRELPEPLFTDELYP 95
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907161909 1206 YWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQ 1272
Cdd:cd04387     96 NFAEGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLR 162
RhoGAP-p50rhoGAP cd04404
RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1116-1295 4.55e-18

RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p50RhoGAP-like proteins; p50RhoGAP, also known as RhoGAP-1, contains a C-terminal RhoGAP domain and an N-terminal Sec14 domain which binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). It is ubiquitously expressed and preferentially active on Cdc42. This subgroup also contains closely related ARHGAP8. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239869 [Multi-domain]  Cd Length: 195  Bit Score: 83.93  E-value: 4.55e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1116 LQDQQLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDarsvkLRAGKHQLEDV---TGVLKSFLS 1192
Cdd:cd04404     13 LKEKNPEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMG-----EPVDFDQYEDVhlpAVILKTFLR 87
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1193 DIDDALLTKELYPYwVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQ 1272
Cdd:cd04404     88 ELPEPLLTFDLYDD-IVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLW 166
                          170       180
                   ....*....|....*....|....*....
gi 1907161909 1273 TKGQ--TSEEVNVI----EDLINNYVEIF 1295
Cdd:cd04404    167 AKDAsmSLSAINPIntftKFLLDHQDEIF 195
ArfGap_ArfGap2_3_like cd08831
Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
695-794 6.29e-18

Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350060 [Multi-domain]  Cd Length: 116  Bit Score: 81.05  E-value: 6.29e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFW---AGNLQK 771
Cdd:cd08831     15 NKVCFDCGAKNPTWASVTFGVFLCLDCSGVHRSLGVHISFVRSTNLDS--WTPEQLRRMKVGGNAKAREFFkqhGGLLSG 92
                           90       100
                   ....*....|....*....|...
gi 1907161909  772 DEElqvdspvEKRKNFITQKYKE 794
Cdd:cd08831     93 DIK-------QKYTSRAAQKYKE 108
ArfGap_ArfGap1_like cd08959
ARF1 GTPase-activating protein 1-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
695-765 1.09e-17

ARF1 GTPase-activating protein 1-like; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350084 [Multi-domain]  Cd Length: 115  Bit Score: 80.25  E-value: 1.09e-17
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFW 765
Cdd:cd08959     14 NKVCFDCGAKNPQWASVTYGIFICLDCSGVHRGLGVHISFVRSTTMDK--WTEEQLRKMKVGGNANAREFF 82
ArfGap_ASAP1 cd08848
ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); ...
695-800 2.06e-17

ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350073 [Multi-domain]  Cd Length: 122  Bit Score: 80.08  E-value: 2.06e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDaSIWSNELIeLFIVIGNKRANDFWAGNL-QKDE 773
Cdd:cd08848     15 NEVCCDCGSPDPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELD-KLGTSELL-LAKNVGNNSFNDIMEGNLpSPSP 92
                           90       100
                   ....*....|....*....|....*...
gi 1907161909  774 ELQVDSPVEKRKNFITQKYKEGKF-RKT 800
Cdd:cd08848     93 KPSPSSDMTARKEYITAKYVEHRFsRKT 120
RhoGAP_MgcRacGAP cd04382
RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1126-1296 4.09e-17

RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in MgcRacGAP proteins. MgcRacGAP plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling. ii) after phosphorylation by aurora B MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain a N-terminal C1-like domain, and a C-terminal RhoGAP domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239847  Cd Length: 193  Bit Score: 81.19  E-value: 4.09e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLraGKHQLEDVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04382     17 IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNL--SKVDIHVICGCLKDFLRSLKEPLITFALWK 94
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1206 YWVSALDTQDEKE-RTSKYRAfIRSLPGVNRATLAALIEHLYRVQKCSEiNHMNAHNLAMVFSSCLFQTKGQTSEEVNVI 1284
Cdd:cd04382     95 EFMEAAEILDEDNsRAALYQA-ISELPQPNRDTLAFLILHLQRVAQSPE-CKMDINNLARVFGPTIVGYSVPNPDPMTIL 172
                          170
                   ....*....|..
gi 1907161909 1285 EDlINNYVEIFE 1296
Cdd:cd04382    173 QD-TVRQPRVVE 183
ArfGap_ASAP3 cd17900
ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ...
695-797 5.44e-17

ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP1 and ASAP2, ASAP3 do not have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350087 [Multi-domain]  Cd Length: 124  Bit Score: 78.74  E-value: 5.44e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsIWSNELIeLFIVIGNKRANDFWAGNL--QKD 772
Cdd:cd17900     15 NSQCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVRYSRIQSLTLDL-LSTSELL-LAVSMGNTRFNEVMEATLpaHGG 92
                           90       100
                   ....*....|....*....|....*
gi 1907161909  773 EELQVDSPVEKRKNFITQKYKEGKF 797
Cdd:cd17900     93 PKPSAESDMGTRKDYIMAKYVEHRF 117
RhoGAP_myosin_IXA cd04406
RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1126-1287 5.94e-17

RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXA. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239871  Cd Length: 186  Bit Score: 80.82  E-value: 5.94e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLraGKHQLEDVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04406     15 VPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDANSVNL--DDYNIHVIASVFKQWLRDLPNPLMTFELYE 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1206 YWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKgQTSEEVNVIE 1285
Cdd:cd04406     93 EFLRAMGLQERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPCILRCP-DTTDPLQSVQ 171

                   ..
gi 1907161909 1286 DL 1287
Cdd:cd04406    172 DI 173
RhoGAP_ARHGAP6 cd04376
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1126-1301 6.71e-17

RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP6-like proteins. ArhGAP6 shows GAP activity towards RhoA, but not towards Cdc42 and Rac1. ArhGAP6 is often deleted in microphthalmia with linear skin defects syndrome (MLS); MLS is a severe X-linked developmental disorder. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239841  Cd Length: 206  Bit Score: 80.95  E-value: 6.71e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKdARSVKLRAgKHQLEDVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04376      9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDR-GIDVVLDE-NHSVHDVAALLKEFFRDMPDPLLPRELYT 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1206 YWVSALdTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINH-----------MNAHNLAMVFSSCLFQ-T 1273
Cdd:cd04376     87 AFIGTA-LLEPDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADSIdedgqevsgnkMTSLNLATIFGPNLLHkQ 165
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1907161909 1274 KGQTSEE-------------VNVIEDLINNYVEIFEISPVM 1301
Cdd:cd04376    166 KSGEREFvqaslrieestaiINVVQTMIDNYEELFMVSPEL 206
RhoGAP_GMIP cd04408
RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP ...
1125-1290 8.51e-17

RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239873  Cd Length: 200  Bit Score: 80.63  E-value: 8.51e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1125 DVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLraGKHQLEDVTGVLKSFLSDIDDALLTKELY 1204
Cdd:cd04408     15 EVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGRDLVDL--SGHSPHDITSVLKHFLKELPEPVLPFQLY 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1205 PYWVS-----ALDTQDEKERTSKYRAFIRS-------LPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFS----- 1267
Cdd:cd04408     93 DDFIAlakelQRDSEKAAESPSIVENIIRSlkellgrLPVSNYNTLRHLMAHLYRVAERFEDNKMSPNNLGIVFGptllr 172
                          170       180       190
                   ....*....|....*....|....*....|..
gi 1907161909 1268 ---------SCLFQTKGQTseevNVIEDLINN 1290
Cdd:cd04408    173 plvggdvsmICLLDTGYQA----QLVEFLISN 200
RhoGAP_nadrin cd04386
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1113-1295 1.25e-16

RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Nadrin-like proteins. Nadrin, also named Rich-1, has been shown to be involved in the regulation of Ca2+-dependent exocytosis in neurons and recently has been implicated in tight junction maintenance in mammalian epithelium. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239851  Cd Length: 203  Bit Score: 80.19  E-value: 1.25e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1113 GNALQDQ-QLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFkkDARSVKLRAgKHQLED---VTGVLK 1188
Cdd:cd04386      6 GTPLEEHlKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAAL--DAGTFSLPL-DEFYSDphaVASALK 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1189 SFLSDIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSS 1268
Cdd:cd04386     83 SYLRELPDPLLTYNLYEDWVQAANKPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAP 162
                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1907161909 1269 CLFQTK----------GQTSEEVNVIEDLINNYVEIF 1295
Cdd:cd04386    163 NLLWAKnegslaemaaGTSVHVVAIVELIISHADWFF 199
RhoGAP_CdGAP cd04384
RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1125-1274 4.43e-16

RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of CdGAP-like proteins; CdGAP contains an N-terminal RhoGAP domain and a C-terminal proline-rich region, and it is active on both Cdc42 and Rac1 but not RhoA. CdGAP is recruited to focal adhesions via the interaction with the scaffold protein actopaxin (alpha-parvin). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239849 [Multi-domain]  Cd Length: 195  Bit Score: 78.31  E-value: 4.43e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1125 DVPIIVNSCIAFVTQYGLgCKYIYQKDGDPLHISELLESFKKDAR-SVKLRAGKHQLEDVTGVLKSFLSDIDDALLTKEL 1203
Cdd:cd04384     17 DVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIpDLTKDVYIQDIHSVSSLCKLYFRELPNPLLTYQL 95
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907161909 1204 YPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTK 1274
Cdd:cd04384     96 YEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAPNLLRSK 166
ArfGap_ASAP2 cd08849
ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2) ...
695-799 4.91e-16

ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2); The Arf GAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf , thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport.


Pssm-ID: 350074 [Multi-domain]  Cd Length: 123  Bit Score: 76.17  E-value: 4.91e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsIWSNELIeLFIVIGNKRANDFWAGNLQKDEE 774
Cdd:cd08849     15 NDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDV-LGTSELL-LAKNIGNAGFNEIMEACLPAEDV 92
                           90       100
                   ....*....|....*....|....*..
gi 1907161909  775 LQVD--SPVEKRKNFITQKYKEGKFRK 799
Cdd:cd08849     93 VKPNpgSDMNARKDYITAKYIERRYAR 119
ArfGap_ADAP2 cd08844
ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
694-763 6.99e-16

ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350070 [Multi-domain]  Cd Length: 112  Bit Score: 75.19  E-value: 6.99e-16
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  694 SNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLgPKDSKVRSLKMDasIWSNELIELFIVIGNKRAND 763
Cdd:cd08844     16 GNSVCADCGAPDPDWASYTLGIFICLNCSGVHRNL-PDISRVKSIRLD--FWEDELVEFMKENGNLKAKA 82
ArfGap_ADAP1 cd08843
ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
695-761 7.64e-16

ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350069 [Multi-domain]  Cd Length: 112  Bit Score: 75.04  E-value: 7.64e-16
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLgPKDSKVRSLKMDAsiWSNELIELFIVIGNKRA 761
Cdd:cd08843     17 NARCADCGAPDPDWASYTLGVFICLSCSGIHRNI-PQVSKVKSVRLDA--WEEAQVEFMASHGNDAA 80
RhoGAP_GMIP_PARG1 cd04378
RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1126-1290 1.83e-15

RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein) and PARG1 (PTPL1-associated RhoGAP1). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239843  Cd Length: 203  Bit Score: 76.69  E-value: 1.83e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLraGKHQLEDVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04378     16 VPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLVEL--SELSPHDISSVLKLFLRQLPEPLILFRLYN 93
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1206 YWVS------ALDTQDEKERTS--------KYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFS---- 1267
Cdd:cd04378     94 DFIAlakeiqRDTEEDKAPNTPievnriirKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEENKMSPNNLGIVFGptli 173
                          170       180       190
                   ....*....|....*....|....*....|....
gi 1907161909 1268 -----------SCLFQTKGQTseevNVIEDLINN 1290
Cdd:cd04378    174 rprpgdadvslSSLVDYGYQA----RLVEFLITN 203
RhoGAP_FAM13A1a cd04393
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1116-1271 4.97e-15

RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of FAM13A1, isoform a-like proteins. The function of FAM13A1a is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by up several orders of magnitude.


Pssm-ID: 239858 [Multi-domain]  Cd Length: 189  Bit Score: 75.19  E-value: 4.97e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1116 LQDQQLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDplhiSELLESFKKdarsvKLRAGKHQ-------LEDVTGVLK 1188
Cdd:cd04393     10 LQQAGQPENGVPAVVRHIVEYLEQHGLEQEGLFRVNGN----AETVEWLRQ-----RLDSGEEVdlskeadVCSAASLLR 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1189 SFLSDIDDALLTKELYPYWVSAL-DTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFS 1267
Cdd:cd04393     81 LFLQELPEGLIPASLQIRLMQLYqDYNGEDEFGRKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVFG 160

                   ....
gi 1907161909 1268 SCLF 1271
Cdd:cd04393    161 PDVF 164
ArfGap_GIT2 cd08847
GIT2 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
694-769 7.06e-15

GIT2 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350072 [Multi-domain]  Cd Length: 111  Bit Score: 72.36  E-value: 7.06e-15
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907161909  694 SNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVIGNKRANDFWAGNL 769
Cdd:cd08847      7 SSEVCADCSTSDPRWASVNRGVLICDECCSVHRSLGRHISQVRHLKHTS--WPPTLLQMVQTLYNNGANSIWEHSL 80
RhoGap_RalBP1 cd04381
RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1125-1267 1.13e-14

RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in RalBP1 proteins, also known as RLIP, RLIP76 or cytocentrin. RalBP1 plays an important role in endocytosis during interphase. During mitosis, RalBP1 transiently associates with the centromere and has been shown to play an essential role in the proper assembly of the mitotic apparatus. RalBP1 is an effector of the Ral GTPase which itself is an effector of Ras. RalBP1 contains a RhoGAP domain, which shows weak activity towards Rac1 and Cdc42, but not towards Ral, and a Ral effector domain binding motif. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239846 [Multi-domain]  Cd Length: 182  Bit Score: 74.01  E-value: 1.13e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1125 DVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKkdarsvklRAGKHQLED-----VTGVLKSFLSDIDDALL 1199
Cdd:cd04381     19 DLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYN--------RRESPNLEEyepptVASLLKQYLRELPEPLL 90
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907161909 1200 TKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFS 1267
Cdd:cd04381     91 TKELMPRFEEACGRPTEAEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNISIVLS 158
RA_ARAP1 cd17226
Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH ...
1296-1367 3.92e-14

Ras-associating (RA) domain found in Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1); ARAP1, also termed Centaurin-delta-2 (Cnt-d2), is a phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3))-dependent Arf Rap-activated guanosine triphosphatase (GTPase)-activating protein (GAP) that inhibits the trafficking of epidermal growth factor receptor (EGFR) to the early endosome. It associates with the Cbl-interacting protein of 85 kDa (CIN85), regulates endocytic trafficking of the EGFR, and thus affects ubiquitination of EGFR. It also regulates the ring size of circular dorsal ruffles through Arf1 and Arf5. ARAP1 contains multiple functional domains, including ArfGAP and RhoGAP domains, as well as a sterile alpha motif (Sam) domain, five PH domains, and a RA domain. The RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes.


Pssm-ID: 340746  Cd Length: 93  Bit Score: 69.50  E-value: 3.92e-14
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907161909 1296 EISPVMEAEELTNDILAIKNIIPMKGDIWATFEVIENEELERPLHYTENVLEQVLQWSSlaepgSAYLVVKR 1367
Cdd:cd17226     22 QVPASMTAEELTFEILDRRNIHTREKDYWSCFEVNEREEAERPLHFSEKVLPIFHSLGS-----DSHLVVKK 88
RhoGAP_SYD1 cd04379
RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
1125-1271 1.92e-13

RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239844  Cd Length: 207  Bit Score: 70.96  E-value: 1.92e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1125 DVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLEDV-TGVLKSFLSDIDDALLTKEL 1203
Cdd:cd04379     17 DVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDINViTGVLKDYLRELPEPLITPQL 96
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907161909 1204 YPYWVSAL--DTQDEKERTSKY-RAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLF 1271
Cdd:cd04379     97 YEMVLEALavALPNDVQTNTHLtLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAVCFGPVLM 167
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
483-567 3.66e-13

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 66.80  E-value: 3.66e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  483 KCGWLDKLSPQGKRMFQKRWVKFDGLSISYYNNDREM--YSKGIIPLTAISTVRAQGD----NKFEIVTT-QRTFVFRVE 555
Cdd:cd00821      1 KEGYLLKRGGGGLKSWKKRWFVLFEGVLLYYKSKKDSsyKPKGSIPLSGILEVEEVSPkerpHCFELVTPdGRTYYLQAD 80
                           90
                   ....*....|..
gi 1907161909  556 KEEERNDWISIL 567
Cdd:cd00821     81 SEEERQEWLKAL 92
ArfGap_GIT1 cd08846
GIT1 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
698-792 4.19e-13

GIT1 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350071 [Multi-domain]  Cd Length: 111  Bit Score: 67.05  E-value: 4.19e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  698 CADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMdaSIWSNELIELFIVIGNKRANDFWAGNLQKDEELQV 777
Cdd:cd08846     11 CADCSAPDPGWASINRGVLICDECCSVHRSLGRHISIVKHLRH--SAWPPTLLQMVHTLASNGANSIWEHSLLDPAQVQS 88
                           90       100
                   ....*....|....*....|...
gi 1907161909  778 D----SPVEK----RKNFITQKY 792
Cdd:cd08846     89 GrrkaNPQDKvhptKSEFIRAKY 111
ArfGap_AGFG cd08838
ArfGAP domain of the AGFG subfamily (ArfGAP domain and FG repeat-containing proteins); The ...
693-797 9.34e-13

ArfGAP domain of the AGFG subfamily (ArfGAP domain and FG repeat-containing proteins); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG1 (alias: HIV-1 Rev binding protein, HRB; Rev interacting protein, RIP; Rev/Rex activating domain-binding protein, RAB) and AGFG2 are involved in the maintenance and spread of immunodeficiency virus type 1 (HIV-1) infection. The ArfGAP domain of AGFG is related to nucleoporins, which is a class of proteins that mediate nucleocytoplasmic transport. AGFG plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs, possibly together by the nuclear export receptor CRM1. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.


Pssm-ID: 350067 [Multi-domain]  Cd Length: 113  Bit Score: 66.06  E-value: 9.34e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  693 ESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGpkdSKVRSLKMdaSIWSNELIELFIVIGNKRANDFWAGNL-QK 771
Cdd:cd08838     11 PENKRCFDCGQRGPTYVNLTFGTFVCTTCSGIHREFN---HRVKSISM--STFTPEEVEFLQAGGNEVARKIWLAKWdPR 85
                           90       100
                   ....*....|....*....|....*.
gi 1907161909  772 DEELQVDSPVEKRKNFITQKYKEGKF 797
Cdd:cd08838     86 TDPEPDSGDDQKIREFIRLKYVDKRW 111
RhoGAP_fLRG1 cd04397
RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1126-1299 1.16e-12

RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal LRG1-like proteins. Yeast Lrg1p is required for efficient cell fusion, and mother-daughter cell separation, possibly through acting as a RhoGAP specifically regulating 1,3-beta-glucan synthesis. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239862  Cd Length: 213  Bit Score: 68.93  E-value: 1.16e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLEdVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04397     27 IPALIDDIISAMRQMDMSVEGVFRKNGNIRRLKELTEEIDKNPTEVPDLSKENPVQ-LAALLKKFLRELPDPLLTFKLYR 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1206 YWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEI-----NHMNAHNLAMVFSSCLFQTKGQTSEE 1280
Cdd:cd04397    106 LWISSQKIEDEEERKRVLHLVYCLLPKYHRDTMEVLFSFLKWVSSFSHIdeetgSKMDIHNLATVITPNILYSKTDNPNT 185
                          170       180
                   ....*....|....*....|....*.
gi 1907161909 1281 VN-------VIEDLINNYVEIFEISP 1299
Cdd:cd04397    186 GDeyflaieAVNYLIENNEEFCEVPD 211
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
483-572 1.66e-12

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 65.26  E-value: 1.66e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909   483 KCGWLDKLSPQGKRMFQKRWVKFDGLSISYYNNDREMYS---KGIIPLTAIS------TVRAQGDNKFEIVTTQR-TFVF 552
Cdd:smart00233    3 KEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSykpKGSIDLSGCTvreapdPDSSKKPHCFEIKTSDRkTLLL 82
                            90       100
                    ....*....|....*....|
gi 1907161909   553 RVEKEEERNDWISILLSALK 572
Cdd:smart00233   83 QAESEEEREKWVEALRKAIA 102
RhoGAP_srGAP cd04383
RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1113-1270 2.31e-12

RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in srGAPs. srGAPs are components of the intracellular part of Slit-Robo signalling pathway that is important for axon guidance and cell migration. srGAPs contain an N-terminal FCH domain, a central RhoGAP domain and a C-terminal SH3 domain; this SH3 domain interacts with the intracellular proline-rich-tail of the Roundabout receptor (Robo). This interaction with Robo then activates the rhoGAP domain which in turn inhibits Cdc42 activity. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239848  Cd Length: 188  Bit Score: 67.45  E-value: 2.31e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1113 GNALQDQQLCKNDVPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKLRAGKHQLEDVTGVLKSFLS 1192
Cdd:cd04383      5 GSLEEYIQDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADDQNDHDINSVAGVLKLYFR 84
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907161909 1193 DIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCL 1270
Cdd:cd04383     85 GLENPLFPKERFEDLMSCVKLENPTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTL 162
RhoGAP_fBEM3 cd04400
RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of ...
1125-1297 4.02e-12

RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of fungal BEM3-like proteins. Bem3 is a GAP protein of Cdc42, and is specifically involved in the control of the initial assembly of the septin ring in yeast bud formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239865 [Multi-domain]  Cd Length: 190  Bit Score: 66.61  E-value: 4.02e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1125 DVPIIVNSCIafvtQYGLGCKYIYQK-----DGDPLHISELLESFKKDARSVKLRAG-KHQLEDVTGVLKSFLSDIDDAL 1198
Cdd:cd04400     21 DLPSVVYRCI----EYLDKNRAIYEEgifrlSGSASVIKQLKERFNTEYDVDLFSSSlYPDVHTVAGLLKLYLRELPTLI 96
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1199 LTKELYPYWVSALDTQ-DEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLfqtkgQT 1277
Cdd:cd04400     97 LGGELHNDFKRLVEENhDRSQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLRNVCIVFSPTL-----NI 171
                          170       180
                   ....*....|....*....|
gi 1907161909 1278 SEEVNVIedLINNYVEIFEI 1297
Cdd:cd04400    172 PAGIFVL--FLTDFDCIFGG 189
ArfGap_ArfGap2 cd09029
Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
694-765 5.17e-12

Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350086 [Multi-domain]  Cd Length: 120  Bit Score: 64.31  E-value: 5.17e-12
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907161909  694 SNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASiWSNELIELFIVIGNKRANDFW 765
Cdd:cd09029     18 TNKACFDCGAKNPSWASITYGVFLCIDCSGVHRSLGVHLSFIRSTELDSN-WNWFQLRCMQVGGNANATAFF 88
PH pfam00169
PH domain; PH stands for pleckstrin homology.
482-572 7.51e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 63.35  E-value: 7.51e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  482 EKCGWLDKLSPQGKRMFQKRWVKFDGLSISYYNNDREMYS---KGIIPLTAISTVRA------QGDNKFEIVTTQ----R 548
Cdd:pfam00169    2 VKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDDKSGKSkepKGSISLSGCEVVEVvasdspKRKFCFELRTGErtgkR 81
                           90       100
                   ....*....|....*....|....
gi 1907161909  549 TFVFRVEKEEERNDWISILLSALK 572
Cdd:pfam00169   82 TYLLQAESEEERKDWIKAIQSAIR 105
RhoGAP_ARHGAP18 cd04391
RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1182-1282 1.12e-11

RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP18-like proteins. The function of ArhGAP18 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239856  Cd Length: 216  Bit Score: 66.22  E-value: 1.12e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1182 DVTGVLKSFLSDIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHN 1261
Cdd:cd04391     78 DAASLLKLFIRELPQPLLTVEYLPAFYSVQGLPSKKDQLQALNLLVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWN 157
                           90       100
                   ....*....|....*....|.
gi 1907161909 1262 LAMVFSSCLFQTKGQTSEEVN 1282
Cdd:cd04391    158 VAMIMAPNLFPPRGKHSKDNE 178
ArfGap_ArfGap3 cd09028
Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
694-765 2.71e-11

Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350085 [Multi-domain]  Cd Length: 120  Bit Score: 62.39  E-value: 2.71e-11
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907161909  694 SNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASiWSNELIELFIVIGNKRANDFW 765
Cdd:cd09028     18 TNKVCFDCGAKNPSWASITYGVFLCIDCSGIHRSLGVHLSFIRSTELDSN-WSWFQLRCMQVGGNANASAFF 88
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
677-765 6.59e-11

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 66.42  E-value: 6.59e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  677 AETLSD-YEVAEKIWFNESNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIV 755
Cdd:PLN03114     3 SENLNDkISVFKKLKAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDS--WSSEQLKMMIY 80
                           90
                   ....*....|
gi 1907161909  756 IGNKRANDFW 765
Cdd:PLN03114    81 GGNNRAQVFF 90
RhoGAP_Graf cd04374
RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase ...
1129-1290 1.59e-10

RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase regulator associated with focal adhesion kinase); Graf is a multi-domain protein, containing SH3 and PH domains, that binds focal adhesion kinase and influences cytoskeletal changes mediated by Rho proteins. Graf exhibits GAP activity toward RhoA and Cdc42, but only weakly activates Rac1. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239839  Cd Length: 203  Bit Score: 62.41  E-value: 1.59e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1129 IVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESF----KKDARSVKLRAGKHQLEDVTGVLKSFLSDIDDALLTKELY 1204
Cdd:cd04374     31 FVRKCIEAVETRGINEQGLYRVVGVNSKVQKLLSLGldpkTSTPGDVDLDNSEWEIKTITSALKTYLRNLPEPLMTYELH 110
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1205 PYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKGQTSEEV--- 1281
Cdd:cd04374    111 NDFINAAKSENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQEETVAAImdi 190
                          170
                   ....*....|...
gi 1907161909 1282 ---N-VIEDLINN 1290
Cdd:cd04374    191 kfqNiVVEILIEN 203
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
483-572 2.16e-10

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 58.85  E-value: 2.16e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  483 KCGWLDKLSPQGKRmFQKRWVKFDGLSISYYNNDREMYSK--GIIPL-TAISTVRAQGDNKFEIVTTQRTFVFRVEKEEE 559
Cdd:cd13282      1 KAGYLTKLGGKVKT-WKRRWFVLKNGELFYYKSPNDVIRKpqGQIALdGSCEIARAEGAQTFEIVTEKRTYYLTADSEND 79
                           90
                   ....*....|...
gi 1907161909  560 RNDWISILLSALK 572
Cdd:cd13282     80 LDEWIRVIQNVLR 92
RhoGAP-ARHGAP11A cd04394
RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1164-1294 4.55e-10

RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP11A-like proteins. The mouse homolog of human ArhGAP11A has been detected as a gene exclusively expressed in immature ganglion cells, potentially playing a role in retinal development. The exact function of ArhGAP11A is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239859 [Multi-domain]  Cd Length: 202  Bit Score: 60.95  E-value: 4.55e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1164 FKKDARSVKLRAGKHQLE------------DVTGVLKSFLSDIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLP 1231
Cdd:cd04394     41 FRKSGSVVRQKELKAKLEggeaclssalpcDVAGLLKQFFRELPEPLLPYDLHEALLKAQELPTDEERKSATLLLTCLLP 120
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907161909 1232 GVNRATLAALIEHLYRV-QKCSEiNHMNAHNLAMVFSSCLFQTKG-----------QTSEEVNVIEDLINNYVEI 1294
Cdd:cd04394    121 DEHVNTLRYFFSFLYDVaQRCSE-NKMDSSNLAVIFAPNLFQSEEggekmssstekRLRLQAAVVQTLIDNASNI 194
RhoGAP_ARHGAP19 cd04392
RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1107-1299 4.81e-10

RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP19-like proteins. The function of ArhGAP19 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239857  Cd Length: 208  Bit Score: 60.94  E-value: 4.81e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1107 KAAGTDGNALQDQQLckndvpiivnscIAFVTQyGLGCKYIYQKDGDPLHISELLESFKKDArSVKLRAGKHQLEDVTGV 1186
Cdd:cd04392      2 GAPLTEEGIAQIYQL------------IEYLEK-NLRVEGLFRKPGNSARQQELRDLLNSGT-DLDLESGGFHAHDCATV 67
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1187 LKSFLSDIDDALLTKELYPYW--VSALDTQDEKERTSKYRAFIRS----------LPGVNRATLAALIEHLYRVQKCSEI 1254
Cdd:cd04392     68 LKGFLGELPEPLLTHAHYPAHlqIADLCQFDEKGNKTSAPDKERLlealqlllllLPEENRNLLKLILDLLYQTAKHEDK 147
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1907161909 1255 NHMNAHNLAMVFSSCLFQTKGQTSEEVNVIEDLINNYV--------EIFEISP 1299
Cdd:cd04392    148 NKMSADNLALLFTPHLICPRNLTPEDLHENAQKLNSIVtfmikhsqKLFKAPA 200
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
1382-1483 5.48e-10

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 57.94  E-value: 5.48e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  1382 IKEGILKLKEEPSKilsgNKFQDRCVVLRDGHLFIYKDPK---SSKHDKMFPLRAMKFYLGVKKKMKpPTSWGLTV-YSE 1457
Cdd:smart00233    2 IKEGWLYKKSGGGK----KSWKKRYFVLFNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREAPDPDSS-KKPHCFEIkTSD 76
                            90       100
                    ....*....|....*....|....*.
gi 1907161909  1458 KHHWHLCCDSLQAQMEWMASIFIAQH 1483
Cdd:smart00233   77 RKTLLLQAESEEEREKWVEALRKAIA 102
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
483-573 7.68e-10

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241282  Cd Length: 105  Bit Score: 57.60  E-value: 7.68e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  483 KCGWLDKLSPQGKRMFQKRWVKFDGLSISYYNNDREMYSKGIIPL-----------TAISTVRAQGDNKFEIVTTQRTFV 551
Cdd:cd01251      4 KEGYLEKTGPKQTDGFRKRWFTLDDRRLMYFKDPLDAFPKGEIFIgskeegysvreGLPPGIKGHWGFGFTLVTPDRTFL 83
                           90       100
                   ....*....|....*....|..
gi 1907161909  552 FRVEKEEERNDWISILLSALKS 573
Cdd:cd01251     84 LSAETEEERREWITAIQKVLER 105
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
483-567 1.06e-09

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270075  Cd Length: 110  Bit Score: 57.42  E-value: 1.06e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  483 KCGWLDKLSPQGKRmFQKRWVKFDGLSISYYNNDREMYSKGIIPLTAISTVRA----QGDNKFEIVTTQRTFVFRVEKEE 558
Cdd:cd13255      8 KAGYLEKKGERRKT-WKKRWFVLRPTKLAYYKNDKEYRLLRLIDLTDIHTCTEvqlkKHDNTFGIVTPARTFYVQADSKA 86

                   ....*....
gi 1907161909  559 ERNDWISIL 567
Cdd:cd13255     87 EMESWISAI 95
RhoGAP_PARG1 cd04409
RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1126-1283 1.91e-09

RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of PARG1 (PTPL1-associated RhoGAP1). PARG1 was originally cloned as an interaction partner of PTPL1, an intracellular protein-tyrosine phosphatase. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239874  Cd Length: 211  Bit Score: 59.44  E-value: 1.91e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDARSVKL-RAGKHqleDVTGVLKSFLSDIDDALLTKELY 1204
Cdd:cd04409     16 IPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFENGKDLVELsELSPH---DISNVLKLYLRQLPEPLILFRLY 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1205 PYWV-------SALDTQDEKERTS---------------KYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNL 1262
Cdd:cd04409     93 NEFIglakesqHVNETQEAKKNSDkkwpnmctelnrillKSKDLLRQLPAPNYNTLQFLIVHLHRVSEQAEENKMSASNL 172
                          170       180
                   ....*....|....*....|.
gi 1907161909 1263 AMVFSSCLFQTKgQTSEEVNV 1283
Cdd:cd04409    173 GIIFGPTLIRPR-PTDATVSL 192
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
483-567 2.91e-09

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 56.09  E-value: 2.91e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  483 KCGWLDKLSpQGKRMFQKRWVKFDGLSISYYNNDREMYSKGIIPLTAISTV----RAQGDNKFEIVTTQRTFVFRVEKEE 558
Cdd:cd13298      8 KSGYLLKRS-RKTKNWKKRWVVLRPCQLSYYKDEKEYKLRRVINLSELLAVaplkDKKRKNVFGIYTPSKNLHFRATSEK 86

                   ....*....
gi 1907161909  559 ERNDWISIL 567
Cdd:cd13298     87 DANEWVEAL 95
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
586-677 5.45e-09

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 55.25  E-value: 5.45e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909   586 PEKCGYLELRGYKA-----KIFTVLRGNSVWLCKNEQDFKSGLGITIIPMNVANVKQVDRA----VKQSFEIITPYR-SF 655
Cdd:smart00233    1 VIKEGWLYKKSGGGkkswkKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPdsskKPHCFEIKTSDRkTL 80
                            90       100
                    ....*....|....*....|..
gi 1907161909   656 SFTADSEREKQEWIEAVQQSIA 677
Cdd:smart00233   81 LLQAESEEEREKWVEALRKAIA 102
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
919-996 5.95e-09

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 55.25  E-value: 5.95e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909   919 KKWCVLEGGFLSYYEND---RCTTPNGTINISEVICLAVHKEDfylNTGPIFVFEIYLPSERVFLFGAETSQIQRKWTET 995
Cdd:smart00233   20 KRYFVLFNSTLLYYKSKkdkKSYKPKGSIDLSGCTVREAPDPD---SSKKPHCFEIKTSDRKTLLLQAESEEEREKWVEA 96

                    .
gi 1907161909   996 I 996
Cdd:smart00233   97 L 97
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
10-67 9.64e-09

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.


Pssm-ID: 425739  Cd Length: 64  Bit Score: 53.04  E-value: 9.64e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907161909   10 DIRDFLMSINLEQYLLHFREfGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMI 67
Cdd:pfam00536    7 DVGEWLESIGLGQYIDSFRA-GYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRL 63
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
10-67 7.91e-08

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 50.76  E-value: 7.91e-08
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907161909    10 DIRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMI 67
Cdd:smart00454    8 SVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKL 65
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
919-996 9.16e-08

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 51.39  E-value: 9.16e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  919 KKWCVLEGGFLSYY--ENDRCTTPNGTINISEVICLAVHKEDFYLNtgpifVFEIYLPSERVFLFGAETSQIQRKWTETI 996
Cdd:cd00821     18 KRWFVLFEGVLLYYksKKDSSYKPKGSIPLSGILEVEEVSPKERPH-----CFELVTPDGRTYYLQADSEEERQEWLKAL 92
RhoGAP_fSAC7_BAG7 cd04396
RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
1126-1297 1.19e-07

RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal SAC7 and BAG7-like proteins. Both proteins are GTPase activating proteins of Rho1, but differ functionally in vivo: SAC7, but not BAG7, is involved in the control of Rho1-mediated activation of the PKC-MPK1 pathway. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239861  Cd Length: 225  Bit Score: 54.34  E-value: 1.19e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFKKDAR-SVKLRAGKHQLEDVTGVLKSFLSDIDDALLTKELY 1204
Cdd:cd04396     32 IPVVVAKCGVYLKENATEVEGIFRVAGSSKRIRELQLIFSTPPDyGKSFDWDGYTVHDAASVLRRYLNNLPEPLVPLDLY 111
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1205 -----------------PYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFS 1267
Cdd:cd04396    112 eefrnplrkrprilqymKGRINEPLNTDIDQAIKEYRDLITRLPNLNRQLLLYLLDLLAVFARNSDKNLMTASNLAAIFQ 191
                          170       180       190
                   ....*....|....*....|....*....|
gi 1907161909 1268 SCLFqtkGQTSEEVNVIEDLINNYVEIFEI 1297
Cdd:cd04396    192 PGIL---SHPDHEMDPKEYKLSRLVVEFLI 218
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
483-575 1.55e-07

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270095  Cd Length: 106  Bit Score: 51.16  E-value: 1.55e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  483 KCGWLDKlspQGK--RMFQKRW-VKFDGLSISYYNNDREMYSK--GIIPLTAISTVRAQGD-----NKFEIVTTQRTFVF 552
Cdd:cd13276      1 KAGWLEK---QGEfiKTWRRRWfVLKQGKLFWFKEPDVTPYSKprGVIDLSKCLTVKSAEDatnkeNAFELSTPEETFYF 77
                           90       100
                   ....*....|....*....|...
gi 1907161909  553 RVEKEEERNDWISILLSALKSPS 575
Cdd:cd13276     78 IADNEKEKEEWIGAIGRAIVKHS 100
RhoGAP_ARHGAP22_24_25 cd04390
RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
1126-1274 2.05e-07

RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP22, 24 and 25-like proteins; longer isoforms of these proteins contain an additional N-terminal pleckstrin homology (PH) domain. ARHGAP25 (KIA0053) has been identified as a GAP for Rac1 and Cdc42. Short isoforms (without the PH domain) of ARHGAP24, called RC-GAP72 and p73RhoGAP, and of ARHGAP22, called p68RacGAP, has been shown to be involved in angiogenesis and endothelial cell capillary formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239855 [Multi-domain]  Cd Length: 199  Bit Score: 53.22  E-value: 2.05e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1126 VPIIVNSCIAFVTQYGLGCKYIYQKDGDPLHISELLESFkkDARSVKLRAGKHQLEDVTGVLKSFLSDIDDALLTKELYP 1205
Cdd:cd04390     22 VPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAF--DAGERPSFDSDTDVHTVASLLKLYLRELPEPVIPWAQYE 99
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907161909 1206 YWVSA--LDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTK 1274
Cdd:cd04390    100 DFLSCaqLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILRPK 170
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
469-567 2.10e-07

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275402  Cd Length: 116  Bit Score: 51.08  E-value: 2.10e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  469 SPYACFYGSSAAKE----KCGWLDKLSpQGKRMFQKRWVKFDGLSISYYNNDREMY-SKGIIPL---TAISTVRAQGDN- 539
Cdd:cd13215      5 SKHLCFFAYLPKRSgaviKSGYLSKRS-KRTLRYTRYWFVLKGDTLSWYNSSTDLYfPAGTIDLryaTSIELSKSNGEAt 83
                           90       100
                   ....*....|....*....|....*....
gi 1907161909  540 -KFEIVTTQRTFVFRVEKEEERNDWISIL 567
Cdd:cd13215     84 tSFKIVTNSRTYKFKADSETSADEWVKAL 112
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
588-672 2.71e-07

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 49.85  E-value: 2.71e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  588 KCGYLELRGYKAKI-----FTVLRGNSVWLCKNEQDFKSGLGITIIPMNVANVKQVDR-AVKQSFEIITP-YRSFSFTAD 660
Cdd:cd00821      1 KEGYLLKRGGGGLKswkkrWFVLFEGVLLYYKSKKDSSYKPKGSIPLSGILEVEEVSPkERPHCFELVTPdGRTYYLQAD 80
                           90
                   ....*....|..
gi 1907161909  661 SEREKQEWIEAV 672
Cdd:cd00821     81 SEEERQEWLKAL 92
RhoGAP_fRGD2 cd04399
RhoGAP_fRGD2: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1183-1296 6.63e-07

RhoGAP_fRGD2: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD2-like proteins. Yeast Rgd2 is a GAP protein for Cdc42 and Rho5. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239864  Cd Length: 212  Bit Score: 51.95  E-value: 6.63e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1183 VTGVLKSFLSDIDDALLT-------KELYPYWVSALDTQDEKeRTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEIN 1255
Cdd:cd04399     81 VASVLKLYLLELPDSLIPhdiydliRSLYSAYPPSQEDSDTA-RIQGLQSTLSQLPKSHIATLDAIITHFYRLIEITKMG 159
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1256 HMN-------AHNLAMVFSSCLFQTKGQTSEE--VNVIEDLINNYVEIFE 1296
Cdd:cd04399    160 ESEeeyadklATSLSREILRPIIESLLTIGDKhgYKFFRDLLTHKDQIFS 209
PLN03131 PLN03131
hypothetical protein; Provisional
695-797 1.02e-06

hypothetical protein; Provisional


Pssm-ID: 178677 [Multi-domain]  Cd Length: 705  Bit Score: 53.63  E-value: 1.02e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLgpkDSKVRSLKMdaSIWSNELIELFIVIGNKRANDFWAGNL-QKDE 773
Cdd:PLN03131    23 NRRCINCNSLGPQFVCTNFWTFICMTCSGIHREF---THRVKSVSM--SKFTSQDVEALQNGGNQRAREIYLKDWdQQRQ 97
                           90       100
                   ....*....|....*....|....
gi 1907161909  774 ELQVDSPVEKRKNFITQKYKEGKF 797
Cdd:PLN03131    98 RLPDNSKVDKIREFIKDIYVDKKY 121
SAM_superfamily cd09487
SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of ...
10-65 1.10e-06

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.


Pssm-ID: 188886 [Multi-domain]  Cd Length: 56  Bit Score: 47.23  E-value: 1.10e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907161909   10 DIRDFLMSINLEQYLLHFREfGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQ 65
Cdd:cd09487      1 DVAEWLESLGLEQYADLFRK-NEIDGDALLLLTDEDLKELGITSPGHRKKILRAIQ 55
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
483-567 1.12e-06

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270108  Cd Length: 103  Bit Score: 48.62  E-value: 1.12e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  483 KCGWLDK----LSPQGKRMFQKRWVKFDGLSISYYNNDREM-YSKGIIPLTAISTV--RAQGDNKFEIVTTQRTFVFRVE 555
Cdd:cd13296      1 KSGWLTKkgggSSTLSRRNWKSRWFVLRDTVLKYYENDQEGeKLLGTIDIRSAKEIvdNDPKENRLSITTEERTYHLVAE 80
                           90
                   ....*....|..
gi 1907161909  556 KEEERNDWISIL 567
Cdd:cd13296     81 SPEDASQWVNVL 92
SAM_2 pfam07647
SAM domain (Sterile alpha motif);
8-65 1.55e-06

SAM domain (Sterile alpha motif);


Pssm-ID: 429573  Cd Length: 66  Bit Score: 46.88  E-value: 1.55e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907161909    8 NADIRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQ 65
Cdd:pfam07647    6 LESVADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGITSVGHRRKILKKIQ 63
SAM_EPH-A4 cd09545
SAM domain of EPH-A4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
9-72 1.94e-06

SAM domain of EPH-A4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A4 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of EPH-A4 receptors can form homodimers. EPH-A4 receptors bind ligands such as erphirin A1, A4, A5. They are known to interact with a number of different proteins, including meltrin beta metalloprotease, Cdk5, and EFS2alpha, however SAM domain doesn't participate in these interactions. EPH-A4 receptors are involved in regulation of corticospinal tract formation, in pathway controlling voluntary movements, in formation of motor neurons, and in axon guidance (SAM domain is not required for axon guidance or for EPH-A4 kinase signaling). In Xenopus embryos EPH-A4 induces loss of cell adhesion, ventro-lateral protrusions, and severely expanded posterior structures. Mutations in SAM domain conserved tyrosine (Y928F) enhance the ability of EPH-A4 to induce these phenotypes, thus supporting the idea that the SAM domain may negatively regulate some aspects of EPH-A4 activity. EphA4 gene was found overexpressed in a number of different cancers including human gastric cancer, colorectal cancer, and pancreatic ductal adenocarcinoma. It is likely to be a promising molecular target for the cancer therapy.


Pssm-ID: 188944  Cd Length: 71  Bit Score: 46.87  E-value: 1.94e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907161909    9 ADIRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMIFSKMQ 72
Cdd:cd09545      4 ASVDDWLQAIKMERYKDNFTAAGYTTLEAVVHMNQDDLARIGISAIAHQNKILSSVQGMRSQMQ 67
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
646-681 2.13e-06

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270070  Cd Length: 98  Bit Score: 47.60  E-value: 2.13e-06
                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1907161909  646 FEIITPYRSFSFTADSEREKQEWIEAVQQSIAETLS 681
Cdd:cd13250     63 FEVISPTKSYMLQAESEEDRQAWIQAIQSAIASALN 98
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
484-573 2.30e-06

TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1/Prostate antigen recognized and identified by SEREX 1 and ARMUS) contains a PH domain and a TBC-type GTPase catalytic domain. TBC1D2A integrates signaling between Arf6, Rac1, and Rab7 during junction disassembly. Activated Rac1 recruits TBC1D2A to locally inactivate Rab7 via its C-terminal TBC/RabGAP domain and facilitate E-cadherin degradation in lysosomes. The TBC1D2A PH domain mediates localization at cell-cell contacts and coprecipitates with cadherin complexes. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269966  Cd Length: 102  Bit Score: 47.70  E-value: 2.30e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  484 CGWLDKLSPQGKRM--FQKRWVKFD--GLSISYYNNDREMYSKGIIPLT--AISTVRAQGDNKFEIVTTQRTFVFRVEKE 557
Cdd:cd01265      3 CGYLNKLETRGLGLkgWKRRWFVLDesKCQLYYYRSPQDATPLGSIDLSgaAFSYDPEAEPGQFEIHTPGRVHILKASTR 82
                           90
                   ....*....|....*.
gi 1907161909  558 EERNDWisilLSALKS 573
Cdd:cd01265     83 QAMLYW----LQALQS 94
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
640-676 2.77e-06

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241282  Cd Length: 105  Bit Score: 47.58  E-value: 2.77e-06
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1907161909  640 RAVKQSFEIITPYRSFSFTADSEREKQEWIEAVQQSI 676
Cdd:cd01251     67 GHWGFGFTLVTPDRTFLLSAETEEERREWITAIQKVL 103
RhoGAP_KIAA1688 cd04389
RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
1187-1284 2.99e-06

RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in KIAA1688-like proteins; KIAA1688 is a protein of unknown function that contains a RhoGAP domain and a myosin tail homology 4 (MyTH4) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239854  Cd Length: 187  Bit Score: 49.31  E-value: 2.99e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1187 LKSFLSDIDDALLTKELYPYWVSALDTQDekertsKYRAFIRSLPGVNRATLAALIEHLyrvQKCS-----EINHMNAHN 1261
Cdd:cd04389     80 LKLWLRELEEPLIPDALYQQCISASEDPD------KAVEIVQKLPIINRLVLCYLINFL---QVFAqpenvAHTKMDVSN 150
                           90       100
                   ....*....|....*....|...
gi 1907161909 1262 LAMVFSSCLFQTkgqTSEEVNVI 1284
Cdd:cd04389    151 LAMVFAPNILRC---TSDDPRVI 170
PH2_PH_fungal cd13299
Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal ...
590-676 3.30e-06

Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270111  Cd Length: 102  Bit Score: 47.24  E-value: 3.30e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  590 GYLEL---RGYK--AKIFTVLRGNSVWLCKNEQDFKSglgITIIPMN-VANVKQVD---RAVKQSFEIITPYRSFSFTAD 660
Cdd:cd13299     10 GYLQVlkkKGVNqwKKYWLVLRNRSLSFYKDQSEYSP---VKIIPIDdIIDVVELDplsKSKKWCLQIITPEKRIRFCAD 86
                           90
                   ....*....|....*.
gi 1907161909  661 SEREKQEWIEAVQQSI 676
Cdd:cd13299     87 DEESLIKWLGALKSLL 102
ArfGap_AGFG1 cd08857
ArfGAP domain of AGFG1 (ArfGAP domain and FG repeat-containing protein 1); The ArfGAP domain ...
695-797 5.38e-06

ArfGAP domain of AGFG1 (ArfGAP domain and FG repeat-containing protein 1); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG1 (alias: HIV-1 Rev binding protein, HRB; Rev interacting protein, RIP; Rev/Rex activating domain-binding protein, RAB) and AGFG2 are involved in the maintenance and spread of immunodeficiency virus type 1 (HIV-1) infection. The ArfGAP domain of AGFG1 is related to nucleoporins, which is a class of proteins that mediate nucleocytoplasmic transport. AGFG1 plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs, possibly together by the nuclear export receptor CRM1. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG1 promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.


Pssm-ID: 350082 [Multi-domain]  Cd Length: 116  Bit Score: 46.96  E-value: 5.38e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKdSKVRSLKMdaSIWSNELIELFIVIGNKRANDFWAGnLQKDEE 774
Cdd:cd08857     14 NRKCFDCDQRGPTYANMTVGSFVCTSCSGILRGLNPP-HRVKSISM--TTFTQQEIEFLQKHGNEVCKQIWLG-LFDDRS 89
                           90       100
                   ....*....|....*....|....*
gi 1907161909  775 LQVDS--PVEKRKNFITQKYKEGKF 797
Cdd:cd08857     90 SAIPDfrDPQKVKEFLQEKYEKKRW 114
RhoGAP_DLC1 cd04375
RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
1179-1272 6.65e-06

RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of DLC1-like proteins. DLC1 shows in vitro GAP activity towards RhoA and CDC42. Beside its C-terminal GAP domain, DLC1 also contains a SAM (sterile alpha motif) and a START (StAR-related lipid transfer action) domain. DLC1 has tumor suppressor activity in cell culture. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239840  Cd Length: 220  Bit Score: 48.95  E-value: 6.65e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1179 QLEDVTGVLKSFLSDIDDALLTKELYPYWVSALDTQDEKERTSKYRAFIRSLPGVNRATLAALIEHLYRVQKCSEINHMN 1258
Cdd:cd04375     71 QAYDVADMLKQYFRDLPEPLLTNKLSETFIAIFQYVPKEQRLEAVQCAILLLPDENREVLQTLLYFLSDVAANSQENQMT 150
                           90
                   ....*....|....
gi 1907161909 1259 AHNLAMVFSSCLFQ 1272
Cdd:cd04375    151 ATNLAVCLAPSLFH 164
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
483-573 1.14e-05

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP1 and TAPP2 contain two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270090  Cd Length: 114  Bit Score: 46.19  E-value: 1.14e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  483 KCGWLDKlspQGKRM--FQKRWVKFDGLSISYYNNDREMYSKGIIPLTAISTVRA-------QGDNKFEIVTTQRTFVFR 553
Cdd:cd13271     10 KSGYCVK---QGAVRknWKRRFFILDDNTISYYKSETDKEPLRTIPLREVLKVHEclvksllMRDNLFEIITTSRTFYIQ 86
                           90       100
                   ....*....|....*....|
gi 1907161909  554 VEKEEERNDWISILLSALKS 573
Cdd:cd13271     87 ADSPEEMHSWIKAISGAIVA 106
SAM_EPH-A1 cd09542
SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
11-65 1.51e-05

SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A1 subfamily of the receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A1 receptors and appears to mediate cell-cell initiated signal transduction. Activation of these receptors leads to inhibition of cell spreading and migration in a RhoA-ROCK-dependent manner. EPH-A1 receptors are known to bind ILK (integrin-linked kinase) which is the mediator of interactions between integrin and the actin cytoskeleton. However SAM is not sufficient for this interaction; it rather plays an ancillary role. SAM domains of Eph-A1 receptors do not form homo/hetero dimers/oligomers. EphA1 gene was found expressed widely in differentiated epithelial cells. In a number of different malignant tumors EphA1 genes are downregulated. In breast carcinoma the downregulation is associated with invasive behavior of the cell.


Pssm-ID: 188941  Cd Length: 63  Bit Score: 44.23  E-value: 1.51e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1907161909   11 IRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQ 65
Cdd:cd09542      7 VSEWLESIRMKRYILHFRSAGLDTMECVLELTAEDLTQMGITLPGHQKRILCSIQ 61
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
588-674 1.52e-05

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270075  Cd Length: 110  Bit Score: 45.48  E-value: 1.52e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  588 KCGYLELRGYKAKIFT----VLRGNSVWLCKNEQDFKSglgITIIPMN----VANVkQVDRAVkQSFEIITPYRSFSFTA 659
Cdd:cd13255      8 KAGYLEKKGERRKTWKkrwfVLRPTKLAYYKNDKEYRL---LRLIDLTdihtCTEV-QLKKHD-NTFGIVTPARTFYVQA 82
                           90
                   ....*....|....*
gi 1907161909  660 DSEREKQEWIEAVQQ 674
Cdd:cd13255     83 DSKAEMESWISAINL 97
PH pfam00169
PH domain; PH stands for pleckstrin homology.
919-996 1.64e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 45.25  E-value: 1.64e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  919 KKWCVLEGGFLSYYENDRCT---TPNGTINISEVICLAVHKEDfylNTGPIFVFEIYLPS---ERVFLFGAETSQIQRKW 992
Cdd:pfam00169   20 KRYFVLFDGSLLYYKDDKSGkskEPKGSISLSGCEVVEVVASD---SPKRKFCFELRTGErtgKRTYLLQAESEEERKDW 96

                   ....
gi 1907161909  993 TETI 996
Cdd:pfam00169   97 IKAI 100
PH_ORP9 cd13290
Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 ...
499-567 1.77e-05

Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 is proposed to function in regulation of Akt phosphorylation. ORP9 has 2 forms, a long (ORP9L) and a short (ORP9S). ORP9L contains an N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP1S is truncated and contains a FFAT motif and an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241444  Cd Length: 102  Bit Score: 45.13  E-value: 1.77e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907161909  499 QKRWVKFD---GLsISYYNNDREMYS---KGIIPLT-AISTVRAQGDNKFEIVTTQRTFVFRVEKEEERNDWISIL 567
Cdd:cd13290     16 QYRWFVLDdnaGL-LSYYTSKEKMMRgsrRGCVRLKgAVVGIDDEDDSTFTITVDQKTFHFQARDAEERERWIRAL 90
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
1289-1367 1.77e-05

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.


Pssm-ID: 425871  Cd Length: 93  Bit Score: 45.02  E-value: 1.77e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907161909 1289 NNYVEIfEISPVMEAEELTNDILAIKNIIPMKGDiWATFEVIENEELERPLHYTENVLEQVLQWSSlaEPGSAYLVVKR 1367
Cdd:pfam00788   16 TTYKTI-LVSSSTTAEEVIEALLEKFGLEDDPRD-YVLVEVLERGGGERRLPDDECPLQIQLQWPR--DASDSRFLLRK 90
SAM_caskin1,2_repeat2 cd09498
SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 ...
4-65 2.47e-05

SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and may play a role in neural development, synaptic protein targeting, and regulation of gene expression.


Pssm-ID: 188897  Cd Length: 71  Bit Score: 43.82  E-value: 2.47e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907161909    4 VSEVNADIRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRI------LKQLQ 65
Cdd:cd09498      3 PDYPPNDLLEWLSLLGLPQYHKVLVENGYDSIDFVTDLTWEDLQDIGITKLGHQKKLmlaikkLKDLQ 70
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
588-683 2.87e-05

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270095  Cd Length: 106  Bit Score: 44.62  E-value: 2.87e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  588 KCGYLELRGYKAKI----FTVLRGNSVWLCKNEQDFKSGLGITIIPMN-VANVKQVDRAVKQ--SFEIITPYRSFSFTAD 660
Cdd:cd13276      1 KAGWLEKQGEFIKTwrrrWFVLKQGKLFWFKEPDVTPYSKPRGVIDLSkCLTVKSAEDATNKenAFELSTPEETFYFIAD 80
                           90       100
                   ....*....|....*....|...
gi 1907161909  661 SEREKQEWIEAVQQSIAETLSDY 683
Cdd:cd13276     81 NEKEKEEWIGAIGRAIVKHSRSV 103
PH pfam00169
PH domain; PH stands for pleckstrin homology.
1382-1483 3.14e-05

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 44.48  E-value: 3.14e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1382 IKEGILKLKEEPSKilsgNKFQDRCVVLRDGHLFIYKDPKSSKHDK---MFPLRAMKFYLGVKKKMKP-PTSWGLTVY-- 1455
Cdd:pfam00169    2 VKEGWLLKKGGGKK----KSWKKRYFVLFDGSLLYYKDDKSGKSKEpkgSISLSGCEVVEVVASDSPKrKFCFELRTGer 77
                           90       100
                   ....*....|....*....|....*...
gi 1907161909 1456 SEKHHWHLCCDSLQAQMEWMASIFIAQH 1483
Cdd:pfam00169   78 TGKRTYLLQAESEEERKDWIKAIQSAIR 105
SAM_AIDA1AB-like_repeat1 cd09499
SAM domain of AIDA1AB-like proteins, repeat 1; SAM (sterile alpha motif) domain repeat 1 of ...
11-67 3.45e-05

SAM domain of AIDA1AB-like proteins, repeat 1; SAM (sterile alpha motif) domain repeat 1 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM1 domain has a potential phosphorylation site for CMGC group of serine/threonine kinases. SAM domains of the AIDA1-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.


Pssm-ID: 188898  Cd Length: 67  Bit Score: 43.06  E-value: 3.45e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907161909   11 IRDFLMSINLEQYLLHFREFGFYTVR--DCTSINDSVLHQIGISPTGHRRRILKQLQMI 67
Cdd:cd09499      5 VGQWLESIGLPQYESKLLLNGFDDVDflGSGVMEDQDLKEIGITDEQHRQIILQAARSL 63
RhoGAP_p85 cd04388
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
1141-1288 4.82e-05

RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in the p85 isoforms of the regulatory subunit of the class IA PI3K (phosphatidylinositol 3'-kinase). This domain is also called Bcr (breakpoint cluster region protein) homology (BH) domain. Class IA PI3Ks are heterodimers, containing a regulatory subunit (p85) and a catalytic subunit (p110) and are activated by growth factor receptor tyrosine kinases (RTKs); this activation is mediated by the p85 subunit. p85 isoforms, alpha and beta, contain a C-terminal p110-binding domain flanked by two SH2 domains, an N-terminal SH3 domain, and a RhoGAP domain flanked by two proline-rich regions. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239853  Cd Length: 200  Bit Score: 46.02  E-value: 4.82e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1141 GLGCKYIYQKDgDPLHISELLESFKKDARSVKLRA-GKHQLEDVtgvLKSFLSDIDDALLTKELYPYWVS-ALDTQDEKE 1218
Cdd:cd04388     30 GLESSTLYRTQ-SSSSLTELRQILDCDAASVDLEQfDVAALADA---LKRYLLDLPNPVIPAPVYSEMISrAQEVQSSDE 105
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907161909 1219 RTSKYRAFIRS--LPGVNRATLAALIEHLYRVQKCSEINHMNAHNLAMVFSSCLFQTKGQTSEE----VNVIEDLI 1288
Cdd:cd04388    106 YAQLLRKLIRSpnLPHQYWLTLQYLLKHFFRLCQSSSKNLLSARALAEIFSPLLFRFQPASSDSpefhIRIIEVLI 181
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
643-674 4.85e-05

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 43.83  E-value: 4.85e-05
                           10        20        30
                   ....*....|....*....|....*....|..
gi 1907161909  643 KQSFEIITPYRSFSFTADSEREKQEWIEAVQQ 674
Cdd:cd13282     58 AQTFEIVTEKRTYYLTADSENDLDEWIRVIQN 89
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
588-677 5.10e-05

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270092  Cd Length: 110  Bit Score: 44.21  E-value: 5.10e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  588 KCGYLELRGYKAKIFT----VLRGNSVWLCKNEqDFKSGLGITIIPMN-VANVKQVDRAVKQSFEIITPYRSFSFTADSE 662
Cdd:cd13273     10 KKGYLWKKGHLLPTWTerwfVLKPNSLSYYKSE-DLKEKKGEIALDSNcCVESLPDREGKKCRFLVKTPDKTYELSASDH 88
                           90
                   ....*....|....*
gi 1907161909  663 REKQEWIEAVQQSIA 677
Cdd:cd13273     89 KTRQEWIAAIQTAIR 103
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
1383-1478 6.28e-05

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 43.30  E-value: 6.28e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1383 KEGILKLKEEPSKilsgNKFQDRCVVLRDGHLFIYKDPK--SSKHDKMFPLRAmKFYLGVKKKMKPPTSWGLtVYSEKHH 1460
Cdd:cd00821      1 KEGYLLKRGGGGL----KSWKKRWFVLFEGVLLYYKSKKdsSYKPKGSIPLSG-ILEVEEVSPKERPHCFEL-VTPDGRT 74
                           90
                   ....*....|....*...
gi 1907161909 1461 WHLCCDSLQAQMEWMASI 1478
Cdd:cd00821     75 YYLQADSEEERQEWLKAL 92
SAM_Samd5 cd09527
SAM domain of Samd5 subfamily; SAM (sterile alpha motif) domain of Samd5 subfamily is a ...
11-65 6.79e-05

SAM domain of Samd5 subfamily; SAM (sterile alpha motif) domain of Samd5 subfamily is a putative protein-protein interaction domain. Proteins of this subfamily have a SAM domain at the N-terminus. SAM is a widespread domain in signaling and regulatory proteins. In many cases SAM mediates dimerization/oligomerization. The exact function of proteins belonging to this subfamily is unknown.


Pssm-ID: 188926  Cd Length: 63  Bit Score: 42.43  E-value: 6.79e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1907161909   11 IRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQ 65
Cdd:cd09527      5 VYDWLRTLQLEQYAEKFVDNGYDDLEVCKQIGDPDLDAIGVMNPAHRKRILEAVR 59
PLN03119 PLN03119
putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional
695-797 7.42e-05

putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional


Pssm-ID: 178666  Cd Length: 648  Bit Score: 47.53  E-value: 7.42e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  695 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLgpkDSKVRSLKMdaSIWSNELIELFIVIGNKRANDFWAGNL-QKDE 773
Cdd:PLN03119    23 NRRCINCNSLGPQYVCTTFWTFVCMACSGIHREF---THRVKSVSM--SKFTSKEVEVLQNGGNQRAREIYLKNWdHQRQ 97
                           90       100
                   ....*....|....*....|....
gi 1907161909  774 ELQVDSPVEKRKNFITQKYKEGKF 797
Cdd:PLN03119    98 RLPENSNAERVREFIKNVYVQKKY 121
SAM_EPH-R cd09488
SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH ...
13-67 8.02e-05

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.


Pssm-ID: 188887  Cd Length: 61  Bit Score: 41.83  E-value: 8.02e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1907161909   13 DFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMI 67
Cdd:cd09488      7 EWLESIKMGRYKENFTAAGYTSLDAVAQMTAEDLTRLGVTLVGHQKKILNSIQAL 61
ArfGap_AGFG2 cd17903
ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain ...
694-797 8.72e-05

ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG2 is a member of the HIV-1 Rev binding protein (HRB) family and contains one Arf-GAP zinc finger domain, several Phe-Gly (FG) motifs, and four Asn-Pro-Phe (NPF) motifs. AGFG2 interacts with Eps15 homology (EH) domains and plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.


Pssm-ID: 350090 [Multi-domain]  Cd Length: 116  Bit Score: 43.44  E-value: 8.72e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  694 SNRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKdSKVRSLKMdaSIWSNELIELFIVIGNKRANDFWAGNLQKDE 773
Cdd:cd17903     13 ANRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPP-HRVKSISM--TTFTEPEVLFLQARGNEVCRKIWLGLFDART 89
                           90       100
                   ....*....|....*....|....*
gi 1907161909  774 ELQVDS-PVEKRKNFITQKYKEGKF 797
Cdd:cd17903     90 SLIPDSrDPQKVKEFLQEKYEKKRW 114
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
588-682 1.14e-04

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270108  Cd Length: 103  Bit Score: 42.84  E-value: 1.14e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  588 KCGYLELRG----------YKAKIFtVLRGNSVWLCKNEQDFKSGLGiTIipmNV-ANVKQVDRAVKQ-SFEIITPYRSF 655
Cdd:cd13296      1 KSGWLTKKGggsstlsrrnWKSRWF-VLRDTVLKYYENDQEGEKLLG-TI---DIrSAKEIVDNDPKEnRLSITTEERTY 75
                           90       100
                   ....*....|....*....|....*..
gi 1907161909  656 SFTADSEREKQEWIEAVQQSIAETLSD 682
Cdd:cd13296     76 HLVAESPEDASQWVNVLTRVISATDLE 102
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
483-575 1.15e-04

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270083  Cd Length: 114  Bit Score: 43.14  E-value: 1.15e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  483 KCGWLDKlspQGK--RMFQKRWVKFDGLSISYYNNDREMYSKGIIPLTAiSTVR-----AQGDNK--FEIV--------- 544
Cdd:cd13263      5 KSGWLKK---QGSivKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPG-NKVKevpfnPEEPGKflFEIIpggggdrmt 80
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1907161909  545 TTQRTFVFRVEKEEERNDWISILLSALKSPS 575
Cdd:cd13263     81 SNHDSYLLMANSQAEMEEWVKVIRRVIGSPF 111
SAM_EPH-B4 cd09554
SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
9-70 1.27e-04

SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B4 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B4 protein kinase performs kinase-dependent and kinase-independent functions. These receptors play a role in the regular vascular system development during embryogenesis. They were found overexpressed in a variety of cancers, including carcinoma of the head and neck, ovarian cancer, bladder cancer, and downregulated in bone myeloma. Thus, EphB4 is a potential biomarker and a target for drug design.


Pssm-ID: 188953  Cd Length: 67  Bit Score: 41.77  E-value: 1.27e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907161909    9 ADIRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMIFSK 70
Cdd:cd09554      4 GSVGEWLRAIKMERYEDSFLQAGFTTFQLVSQISTEDLLRMGVTLAGHQKKILSSIQAMGIQ 65
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
918-996 1.46e-04

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 42.61  E-value: 1.46e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907161909  918 NKKWCVLEGGFLSYYENDRCTTPNGTINISEVICLAVHKEDFYLNtgpifVFEIYLPSeRVFLFGAETSQIQRKWTETI 996
Cdd:cd13298     23 KKRWVVLRPCQLSYYKDEKEYKLRRVINLSELLAVAPLKDKKRKN-----VFGIYTPS-KNLHFRATSEKDANEWVEAL 95
PH pfam00169
PH domain; PH stands for pleckstrin homology.
586-677 1.62e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 42.55  E-value: 1.62e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  586 PEKCGYLELRGYKAKI-----FTVLRGNSVWLCKNEQDFKSGLGITIIPMN----VANVKQVDRAVKQSFEIIT----PY 652
Cdd:pfam00169    1 VVKEGWLLKKGGGKKKswkkrYFVLFDGSLLYYKDDKSGKSKEPKGSISLSgcevVEVVASDSPKRKFCFELRTgertGK 80
                           90       100
                   ....*....|....*....|....*
gi 1907161909  653 RSFSFTADSEREKQEWIEAVQQSIA 677
Cdd:pfam00169   81 RTYLLQAESEEERKDWIKAIQSAIR 105
PH2_ARAP cd13254
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
476-564 1.89e-04

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 2; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the second PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270074  Cd Length: 90  Bit Score: 42.02  E-value: 1.89e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  476 GSSAAKEKCGWLDKLSPQGKRmfqkrWVKFDGLSISYYNNDREmYSKGI----IPLTAiSTVRaQGDNK-FEIVTTQRTF 550
Cdd:cd13254      1 PRKPNPDKCGYLELRGYKAKV-----YAALMGDEVWLYKNEQD-FRLGIgitvIEMNG-ANVK-DVDRRsFDLTTPYRSF 72
                           90
                   ....*....|....
gi 1907161909  551 VFRVEKEEERNDWI 564
Cdd:cd13254     73 SFTAESEHEKQEWI 86
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
485-564 2.51e-04

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270133  Cd Length: 112  Bit Score: 42.01  E-value: 2.51e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  485 GWLDKlSPQGKRMFQKRWVK--F---------DGLSISYYNNDREMYSKGIIPLTAISTVRAQGDNK---------FEIV 544
Cdd:cd13324      5 GWLTK-SPPEKKIWRAAWRRrwFvlrsgrlsgGQDVLEYYTDDHCKKLKGIIDLDQCEQVDAGLTFEkkkfknqfiFDIR 83
                           90       100
                   ....*....|....*....|
gi 1907161909  545 TTQRTFVFRVEKEEERNDWI 564
Cdd:cd13324     84 TPKRTYYLVAETEEEMNKWV 103
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
485-570 2.78e-04

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270068  Cd Length: 104  Bit Score: 41.87  E-value: 2.78e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  485 GWLDKLSPQGKRMFQKRWVKFDGLSISYYNNDREMYSKGIIPLTA--ISTVRAQGD--NKFEIV---TTQRTFVFRVEKE 557
Cdd:cd13248     11 GWLHKQGGSGLKNWRKRWFVLKDNCLYYYKDPEEEKALGSILLPSytISPAPPSDEisRKFAFKaehANMRTYYFAADTA 90
                           90
                   ....*....|...
gi 1907161909  558 EERNDWISILLSA 570
Cdd:cd13248     91 EEMEQWMNAMSLA 103
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
477-567 3.03e-04

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270071  Cd Length: 108  Bit Score: 41.96  E-value: 3.03e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  477 SSAAKEKCGWLDKLSPQG-KRMFQKRWVK-FDG-LSISYYNNDREMYSKGIipLTAISTVRAQGDNKFEIVTTQRTFVFR 553
Cdd:cd13251      6 KSHGTEKSGYLLKKSEGKiRKVWQKRRCSiKDGfLTISHADENKPPAKLNL--LTCQVKLVPEDKKCFDLISHNRTYHFQ 83
                           90
                   ....*....|....
gi 1907161909  554 VEKEEERNDWISIL 567
Cdd:cd13251     84 AEDENDANAWMSVL 97
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
919-998 3.46e-04

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270133  Cd Length: 112  Bit Score: 41.63  E-value: 3.46e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  919 KKWCVLEGG-------FLSYYENDRCTTPNGTINISEviC------LAVHKEDFYLNtgpiFVFEIYLPsERVFLFGAET 985
Cdd:cd13324     23 RRWFVLRSGrlsggqdVLEYYTDDHCKKLKGIIDLDQ--CeqvdagLTFEKKKFKNQ----FIFDIRTP-KRTYYLVAET 95
                           90
                   ....*....|...
gi 1907161909  986 SQIQRKWTETIAK 998
Cdd:cd13324     96 EEEMNKWVRCICQ 108
PH_Boi cd13316
Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally ...
485-570 4.75e-04

Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally redundant and important for cell growth with Boi mutants displaying defects in bud formation and in the maintenance of cell polarity.They appear to be linked to Rho-type GTPase, Cdc42 and Rho3. Boi1 and Boi2 display two-hybrid interactions with the GTP-bound ("active") form of Cdc42, while Rho3 can suppress of the lethality caused by deletion of Boi1 and Boi2. These findings suggest that Boi1 and Boi2 are targets of Cdc42 that promote cell growth in a manner that is regulated by Rho3. Boi proteins contain a N-terminal SH3 domain, followed by a SAM (sterile alpha motif) domain, a proline-rich region, which mediates binding to the second SH3 domain of Bem1, and C-terminal PH domain. The PH domain is essential for its function in cell growth and is important for localization to the bud, while the SH3 domain is needed for localization to the neck. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270126  Cd Length: 97  Bit Score: 40.82  E-value: 4.75e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  485 GWLDKlspQGKRM--FQKRWVKFDGLSISYYNNDREMYSKGIIPLTAISTVRAQGDNK------FEIV--TTQRTFVFRV 554
Cdd:cd13316      4 GWMKK---RGERYgtWKTRYFVLKGTRLYYLKSENDDKEKGLIDLTGHRVVPDDSNSPfrgsygFKLVppAVPKVHYFAV 80
                           90
                   ....*....|....*.
gi 1907161909  555 EKEEERNDWISILLSA 570
Cdd:cd13316     81 DEKEELREWMKALMKA 96
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
483-567 5.93e-04

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270118  Cd Length: 113  Bit Score: 41.24  E-value: 5.93e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  483 KCGWLDKL--SPQGKRMFQKRWVKFDGLSISYYNNDREMYSKGIIPLTAISTVRAQGDNK-----FEIVTTQ---RTFVF 552
Cdd:cd13308     11 HSGTLTKKggSQKTLQNWQLRYVIIHQGCVYYYKNDQSAKPKGVFSLNGYNRRAAEERTSklkfvFKIIHLSpdhRTWYF 90
                           90
                   ....*....|....*
gi 1907161909  553 RVEKEEERNDWISIL 567
Cdd:cd13308     91 AAKSEDEMSEWMEYI 105
PH_OSBP_ORP4 cd13284
Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; ...
485-567 6.52e-04

Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; Human OSBP is proposed to function is sterol-dependent regulation of ERK dephosphorylation and sphingomyelin synthesis as well as modulation of insulin signaling and hepatic lipogenesis. It contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBPs and Osh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. ORP4 is proposed to function in Vimentin-dependent sterol transport and/or signaling. Human ORP4 has 2 forms, a long (ORP4L) and a short (ORP4S). ORP4L contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP4S is truncated and contains only an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270101  Cd Length: 99  Bit Score: 40.44  E-value: 6.52e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  485 GWLDKLSPQGKRmFQKRWVKFDGLSISYYNNDREM--YSKGIIPLtAISTVRAQGDNKFEIVT-TQRTFVFRVEKEEERN 561
Cdd:cd13284      3 GWLLKWTNYIKG-YQRRWFVLSNGLLSYYRNQAEMahTCRGTINL-AGAEIHTEDSCNFVISNgGTQTFHLKASSEVERQ 80

                   ....*.
gi 1907161909  562 DWISIL 567
Cdd:cd13284     81 RWVTAL 86
PH_Phafin2-like cd01218
Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; ...
627-670 8.58e-04

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269927 [Multi-domain]  Cd Length: 123  Bit Score: 41.09  E-value: 8.58e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1907161909  627 IIPMNVANVKQVD--RAVKQSFEIITPYRSFSFTADSEREKQEWIE 670
Cdd:cd01218     73 IIPLEDVKIEDLEdtGELKNGWQIISPKKSFVVYAATATEKSEWMD 118
PH_Skap_family cd13266
Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...
483-575 9.17e-04

Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270086  Cd Length: 106  Bit Score: 40.58  E-value: 9.17e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  483 KCGWLDKLSPQGK---RMFQKRWVKFDGLSISYYNNDREMYSKGIIPLT-----AISTVRAQG--DNKFEIVT-TQRTFV 551
Cdd:cd13266      3 KAGYLEKRRKDHSffgSEWQKRWCAISKNVFYYYGSDKDKQQKGEFAINgydvrMNPTLRKDGkkDCCFELVCpDKRTYQ 82
                           90       100
                   ....*....|....*....|....
gi 1907161909  552 FRVEKEEERNDWISILLSALKSPS 575
Cdd:cd13266     83 FTAASPEDAEDWVDQISFILQDLS 106
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
1382-1478 9.72e-04

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270118  Cd Length: 113  Bit Score: 40.47  E-value: 9.72e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909 1382 IKEGILKLKEEPSKILSgnKFQDRCVVLRDGHLFIYKDPKSSKHDKMFPL----RAMKFYLGVKKKmkpptsWGLTVY-- 1455
Cdd:cd13308     10 IHSGTLTKKGGSQKTLQ--NWQLRYVIIHQGCVYYYKNDQSAKPKGVFSLngynRRAAEERTSKLK------FVFKIIhl 81
                           90       100
                   ....*....|....*....|....
gi 1907161909 1456 -SEKHHWHLCCDSLQAQMEWMASI 1478
Cdd:cd13308     82 sPDHRTWYFAAKSEDEMSEWMEYI 105
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
917-998 1.12e-03

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275402  Cd Length: 116  Bit Score: 40.30  E-value: 1.12e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  917 TNKKWCVLEGGFLSYYENDRCTT-PNGTINISEVIclAVHKEDfyLNTGPIFVFEIYLpSERVFLFGAETSQIQRKWTET 995
Cdd:cd13215     37 YTRYWFVLKGDTLSWYNSSTDLYfPAGTIDLRYAT--SIELSK--SNGEATTSFKIVT-NSRTYKFKADSETSADEWVKA 111

                   ...
gi 1907161909  996 IAK 998
Cdd:cd13215    112 LKK 114
PH_Skap1 cd13380
Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 ...
919-996 1.23e-03

Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 (also called Skap55/Src kinase-associated phosphoprotein of 55 kDa) and its partner, ADAP (adhesion and degranulation promoting adapter protein) help reorganize the cytoskeleton and/or promote integrin-mediated adhesion upon immunoreceptor activation. Skap1 is also involved in T Cell Receptor (TCR)-induced RapL-Rap1 complex formation and LFA-1 activation. Skap1 has an N-terminal coiled-coil conformation which is proposed to be involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap1 PH domain plays a role in controlling integrin function via recruitment of ADAP-SKAP complexes to integrins as well as in controlling the ability of ADAP to interact with the CBM signalosome and regulate NF-kappaB. SKAP1 is necessary for RapL binding to membranes in a PH domain-dependent manner and the PI3K pathway. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Skap55/Skap1, Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270180  Cd Length: 106  Bit Score: 40.23  E-value: 1.23e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  919 KKWCVLEGGFLSYYENDRCTTPNGTINISEVIC-LAVH-KEDFYLNTgpifVFEIYLPSERVFLFGAETSQIQRKWTETI 996
Cdd:cd13380     23 KRWCVLTNRAFYYYASEKSKQPKGGFLIKGYSAqMAPHlRKDSRRDS----CFELTTPGRRTYQFTAASPSEARDWVDQI 98
RA cd17043
Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA ...
1297-1367 1.47e-03

Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in various functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. RA-containing proteins include RalGDS, AF6, RIN, RASSF1, SNX27, CYR1, STE50, and phospholipase C epsilon.


Pssm-ID: 340563  Cd Length: 87  Bit Score: 39.22  E-value: 1.47e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907161909 1297 ISPVMEAEELTNdILAIKNIIPMKGDIWATFEVIENEELERPLHYTENVLEQVLQWSSLAEPGSayLVVKR 1367
Cdd:cd17043     20 VSSTTTAREVVQ-LLLEKYGLEEDPEDYSLYEVSEKQETERVLHDDECPLLIQLEWGPQGTEFR--FVLKR 87
SAM_EPH-A6 cd09547
SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
11-67 1.51e-03

SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A6 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A6 gene is preferentially expressed in the nervous system. EPH-A6 receptors are involved in primate retina vascular and axon guidance, and in neural circuits responsible for learning and memory. EphA6 gene was significantly down regulated in colorectal cancer and in malignant melanomas. It is a potential molecular marker for these cancers.


Pssm-ID: 188946  Cd Length: 64  Bit Score: 38.71  E-value: 1.51e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907161909   11 IRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMI 67
Cdd:cd09547      6 VSDWLDSIKMGQYKNNFMAAGFTTLDMVSRMTIDDIRRIGVTLIGHQRRIVSSIQTL 62
PH1_FGD5_FGD6 cd13389
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal ...
638-678 2.25e-03

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275424  Cd Length: 124  Bit Score: 39.56  E-value: 2.25e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1907161909  638 VDRAVKQSFEIITPYRSFSFTADSEREKQEWIEAVQQSIAE 678
Cdd:cd13389     69 EDEEYSNEFQIISTKRSFTLIASSEEERDEWVKALSRAIEE 109
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
588-674 2.52e-03

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 39.15  E-value: 2.52e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  588 KCGYLELRGYKA----KIFTVLRGNSVWLCKNEQDFKSGLGITIIPMN-VANVKqvDRAVKQSFEIITPYRSFSFTADSE 662
Cdd:cd13298      8 KSGYLLKRSRKTknwkKRWVVLRPCQLSYYKDEKEYKLRRVINLSELLaVAPLK--DKKRKNVFGIYTPSKNLHFRATSE 85
                           90
                   ....*....|..
gi 1907161909  663 REKQEWIEAVQQ 674
Cdd:cd13298     86 KDANEWVEALRE 97
PH2_PH_fungal cd13299
Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal ...
485-573 2.77e-03

Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270111  Cd Length: 102  Bit Score: 38.76  E-value: 2.77e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  485 GWLDKLSPQGKRMFQKRWVKFDGLSISYYNNDREMYSKGIIPLTAI-STVRAQGDNK-----FEIVTTQRTFVFRVEKEE 558
Cdd:cd13299     10 GYLQVLKKKGVNQWKKYWLVLRNRSLSFYKDQSEYSPVKIIPIDDIiDVVELDPLSKskkwcLQIITPEKRIRFCADDEE 89
                           90
                   ....*....|....*
gi 1907161909  559 ERNDWisilLSALKS 573
Cdd:cd13299     90 SLIKW----LGALKS 100
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
646-677 2.88e-03

KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA (Caenorhabditis elegans homolog unc-104) and KIFIB transport synaptic vesicle precursors that contain synaptic vesicle proteins, such as synaptophysin, synaptotagmin and the small GTPase RAB3A, but they do not transport organelles that contain plasma membrane proteins. They have a N-terminal motor domain, followed by a coiled-coil domain, and a C-terminal PH domain. KIF1A adopts a monomeric form in vitro, but acts as a processive dimer in vivo. KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein; this results in their different motor activities. KIF1A and KIF1B bind to RAB3 proteins through the adaptor protein mitogen-activated protein kinase (MAPK) -activating death domain (MADD; also calledDENN), which was first identified as a RAB3 guanine nucleotide exchange factor (GEF). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269939  Cd Length: 103  Bit Score: 38.73  E-value: 2.88e-03
                           10        20        30
                   ....*....|....*....|....*....|..
gi 1907161909  646 FEIITPYRSFSFTADSEREKQEWIEAVQQSIA 677
Cdd:cd01233     72 FAVYTPTNSYLLQARSEKEMQDWLYAIDPLLA 103
PH_Skap_family cd13266
Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...
586-672 2.91e-03

Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270086  Cd Length: 106  Bit Score: 39.04  E-value: 2.91e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  586 PEKCGYLELRGYKAKIF--------TVLRGNSVWLCKNEQDFKSGLGITIIPMNVANVKQVDRAVKQ--SFEIITP-YRS 654
Cdd:cd13266      1 VIKAGYLEKRRKDHSFFgsewqkrwCAISKNVFYYYGSDKDKQQKGEFAINGYDVRMNPTLRKDGKKdcCFELVCPdKRT 80
                           90
                   ....*....|....*...
gi 1907161909  655 FSFTADSEREKQEWIEAV 672
Cdd:cd13266     81 YQFTAASPEDAEDWVDQI 98
SAM_EPH-B6 cd09555
SAM domain of EPH-B6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
12-67 3.00e-03

SAM domain of EPH-B6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B6 receptors and appears to mediate cell-cell initiated signal transduction. Receptors of this type are highly expressed in embryo and adult nervous system, in thymus and also in T-cells. They are involved in regulation of cell adhesion and migration. (EPH-B6 receptor is unusual; it fails to show catalytic activity due to alteration in kinase domain). EPH-B6 may be considered as a biomarker in some types of tumors; EPH-B6 activates MAP kinase signaling in lung adenocarcinoma, suppresses metastasis formation in non-small cell lung cancer, and slows invasiveness in some breast cancer cell lines.


Pssm-ID: 188954  Cd Length: 69  Bit Score: 37.99  E-value: 3.00e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907161909   12 RDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQMI 67
Cdd:cd09555     10 QAWLSAIGLECYQDNFSKFGLCTFSDVAQLSLEDLPALGITLAGHQKKLLHHIQLL 65
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
919-996 3.14e-03

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270118  Cd Length: 113  Bit Score: 38.93  E-value: 3.14e-03
                           10        20        30        40        50        60        70        80
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gi 1907161909  919 KKWCVLEGGFLSYYENDRCTTPNGTINISEVICLAvhKEDfyLNTGPIFVFEIYLPS--ERVFLFGAETSQIQRKWTETI 996
Cdd:cd13308     30 LRYVIIHQGCVYYYKNDQSAKPKGVFSLNGYNRRA--AEE--RTSKLKFVFKIIHLSpdHRTWYFAAKSEDEMSEWMEYI 105
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
919-999 3.18e-03

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270073  Cd Length: 94  Bit Score: 38.52  E-value: 3.18e-03
                           10        20        30        40        50        60        70        80
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gi 1907161909  919 KKWCVLEGGFLSYYENDRCTTPNGTINISEVICLAVHKEdfylntgpiFVFEIyLPSERVFLFGAETSQIQRKWTETIAK 998
Cdd:cd13253     20 KRWVVFDGLSLRYFDSEKDAYSKRIIPLSAISTVRAVGD---------NKFEL-VTTNRTFVFRAESDDERNLWCSTLQA 89

                   .
gi 1907161909  999 R 999
Cdd:cd13253     90 A 90
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
483-570 3.85e-03

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269959  Cd Length: 106  Bit Score: 38.42  E-value: 3.85e-03
                           10        20        30        40        50        60        70        80
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gi 1907161909  483 KCGWLDKLSPQGKRMFQKRWVKFDGLS-ISYYNNDREMYS----KGIIPLTAISTV--RAQGDNKFEIV--TTQRTFVFR 553
Cdd:cd01257      5 KSGYLKKLKTMRKRYFVLRAESHGGPArLEYYENEKKFRRnaepKRVIPLSSCFNInkRADAKHKHLIAlyTKDECFGLV 84
                           90
                   ....*....|....*..
gi 1907161909  554 VEKEEERNDWISILLSA 570
Cdd:cd01257     85 AESEEEQDEWYQALLEL 101
PH_Skap_family cd13266
Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...
919-998 4.17e-03

Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270086  Cd Length: 106  Bit Score: 38.66  E-value: 4.17e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  919 KKWCVLEGGFLSYYENDRCTTPNGTINIseviclavhkEDFYLNTGPIF--------VFEIYLPSERVFLFGAETSQIQR 990
Cdd:cd13266     23 KRWCAISKNVFYYYGSDKDKQQKGEFAI----------NGYDVRMNPTLrkdgkkdcCFELVCPDKRTYQFTAASPEDAE 92

                   ....*...
gi 1907161909  991 KWTETIAK 998
Cdd:cd13266     93 DWVDQISF 100
PH_CNK_insect-like cd13326
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
589-672 4.34e-03

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from insects, spiders, mollusks, and nematodes. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270135  Cd Length: 91  Bit Score: 38.09  E-value: 4.34e-03
                           10        20        30        40        50        60        70        80
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gi 1907161909  589 CGYLELR-------GYKAKIFTVLRGNSVWLCKNEQDFKSGLGITIIPMNVANVKQVdRAVKQSFEIITPYRSFSFTADS 661
Cdd:cd13326      2 QGWLYQRrrkgkggGKWAKRWFVLKGSNLYGFRSQESTKADCVIFLPGFTVSPAPEV-KSRKYAFKVYHTGTVFYFAAES 80
                           90
                   ....*....|.
gi 1907161909  662 EREKQEWIEAV 672
Cdd:cd13326     81 QEDMKKWLDLL 91
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
602-677 5.28e-03

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP1 and TAPP2 contain two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270090  Cd Length: 114  Bit Score: 38.49  E-value: 5.28e-03
                           10        20        30        40        50        60        70        80
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gi 1907161909  602 FTVLRGNSVWLCKNEQDFKSglgITIIPM-NVANVKQVDraVKQS------FEIITPYRSFSFTADSEREKQEWIEAVQQ 674
Cdd:cd13271     28 FFILDDNTISYYKSETDKEP---LRTIPLrEVLKVHECL--VKSLlmrdnlFEIITTSRTFYIQADSPEEMHSWIKAISG 102

                   ...
gi 1907161909  675 SIA 677
Cdd:cd13271    103 AIV 105
PH_Gab1_Gab2 cd01266
Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily ...
485-564 5.38e-03

Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. The members in this cd include the Gab1 and Gab2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241297  Cd Length: 123  Bit Score: 38.77  E-value: 5.38e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  485 GWLDKLSPQGK---RMFQKRWVKF-------DGLSISYYNNDREMYSKGIIPLTAISTVRA---------QGDNKFEIVT 545
Cdd:cd01266      8 GWLRKSPPEKKlrrYAWKKRWFVLrsgrlsgDPDVLEYYKNDHAKKPIRVIDLNLCEQVDAgltfnkkelENSYIFDIKT 87
                           90
                   ....*....|....*....
gi 1907161909  546 TQRTFVFRVEKEEERNDWI 564
Cdd:cd01266     88 IDRIFYLVAETEEDMNKWV 106
PH_DGK_type2 cd13274
Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes ...
640-675 5.79e-03

Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low and DAG is used for glycerophospholipid biosynthesis. Upon receptor activation of the phosphoinositide pathway, DGK activity increases which drives the conversion of DAG to PA. DGK acts as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another. There are 9 mammalian DGK isoforms all with conserved catalytic domains and two cysteine rich domains. These are further classified into 5 groups according to the presence of additional functional domains and substrate specificity: Type 1 - DGK-alpha, DGK-beta, DGK-gamma - contain EF-hand motifs and a recoverin homology domain; Type 2 - DGK-delta, DGK-eta, and DGK-kappa- contain a pleckstrin homology domain, two cysteine-rich zinc finger-like structures, and a separated catalytic region; Type 3 - DGK-epsilon - has specificity for arachidonate-containing DAG; Type 4 - DGK-zeta, DGK-iota- contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localization signal, and a PDZ-binding motif; Type 5 - DGK-theta - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region. The type 2 DGKs are present as part of this Metazoan DGK hierarchy. They have a N-terminal PH domain, two cysteine rich domains, followed by bipartite catalytic domains, and a C-terminal SAM domain. Their catalytic domains and perhaps other DGK catalytic domains may function as two independent units in a coordinated fashion. They may also require other motifs for maximal activity because several DGK catalytic domains have very little DAG kinase activity when expressed as isolated subunits. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270093  Cd Length: 97  Bit Score: 37.76  E-value: 5.79e-03
                           10        20        30
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gi 1907161909  640 RAVKQSFEIITPYRSFSFTADSEREKQEWIEAVQQS 675
Cdd:cd13274     55 KNVNNSFTVITPFRKLILCAESRKEMEEWISALKTV 90
SAM_EPH-B1 cd09551
SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
11-65 5.89e-03

SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B1 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH- B1 receptors. In human vascular endothelial cells it appears to mediate cell-cell initiated signal transduction via the binding of the adaptor protein GRB10 (growth factor) through its SH2 domain to a conserved tyrosine that is phosphorylated. EPH-B1 receptors play a role in neurogenesis, in particular in regulation of proliferation and migration of neural progenitors in the hippocampus and in corneal neovascularization; they are involved in converting the crossed retinal projection to ipsilateral retinal projection. They may be potential targets in angiogenesis-related disorders.


Pssm-ID: 188950  Cd Length: 68  Bit Score: 36.94  E-value: 5.89e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1907161909   11 IRDFLMSINLEQYLLHFREFGFYTVRDCTSINDSVLHQIGISPTGHRRRILKQLQ 65
Cdd:cd09551      9 VEDWLSAIKMSQYRDNFLSSGFTSLQLVAQMTSEDLLRIGVTLAGHQKKILNSIQ 63
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
918-992 6.04e-03

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270080  Cd Length: 103  Bit Score: 38.09  E-value: 6.04e-03
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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  918 NKKW----CVLEGG--FLSYYENDRCTTPNGTINISEVICLAVHKEDFylntGPIFVFEI---YLPSERVFLFGAETSQI 988
Cdd:cd13260     16 NKKWknlyFVLEGKeqHLYFFDNEKRTKPKGLIDLSYCSLYPVHDSLF----GRPNCFQIvvrALNESTITYLCADTAEL 91

                   ....
gi 1907161909  989 QRKW 992
Cdd:cd13260     92 AQEW 95
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
485-564 6.19e-03

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269941  Cd Length: 106  Bit Score: 38.08  E-value: 6.19e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  485 GWLDKlspQGKRM--FQKRWVKFDGLS--ISYYNNDREMYSKGIIPLTAISTVRA---------QGDNK--FEIVTTQRT 549
Cdd:cd01235      7 GYLYK---RGALLkgWKQRWFVLDSTKhqLRYYESREDTKCKGFIDLAEVESVTPatpiigapkRADEGafFDLKTNKRV 83
                           90
                   ....*....|....*
gi 1907161909  550 FVFRVEKEEERNDWI 564
Cdd:cd01235     84 YNFCAFDAESAQQWI 98
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
588-673 6.26e-03

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275402  Cd Length: 116  Bit Score: 38.37  E-value: 6.26e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  588 KCGYLELRGYKAKIFT----VLRGNSVWLCKNEQD--FKSGlgiTIIPMNVANVKQVDRAVKQ--SFEIITPYRSFSFTA 659
Cdd:cd13215     23 KSGYLSKRSKRTLRYTrywfVLKGDTLSWYNSSTDlyFPAG---TIDLRYATSIELSKSNGEAttSFKIVTNSRTYKFKA 99
                           90
                   ....*....|....
gi 1907161909  660 DSEREKQEWIEAVQ 673
Cdd:cd13215    100 DSETSADEWVKALK 113
SAM_caskin1,2_repeat1 cd09497
SAM domain of caskin protein repeat 1; SAM (sterile alpha motif) domain repeat 1 of caskin1,2 ...
11-64 8.09e-03

SAM domain of caskin protein repeat 1; SAM (sterile alpha motif) domain repeat 1 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and apparently may play a role in neural development, synaptic protein targeting, and regulation of gene expression.


Pssm-ID: 188896  Cd Length: 66  Bit Score: 36.47  E-value: 8.09e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907161909   11 IRDFLMSINLEQYLLHFREFGFytvrDCTSIN-----DsvLHQIGISPTGHRRRILKQL 64
Cdd:cd09497      7 IFDWLREFGLEEYTPNFIKAGY----DLPTISrmtpeD--LTAIGITKPGHRKKLKSEI 59
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
485-575 9.75e-03

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269944 [Multi-domain]  Cd Length: 140  Bit Score: 38.36  E-value: 9.75e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161909  485 GWLDKLSPQGKRM----FQKRWVKFDGLSISYYNND--REMYSKGIIPLTAISTVraqgdnkfEIVTT----QRTFVFRV 554
Cdd:cd01238      3 GLLVKRSQGKKRFgpvnYKERWFVLTKSSLSYYEGDgeKRGKEKGSIDLSKVRCV--------EEVKDeaffERKYPFQV 74
                           90       100       110
                   ....*....|....*....|....*....|..
gi 1907161909  555 -----------EKEEERNDWISILLSALKSPS 575
Cdd:cd01238     75 vyddytlyvfaPSEEDRDEWIAALRKVCRNNS 106
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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