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Conserved domains on  [gi|635372929|ref|NP_001278948|]
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cytohesin-1 isoform 3 [Homo sapiens]

Protein Classification

cytohesin( domain architecture ID 10475580)

cytohesin promotes the activation of ARF factors through replacement of GDP with GTP, and plays an important role in membrane trafficking

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
Sec7 pfam01369
Sec7 domain; The Sec7 domain is a guanine-nucleotide-exchange-factor (GEF) for the pfam00025 ...
3-185 2.34e-107

Sec7 domain; The Sec7 domain is a guanine-nucleotide-exchange-factor (GEF) for the pfam00025 family.


:

Pssm-ID: 460178  Cd Length: 183  Bit Score: 311.32  E-value: 2.34e-107
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929    3 RNKQVAMGRKKFNMDPKKGIQFLIENDLLKNTCEDIAQFLYKGEGLNKTAIGDYLGERDEFNIQVLHAFVELHEFTDLNL 82
Cdd:pfam01369   1 RKKLLREGIEKFNKKPKKGIEYLIEKGFIEDDPESIAKFLFETPGLDKKAIGEYLGKPDEFNIEVLKAFVDLFDFKGLRI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929   83 VQALRQFLWSFRLPGEAQKIDRMMEAFAQRYCQCNNGVFQSTDTCYVLSFAIIMLNTSLHNPNVKDKPTVERFIAMNRGI 162
Cdd:pfam01369  81 DEALRLFLESFRLPGEAQKIDRIMEAFAERYYEQNPGVFANADAAYVLAYSIIMLNTDLHNPNVKKKMTLEDFIRNLRGI 160
                         170       180
                  ....*....|....*....|...
gi 635372929  163 NDGGDLPEELLRNLYESIKNEPF 185
Cdd:pfam01369 161 NDGKDFPDEYLEEIYDSIKKNEI 183
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
200-320 3.42e-85

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. 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: 269954  Cd Length: 119  Bit Score: 252.62  E-value: 3.42e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 200 FNPDREGWLLKLGGgRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREVEDSKKPNCFELYIPDNKdQVIKA 279
Cdd:cd01252    1 FNPDREGWLLKLGG-RVKSWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSVREVEDKKKPFCFELYSPSNG-QVIKA 78
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 635372929 280 CKTEADGRVVEGNHTVYRISAPTPEEKEEWIKCIKAAISRD 320
Cdd:cd01252   79 CKTDSDGKVVEGNHTVYRISAASEEERDEWIKSIKASISRD 119
 
Name Accession Description Interval E-value
Sec7 pfam01369
Sec7 domain; The Sec7 domain is a guanine-nucleotide-exchange-factor (GEF) for the pfam00025 ...
3-185 2.34e-107

Sec7 domain; The Sec7 domain is a guanine-nucleotide-exchange-factor (GEF) for the pfam00025 family.


Pssm-ID: 460178  Cd Length: 183  Bit Score: 311.32  E-value: 2.34e-107
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929    3 RNKQVAMGRKKFNMDPKKGIQFLIENDLLKNTCEDIAQFLYKGEGLNKTAIGDYLGERDEFNIQVLHAFVELHEFTDLNL 82
Cdd:pfam01369   1 RKKLLREGIEKFNKKPKKGIEYLIEKGFIEDDPESIAKFLFETPGLDKKAIGEYLGKPDEFNIEVLKAFVDLFDFKGLRI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929   83 VQALRQFLWSFRLPGEAQKIDRMMEAFAQRYCQCNNGVFQSTDTCYVLSFAIIMLNTSLHNPNVKDKPTVERFIAMNRGI 162
Cdd:pfam01369  81 DEALRLFLESFRLPGEAQKIDRIMEAFAERYYEQNPGVFANADAAYVLAYSIIMLNTDLHNPNVKKKMTLEDFIRNLRGI 160
                         170       180
                  ....*....|....*....|...
gi 635372929  163 NDGGDLPEELLRNLYESIKNEPF 185
Cdd:pfam01369 161 NDGKDFPDEYLEEIYDSIKKNEI 183
Sec7 cd00171
Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product. The Sec7 domain is the ...
3-185 1.68e-102

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product. The Sec7 domain is the central domain of the guanine-nucleotide-exchange factors (GEFs) of the ADP-ribosylation factor family of small GTPases (ARFs) . It carries the exchange factor activity.


Pssm-ID: 238100  Cd Length: 185  Bit Score: 299.14  E-value: 1.68e-102
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929   3 RNKQVAMGRKKFNMDPKKGIQFLIENDLLK-NTCEDIAQFLYKGEGLNKTAIGDYLGERDEFNIQVLHAFVELHEFTDLN 81
Cdd:cd00171    1 RKTLLSEGRQLFNRKPKKGISFLIEKGFLEdDSPKEIAKFLYETEGLNKKAIGEYLGENNEFNSLVLHEFVDLFDFSGLR 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929  82 LVQALRQFLWSFRLPGEAQKIDRMMEAFAQRYCQCNNGVFQ-STDTCYVLSFAIIMLNTSLHNPNVKDKPTVERFIAMNR 160
Cdd:cd00171   81 LDEALRKFLQSFRLPGEAQKIDRLLEKFSERYCECNPGIFSsSADAAYTLAYSIIMLNTDLHNPNVKKKMTLEDFIKNLR 160
                        170       180
                 ....*....|....*....|....*
gi 635372929 161 GINDGGDLPEELLRNLYESIKNEPF 185
Cdd:cd00171  161 GINDGEDFPREFLKELYDSIKNNEI 185
Sec7 smart00222
Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product, which is required for ...
1-185 4.92e-94

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product, which is required for proper protein transport through the Golgi. The domain facilitates guanine nucleotide exchange on the small GTPases, ARFs (ADP ribosylation factors).


Pssm-ID: 214569 [Multi-domain]  Cd Length: 189  Bit Score: 277.63  E-value: 4.92e-94
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929     1 MQRNKQVAMGRKKFNMDPKKGIQFLIENDLLKN-TCEDIAQFLYKGEGLNKTAIGDYLGERDEFNIQVLHAFVELHEFTD 79
Cdd:smart00222   2 KGRKKLLSEGIVKFNDKPKKGIQSLQEKGFLANeDPQDVADFLSKNEGLNKKAIGDYLGEHDEFNRLVLHAFVDLFDFSA 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929    80 LNLVQALRQFLWSFRLPGEAQKIDRMMEAFAQRYCQCNNGVFQ--STDTCYVLSFAIIMLNTSLHNPNVKDKPTVERFIA 157
Cdd:smart00222  82 KDLDQALREFLESFRLPGEAQKIDRLLEAFSSRYCECNPGVFSkaNADAAYTLAYSLIMLNTDLHNPNVKKKMTLEDFIK 161
                          170       180
                   ....*....|....*....|....*...
gi 635372929   158 MNRGINDGGDLPEELLRNLYESIKNEPF 185
Cdd:smart00222 162 NVRGSNDGEDLPREFLEELYDSIKNNEI 189
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
200-320 3.42e-85

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. 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: 269954  Cd Length: 119  Bit Score: 252.62  E-value: 3.42e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 200 FNPDREGWLLKLGGgRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREVEDSKKPNCFELYIPDNKdQVIKA 279
Cdd:cd01252    1 FNPDREGWLLKLGG-RVKSWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSVREVEDKKKPFCFELYSPSNG-QVIKA 78
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 635372929 280 CKTEADGRVVEGNHTVYRISAPTPEEKEEWIKCIKAAISRD 320
Cdd:cd01252   79 CKTDSDGKVVEGNHTVYRISAASEEERDEWIKSIKASISRD 119
PLN03076 PLN03076
ARF guanine nucleotide exchange factor (ARF-GEF); Provisional
14-191 3.07e-72

ARF guanine nucleotide exchange factor (ARF-GEF); Provisional


Pssm-ID: 215560 [Multi-domain]  Cd Length: 1780  Bit Score: 243.58  E-value: 3.07e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929   14 FNMDPKKGIQFLIENDLLKNTCEDIAQFLYKGEGLNKTAIGDYLGERDEFNIQVLHAFVELHEFTDLNLVQALRQFLWSF 93
Cdd:PLN03076  627 FNRKPKKGIEFLINANKVGESPEEIAAFLKDASGLNKTLIGDYLGEREDLSLKVMHAYVDSFDFQGMEFDEAIRAFLQGF 706
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929   94 RLPGEAQKIDRMMEAFAQRYCQCNNGVFQSTDTCYVLSFAIIMLNTSLHNPNVKDKPTVERFIAMNRGINDGGDLPEELL 173
Cdd:PLN03076  707 RLPGEAQKIDRIMEKFAERYCKCNPKAFSSADTAYVLAYSVIMLNTDAHNPMVKNKMSADDFIRNNRGIDDGKDLPEEFM 786
                         170
                  ....*....|....*...
gi 635372929  174 RNLYESIKNEPFKIPEDD 191
Cdd:PLN03076  787 RSLYERISKNEIKMKEDD 804
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
202-318 8.45e-24

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: 93.77  E-value: 8.45e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929   202 PDREGWLLKLGGGRVKTWKRRWFILTDNCLYYFE---YTTDKEPRGIIPLENLSIREVEDS---KKPNCFELYIPDNKdq 275
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKskkDKKSYKPKGSIDLSGCTVREAPDPdssKKPHCFEIKTSDRK-- 78
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 635372929   276 vikackteadgrvvegnhtVYRISAPTPEEKEEWIKCIKAAIS 318
Cdd:smart00233  79 -------------------TLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
204-318 4.78e-23

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 91.86  E-value: 4.78e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929  204 REGWLLKLGGGRVKTWKRRWFILTDNCLYYFEY---TTDKEPRGIIPLENLSIREV---EDSKKPNCFELYIPDNkdqvi 277
Cdd:pfam00169   3 KEGWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDdksGKSKEPKGSISLSGCEVVEVvasDSPKRKFCFELRTGER----- 77
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 635372929  278 kackteadgrvveGNHTVYRISAPTPEEKEEWIKCIKAAIS 318
Cdd:pfam00169  78 -------------TGKRTYLLQAESEEERKDWIKAIQSAIR 105
 
Name Accession Description Interval E-value
Sec7 pfam01369
Sec7 domain; The Sec7 domain is a guanine-nucleotide-exchange-factor (GEF) for the pfam00025 ...
3-185 2.34e-107

Sec7 domain; The Sec7 domain is a guanine-nucleotide-exchange-factor (GEF) for the pfam00025 family.


Pssm-ID: 460178  Cd Length: 183  Bit Score: 311.32  E-value: 2.34e-107
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929    3 RNKQVAMGRKKFNMDPKKGIQFLIENDLLKNTCEDIAQFLYKGEGLNKTAIGDYLGERDEFNIQVLHAFVELHEFTDLNL 82
Cdd:pfam01369   1 RKKLLREGIEKFNKKPKKGIEYLIEKGFIEDDPESIAKFLFETPGLDKKAIGEYLGKPDEFNIEVLKAFVDLFDFKGLRI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929   83 VQALRQFLWSFRLPGEAQKIDRMMEAFAQRYCQCNNGVFQSTDTCYVLSFAIIMLNTSLHNPNVKDKPTVERFIAMNRGI 162
Cdd:pfam01369  81 DEALRLFLESFRLPGEAQKIDRIMEAFAERYYEQNPGVFANADAAYVLAYSIIMLNTDLHNPNVKKKMTLEDFIRNLRGI 160
                         170       180
                  ....*....|....*....|...
gi 635372929  163 NDGGDLPEELLRNLYESIKNEPF 185
Cdd:pfam01369 161 NDGKDFPDEYLEEIYDSIKKNEI 183
Sec7 cd00171
Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product. The Sec7 domain is the ...
3-185 1.68e-102

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product. The Sec7 domain is the central domain of the guanine-nucleotide-exchange factors (GEFs) of the ADP-ribosylation factor family of small GTPases (ARFs) . It carries the exchange factor activity.


Pssm-ID: 238100  Cd Length: 185  Bit Score: 299.14  E-value: 1.68e-102
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929   3 RNKQVAMGRKKFNMDPKKGIQFLIENDLLK-NTCEDIAQFLYKGEGLNKTAIGDYLGERDEFNIQVLHAFVELHEFTDLN 81
Cdd:cd00171    1 RKTLLSEGRQLFNRKPKKGISFLIEKGFLEdDSPKEIAKFLYETEGLNKKAIGEYLGENNEFNSLVLHEFVDLFDFSGLR 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929  82 LVQALRQFLWSFRLPGEAQKIDRMMEAFAQRYCQCNNGVFQ-STDTCYVLSFAIIMLNTSLHNPNVKDKPTVERFIAMNR 160
Cdd:cd00171   81 LDEALRKFLQSFRLPGEAQKIDRLLEKFSERYCECNPGIFSsSADAAYTLAYSIIMLNTDLHNPNVKKKMTLEDFIKNLR 160
                        170       180
                 ....*....|....*....|....*
gi 635372929 161 GINDGGDLPEELLRNLYESIKNEPF 185
Cdd:cd00171  161 GINDGEDFPREFLKELYDSIKNNEI 185
Sec7 smart00222
Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product, which is required for ...
1-185 4.92e-94

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product, which is required for proper protein transport through the Golgi. The domain facilitates guanine nucleotide exchange on the small GTPases, ARFs (ADP ribosylation factors).


Pssm-ID: 214569 [Multi-domain]  Cd Length: 189  Bit Score: 277.63  E-value: 4.92e-94
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929     1 MQRNKQVAMGRKKFNMDPKKGIQFLIENDLLKN-TCEDIAQFLYKGEGLNKTAIGDYLGERDEFNIQVLHAFVELHEFTD 79
Cdd:smart00222   2 KGRKKLLSEGIVKFNDKPKKGIQSLQEKGFLANeDPQDVADFLSKNEGLNKKAIGDYLGEHDEFNRLVLHAFVDLFDFSA 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929    80 LNLVQALRQFLWSFRLPGEAQKIDRMMEAFAQRYCQCNNGVFQ--STDTCYVLSFAIIMLNTSLHNPNVKDKPTVERFIA 157
Cdd:smart00222  82 KDLDQALREFLESFRLPGEAQKIDRLLEAFSSRYCECNPGVFSkaNADAAYTLAYSLIMLNTDLHNPNVKKKMTLEDFIK 161
                          170       180
                   ....*....|....*....|....*...
gi 635372929   158 MNRGINDGGDLPEELLRNLYESIKNEPF 185
Cdd:smart00222 162 NVRGSNDGEDLPREFLEELYDSIKNNEI 189
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
200-320 3.42e-85

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. 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: 269954  Cd Length: 119  Bit Score: 252.62  E-value: 3.42e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 200 FNPDREGWLLKLGGgRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREVEDSKKPNCFELYIPDNKdQVIKA 279
Cdd:cd01252    1 FNPDREGWLLKLGG-RVKSWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSVREVEDKKKPFCFELYSPSNG-QVIKA 78
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 635372929 280 CKTEADGRVVEGNHTVYRISAPTPEEKEEWIKCIKAAISRD 320
Cdd:cd01252   79 CKTDSDGKVVEGNHTVYRISAASEEERDEWIKSIKASISRD 119
PLN03076 PLN03076
ARF guanine nucleotide exchange factor (ARF-GEF); Provisional
14-191 3.07e-72

ARF guanine nucleotide exchange factor (ARF-GEF); Provisional


Pssm-ID: 215560 [Multi-domain]  Cd Length: 1780  Bit Score: 243.58  E-value: 3.07e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929   14 FNMDPKKGIQFLIENDLLKNTCEDIAQFLYKGEGLNKTAIGDYLGERDEFNIQVLHAFVELHEFTDLNLVQALRQFLWSF 93
Cdd:PLN03076  627 FNRKPKKGIEFLINANKVGESPEEIAAFLKDASGLNKTLIGDYLGEREDLSLKVMHAYVDSFDFQGMEFDEAIRAFLQGF 706
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929   94 RLPGEAQKIDRMMEAFAQRYCQCNNGVFQSTDTCYVLSFAIIMLNTSLHNPNVKDKPTVERFIAMNRGINDGGDLPEELL 173
Cdd:PLN03076  707 RLPGEAQKIDRIMEKFAERYCKCNPKAFSSADTAYVLAYSVIMLNTDAHNPMVKNKMSADDFIRNNRGIDDGKDLPEEFM 786
                         170
                  ....*....|....*...
gi 635372929  174 RNLYESIKNEPFKIPEDD 191
Cdd:PLN03076  787 RSLYERISKNEIKMKEDD 804
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
202-318 8.45e-24

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: 93.77  E-value: 8.45e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929   202 PDREGWLLKLGGGRVKTWKRRWFILTDNCLYYFE---YTTDKEPRGIIPLENLSIREVEDS---KKPNCFELYIPDNKdq 275
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYYKskkDKKSYKPKGSIDLSGCTVREAPDPdssKKPHCFEIKTSDRK-- 78
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 635372929   276 vikackteadgrvvegnhtVYRISAPTPEEKEEWIKCIKAAIS 318
Cdd:smart00233  79 -------------------TLLLQAESEEEREKWVEALRKAIA 102
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
204-313 1.25e-23

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: 92.99  E-value: 1.25e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLGGGRVKTWKRRWFILTDNCLYYFEYTTD--KEPRGIIPLEN-LSIREVEDSKKPNCFELYIPDNKdqvikac 280
Cdd:cd00821    1 KEGYLLKRGGGGLKSWKKRWFVLFEGVLLYYKSKKDssYKPKGSIPLSGiLEVEEVSPKERPHCFELVTPDGR------- 73
                         90       100       110
                 ....*....|....*....|....*....|...
gi 635372929 281 kteadgrvvegnhtVYRISAPTPEEKEEWIKCI 313
Cdd:cd00821   74 --------------TYYLQADSEEERQEWLKAL 92
PH pfam00169
PH domain; PH stands for pleckstrin homology.
204-318 4.78e-23

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 91.86  E-value: 4.78e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929  204 REGWLLKLGGGRVKTWKRRWFILTDNCLYYFEY---TTDKEPRGIIPLENLSIREV---EDSKKPNCFELYIPDNkdqvi 277
Cdd:pfam00169   3 KEGWLLKKGGGKKKSWKKRYFVLFDGSLLYYKDdksGKSKEPKGSISLSGCEVVEVvasDSPKRKFCFELRTGER----- 77
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 635372929  278 kackteadgrvveGNHTVYRISAPTPEEKEEWIKCIKAAIS 318
Cdd:pfam00169  78 -------------TGKRTYLLQAESEEERKDWIKAIQSAIR 105
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
204-319 6.19e-20

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: 83.52  E-value: 6.19e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKlGGGRVKTWKRRWFILTDNCLYYF---EYTTDKEPRGIIPLEN-LSIREVEDS-KKPNCFELYIPdnkdqvik 278
Cdd:cd13276    1 KAGWLEK-QGEFIKTWRRRWFVLKQGKLFWFkepDVTPYSKPRGVIDLSKcLTVKSAEDAtNKENAFELSTP-------- 71
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 635372929 279 ackteadgrvvegNHTVYRIsAPTPEEKEEWIKCIKAAISR 319
Cdd:cd13276   72 -------------EETFYFI-ADNEKEKEEWIGAIGRAIVK 98
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
201-326 1.35e-19

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single 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: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 83.06  E-value: 1.35e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 201 NPDREGWLLKlGGGRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIrEVEDSKKPNCFELYIPDnkdqvikac 280
Cdd:cd13288    7 PVDKEGYLWK-KGERNTSYQKRWFVLKGNLLFYFEKKGDREPLGVIVLEGCTV-ELAEDAEPYAFAIRFDG--------- 75
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 635372929 281 kteadgrvveGNHTVYRISAPTPEEKEEWIKcikaAISRDPfYEML 326
Cdd:cd13288   76 ----------PGARSYVLAAENQEDMESWMK----ALSRAS-YDYL 106
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
201-316 2.41e-18

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: 79.24  E-value: 2.41e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 201 NPDREGWLLKLGGGRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREV---EDSKKPNCFelyipdnkdqvi 277
Cdd:cd13248    6 PVVMSGWLHKQGGSGLKNWRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISPAppsDEISRKFAF------------ 73
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 635372929 278 KACKTEAdgrvvegnhTVYRISAPTPEEKEEWIKCIKAA 316
Cdd:cd13248   74 KAEHANM---------RTYYFAADTAEEMEQWMNAMSLA 103
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
201-317 9.39e-17

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: 75.11  E-value: 9.39e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 201 NPDREGWLLKLGGgRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREVEdskkpncfelYIPDNKDQVIKAC 280
Cdd:cd13263    2 RPIKSGWLKKQGS-IVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVP----------FNPEEPGKFLFEI 70
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 635372929 281 KTEADGRVVEGNHTVYRISAPTPEEKEEWIKCIKAAI 317
Cdd:cd13263   71 IPGGGGDRMTSNHDSYLLMANSQAEMEEWVKVIRRVI 107
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
204-319 7.04e-16

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: 72.25  E-value: 7.04e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLGGGRVKTWKRRWFILTDNCLYYfeYTTDKEPRGIIPLENL---SIREVEDSKKPNCFElyipdnkdqVIKAC 280
Cdd:cd13250    1 KEGYLFKRSSNAFKTWKRRWFSLQNGQLYY--QKRDKKDEPTVMVEDLrlcTVKPTEDSDRRFCFE---------VISPT 69
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 635372929 281 KTeadgrvvegnhtvYRISAPTPEEKEEWIKCIKAAISR 319
Cdd:cd13250   70 KS-------------YMLQAESEEDRQAWIQAIQSAIAS 95
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
204-317 1.32e-14

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first 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: 270113  Cd Length: 108  Bit Score: 68.94  E-value: 1.32e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKlGGGRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIRE--VEDSKKPNCFELYIPDNKDQVIKACk 281
Cdd:cd13301    5 KEGYLVK-KGHVVNNWKARWFVLKEDGLEYYKKKTDSSPKGMIPLKGCTITSpcLEYGKRPLVFKLTTAKGQEHFFQAC- 82
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 635372929 282 teadgrvvegnhtvyrisapTPEEKEEWIKCIKAAI 317
Cdd:cd13301   83 --------------------SREERDAWAKDITKAI 98
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
204-319 1.98e-14

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: 68.09  E-value: 1.98e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLGGgRVKTWKRRWFILTDNCLYYFEYTTD--KEPRGIIPLENLSirEVEDSKKPNCFELyipdnkdqvikacK 281
Cdd:cd13282    1 KAGYLTKLGG-KVKTWKRRWFVLKNGELFYYKSPNDviRKPQGQIALDGSC--EIARAEGAQTFEI-------------V 64
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 635372929 282 TEadgrvvegnHTVYRISAPTPEEKEEWIKCIKAAISR 319
Cdd:cd13282   65 TE---------KRTYYLTADSENDLDEWIRVIQNVLRR 93
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
204-315 4.54e-14

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. 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: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 66.96  E-value: 4.54e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLGGgRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREVEDSK-KPNCFELYIPDNkdqvikackt 282
Cdd:cd10573    5 KEGYLTKLGG-IVKNWKTRWFVLRRNELKYFKTRGDTKPIRVLDLRECSSVQRDYSQgKVNCFCLVFPER---------- 73
                         90       100       110
                 ....*....|....*....|....*....|...
gi 635372929 283 eadgrvvegnhtVYRISAPTPEEKEEWIKCIKA 315
Cdd:cd10573   74 ------------TFYMYANTEEEADEWVKLLKW 94
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
201-319 6.11e-14

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: 67.38  E-value: 6.11e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 201 NPDREGWLLKLGGGRvKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLenlsiREVEDSKKPNCFELYIPDNKDQVIKAc 280
Cdd:cd13271    7 NVIKSGYCVKQGAVR-KNWKRRFFILDDNTISYYKSETDKEPLRTIPL-----REVLKVHECLVKSLLMRDNLFEIITT- 79
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 635372929 281 kteadgrvvegNHTVYrISAPTPEEKEEWIKCIKAAISR 319
Cdd:cd13271   80 -----------SRTFY-IQADSPEEMHSWIKAISGAIVA 106
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
200-315 1.04e-13

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: 66.21  E-value: 1.04e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 200 FNPDREGWLLKLGGGRVKtWKRRWFIL--TDNCLYYFEYTTDKEPRGIIPLENLSIREVEDS--KKPNCFELyipdnkdq 275
Cdd:cd13260    1 KGIDKKGYLLKKGGKNKK-WKNLYFVLegKEQHLYFFDNEKRTKPKGLIDLSYCSLYPVHDSlfGRPNCFQI-------- 71
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 635372929 276 VIKACkteadgrvveGNHTVYRISAPTPEEKEEWIKCIKA 315
Cdd:cd13260   72 VVRAL----------NESTITYLCADTAELAQEWMRALRA 101
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
206-320 2.84e-13

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: 65.18  E-value: 2.84e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 206 GWLLKLGGGRV----KTWKRRWFILTDNCLYYFEYTTDKE-PRGIIplenlSIRE----VEDSKKPNCFELYIPDNkdqv 276
Cdd:cd13296    3 GWLTKKGGGSStlsrRNWKSRWFVLRDTVLKYYENDQEGEkLLGTI-----DIRSakeiVDNDPKENRLSITTEER---- 73
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 635372929 277 ikackteadgrvvegnhtVYRISAPTPEEKEEWIKCIKAAISRD 320
Cdd:cd13296   74 ------------------TYHLVAESPEDASQWVNVLTRVISAT 99
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
206-321 4.28e-13

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: 64.57  E-value: 4.28e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 206 GWLLKLGGGRvKTWKRRWFILTDNCLYYfeYTTDKE--PRGIIPLENL-SIREVEDSKKPNCFELYIPDNkdqvikackt 282
Cdd:cd13298   10 GYLLKRSRKT-KNWKKRWVVLRPCQLSY--YKDEKEykLRRVINLSELlAVAPLKDKKRKNVFGIYTPSK---------- 76
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 635372929 283 eadgrvvegnhtVYRISAPTPEEKEEWIKCIKAAISRDP 321
Cdd:cd13298   77 ------------NLHFRATSEKDANEWVEALREEFRLDD 103
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
203-319 1.10e-12

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: 63.58  E-value: 1.10e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 203 DREGWLLKLGGGR--VKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREVED--SKKPNCFELYIPDNKdqvik 278
Cdd:cd13308   10 IHSGTLTKKGGSQktLQNWQLRYVIIHQGCVYYYKNDQSAKPKGVFSLNGYNRRAAEErtSKLKFVFKIIHLSPD----- 84
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 635372929 279 ackteadgrvvegnHTVYRISAPTPEEKEEWIKCIKAAISR 319
Cdd:cd13308   85 --------------HRTWYFAAKSEDEMSEWMEYIRREIDH 111
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
205-318 3.52e-12

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: 61.96  E-value: 3.52e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 205 EGWLLKLGGgRVKTWKRRWFIL--TDNCLYYFEYTTDKEPRGIIPLENlsIREVEDSkkpncfelyipdnkDQVIKACKT 282
Cdd:cd01235    6 EGYLYKRGA-LLKGWKQRWFVLdsTKHQLRYYESREDTKCKGFIDLAE--VESVTPA--------------TPIIGAPKR 68
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 635372929 283 EADGRV--VEGNHTVYRISAPTPEEKEEWIKCIKAAIS 318
Cdd:cd01235   69 ADEGAFfdLKTNKRVYNFCAFDAESAQQWIEKIQSCLS 106
PH_RhoGap24 cd13379
Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ...
204-317 3.51e-11

Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ARHGAP24, p73RhoGAp, and Filamin-A-associated RhoGAP) 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. 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: 241530  Cd Length: 114  Bit Score: 59.60  E-value: 3.51e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKlGGGRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIRE---VEDSKKPNCFELYIPDNKDQVIkac 280
Cdd:cd13379    5 KCGWLRK-QGGFVKTWHTRWFVLKGDQLYYFKDEDETKPLGTIFLPGNRVTEhpcNEEEPGKFLFEVVPGGDRERMT--- 80
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 635372929 281 kteadgrvveGNHTVYRISAPTPEEKEEWIKCIKAAI 317
Cdd:cd13379   81 ----------ANHETYLLMASTQNDMEDWVKSIRRVI 107
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
204-317 7.97e-11

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: 58.46  E-value: 7.97e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKlGGGRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLenlsireveDSkkpNCFELYIPDNKDqviKACKTe 283
Cdd:cd13273   10 KKGYLWK-KGHLLPTWTERWFVLKPNSLSYYKSEDLKEKKGEIAL---------DS---NCCVESLPDREG---KKCRF- 72
                         90       100       110
                 ....*....|....*....|....*....|....
gi 635372929 284 adgrVVEGNHTVYRISAPTPEEKEEWIKCIKAAI 317
Cdd:cd13273   73 ----LVKTPDKTYELSASDHKTRQEWIAAIQTAI 102
PH_PLEKHJ1 cd13258
Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; ...
201-316 8.27e-11

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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: 270078  Cd Length: 123  Bit Score: 58.87  E-value: 8.27e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 201 NPDREGWLLKLGGG---RVKTWKRRWFILTDNCLYYF---EYTTDKEPRGIIPLENLSIREVEDSKKPNCFEL-YIPDNK 273
Cdd:cd13258   15 PAEKEGKIAERQMGgpkKSEVFKERWFKLKGNLLFYFrtnEFGDCSEPIGAIVLENCRVQMEEITEKPFAFSIvFNDEPE 94
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 635372929 274 DQVIKACKTEadgrvvegnhtvyrisaptpEEKEEWIKCIKAA 316
Cdd:cd13258   95 KKYIFSCRSE--------------------EQCEQWIEALRQA 117
PH2_Pleckstrin_2 cd13302
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 2; Pleckstrin is a protein found in ...
204-316 1.56e-10

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 2; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. 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: 270114  Cd Length: 109  Bit Score: 57.52  E-value: 1.56e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKlGGGRVKTWKRRWFILTDN--CLYYFEYTTDKEPRGIIPLENLSIREVEDSKKPNCFElyIPDNKDQVIKACK 281
Cdd:cd13302    9 KQGCLLK-QGHRRKNWKVRKFVLRDDpaYLHYYDPAKGEDPLGAIHLRGCVVTAVEDNSNPRKGS--VEGNLFEIITADE 85
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 635372929 282 TEadgrvvegnhtvYRISAPTPEEKEEWIKCIKAA 316
Cdd:cd13302   86 VH------------YYLQAATPAERTEWIKAIQMA 108
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
204-322 1.69e-10

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: 58.39  E-value: 1.69e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLGGGRVKT----WKRRWFILTDNCLYYFEY--TTDKEPRGIIPLEnlSIREVE------DSKKPNCFElyipd 271
Cdd:cd01238    1 LEGLLVKRSQGKKRFgpvnYKERWFVLTKSSLSYYEGdgEKRGKEKGSIDLS--KVRCVEevkdeaFFERKYPFQ----- 73
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 635372929 272 nkdqvikackteadgrVVEGNHTVYrISAPTPEEKEEWIKCIKAAISRDPF 322
Cdd:cd01238   74 ----------------VVYDDYTLY-VFAPSEEDRDEWIAALRKVCRNNSN 107
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
203-318 2.78e-10

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: 56.63  E-value: 2.78e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 203 DREGWLLKLGG-GRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLS-IREVEDSKkpncFElyipdnkdqvikac 280
Cdd:cd13253    1 IKSGYLDKQGGqGNNKGFQKRWVVFDGLSLRYFDSEKDAYSKRIIPLSAIStVRAVGDNK----FE-------------- 62
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 635372929 281 kteadgrvVEGNHTVYRISAPTPEEKEEWIKCIKAAIS 318
Cdd:cd13253   63 --------LVTTNRTFVFRAESDDERNLWCSTLQAAIS 92
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
203-319 3.92e-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: 56.44  E-value: 3.92e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 203 DREGWLLKLGGGRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPL----ENLSIREvedskkpncfelyipdnkDQVIK 278
Cdd:cd01251    3 LKEGYLEKTGPKQTDGFRKRWFTLDDRRLMYFKDPLDAFPKGEIFIgskeEGYSVRE------------------GLPPG 64
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 635372929 279 ACKTEADGRVVEGNHTVYRISAPTPEEKEEWIKCIKAAISR 319
Cdd:cd01251   65 IKGHWGFGFTLVTPDRTFLLSAETEEERREWITAIQKVLER 105
PH_Skap_family cd13266
Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...
219-314 4.37e-10

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: 56.38  E-value: 4.37e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 219 WKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREV----EDSKKPNCFELYIPDNKdqvikackteadgrvvegnht 294
Cdd:cd13266   21 WQKRWCAISKNVFYYYGSDKDKQQKGEFAINGYDVRMNptlrKDGKKDCCFELVCPDKR--------------------- 79
                         90       100
                 ....*....|....*....|
gi 635372929 295 VYRISAPTPEEKEEWIKCIK 314
Cdd:cd13266   80 TYQFTAASPEDAEDWVDQIS 99
PH_Skap-hom_Skap2 cd13381
Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; ...
219-317 6.93e-10

Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; Adaptor protein Skap-hom, a homolog of Skap55, which interacts with actin and with ADAP (adhesion and degranulation promoting adapter protein) undergoes tyrosine phosphorylation in response to plating of bone marrow-derived macrophages on fibronectin. Skap-hom has an N-terminal coiled-coil conformation that is involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap-hom PH domain regulates intracellular targeting; its interaction with the DM domain inhibits Skap-hom actin-based ruffles in macrophages and its binding to 3'-phosphoinositides reverses this autoinhibition. The Skap-hom PH domain binds PI[3,4]P2 and PI[3,4,5]P3, but not to PI[3]P, PI[5]P, or PI[4,5]P2. Skap2 is a downstream target of Heat shock transcription factor 4 (HSF4) and functions in the regulation of actin reorganization during lens differentiation. It is thought that SKAP2 anchors the complex of tyrosine kinase adaptor protein 2 (NCK20/focal adhesion to fibroblast growth factor receptors at the lamellipodium in lens epithelial cells. Skap2 has an N-terminal coiled-coil conformation which interacts with the SH2 domain of NCK2, a central PH domain and a C-terminal SH3 domain that associates with ADAP (adhesion and degranulation promoting adapter protein)/FYB (the Fyn binding protein). Skap2 PH domain binds to membrane lipids. 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-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: 270181  Cd Length: 106  Bit Score: 55.73  E-value: 6.93e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 219 WKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIRE----VEDSKKPNCFELYIPDNKdqvikackteadgrvvegnht 294
Cdd:cd13381   21 WQKRWCALSNSVFYYYGSDKDKQQKGEFAIDGYDVKMnntlRKDAKKDCCFEICAPDKR--------------------- 79
                         90       100
                 ....*....|....*....|...
gi 635372929 295 VYRISAPTPEEKEEWIKCIKAAI 317
Cdd:cd13381   80 VYQFTAASPKEAEEWVQQIKFIL 102
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
204-316 1.26e-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: 55.11  E-value: 1.26e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLGGGRvKTWKRRWFILTDNCLYYfeYTTDKEPR--GIIPLENL-SIREVEDSKKPNCFELYIPdnkdqvikac 280
Cdd:cd13255    8 KAGYLEKKGERR-KTWKKRWFVLRPTKLAY--YKNDKEYRllRLIDLTDIhTCTEVQLKKHDNTFGIVTP---------- 74
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 635372929 281 kteadgrvvegNHTVYrISAPTPEEKEEWIKCIKAA 316
Cdd:cd13255   75 -----------ARTFY-VQADSKAEMESWISAINLA 98
PH3_MyoX-like cd13297
Myosin X-like Pleckstrin homology (PH) domain, repeat 3; MyoX, a MyTH-FERM myosin, is a ...
206-325 6.07e-09

Myosin X-like Pleckstrin homology (PH) domain, repeat 3; 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 third MyoX PH repeat. PLEKHH3/Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) member 3 is also part of this CD and like MyoX contains a FERM domain, a MyTH4 domain, and a single PH domain. Not much is known about the function of PLEKHH3. 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: 270109  Cd Length: 126  Bit Score: 53.59  E-value: 6.07e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 206 GWLLKLGGGRVK----TWKRRWFILTDNCL-YYFEYTTDKEPRGIIPLENLsirevedskkpnCfELYIPDNKDQVIKAC 280
Cdd:cd13297   17 GWLYKEGGKGGArgnlTKKKRWFVLTGNSLdYYKSSEKNSLKLGTLVLNSL------------C-SVVPPDEKMAKETGY 83
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 635372929 281 KTeadgRVVEGNHTVYRISAPTPEEKEEWIKCIKAAISRDPFYEM 325
Cdd:cd13297   84 WT----FTVHGRKHSFRLYTKLQEEAMRWVNAIQDVIDSKPPIET 124
PH_Skap1 cd13380
Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 ...
219-313 8.90e-09

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: 52.55  E-value: 8.90e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 219 WKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREV----EDSKKPNCFELYIPDNKdqvikackteadgrvvegnht 294
Cdd:cd13380   21 WQKRWCVLTNRAFYYYASEKSKQPKGGFLIKGYSAQMAphlrKDSRRDSCFELTTPGRR--------------------- 79
                         90
                 ....*....|....*....
gi 635372929 295 VYRISAPTPEEKEEWIKCI 313
Cdd:cd13380   80 TYQFTAASPSEARDWVDQI 98
PH_RhoGAP2 cd13378
Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 ...
204-317 3.61e-08

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. 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: 241529  Cd Length: 116  Bit Score: 51.10  E-value: 3.61e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKlGGGRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREV----EDSKKpNCFELyipdnkdqvikA 279
Cdd:cd13378    5 KAGWLKK-QRSIMKNWQQRWFVLRGDQLFYYKDEEETKPQGCISLQGSQVNELppnpEEPGK-HLFEI-----------L 71
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 635372929 280 CKTEADGRVVEGNHTVYRISAPTPEEKEEWIKCIKAAI 317
Cdd:cd13378   72 PGGAGDREKVPMNHEAFLLMANSQSDMEDWVKAIRRVI 109
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
201-320 3.90e-08

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, with the exception of CNK3, 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 mammals, chickens, amphibians, fish, and crustacea. 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: 269962  Cd Length: 114  Bit Score: 50.87  E-value: 3.90e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 201 NPDREGWLLK---LGGGRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREVEDSKkpncfelyipdnKDQVI 277
Cdd:cd01260   12 RGDCQGWLWKkkeAKSFFGQKWKKYWFVLKGSSLYWYSNQQDEKAEGFINLPDFKIERASECK------------KKYAF 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 635372929 278 KACkteadgrvvegnHTVYR---ISAPTPEEKEEWIKCIKAAISRD 320
Cdd:cd01260   80 KAC------------HPKIKtfyFAAENLDDMNKWLSKLNMAINKY 113
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
206-279 4.95e-08

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: 50.40  E-value: 4.95e-08
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 635372929 206 GWLLKL--GGGRVKTWKRRWFILTDN-C-LYYFEYTTDKEPRGIIPLENLSIrEVEDSKKPNCFELYIPdNKDQVIKA 279
Cdd:cd01265    4 GYLNKLetRGLGLKGWKRRWFVLDESkCqLYYYRSPQDATPLGSIDLSGAAF-SYDPEAEPGQFEIHTP-GRVHILKA 79
PH_Boi cd13316
Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally ...
203-313 5.71e-08

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: 50.06  E-value: 5.71e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 203 DREGWLLKlGGGRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREVEDSKKPN---CFELYIPDNKDqvika 279
Cdd:cd13316    1 DHSGWMKK-RGERYGTWKTRYFVLKGTRLYYLKSENDDKEKGLIDLTGHRVVPDDSNSPFRgsyGFKLVPPAVPK----- 74
                         90       100       110
                 ....*....|....*....|....*....|....
gi 635372929 280 ckteadgrvvegnhtVYRISAPTPEEKEEWIKCI 313
Cdd:cd13316   75 ---------------VHYFAVDEKEELREWMKAL 93
PH_PLEKHD1 cd13281
Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH ...
206-316 5.77e-08

Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH domain; Human PLEKHD1 (also called UPF0639, pleckstrin homology domain containing, family D (with M protein repeats) member 1) is a single transcript and contains a single PH domain. PLEKHD1 is conserved in human, chimpanzee, , dog, cow, mouse, chicken, zebrafish, and Caenorhabditis elegans. 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: 270099  Cd Length: 139  Bit Score: 51.17  E-value: 5.77e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 206 GWLLKLGGGRVKT-WKRRWFILTDNCLYYFEYTTDKE----------PRGIIPLENLSIREVEDSKKPNCFELYIPDNKD 274
Cdd:cd13281   16 GILWKKPFGHQSAkWSKRFFIIKEGFLLYYSESEKKDfektrhfnihPKGVIPLGGCSIEAVEDPGKPYAISISHSDFKG 95
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 635372929 275 QVIKAckteadgrvvegnhtvyrisAPTPEEKEEWIKCIKAA 316
Cdd:cd13281   96 NIILA--------------------ADSEFEQEKWLDMLRES 117
PH_dynamin cd01256
Dynamin pleckstrin homology (PH) domain; Dynamin is a GTPase that regulates endocytic vesicle ...
204-309 1.23e-07

Dynamin pleckstrin homology (PH) domain; Dynamin is a GTPase that regulates endocytic vesicle formation. It has an N-terminal GTPase domain, followed by a PH domain, a GTPase effector domain and a C-terminal proline arginine rich domain. Dynamin-like proteins, which are found in metazoa, plants and yeast have the same domain architecture as dynamin, but lack the 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: 269958  Cd Length: 112  Bit Score: 49.63  E-value: 1.23e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLGGGRVK-TWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREVED---SKKPNcFELYIPDNKDqvika 279
Cdd:cd01256    5 RKGWLTINNIGFMKgGSKEYWFVLTAESLSWYKDEEEKEKKYMLPLDGLKLRDVEKgfmSRKHI-FALFNTDQRN----- 78
                         90       100       110
                 ....*....|....*....|....*....|
gi 635372929 280 ckteadgrvVEGNHTVYRISAPTPEEKEEW 309
Cdd:cd01256   79 ---------VYKDYKQLELSCETQEEVDSW 99
PH_CpORP2-like cd13293
Cryptosporidium-like Oxysterol binding protein related protein 2 Pleckstrin homology (PH) ...
205-316 1.45e-07

Cryptosporidium-like Oxysterol binding protein related protein 2 Pleckstrin homology (PH) domain; There are 2 types of ORPs found in Cryptosporidium: CpORP1 and CpORP2. Cryptosporium differs from other apicomplexans like Plasmodium, Toxoplasma, and Eimeria which possess only a single long-type ORP consisting of an N-terminal PH domain followed by a C-terminal ligand binding (LB) domain. CpORP2 is like this, but CpORP1 differs and has a truncated N-terminus resulting in only having a LB domain present. The exact functions of these proteins are largely unknown though CpORP1 is thought to be involved in lipid transport across the parasitophorous vacuole membrane. 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: 241447  Cd Length: 88  Bit Score: 48.48  E-value: 1.45e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 205 EGWLLKLGGgRVKTWKRRWFILTDNCLYYFEyTTDKEPRGIIPLENLSIREVEDskKPNCFELYIPDNKDQVIkacktea 284
Cdd:cd13293    2 EGYLKKWTN-IFNSWKPRYFILYPGILCYSK-QKGGPKKGTIHLKICDIRLVPD--DPLRIIINTGTNQLHLR------- 70
                         90       100       110
                 ....*....|....*....|....*....|..
gi 635372929 285 dgrvvegnhtvyrisAPTPEEKEEWIKCIKAA 316
Cdd:cd13293   71 ---------------ASSVEEKLKWYNALKYA 87
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
204-317 1.73e-07

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. 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: 270087  Cd Length: 126  Bit Score: 49.25  E-value: 1.73e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLK--LGGGRV------KTWKRRWFILT---DNClYYFEYTTD---KEPRGIIPLENLSirEVEDSKKPN--CFEL 267
Cdd:cd13267    8 KEGYLYKgpENSSDSfislamKSFKRRFFHLKqlvDGS-YILEFYKDekkKEAKGTIFLDSCT--GVVQNSKRRkfCFEL 84
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 635372929 268 YIPDNKdqvikackteadgrvvegnhtVYRISAPTPEEKEEWIKCIKAAI 317
Cdd:cd13267   85 RMQDKK---------------------SYVLAAESEAEMDEWISKLNKIL 113
PH_SKIP cd13309
SifA and kinesin-interacting protein Pleckstrin homology (PH) domain; SKIP (also called ...
218-318 3.05e-07

SifA and kinesin-interacting protein Pleckstrin homology (PH) domain; SKIP (also called PLEKHM2/Pleckstrin homology domain-containing family M member 2) is a soluble cytosolic protein that contains a RUN domain and a PH domain separated by a unstructured linker region. SKIP is a target of the Salmonella effector protein SifA and the SifA-SKIP complex regulates kinesin-1 on the bacterial vacuole. The PH domain of SKIP binds to the N-terminal region of SifA while the N-terminus of SKIP is proposed to bind the TPR domain of the kinesin light chain. The opposite side of the SKIP PH domain is proposed to bind phosphoinositides. TSifA, SKIP, SseJ, and RhoA family GTPases are also thought to promote host membrane tubulation. Recently, it was shown that the lysosomal GTPase Arl8 binds to the kinesin-1 linker SKIP and that both are required for the normal intracellular distribution of lysosomes. Interestingly, two kinesin light chain binding motifs (WD) in SKIP have now been identified to match a consensus sequence for a kinesin light chain binding site found in several proteins including calsyntenin-1/alcadein, caytaxin, and vaccinia virus A36. SKIP has also been shown to interact with Rab1A. 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: 270119  Cd Length: 103  Bit Score: 48.14  E-value: 3.05e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 218 TWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSI---REVEDSKKPNCFELYIPDNKdqvikackteadgrvvegnht 294
Cdd:cd13309   19 TWKPGYFLLKNGVLYQYPDRSDRLPLLSISLGGEQCggcRRINNTERPHTFELILTDRS--------------------- 77
                         90       100
                 ....*....|....*....|....
gi 635372929 295 VYRISAPTPEEKEEWIKCIKAAIS 318
Cdd:cd13309   78 SLELAAPDEYEASEWLQSLCQSAS 101
Niban-like cd23949
Niban-like protein; Niban-like proteins contain an N-terminal Pleckstrin-Homology (PH) domain ...
205-319 4.99e-07

Niban-like protein; Niban-like proteins contain an N-terminal Pleckstrin-Homology (PH) domain that may be involved in binding to specific ligands. Phosphatidylinositol (3)-phosphate (PI3P) was recognized as the innate ligand of the PH domain of MINERVA (melanoma invasion by ERK, also known as FAM129B) PH. Niban family proteins have been found to regulate phosphorylation of a number of proteins involved in the regularion of translation, such as EIF2A, EIF4EBP1 and RPS6KB1. They may also be involved in the endoplasmic reticulum stress response (FAM129A, Niban-like protein 1), suggested to play a role in apoptosis suppression in cancer cells, while Niban-like protein 2 (FAM129C) is a B-cell membrane protein that is overexpressed in chronic lymphocytic leukemia.


Pssm-ID: 469558 [Multi-domain]  Cd Length: 550  Bit Score: 51.14  E-value: 4.99e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 205 EGWLLKLGGGRvKTWKRRWFILTDN-CLYYFE----YTTDKEPRGIIPLENLSIreVEDSKKPNCfelyIPDNKDQVIKA 279
Cdd:cd23949   65 SGKLSKYGEDS-KKWKERFCVVRGDyNLEYYEskeaYERGKKPKGSINLAGYKV--LTSPEEYLE----LVDRKFPDLAG 137
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 635372929 280 CKTEADGRVVE--GNHTV-----YR----ISAPTPEEKEEWIKCIKAAISR 319
Cdd:cd23949  138 KSEKASVPFPErpPPFTLelyhpYRrhyyFCFETEKEQEEWVAVLQDCIRH 188
PH2_PH_fungal cd13299
Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal ...
205-317 7.89e-07

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: 46.85  E-value: 7.89e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 205 EGWLLKLGGGRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENL-SIREVE--DSKKPNCFelyipdnkdQVIKACK 281
Cdd:cd13299    9 QGYLQVLKKKGVNQWKKYWLVLRNRSLSFYKDQSEYSPVKIIPIDDIiDVVELDplSKSKKWCL---------QIITPEK 79
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 635372929 282 TeadgrvvegnhtvYRISAPTPEEKEEWIKCIKAAI 317
Cdd:cd13299   80 R-------------IRFCADDEESLIKWLGALKSLL 102
PH_Cla4_Ste20 cd13279
Pleckstrin homology (PH) domain; Budding yeast contain two main p21-activated kinases (PAKs), ...
204-285 9.08e-07

Pleckstrin homology (PH) domain; Budding yeast contain two main p21-activated kinases (PAKs), Cla4 and Ste20. The yeast Ste20 protein kinase is involved in pheromone response, though the function of Ste20 mammalian homologs is unknown. Cla4 is involved in budding and cytokinesis and interacts with Cdc42, a GTPase required for polarized cell growth as is Pak. Cla4 and Ste20 kinases share a function in localizing cell growth with respect to the septin ring. They both contain a PH domain, a Cdc42/Rac interactive binding (CRIB) domain, and a C-terminal Protein Kinase catalytic (PKc) 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: 270097  Cd Length: 92  Bit Score: 46.47  E-value: 9.08e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWL-LKLGGGRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREVEDSkKPNCFELYIPDNKDQVIKACKT 282
Cdd:cd13279    3 KSGWVsVKEDGLLSFRWSKRYLVLREQSLDFYKNESSSSASLSIPLKDISNVSRTDL-KPYCFEIVRKSSTKSIYISVKS 81

                 ...
gi 635372929 283 EAD 285
Cdd:cd13279   82 DDE 84
PH1_FARP1-like cd01220
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
204-317 1.52e-06

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 1; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains 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: 269928  Cd Length: 109  Bit Score: 46.15  E-value: 1.52e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLGGgrvKTWKRRWFILTDNCLYYfeytTDKEP--------RGIIPLENLSIREVEDSKK-PNCFELYipdnkd 274
Cdd:cd01220   10 REGCLQKLSK---KGLQQRMFFLFSDVLLY----TSRSPtpslqfkvHGQLPLRGLMVEESEPEWGvAHCFTIY------ 76
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 635372929 275 qvikackteadgrvveGNHTVYRISAPTPEEKEEWIKCIKAAI 317
Cdd:cd01220   77 ----------------GGNRALTVAASSEEEKERWLEDLQRAI 103
PH_M-RIP cd13275
Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed ...
204-317 2.54e-06

Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed to play a role in myosin phosphatase regulation by RhoA. M-RIP contains 2 PH domains followed by a Rho binding domain (Rho-BD), and a C-terminal myosin binding subunit (MBS) binding domain (MBS-BD). The amino terminus of M-RIP with its adjacent PH domains and polyproline motifs mediates binding to both actin and Galpha. M-RIP brings RhoA and MBS into close proximity where M-RIP can target RhoA to the myosin phosphatase complex to regulate the myosin phosphorylation state. M-RIP does this via its C-terminal coiled-coil domain which interacts with the MBS leucine zipper domain of myosin phosphatase, while its Rho-BD, directly binds RhoA in a nucleotide-independent manner. 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: 270094  Cd Length: 104  Bit Score: 45.40  E-value: 2.54e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLGGgRVKTWKRRWFILTDNCLYYFEYTTDKEPR---GIIPLEnlSIREV--EDSKKPNCFELyipdnkdqvik 278
Cdd:cd13275    1 KKGWLMKQGS-RQGEWSKHWFVLRGAALKYYRDPSAEEAGeldGVIDLS--SCTEVteLPVSRNYGFQV----------- 66
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 635372929 279 acKTEADGRVVegnhtvyrISAPTPEEKEEWIKCIKAAI 317
Cdd:cd13275   67 --KTWDGKVYV--------LSAMTSGIRTNWIQALRKAA 95
PH_GAP1-like cd01244
RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; ...
204-271 4.87e-06

RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; RASAL1, GAP1(m), GAP1(IP4BP), and CAPRI are all members of the GAP1 family of GTPase-activating proteins. They contain N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. They act as a suppressor of RAS 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. PH domains 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: 269950  Cd Length: 107  Bit Score: 44.59  E-value: 4.87e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 635372929 204 REGWLLKLGGGR-----VKTWKRRWFILTDNCLYYFEyTTDKEPRGIIPLEN-LSIREVEDS--KKPNCFELYIPD 271
Cdd:cd01244    1 KEGYLIKRAQGRkkkfgRKNFKKRYFRLTNEALSYSK-SKGKQPLCSIPLEDiLAVERVEEEsfKMKNMFQIVQPD 75
PH_11 pfam15413
Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.
205-316 4.98e-06

Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.


Pssm-ID: 405988  Cd Length: 105  Bit Score: 44.89  E-value: 4.98e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929  205 EGWLLKLGGgrvKTWKRRWF-ILTDNCLYYFEYTTDKEPRGIIPLENLSI----REVEDSKKPncfelyipdnKDQVIKA 279
Cdd:pfam15413   2 EGYLKKKGP---KTWKHRWFaVLRNGVLFYYKSEKMKVVKHVIVLSNYIVgklgTDIISGALF----------KIDNIRS 68
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 635372929  280 cKTEADGRVVEGNHT-VYRISAPTPEEKEEWIKCIKAA 316
Cdd:pfam15413  69 -ETSDDLLLEISTETkIFFLYGDNNEETYEWVEALQEA 105
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
204-317 1.10e-05

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: 44.15  E-value: 1.10e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLlKLGGGRVKTWKRRWFILTDNCLYYFEYTTDKE-PRGIIPLENLSIREVEDSKK--PNCFELYIPDNKdqvikac 280
Cdd:cd13215   23 KSGYL-SKRSKRTLRYTRYWFVLKGDTLSWYNSSTDLYfPAGTIDLRYATSIELSKSNGeaTTSFKIVTNSRT------- 94
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 635372929 281 kteadgrvvegnhtvYRISAPTPEEKEEWIKCIKAAI 317
Cdd:cd13215   95 ---------------YKFKADSETSADEWVKALKKQI 116
PH_CNK_insect-like cd13326
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
205-268 1.30e-05

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: 43.10  E-value: 1.30e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 635372929 205 EGWLLK--LGGGRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREVEDSK-KPNCFELY 268
Cdd:cd13326    2 QGWLYQrrRKGKGGGKWAKRWFVLKGSNLYGFRSQESTKADCVIFLPGFTVSPAPEVKsRKYAFKVY 68
PH2_FGD5_FGD6 cd13237
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin ...
206-290 1.49e-05

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin homology (PH) domain, C-terminus; 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: 270057  Cd Length: 91  Bit Score: 42.79  E-value: 1.49e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 206 GWLlKLGGGRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREVEDSKK---PNCFELYIPDNKDQVIKACKT 282
Cdd:cd13237    3 GYL-QRRKKSKKSWKRLWFVLKDKVLYTYKASEDVVALESVPLLGFTVVTIDESFEedeSLVFQLLHKGQLPIIFRADDA 81

                 ....*...
gi 635372929 283 EADGRVVE 290
Cdd:cd13237   82 ETAQRWIE 89
PH_anillin cd01263
Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin ...
218-317 2.05e-05

Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin homology domain-containing family K) is an actin binding protein involved in cytokinesis. It interacts with GTP-bound Rho proteins and results in the inhibition of their GTPase activity. Dysregulation of the Rho signal transduction pathway has been implicated in many forms of cancer. Anillin proteins have a N-terminal HRI domain/ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. The C-terminal PH domain helps target anillin to ectopic septin containing foci. 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: 269964  Cd Length: 121  Bit Score: 43.42  E-value: 2.05e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 218 TWKRRWFILTDNCLYYFEYTTD---KEPRGIIPLENLSIREVEDS-----KKPNCFELYIpdnkdqVIKACKTEADGRVV 289
Cdd:cd01263   19 AWHRRWCVLRGGYLSFWKYPDDeekKKPIGSIDLTKCITEKVEPAprelcARPNTFLLET------LRPAEDDDRDDTNE 92
                         90       100
                 ....*....|....*....|....*...
gi 635372929 290 EGNHTvyrISAPTPEEKEEWIKCIKAAI 317
Cdd:cd01263   93 KIRVL---LSADTKEERIEWLSALNQTL 117
PH_RasGRF1_2 cd13261
Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; ...
219-316 2.18e-05

Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; RasGRF1 (also called GRF1; CDC25Mm/Ras-specific nucleotide exchange factor CDC25; GNRP/Guanine nucleotide-releasing protein) and RasGRF2 (also called GRF2; Ras guanine nucleotide exchange factor 2) are a family of guanine nucleotide exchange factors (GEFs). They both promote the exchange of Ras-bound GDP by GTP, thereby regulating the RAS signaling pathway. RasGRF1 and RasGRF2 form homooligomers and heterooligomers. GRF1 has 3 isoforms and GRF2 has 2 isoforms. The longest isoforms of RasGRF1 and RasGRF2 contain the following domains: a Rho-GEF domain sandwiched between 2 PH domains, IQ domains, a REM (Ras exchanger motif) domain, and a Ras-GEF domainwhich gives them the capacity to activate both Ras and Rac GTPases in response to signals from a variety of neurotransmitter receptors. Their IQ domains allow them to act as calcium sensors to mediate the actions of NMDA-type and calcium-permeable AMPA-type glutamate receptors. GRF1 also mediates the action of dopamine receptors that signal through cAMP. GRF1 and GRF2 play strikingly different roles in regulating MAP kinase family members, neuronal synaptic plasticity, specific forms of learning and memory, and behavioral responses to psychoactive drugs. 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: 270081  Cd Length: 136  Bit Score: 43.57  E-value: 2.18e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 219 WKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREVEDSK----------KPNCFE-LYIPDNKDQVIKACKTEADGr 287
Cdd:cd13261   21 WHERWFALYQNLLFYFENESSSRPSGLYLLEGCYCERLPTPKgalkgkdhleKQHYFTiSFRHENQRQYELRAETESDC- 99
                         90       100
                 ....*....|....*....|....*....
gi 635372929 288 vvegnhtvyrisaptpeekEEWIKCIKAA 316
Cdd:cd13261  100 -------------------DEWVEAIKQA 109
PH_PKB cd01241
Protein Kinase B-like pleckstrin homology (PH) domain; PKB (also called Akt), a member of the ...
204-313 3.24e-05

Protein Kinase B-like pleckstrin homology (PH) domain; PKB (also called Akt), a member of the AGC kinase family, is a phosphatidylinositol 3'-kinase (PI3K)-dependent Ser/Thr kinase which alters the activity of the targeted protein. The name AGC is based on the three proteins that it is most similar to cAMP-dependent protein kinase 1 (PKA; also known as PKAC), cGMP-dependent protein kinase (PKG; also known as CGK1) and protein kinase C (PKC). Human Akt has three isoforms derived for distinct genes: Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma. All Akts have an N-terminal PH domain with an activating Thr phosphorylation site, a kinase domain, and a short C-terminal regulatory tail with an activating Ser phosphorylation site. The PH domain recruits Akt to the plasma membrane by binding to phosphoinositides (PtdIns-3,4-P2) and is required for activation. The phosphorylation of Akt at its Thr and Ser phosphorylation sites leads to increased Akt activity toward forkhead transcription factors, the mammalian target of rapamycin (mTOR), and the Bcl-xL/Bcl-2-associated death promoter (BAD), all of which possess a consensus motif R-X-R-XX-ST-B (X = amino acid, B = bulky hydrophobic residue) for Akt phosphorylation. 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: 269947  Cd Length: 107  Bit Score: 42.23  E-value: 3.24e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKlGGGRVKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSIREVE----DSKKPNCFelYIPDNKDQvika 279
Cdd:cd01241    5 KEGWLLK-RGEYIKNWRPRYFVLKSDGSFIGYKEKPKPNQDPPPLNNFSVAECQlmktEKPKPNTF--IIRCLQWT---- 77
                         90       100       110
                 ....*....|....*....|....*....|....
gi 635372929 280 ckteadgRVVEGNhtvyrISAPTPEEKEEWIKCI 313
Cdd:cd01241   78 -------TVIERT-----FHVESEEEREEWMKAI 99
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
204-324 3.44e-05

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: 42.20  E-value: 3.44e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLGGGRvKTWKRRWFILTDNclYYFEYTTDKEP--RGIIPLENLSI---REVED-SKKPNCFELYIPDNKdqvi 277
Cdd:cd01233    8 KRGYLLFLEDAT-DGWVRRWVVLRRP--YLHIYSSEKDGdeRGVINLSTARVeysPDQEAlLGRPNVFAVYTPTNS---- 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 635372929 278 kackteadgrvvegnhtvYRISAPTPEEKEEWIKCIkaaisrDPFYE 324
Cdd:cd01233   81 ------------------YLLQARSEKEMQDWLYAI------DPLLA 103
PH2_FGD4_insect-like cd13238
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) ...
206-310 4.78e-05

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) domain, C-terminus, in insect and related arthropods; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. This cd contains insects, crustaceans, and chelicerates. 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: 270058  Cd Length: 97  Bit Score: 41.86  E-value: 4.78e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 206 GWLLKLGGGRvKTWKRRWFIL-TDNCLYYFEYTTDKEPRGIIPLENLSIREVEDSKKpncfelYIPDNKDQVIKACKtea 284
Cdd:cd13238    3 GYLKLKTNGR-KTWSRRWFALqPDFVLYSYKSQEDKLPLTATPVPGFLVTLLEKGSA------VDPLNDPKRPRTFK--- 72
                         90       100
                 ....*....|....*....|....*.
gi 635372929 285 dgrvVEGNHTVYRISAPTPEEKEEWI 310
Cdd:cd13238   73 ----MFHVKKSYYFQANDGDEQKKWV 94
PH1_FGD5_FGD6 cd13389
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal ...
204-317 8.10e-05

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: 41.87  E-value: 8.10e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLGGgrvKTWKRRWFILTDNCLYYFEYTTDKEPRGII---PLENLSIREVEDSKKPNCFelyipdnkdQVIKAC 280
Cdd:cd13389   16 KEGELMKVSR---KEMQPRYFFLFNDCLLYTTPVQSSGMLKLNnelPLSGMKVKLPEDEEYSNEF---------QIISTK 83
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 635372929 281 KTeadgrvvegnhtvYRISAPTPEEKEEWIKCIKAAI 317
Cdd:cd13389   84 RS-------------FTLIASSEEERDEWVKALSRAI 107
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
206-320 1.06e-04

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: 40.74  E-value: 1.06e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 206 GWLLKLgggrvKTWKRRWFILTDN------CLYYFE----YTTDKEPRGIIPLEN-LSIREVEDSKKPNCFELYIPDNkd 274
Cdd:cd01257    7 GYLKKL-----KTMRKRYFVLRAEshggpaRLEYYEnekkFRRNAEPKRVIPLSScFNINKRADAKHKHLIALYTKDE-- 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 635372929 275 qvikackteadgrvvegnhtVYRISAPTPEEKEEWIKCIKAAISRD 320
Cdd:cd01257   80 --------------------CFGLVAESEEEQDEWYQALLELQRPA 105
PH_Phafin2-like cd01218
Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; ...
204-310 1.18e-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: 1.18e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLGggRvKTWKRRWFILTDNCLYYFEYTTDKE----PRgIIPLENLSIREVEDSKkpncfelyIPDNKDQVIKA 279
Cdd:cd01218   32 GEGVLTKVC--R-KKPKPRQFFLFNDILVYGSIVINKKkynkQR-IIPLEDVKIEDLEDTG--------ELKNGWQIISP 99
                         90       100       110
                 ....*....|....*....|....*....|.
gi 635372929 280 CKTeadgrvvegnHTVYrisAPTPEEKEEWI 310
Cdd:cd01218  100 KKS----------FVVY---AATATEKSEWM 117
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
202-318 1.33e-04

Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p is proposed to function in postsynthetic sterol regulation, piecemeal microautophagy of the nucleus, and cell polarity establishment. Yeast Osh2p is proposed to function in sterol metabolism and cell polarity establishment. Both Osh1p and Osh2p contain 3 N-terminal ankyrin repeats, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBP andOsh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. 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: 241446  Cd Length: 103  Bit Score: 40.75  E-value: 1.33e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 202 PDREGWLLKLGGGRvKTWKRRWFILTDNCLYYFEYTTD--KEPRGIIPLENLSIRevEDSKKPNCFELYIpdnkdqvika 279
Cdd:cd13292    2 PTMKGYLKKWTNYA-KGYKTRWFVLEDGVLSYYRHQDDegSACRGSINMKNARLV--SDPSEKLRFEVSS---------- 68
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 635372929 280 cKTEADGR-VVEGNHtvyrisaptPEEKEEWIKCIKAAIS 318
Cdd:cd13292   69 -KTSGSPKwYLKANH---------PVEAARWIQALQKAIE 98
PH_Bud4 cd13278
Bud4 Pleckstrin homology (PH) domain; Bud4 is an anillin-like yeast protein involved in the ...
205-322 1.43e-04

Bud4 Pleckstrin homology (PH) domain; Bud4 is an anillin-like yeast protein involved in the formation and the disassembly of the double ring structure formed by the septins during cytokinesis. Bud4 acts with Bud3 and and in parallel with septin phosphorylation by the p21-activated kinase Cla4 and the septin-dependent kinase Gin4. Bud4 is regulated by the cyclin-dependent protein kinase Cdk1, the master regulator of cell cycle progression. Bud4 contains an anillin-like domain followed by a PH domain. In addition there are two consensus Cdk phosphorylation sites: one at the N-terminus and one right before the C-terminal PH domain. Anillins also have C-terminal PH domains. 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: 241432  Cd Length: 139  Bit Score: 41.42  E-value: 1.43e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 205 EGWLLKLGGGrVKTWKRRWFILTDNCLY-YFEYTtdKEPRGIIpleNLS-IREVEDSKKPNcfelyipdNKDQVIKACKT 282
Cdd:cd13278   22 EGYLLQEGGD-CEYWRRRFFKLQGTKLVaYHEVT--RKPRATI---NLLkVVDVVDDDDAR--------ERTSSFKRNFT 87
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 635372929 283 E----ADG-RVVEGNHTVYRISAPTPEEKEEWIKCIKAAISRDPF 322
Cdd:cd13278   88 DlvlfEECfRLVFANGEVIDFYADSKEEKADWYSKLKEVVELNRF 132
PH_Bem3 cd13277
Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces ...
204-317 1.67e-04

Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces cerevisiae involves cell cycle-regulated reorganizations of cortical cytoskeletal elements and requires the action of the Rho-type GTPase Cdc42. Bem3 contains a RhoGAP domain and a PH domain. Though Bem3 and Bem2 both contain a RhoGAP, but only Bem3 is able to stimulate the hydrolysis of GTP on Cdc42. Bem3 is thought to be the GAP for Cdc42. 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: 270096  Cd Length: 111  Bit Score: 40.35  E-value: 1.67e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLG---GGRVKTWKRRWFILTDNCLYYFEyttdkEPRGIIpLENLSIREVEDSKKPNcfelyIPDNKDQVIKA- 279
Cdd:cd13277    5 KEGYLLKRRkktLGSTGGWKLRYGVLDGNILELYE-----SRGGQL-LESIKLRNAQIERQPN-----LPDDKYGTRHGf 73
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 635372929 280 CKTEADGRVVEGNhTVYRISAPTPEEKEEWIKCIKAAI 317
Cdd:cd13277   74 LINEHKKSGLSST-TKYYLCAETDKERDEWVSALSEYI 110
PH_evt cd13265
Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also ...
206-248 1.90e-04

Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also called pleckstrin homology domain containing, family B): evt-1 (also called PLEKHB1) and evt-2 (also called PLEKHB2). evt-1 is specific to the nervous system, where it is expressed in photoreceptors and myelinating glia. evt-2 is widely expressed in both neural and nonneural tissues. Evectins possess a single N-terminal PH domain and a C-terminal hydrophobic region. evt-1 is thought to function as a mediator of post-Golgi trafficking in cells that produce large membrane-rich organelles. It is a candidate gene for the inherited human retinopathy autosomal dominant familial exudative vitreoretinopathy and a susceptibility gene for multiple sclerosis. evt-2 is essential for retrograde endosomal membrane transport from the plasma membrane (PM) to the Golgi. Two membrane trafficking pathways pass through recycling endosomes: a recycling pathway and a retrograde pathway that links the PM to the Golgi/ER. Its PH domain that is unique in that it specifically recognizes phosphatidylserine (PS), but not polyphosphoinositides. PS is an anionic phospholipid class in eukaryotic biomembranes, is highly enriched in the PM, and plays key roles in various physiological processes such as the coagulation cascade, recruitment and activation of signaling molecules, and clearance of apoptotic cells. 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: 270085  Cd Length: 108  Bit Score: 40.36  E-value: 1.90e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 635372929 206 GWLLKLGGgRVKTWKRRWFIL-TDNCLYYFEYTTDKEPRGIIPL 248
Cdd:cd13265    7 GWLLRQST-ILKRWKKNWFVLyGDGNLVYYEDETRREVEGRINM 49
PH_PHLDB1_2 cd14673
Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; ...
206-256 4.67e-04

Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; PHLDB2 (also called LL5beta) and PHLDB1 (also called LL5alpha) are cytoskeleton- and membrane-associated proteins. PHLDB2 has been identified as a key component of the synaptic podosomes that play an important role in in postsynaptic maturation. Both are large proteins containing an N-terminal pleckstrin (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: 270192  Cd Length: 105  Bit Score: 39.09  E-value: 4.67e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 635372929 206 GWLLKLGGgRVKTWKRRWFILTDN--CLYYFEYTTDKEPRGIIPLEnlSIREV 256
Cdd:cd14673    7 GFLTKMGG-KIKTWKKRWFVFDRNkrTLSYYVDKHEKKLKGVIYFQ--AIEEV 56
PH_EFA6 cd13295
Exchange Factor for ARF6 Pleckstrin homology (PH) domain; EFA6 (also called PSD/pleckstrin and ...
204-322 4.75e-04

Exchange Factor for ARF6 Pleckstrin homology (PH) domain; EFA6 (also called PSD/pleckstrin and Sec7 domain containing) is an guanine nucleotide exchange factor for ADP ribosylation factor 6 (ARF6), which is involved in membrane recycling. EFA6 has four structurally related polypeptides: EFA6A, EFA6B, EFA6C and EFA6D. It consists of a N-terminal proline rich region (PR), a SEC7 domain, a PH domain, a PR, a coiled-coil region, and a C-terminal PR. The EFA6 PH domain regulates its association with the plasma membrane. EFA6 activates Arf6 through its Sec7 catalytic domain and modulates this activity through its C-terminal domain, which rearranges the actin cytoskeleton in fibroblastic cell lines. 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: 270107  Cd Length: 126  Bit Score: 39.62  E-value: 4.75e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLK-----LGGGRVKTWKRRW--F--ILTDNCLYYF--EYTTDKEPRGIIPLENLSI------REVEDSKKPNCFE 266
Cdd:cd13295    8 KKGYLMRkccadPDGKKTPFGKRGWkmFyaTLKGLVLYLHkdEYGCKKALRYESLRNAISVhhslatKATDYTKKPHVFR 87
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 635372929 267 LYIpdnkdqvikackteADGRVvegnhtvYRISAPTPEEKEEW---IKCIKAAISRDPF 322
Cdd:cd13295   88 LRT--------------ADWRE-------YLFQASDTKEMQSWieaINLVAAAFSAPPL 125
PH1_ADAP cd13252
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 1; ADAP (also called ...
204-273 9.45e-04

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 1; 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 first 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: 270072  Cd Length: 109  Bit Score: 38.40  E-value: 9.45e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 635372929 204 REGWLLKlgGGRV-KTWKRRWFILT--DNCLYYFEYTTDKEPRGIIPLENLSI-REVEDSKKPNCFEL-YIPDNK 273
Cdd:cd13252    3 KEGFLWK--RGKDnNQFKQRKFVLSerEGTLKYFVKEDAKEPKAVISIEELNAtFQPEKIGHPNGLQItYLKDGS 75
PH_INPP4A_INPP4B cd13272
Type I inositol 3,4-bisphosphate 4-phosphatase and Type II inositol 3,4-bisphosphate ...
222-329 9.47e-04

Type I inositol 3,4-bisphosphate 4-phosphatase and Type II inositol 3,4-bisphosphate 4-phosphatase Pleckstrin homology (PH) domain; INPP4A (also called Inositol polyphosphate 4-phosphatase type I) and INPP4B (also called Inositol polyphosphate 4-phosphatase type II) both catalyze the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate and inositol 1,3,4-trisphosphate. They differ in that INPP4A additionally catalyzes the hydrolysis of the 4-position phosphate of inositol 3,4-bisphosphate, while INPP4B catalyzes the hydrolysis of the 4-position phosphate of inositol 1,4-bisphosphate. They both have a single PH domain followed by a C2 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: 270091  Cd Length: 144  Bit Score: 38.92  E-value: 9.47e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 222 RWFILTDNCLYYFEyttDKEPR----GIIPLENLSIREVEDSKKPNCFELYIpdnkdqvikackteadgrvVEGNHTVYR 297
Cdd:cd13272   44 RWCRLRGNLLFYLK---SKDPWsepaGVIVLEQCRPRIQNDERDSGGYPFDL-------------------VFEDGLCQR 101
                         90       100       110
                 ....*....|....*....|....*....|..
gi 635372929 298 ISAPTPEEKEEWIKCIKAAIsrdpfYEMLAAR 329
Cdd:cd13272  102 LATRTEAERLSWVQAIELAS-----YEVIRAQ 128
PH_Collybistin_ASEF cd01224
Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; ...
191-314 1.10e-03

Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; Collybistin (also called PEM2) is homologous to the Dbl proteins ASEF (also called ARHGEF4/RhoGEF4) and SPATA13 (Spermatogenesis-associated protein 13; also called ASEF2). It activates CDC42 specifically and not any other Rho-family GTPases. Collybistin consists of an SH3 domain, followed by a RhoGEF/DH and PH domain. In Dbl proteins, the DH and PH domains catalyze the exchange of GDP for GTP in Rho GTPases, allowing them to signal to downstream effectors. It induces submembrane clustering of the receptor-associated peripheral membrane protein gephyrin, which is thought to form a scaffold underneath the postsynaptic membrane linking receptors to the cytoskeleton. It also acts as a tumor suppressor that links adenomatous polyposis coli (APC) protein, a negative regulator of the Wnt signaling pathway and promotes the phosphorylation and degradation of beta-catenin, to Cdc42. Autoinhibition of collybistin is accomplished by the binding of its SH3 domain with both the RhoGEF and PH domains to block access of Cdc42 to the GTPase-binding site. Inactivation promotes cancer progression. 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: 269931  Cd Length: 138  Bit Score: 38.78  E-value: 1.10e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 191 DGNDLTHTFFNPDREGWLLKLGGGRVKtwkRRWFILTDNCLYYfeytTDKEP--------RGIIPLENLSIREVEDSKKP 262
Cdd:cd01224   18 EGEDLSDRSSELIHSGELTKISAGRAQ---ERTFFLFDHQLVY----CKKDLlrrknyiyKGRIDTDNMEIEDLPDGKDD 90
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 635372929 263 -------NCFELYipdnkdqvikaCKTEADgrvvegnhtVYRISAPTPEEKEEWIKCIK 314
Cdd:cd01224   91 esgvtvkNAWKIY-----------NASKNK---------WYVLCAKSAEEKQRWLEAFA 129
PH_GAP1_mammal-like cd13371
GAP1(IP4BP) pleckstrin homology (PH) domain; GAP1 (also called IP4BP, RASA3/Ras ...
204-271 1.18e-03

GAP1(IP4BP) pleckstrin homology (PH) domain; GAP1 (also called IP4BP, RASA3/Ras GTPase-activating protein 3, and RAS p21 protein activator (GTPase activating protein) 3/GAPIII/MGC46517/MGC47588)) is a member of the GAP1 family of GTPase-activating proteins, along with RASAL1, GAP1(m), and CAPRI. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. GAP1(IP4BP) contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its C2 domains, like those of GAP1M, do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding. GAP1(IP4BP) is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate) and PIP2 (phosphatidylinositol 4,5-bisphosphate). It suppresses RAS, 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. GAP1(IP4BP) binds tyrosine-protein kinase, HCK. Members here include humans, chickens, frogs, and fish. 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: 241522  Cd Length: 125  Bit Score: 38.48  E-value: 1.18e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 635372929 204 REGWLLKLGGGR----VKTWKRRWFILTdNCLYYFEYTTDKEPRGIIPLEN-LSIREVEDS--KKPNCFELYIPD 271
Cdd:cd13371   18 KEGFMIKRAQGRkrfgMKNFKKRWFRLT-NHEFTYHKSKGDHPLCSIPIENiLAVERLEEEsfKMKNMFQVIQPE 91
PH_RalGPS1_2 cd13310
Ral GEF with PH domain and SH3 binding motif 1 and 2 Pleckstrin homology (PH) domain; RalGPS1 ...
215-322 1.20e-03

Ral GEF with PH domain and SH3 binding motif 1 and 2 Pleckstrin homology (PH) domain; RalGPS1 (also called Ral GEF with PH domain and SH3 binding motif 1;RALGEF2/ Ral guanine nucleotide exchange factor 2; RalA exchange factor RalGPS1; Ral guanine nucleotide exchange factor RalGPS1A2; ras-specific guanine nucleotide-releasing factor RalGPS1) and RalGPS2 (also called Ral GEF with PH domain and SH3 binding motif 2; Ral-A exchange factor RalGPS2; ras-specific guanine nucleotide-releasing factor RalGPS22). They activate small GTPase Ral proteins such as RalA and RalB by stimulating the exchange of Ral bound GDP to GTP, thereby regulating various downstream cellular processes. Structurally they contain an N-terminal Cdc25-like catalytic domain, followed by a PXXP motif and a C-terminal PH domain. The Cdc25-like catalytic domain interacts with Ral and its PH domain ensures the correct membrane localization. Its PXXP motif is thought to interact with the SH3 domain of Grb2. 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: 270120  Cd Length: 116  Bit Score: 38.01  E-value: 1.20e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 215 RVKTWKRRWFILTDNCLYYFEYTTDK---------EPRGIIPLENLSIREVEDSKKPNCFELYIPDnkdqvikacktead 285
Cdd:cd13310   19 TVSSWQRYWVQLWGTSLVYYAPKSLKgtersdfksEPCKIVSISGWMVVLGDDPEHPDSFQLTDPE-------------- 84
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 635372929 286 grvvEGNhtVYRISAPTPEEKEEWIKCIKAAISRDPF 322
Cdd:cd13310   85 ----KGN--VYKFRAGSRSNALLWLKHLKDACKGNRP 115
PH_GAP1m_mammal-like cd13370
GTPase activating protein 1 m pleckstrin homology (PH) domain; GAP1(m) (also called RASA2/RAS ...
204-272 1.68e-03

GTPase activating protein 1 m pleckstrin homology (PH) domain; GAP1(m) (also called RASA2/RAS p21 protein activator (GTPase activating protein) 2) is a member of the GAP1 family of GTPase-activating proteins, along with RASAL1, GAP1(IP4BP), and CAPRI. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. GAP1(m) contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its C2 domains, like those of GAP1IP4BP, do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding. GAP1(m) is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate). It suppresses RAS, 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. GAP1(m) binds inositol tetrakisphosphate (IP4). 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: 241521  Cd Length: 133  Bit Score: 38.00  E-value: 1.68e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLGGGRV----KTWKRRWFILTDNCLYYFEyTTDKEPRGIIPLEN-LSIREVEDS--KKPNCFE-------LYI 269
Cdd:cd13370   18 KEGEMHKRAQGRTrigkKNFKKRWFCLTSRELTYHK-QKGKEAIFTIPVKNiLAVEKLEESafNKKNMFQvihsekpLYV 96

                 ...
gi 635372929 270 PDN 272
Cdd:cd13370   97 QAN 99
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
204-313 2.72e-03

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: 37.01  E-value: 2.72e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLG-GGRVKT--WKRRWFIL-----TDN--CLYYFEYTTDKEPRGIIpleNLSIREVEDSKkpncFELYIPDNK 273
Cdd:cd13324    3 YEGWLTKSPpEKKIWRaaWRRRWFVLrsgrlSGGqdVLEYYTDDHCKKLKGII---DLDQCEQVDAG----LTFEKKKFK 75
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 635372929 274 DQVIKACKTEadgrvvegnHTVYRISAPTPEEKEEWIKCI 313
Cdd:cd13324   76 NQFIFDIRTP---------KRTYYLVAETEEEMNKWVRCI 106
PH_MELT_VEPH1 cd01264
Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone ...
216-319 4.38e-03

Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone expressed PH domain-containing protein homolog 1) is expressed in the developing central nervous system of vertebrates. It contains a single C-terminal PH domain that is required for membrane targeting. 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: 269965  Cd Length: 105  Bit Score: 36.28  E-value: 4.38e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 216 VKTWKRRWFILTDNCLYYFEYTTDKEPRgiiPLENLSIREVEDSKK-----PNCFELYIpDNKDQVIKAckteadgrvVE 290
Cdd:cd01264   18 FKRWRTRYFTLSGAQLSYRGGKSKPDAP---PIELSKIRSVKVVRKkdrsiPKAFEIFT-DDKTYVLKA---------KD 84
                         90       100
                 ....*....|....*....|....*....
gi 635372929 291 GNHTvyrisaptpeekEEWIKCIKAAISR 319
Cdd:cd01264   85 EKNA------------EEWLQCLSIAVAQ 101
PH_APBB1IP cd01259
Amyloid beta (A4) Precursor protein-Binding, family B, member 1 Interacting Protein pleckstrin ...
202-252 6.10e-03

Amyloid beta (A4) Precursor protein-Binding, family B, member 1 Interacting Protein pleckstrin homology (PH) domain; APBB1IP consists of a Ras-associated (RA) domain, a PH domain, a family-specific BPS region, and a C-terminal SH2 domain. Grb7, Grb10 and Grb14 are paralogs that are also present in this hierarchy. These adapter proteins bind a variety of receptor tyrosine kinases, including the insulin and insulin-like growth factor-1 (IGF1) receptors. Grb10 and Grb14 are important tissue-specific negative regulators of insulin and IGF1 signaling based and may contribute to type 2 (non-insulin-dependent) diabetes in humans. RA-PH function as a single structural unit and is dimerized via a helical extension of the PH domain. The PH domain here are proposed to bind phosphoinositides non-cannonically ahd are unlikely to bind an activated GTPase. The tandem RA-PH domains are present in a second adapter-protein family, MRL proteins, Caenorhabditis elegans protein MIG-1012, the mammalian proteins RIAM and lamellipodin and the Drosophila melanogaster protein Pico12, all of which are Ena/VASP-binding proteins involved in actin-cytoskeleton rearrangement. 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: 269961  Cd Length: 124  Bit Score: 36.45  E-value: 6.10e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 635372929 202 PDREGWL-LKLGGGrvKTWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLS 252
Cdd:cd01259    6 PEIEGFLyLKEDGK--KSWKKRYFVLRASGLYYSPKGKSKESRDLQCLAQFD 55
PH1_FDG_family cd13328
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal ...
204-313 6.44e-03

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). 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: 275410  Cd Length: 92  Bit Score: 35.54  E-value: 6.44e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 635372929 204 REGWLLKLGGGRVKTWKRRWFILTDNCLYyfeyTTDKEP--------RGIIPLENLSIREVEDSKKPNCFelyipdnkdq 275
Cdd:cd13328    1 KEGQILKLSAKNGTPQPRYLFLFNDMLLY----CVPKLSlvgqkfsvRNRLDVAGMKVREPVNENYPHTF---------- 66
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 635372929 276 vikackteadgrVVEGNHTVYRISAPTPEEKEEWIKCI 313
Cdd:cd13328   67 ------------KISGKERSLELQASSAEEKDEWIQAI 92
PH_ORP_plant cd13294
Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs ...
217-261 6.83e-03

Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs contain a N-terminal PH domain and a C-terminal OSBP-related domain. Not much is known about its specific function in plants to date. Members here include: Arabidopsis, spruce, and petunia. 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: 241448  Cd Length: 100  Bit Score: 35.55  E-value: 6.83e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 635372929 217 KTWKRRWFILTDNCL-YYFEYTTDK-EPRGIIPLENLSIREVE-DSKK 261
Cdd:cd13294   13 KGWRSRWFVLQDGVLsYYKVHGPDKvKPSGEVHLKVSSIRESRsDDKK 60
 
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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