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Conserved domains on  [gi|2217338151|ref|XP_047296925|]
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rho guanine nucleotide exchange factor TIAM1 isoform X1 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PH2_Tiam1_2 cd01255
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, C-terminal domain; ...
 1235-1406 6.42e-107

T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, C-terminal domain; Tiam1 activates Rac GTPases to induce membrane ruffling and cell motility while Tiam2 (also called STEF (SIF (still life) and Tiam1 like-exchange factor) contributes to neurite growth. Tiam1/2 are Dbl-family of GEFs that possess a Dbl(DH) domain with a PH domain in tandem. DH-PH domain catalyzes the GDP/GTP exchange reaction in the GTPase cycle and facillitating the switch between inactive GDP-bound and active GTP-bound states. The DH domain of Tiam1 interacts with Switch regions 1 and 2 of Rac1 which blocks magnesium binding and GDP is released. Tiam1/2 possess two PH domains, which are often referred to as PHn and PHc domains. The DH-PH tandem domain is made up of the PHc domain while the PHn is part of a novel N-terminal PHCCEx domain which is made up of the PHn domain, a coiled coil region(CC), and an extra region (Ex). PHCCEx mediates binding to plasma membranes and signalling proteins in the activation of Rac GTPases. The PH domain resembles the beta-spectrin PH domain, suggesting non-canonical phosphatidylinositol binding. CC and Ex form a positively charged surface for protein binding. There are 2 motifs in Tiam1/2-interacting proteins that bind to the PHCCEx domain: Motif-I in CD44, ephrinBs, and the NMDA receptor and Motif-II in Par3 and JIP2. 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: 269957  Cd Length: 172  Bit Score: 337.04  E-value: 6.42e-107
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1235 QKIHEEFGAVFDQLIAEQTGEKKEVADLSMGDLLLHTTVIWLNPPASLGKWKKEPELAAFVFKTAVVLVYKDGSKQKKKL 1314
Cdd:cd01255      1 QKIHEEYGAVFDQLIREQSGTKKEVADLSMGDLLLYGTVEWLNPPSSLGKVKKEPELAVFVFKTAVVLVCKERSKQKKKL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1315 VGSHRLSIYEDWDPFRFRHMIPTEALQVRALASADAEANAVCEIVHVKSESEGRPERVFHLCCSSPESRKDFLKAVHSIL 1394
Cdd:cd01255     81 MGSHRKSSYEERDPFRFRHLIPVSALQVRNSNTADTESRCLWELIHTKSELEGRPEKVFQLCCSTPEFKNAFLKVIRSIL 160

                          170
                   ....*....|..
gi 2217338151 1395 RDKHRRQLLKTE 1406
Cdd:cd01255    161 REKVRRQSSKTE 172
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
 432-558 3.97e-82

T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; Tiam1 activates Rac GTPases to induce membrane ruffling and cell motility while Tiam2 (also called STEF (SIF (still life) and Tiam1 like-exchange factor) contributes to neurite growth. Tiam1/2 are Dbl-family of GEFs that possess a Dbl(DH) domain with a PH domain in tandem. DH-PH domain catalyzes the GDP/GTP exchange reaction in the GTPase cycle and facillitating the switch between inactive GDP-bound and active GTP-bound states. Tiam1/2 possess two PH domains, which are often referred to as PHn and PHc domains. The DH-PH tandem domain is made up of the PHc domain while the PHn is part of a novel N-terminal PHCCEx domain which is made up of the PHn domain, a coiled coil region(CC), and an extra region (Ex). PHCCEx mediates binding to plasma membranes and signalling proteins in the activation of Rac GTPases. The PH domain resembles the beta-spectrin PH domain, suggesting non-canonical phosphatidylinositol binding. CC and Ex form a positively charged surface for protein binding. There are 2 motifs in Tiam1/2-interacting proteins that bind to the PHCCEx domain: Motif-I in CD44, ephrinBs, and the NMDA receptor and Motif-II in Par3 and JIP2.Neither of these fall in the PHn 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: 269937  Cd Length: 127  Bit Score: 265.09  E-value: 3.97e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  432 GTVRKAGALAVKNFLVHKKNKKVESATRRKWKHYWVSLKGCTLFFYESDGRSGIDHNSIPKHAVWVENSIVQAVPEHPKK 511
Cdd:cd01230      1 GAVRKAGWLSVKNFLVHKKNKKVELATRRKWKKYWVCLKGCTLLFYECDERSGIDENSEPKHALFVEGSIVQAVPEHPKK 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2217338151  512 DFVFCLSNSLGDAFLFQTTSQTELENWITAIHSACATAVARHHHKED 558
Cdd:cd01230     81 DFVFCLSNSFGDAYLFQATSQTELENWVTAIHSACASAFARQHGKED 127
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 1044-1233 1.84e-51

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


:

Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 179.42  E-value: 1.84e-51
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  1044 VICELLETERTYVKDLNCLMERYLKPLQKE-TFLTQDELDVLFGNLTEMVEFQVEFLKTLEdgvrlvpdleklEKVDQFK 1122
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKElKLLSPNELETLFGNIEEIYEFHRDFLDELE------------ERIEEWD 68

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  1123 KVLFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVKAKTDTAFKAFLDAQNPKQQHSS-TLESYLIKPIQRILKYPLLLR 1201
Cdd:smart00325   69 DSVERIGDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRlTLESLLLKPVQRLTKYPLLLK 148

                           170       180       190
                    ....*....|....*....|....*....|..
gi 2217338151  1202 ELFALTDAESEEHYHLDVAIKTMNKVASHINE 1233
Cdd:smart00325  149 ELLKHTPEDHEDREDLKKALKAIKELANQVNE 180
Tiam_CC_Ex super family cl39723
T-lymphoma invasion and metastasis CC-Ex domain; This is the CC and Ex subdomains found in ...
 572-669 1.06e-34

T-lymphoma invasion and metastasis CC-Ex domain; This is the CC and Ex subdomains found in PH-CC-Ex globular domain from Tiam1 and Tiam2 proteins (T-lymphoma invasion and metastasis). The CC subdomain forms an antiparallel coiled coil with two long alpha-helices, together with the C-terminal Ex subdomain they form a small globular domain comprising three alpha-helices. The CC subdomain of the Tiam2 PHCCEx domain follows the C-terminal alpha1 helix of the PH pfam00169 subdomain through a four-residue linker.


The actual alignment was detected with superfamily member pfam18385:

Pssm-ID: 408184  Cd Length: 98  Bit Score: 128.33  E-value: 1.06e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  572 QKIDMDEKMKKMGEMQLSSVTDSKKKKTILDQIFVWEQNLEQFQMDLFRFRCYLASLQGGELPNPKRLLAFASRPTKVAM 651
Cdd:pfam18385    1 QKIDMDEKMKKMGEMQLSSVTDAKKKKTILDQVFLWGENTEQERLSLFLFAQYLAECQGAELPCPTYMLIYASETDKLAS 80

                           90
                   ....*....|....*...
gi 2217338151  652 GRLGIFSVSSFHALVAAR 669
Cdd:pfam18385   81 GTLGVARVGTYQSQVAAR 98
Ubl1_cv_Nsp3_N-like super family cl28922
first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV ...
 766-832 1.26e-16

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


The actual alignment was detected with superfamily member smart00455:

Pssm-ID: 475130  Cd Length: 70  Bit Score: 75.78  E-value: 1.26e-16
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2217338151   766 PSWFCLPNNQPALTVVRPGDTARDTLELICKTHQLDHSAHYLRL----KFLIENKMQLYVPQpEEDIYELL 832
Cdd:smart00455    1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLrgekKPLDLNQPISSLDG-QELVVEEL 70
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
 858-901 3.55e-07

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.


:

Pssm-ID: 214570 [Multi-domain]  Cd Length: 85  Bit Score: 49.30  E-value: 3.55e-07
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....
gi 2217338151   858 YGFSLSSVEEDGiRRLYVNSVKETGLASKKGLKAGDEILEINNR 901
Cdd:smart00228   14 LGFSLVGGKDEG-GGVVVSSVVPGSPAAKAGLRVGDVILEVNGT 56
 
Name Accession Description Interval E-value
PH2_Tiam1_2 cd01255
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, C-terminal domain; ...
 1235-1406 6.42e-107

T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, C-terminal domain; Tiam1 activates Rac GTPases to induce membrane ruffling and cell motility while Tiam2 (also called STEF (SIF (still life) and Tiam1 like-exchange factor) contributes to neurite growth. Tiam1/2 are Dbl-family of GEFs that possess a Dbl(DH) domain with a PH domain in tandem. DH-PH domain catalyzes the GDP/GTP exchange reaction in the GTPase cycle and facillitating the switch between inactive GDP-bound and active GTP-bound states. The DH domain of Tiam1 interacts with Switch regions 1 and 2 of Rac1 which blocks magnesium binding and GDP is released. Tiam1/2 possess two PH domains, which are often referred to as PHn and PHc domains. The DH-PH tandem domain is made up of the PHc domain while the PHn is part of a novel N-terminal PHCCEx domain which is made up of the PHn domain, a coiled coil region(CC), and an extra region (Ex). PHCCEx mediates binding to plasma membranes and signalling proteins in the activation of Rac GTPases. The PH domain resembles the beta-spectrin PH domain, suggesting non-canonical phosphatidylinositol binding. CC and Ex form a positively charged surface for protein binding. There are 2 motifs in Tiam1/2-interacting proteins that bind to the PHCCEx domain: Motif-I in CD44, ephrinBs, and the NMDA receptor and Motif-II in Par3 and JIP2. 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: 269957  Cd Length: 172  Bit Score: 337.04  E-value: 6.42e-107
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1235 QKIHEEFGAVFDQLIAEQTGEKKEVADLSMGDLLLHTTVIWLNPPASLGKWKKEPELAAFVFKTAVVLVYKDGSKQKKKL 1314
Cdd:cd01255      1 QKIHEEYGAVFDQLIREQSGTKKEVADLSMGDLLLYGTVEWLNPPSSLGKVKKEPELAVFVFKTAVVLVCKERSKQKKKL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1315 VGSHRLSIYEDWDPFRFRHMIPTEALQVRALASADAEANAVCEIVHVKSESEGRPERVFHLCCSSPESRKDFLKAVHSIL 1394
Cdd:cd01255     81 MGSHRKSSYEERDPFRFRHLIPVSALQVRNSNTADTESRCLWELIHTKSELEGRPEKVFQLCCSTPEFKNAFLKVIRSIL 160

                          170
                   ....*....|..
gi 2217338151 1395 RDKHRRQLLKTE 1406
Cdd:cd01255    161 REKVRRQSSKTE 172
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
 432-558 3.97e-82

T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; Tiam1 activates Rac GTPases to induce membrane ruffling and cell motility while Tiam2 (also called STEF (SIF (still life) and Tiam1 like-exchange factor) contributes to neurite growth. Tiam1/2 are Dbl-family of GEFs that possess a Dbl(DH) domain with a PH domain in tandem. DH-PH domain catalyzes the GDP/GTP exchange reaction in the GTPase cycle and facillitating the switch between inactive GDP-bound and active GTP-bound states. Tiam1/2 possess two PH domains, which are often referred to as PHn and PHc domains. The DH-PH tandem domain is made up of the PHc domain while the PHn is part of a novel N-terminal PHCCEx domain which is made up of the PHn domain, a coiled coil region(CC), and an extra region (Ex). PHCCEx mediates binding to plasma membranes and signalling proteins in the activation of Rac GTPases. The PH domain resembles the beta-spectrin PH domain, suggesting non-canonical phosphatidylinositol binding. CC and Ex form a positively charged surface for protein binding. There are 2 motifs in Tiam1/2-interacting proteins that bind to the PHCCEx domain: Motif-I in CD44, ephrinBs, and the NMDA receptor and Motif-II in Par3 and JIP2.Neither of these fall in the PHn 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: 269937  Cd Length: 127  Bit Score: 265.09  E-value: 3.97e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  432 GTVRKAGALAVKNFLVHKKNKKVESATRRKWKHYWVSLKGCTLFFYESDGRSGIDHNSIPKHAVWVENSIVQAVPEHPKK 511
Cdd:cd01230      1 GAVRKAGWLSVKNFLVHKKNKKVELATRRKWKKYWVCLKGCTLLFYECDERSGIDENSEPKHALFVEGSIVQAVPEHPKK 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2217338151  512 DFVFCLSNSLGDAFLFQTTSQTELENWITAIHSACATAVARHHHKED 558
Cdd:cd01230     81 DFVFCLSNSFGDAYLFQATSQTELENWVTAIHSACASAFARQHGKED 127
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 1044-1233 1.84e-51

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 179.42  E-value: 1.84e-51
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  1044 VICELLETERTYVKDLNCLMERYLKPLQKE-TFLTQDELDVLFGNLTEMVEFQVEFLKTLEdgvrlvpdleklEKVDQFK 1122
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKElKLLSPNELETLFGNIEEIYEFHRDFLDELE------------ERIEEWD 68

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  1123 KVLFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVKAKTDTAFKAFLDAQNPKQQHSS-TLESYLIKPIQRILKYPLLLR 1201
Cdd:smart00325   69 DSVERIGDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRlTLESLLLKPVQRLTKYPLLLK 148

                           170       180       190
                    ....*....|....*....|....*....|..
gi 2217338151  1202 ELFALTDAESEEHYHLDVAIKTMNKVASHINE 1233
Cdd:smart00325  149 ELLKHTPEDHEDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 1041-1232 9.22e-51

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 177.49  E-value: 9.22e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1041 LRKVICELLETERTYVKDLNCLMERYLKPLQKE-TFLTQDELDVLFGNLTEMVEFQVEFLKTLEdgvrlvpdlEKLEKVD 1119
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKElLPLSPEEVELLFGNIEEIYEFHRIFLKSLE---------ERVEEWD 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1120 QFKkvlFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVK-AKTDTAFKAFLDAQNpKQQHSSTLESYLIKPIQRILKYPL 1198
Cdd:cd00160     72 KSG---PRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKlKKFNKFFQEFLEKAE-SECGRLKLESLLLKPVQRLTKYPL 147

                          170       180       190
                   ....*....|....*....|....*....|....
gi 2217338151 1199 LLRELFALTDAESEEHYHLDVAIKTMNKVASHIN 1232
Cdd:cd00160    148 LLKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 1044-1232 4.02e-42

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 152.45  E-value: 4.02e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1044 VICELLETERTYVKDLNCLMERYLKPLQKETFLTQDELDVLFGNLTEMVEFQVEFLktledgvrlvpdlekLEKVDQFKK 1123
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL---------------LEELLKEWI 65

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1124 VLFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVKAK-TDTAFKAFLD-AQNPKQQHSSTLESYLIKPIQRILKYPLLLR 1201
Cdd:pfam00621   66 SIQRIGDIFLKFAPGFKVYSTYCSNYPKALKLLKKLLkKNPKFRAFLEeLEANPECRGLDLNSFLIKPVQRIPRYPLLLK 145

                          170       180       190
                   ....*....|....*....|....*....|.
gi 2217338151 1202 ELFALTDAESEEHYHLDVAIKTMNKVASHIN 1232
Cdd:pfam00621  146 ELLKHTPPDHPDYEDLKKALEAIKEVAKQIN 176
Tiam_CC_Ex pfam18385
T-lymphoma invasion and metastasis CC-Ex domain; This is the CC and Ex subdomains found in ...
 572-669 1.06e-34

T-lymphoma invasion and metastasis CC-Ex domain; This is the CC and Ex subdomains found in PH-CC-Ex globular domain from Tiam1 and Tiam2 proteins (T-lymphoma invasion and metastasis). The CC subdomain forms an antiparallel coiled coil with two long alpha-helices, together with the C-terminal Ex subdomain they form a small globular domain comprising three alpha-helices. The CC subdomain of the Tiam2 PHCCEx domain follows the C-terminal alpha1 helix of the PH pfam00169 subdomain through a four-residue linker.


Pssm-ID: 408184  Cd Length: 98  Bit Score: 128.33  E-value: 1.06e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  572 QKIDMDEKMKKMGEMQLSSVTDSKKKKTILDQIFVWEQNLEQFQMDLFRFRCYLASLQGGELPNPKRLLAFASRPTKVAM 651
Cdd:pfam18385    1 QKIDMDEKMKKMGEMQLSSVTDAKKKKTILDQVFLWGENTEQERLSLFLFAQYLAECQGAELPCPTYMLIYASETDKLAS 80

                           90
                   ....*....|....*...
gi 2217338151  652 GRLGIFSVSSFHALVAAR 669
Cdd:pfam18385   81 GTLGVARVGTYQSQVAAR 98
RBD smart00455
Raf-like Ras-binding domain;
766-832 1.26e-16

Raf-like Ras-binding domain;


Pssm-ID: 128731  Cd Length: 70  Bit Score: 75.78  E-value: 1.26e-16
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2217338151   766 PSWFCLPNNQPALTVVRPGDTARDTLELICKTHQLDHSAHYLRL----KFLIENKMQLYVPQpEEDIYELL 832
Cdd:smart00455    1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLrgekKPLDLNQPISSLDG-QELVVEEL 70
RBD pfam02196
Raf-like Ras-binding domain;
766-839 1.45e-16

Raf-like Ras-binding domain;


Pssm-ID: 460485  Cd Length: 69  Bit Score: 75.63  E-value: 1.45e-16
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217338151  766 PSWFCLPNNQPALTVVRPGDTARDTLELICKTHQLDHSAHYLRLKFLienkmQLYVPQPEEDIYELLYKEIEIC 839
Cdd:pfam02196    1 LCRVYLPDGQRTVVQVRPGETVRDALSKLCKKRGLNPEACDVYLVGG-----DKYPLDLDTDSSTLEGEEVRVE 69
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 452-547 5.87e-14

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: 69.11  E-value: 5.87e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151   452 KKVESATRRKWKHYWVSLKGCTLFFYESDGRSGIdhnSIPKHAVWVENSIVQAVPE--HPKKDFVFCLSNSLGDAFLFQT 529
Cdd:smart00233    8 YKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKS---YKPKGSIDLSGCTVREAPDpdSSKKPHCFEIKTSDRKTLLLQA 84

                            90
                    ....*....|....*...
gi 2217338151   530 TSQTELENWITAIHSACA 547
Cdd:smart00233   85 ESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 452-547 4.01e-13

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 66.82  E-value: 4.01e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  452 KKVESATRRKWKHYWVSLKGCTLFFYESDGRsgiDHNSIPKHAVWVENSIVQAV--PEHPKKDFVFCLSNSL---GDAFL 526
Cdd:pfam00169    8 LKKGGGKKKSWKKRYFVLFDGSLLYYKDDKS---GKSKEPKGSISLSGCEVVEVvaSDSPKRKFCFELRTGErtgKRTYL 84

                           90       100
                   ....*....|....*....|.
gi 2217338151  527 FQTTSQTELENWITAIHSACA 547
Cdd:pfam00169   85 LQAESEEERKDWIKAIQSAIR 105
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
 858-901 3.55e-07

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.


Pssm-ID: 214570 [Multi-domain]  Cd Length: 85  Bit Score: 49.30  E-value: 3.55e-07
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....
gi 2217338151   858 YGFSLSSVEEDGiRRLYVNSVKETGLASKKGLKAGDEILEINNR 901
Cdd:smart00228   14 LGFSLVGGKDEG-GGVVVSSVVPGSPAAKAGLRVGDVILEVNGT 56
PDZ pfam00595
PDZ domain; PDZ domains are found in diverse signaling proteins.
 859-901 1.08e-06

PDZ domain; PDZ domains are found in diverse signaling proteins.


Pssm-ID: 395476 [Multi-domain]  Cd Length: 81  Bit Score: 48.05  E-value: 1.08e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2217338151  859 GFSLSSVEEDGIRRLYVNSVKETGLASKKGLKAGDEILEINNR 901
Cdd:pfam00595   13 GFSLKGGSDQGDPGIFVSEVLPGGAAEAGGLKVGDRILSINGQ 55
PDZ3_DLG5-like cd06767
PDZ domain 3 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density ...
 843-903 1.34e-06

PDZ domain 3 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467248 [Multi-domain]  Cd Length: 82  Bit Score: 47.71  E-value: 1.34e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217338151  843 TQSIHIEKSDtaaDTYGFSLSSVEEDGIrrlYVNSVKETGLASKKGLKAGDEILE---INNRAA 903
Cdd:cd06767      3 PRHVSIEKGS---EPLGISIVSGENGGI---FVSSVTEGSLAHQAGLEYGDQLLEvngINLRNA 60
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 1033-1266 3.97e-05

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 48.73  E-value: 3.97e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1033 RQLSDADKLRK-VICELLETERTYVKDLNCLMERYLKPLQKETFLTQDE----LDVLFGNLTEMVEFQVEFLKTLEDGVR 1107
Cdd:COG5422    476 ESLPKQEIKRQeAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENArrnfIKHVFANINEIYAVNSKLLKALTNRQC 555

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1108 LVPdleklekvdqfkkVLFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVKAK-TDTAFKAFLD---AQNPKQQHSstLE 1183
Cdd:COG5422    556 LSP-------------IVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFEREKsVNPNFARFDHeveRLDESRKLE--LD 620

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1184 SYLIKPIQRILKYPLLLRELFALTDAESEEHYHLDVAIKTMNKVASHINEMQKIHEEFGAVFdqLIAEQTGEKKEVADLS 1263
Cdd:COG5422    621 GYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLF--HLNQQLLFKPEYVNLG 698


                   ...
gi 2217338151 1264 MGD 1266
Cdd:COG5422    699 LND 701
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1283-1395 8.13e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 37.54  E-value: 8.13e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1283 GKWKKepelAAFVFKTAVVLVYKDGSKQKKKlvgshrlsiyedwdpfRFRHMIPTEALQV-RALASADAEANAVCEIVHv 1361
Cdd:pfam00169   16 KSWKK----RYFVLFDGSLLYYKDDKSGKSK----------------EPKGSISLSGCEVvEVVASDSPKRKFCFELRT- 74

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2217338151 1362 kseSEGRPERVFHLCCSSPESRKDFLKAVHSILR 1395
Cdd:pfam00169   75 ---GERTGKRTYLLQAESEEERKDWIKAIQSAIR 105
 
Name Accession Description Interval E-value
PH2_Tiam1_2 cd01255
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, C-terminal domain; ...
 1235-1406 6.42e-107

T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, C-terminal domain; Tiam1 activates Rac GTPases to induce membrane ruffling and cell motility while Tiam2 (also called STEF (SIF (still life) and Tiam1 like-exchange factor) contributes to neurite growth. Tiam1/2 are Dbl-family of GEFs that possess a Dbl(DH) domain with a PH domain in tandem. DH-PH domain catalyzes the GDP/GTP exchange reaction in the GTPase cycle and facillitating the switch between inactive GDP-bound and active GTP-bound states. The DH domain of Tiam1 interacts with Switch regions 1 and 2 of Rac1 which blocks magnesium binding and GDP is released. Tiam1/2 possess two PH domains, which are often referred to as PHn and PHc domains. The DH-PH tandem domain is made up of the PHc domain while the PHn is part of a novel N-terminal PHCCEx domain which is made up of the PHn domain, a coiled coil region(CC), and an extra region (Ex). PHCCEx mediates binding to plasma membranes and signalling proteins in the activation of Rac GTPases. The PH domain resembles the beta-spectrin PH domain, suggesting non-canonical phosphatidylinositol binding. CC and Ex form a positively charged surface for protein binding. There are 2 motifs in Tiam1/2-interacting proteins that bind to the PHCCEx domain: Motif-I in CD44, ephrinBs, and the NMDA receptor and Motif-II in Par3 and JIP2. 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: 269957  Cd Length: 172  Bit Score: 337.04  E-value: 6.42e-107
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1235 QKIHEEFGAVFDQLIAEQTGEKKEVADLSMGDLLLHTTVIWLNPPASLGKWKKEPELAAFVFKTAVVLVYKDGSKQKKKL 1314
Cdd:cd01255      1 QKIHEEYGAVFDQLIREQSGTKKEVADLSMGDLLLYGTVEWLNPPSSLGKVKKEPELAVFVFKTAVVLVCKERSKQKKKL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1315 VGSHRLSIYEDWDPFRFRHMIPTEALQVRALASADAEANAVCEIVHVKSESEGRPERVFHLCCSSPESRKDFLKAVHSIL 1394
Cdd:cd01255     81 MGSHRKSSYEERDPFRFRHLIPVSALQVRNSNTADTESRCLWELIHTKSELEGRPEKVFQLCCSTPEFKNAFLKVIRSIL 160

                          170
                   ....*....|..
gi 2217338151 1395 RDKHRRQLLKTE 1406
Cdd:cd01255    161 REKVRRQSSKTE 172
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
 432-558 3.97e-82

T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; Tiam1 activates Rac GTPases to induce membrane ruffling and cell motility while Tiam2 (also called STEF (SIF (still life) and Tiam1 like-exchange factor) contributes to neurite growth. Tiam1/2 are Dbl-family of GEFs that possess a Dbl(DH) domain with a PH domain in tandem. DH-PH domain catalyzes the GDP/GTP exchange reaction in the GTPase cycle and facillitating the switch between inactive GDP-bound and active GTP-bound states. Tiam1/2 possess two PH domains, which are often referred to as PHn and PHc domains. The DH-PH tandem domain is made up of the PHc domain while the PHn is part of a novel N-terminal PHCCEx domain which is made up of the PHn domain, a coiled coil region(CC), and an extra region (Ex). PHCCEx mediates binding to plasma membranes and signalling proteins in the activation of Rac GTPases. The PH domain resembles the beta-spectrin PH domain, suggesting non-canonical phosphatidylinositol binding. CC and Ex form a positively charged surface for protein binding. There are 2 motifs in Tiam1/2-interacting proteins that bind to the PHCCEx domain: Motif-I in CD44, ephrinBs, and the NMDA receptor and Motif-II in Par3 and JIP2.Neither of these fall in the PHn 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: 269937  Cd Length: 127  Bit Score: 265.09  E-value: 3.97e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  432 GTVRKAGALAVKNFLVHKKNKKVESATRRKWKHYWVSLKGCTLFFYESDGRSGIDHNSIPKHAVWVENSIVQAVPEHPKK 511
Cdd:cd01230      1 GAVRKAGWLSVKNFLVHKKNKKVELATRRKWKKYWVCLKGCTLLFYECDERSGIDENSEPKHALFVEGSIVQAVPEHPKK 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2217338151  512 DFVFCLSNSLGDAFLFQTTSQTELENWITAIHSACATAVARHHHKED 558
Cdd:cd01230     81 DFVFCLSNSFGDAYLFQATSQTELENWVTAIHSACASAFARQHGKED 127
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 1044-1233 1.84e-51

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 179.42  E-value: 1.84e-51
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  1044 VICELLETERTYVKDLNCLMERYLKPLQKE-TFLTQDELDVLFGNLTEMVEFQVEFLKTLEdgvrlvpdleklEKVDQFK 1122
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKElKLLSPNELETLFGNIEEIYEFHRDFLDELE------------ERIEEWD 68

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  1123 KVLFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVKAKTDTAFKAFLDAQNPKQQHSS-TLESYLIKPIQRILKYPLLLR 1201
Cdd:smart00325   69 DSVERIGDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRlTLESLLLKPVQRLTKYPLLLK 148

                           170       180       190
                    ....*....|....*....|....*....|..
gi 2217338151  1202 ELFALTDAESEEHYHLDVAIKTMNKVASHINE 1233
Cdd:smart00325  149 ELLKHTPEDHEDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 1041-1232 9.22e-51

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 177.49  E-value: 9.22e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1041 LRKVICELLETERTYVKDLNCLMERYLKPLQKE-TFLTQDELDVLFGNLTEMVEFQVEFLKTLEdgvrlvpdlEKLEKVD 1119
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKElLPLSPEEVELLFGNIEEIYEFHRIFLKSLE---------ERVEEWD 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1120 QFKkvlFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVK-AKTDTAFKAFLDAQNpKQQHSSTLESYLIKPIQRILKYPL 1198
Cdd:cd00160     72 KSG---PRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKlKKFNKFFQEFLEKAE-SECGRLKLESLLLKPVQRLTKYPL 147

                          170       180       190
                   ....*....|....*....|....*....|....
gi 2217338151 1199 LLRELFALTDAESEEHYHLDVAIKTMNKVASHIN 1232
Cdd:cd00160    148 LLKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 1044-1232 4.02e-42

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 152.45  E-value: 4.02e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1044 VICELLETERTYVKDLNCLMERYLKPLQKETFLTQDELDVLFGNLTEMVEFQVEFLktledgvrlvpdlekLEKVDQFKK 1123
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL---------------LEELLKEWI 65

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1124 VLFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVKAK-TDTAFKAFLD-AQNPKQQHSSTLESYLIKPIQRILKYPLLLR 1201
Cdd:pfam00621   66 SIQRIGDIFLKFAPGFKVYSTYCSNYPKALKLLKKLLkKNPKFRAFLEeLEANPECRGLDLNSFLIKPVQRIPRYPLLLK 145

                          170       180       190
                   ....*....|....*....|....*....|.
gi 2217338151 1202 ELFALTDAESEEHYHLDVAIKTMNKVASHIN 1232
Cdd:pfam00621  146 ELLKHTPPDHPDYEDLKKALEAIKEVAKQIN 176
Tiam_CC_Ex pfam18385
T-lymphoma invasion and metastasis CC-Ex domain; This is the CC and Ex subdomains found in ...
 572-669 1.06e-34

T-lymphoma invasion and metastasis CC-Ex domain; This is the CC and Ex subdomains found in PH-CC-Ex globular domain from Tiam1 and Tiam2 proteins (T-lymphoma invasion and metastasis). The CC subdomain forms an antiparallel coiled coil with two long alpha-helices, together with the C-terminal Ex subdomain they form a small globular domain comprising three alpha-helices. The CC subdomain of the Tiam2 PHCCEx domain follows the C-terminal alpha1 helix of the PH pfam00169 subdomain through a four-residue linker.


Pssm-ID: 408184  Cd Length: 98  Bit Score: 128.33  E-value: 1.06e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  572 QKIDMDEKMKKMGEMQLSSVTDSKKKKTILDQIFVWEQNLEQFQMDLFRFRCYLASLQGGELPNPKRLLAFASRPTKVAM 651
Cdd:pfam18385    1 QKIDMDEKMKKMGEMQLSSVTDAKKKKTILDQVFLWGENTEQERLSLFLFAQYLAECQGAELPCPTYMLIYASETDKLAS 80

                           90
                   ....*....|....*...
gi 2217338151  652 GRLGIFSVSSFHALVAAR 669
Cdd:pfam18385   81 GTLGVARVGTYQSQVAAR 98
RBD smart00455
Raf-like Ras-binding domain;
766-832 1.26e-16

Raf-like Ras-binding domain;


Pssm-ID: 128731  Cd Length: 70  Bit Score: 75.78  E-value: 1.26e-16
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2217338151   766 PSWFCLPNNQPALTVVRPGDTARDTLELICKTHQLDHSAHYLRL----KFLIENKMQLYVPQpEEDIYELL 832
Cdd:smart00455    1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLrgekKPLDLNQPISSLDG-QELVVEEL 70
RBD pfam02196
Raf-like Ras-binding domain;
766-839 1.45e-16

Raf-like Ras-binding domain;


Pssm-ID: 460485  Cd Length: 69  Bit Score: 75.63  E-value: 1.45e-16
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217338151  766 PSWFCLPNNQPALTVVRPGDTARDTLELICKTHQLDHSAHYLRLKFLienkmQLYVPQPEEDIYELLYKEIEIC 839
Cdd:pfam02196    1 LCRVYLPDGQRTVVQVRPGETVRDALSKLCKKRGLNPEACDVYLVGG-----DKYPLDLDTDSSTLEGEEVRVE 69
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 452-547 5.87e-14

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: 69.11  E-value: 5.87e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151   452 KKVESATRRKWKHYWVSLKGCTLFFYESDGRSGIdhnSIPKHAVWVENSIVQAVPE--HPKKDFVFCLSNSLGDAFLFQT 529
Cdd:smart00233    8 YKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKS---YKPKGSIDLSGCTVREAPDpdSSKKPHCFEIKTSDRKTLLLQA 84

                            90
                    ....*....|....*...
gi 2217338151   530 TSQTELENWITAIHSACA 547
Cdd:smart00233   85 ESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 452-547 4.01e-13

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 66.82  E-value: 4.01e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  452 KKVESATRRKWKHYWVSLKGCTLFFYESDGRsgiDHNSIPKHAVWVENSIVQAV--PEHPKKDFVFCLSNSL---GDAFL 526
Cdd:pfam00169    8 LKKGGGKKKSWKKRYFVLFDGSLLYYKDDKS---GKSKEPKGSISLSGCEVVEVvaSDSPKRKFCFELRTGErtgKRTYL 84

                           90       100
                   ....*....|....*....|.
gi 2217338151  527 FQTTSQTELENWITAIHSACA 547
Cdd:pfam00169   85 LQAESEEERKDWIKAIQSAIR 105
PH_EFA6 cd13295
Exchange Factor for ARF6 Pleckstrin homology (PH) domain; EFA6 (also called PSD/pleckstrin and ...
 443-548 5.85e-11

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: 61.58  E-value: 5.85e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  443 KNFLVHK----KNKKVESATRRKWKHYWVSLKGCTLFFYESDGRSGIDHNSI-PKHAVWVENSIVQAVPEHPKKDFVFCL 517
Cdd:cd13295      9 KGYLMRKccadPDGKKTPFGKRGWKMFYATLKGLVLYLHKDEYGCKKALRYEsLRNAISVHHSLATKATDYTKKPHVFRL 88

                           90       100       110
                   ....*....|....*....|....*....|.
gi 2217338151  518 SNSLGDAFLFQTTSQTELENWITAIHSACAT 548
Cdd:cd13295     89 RTADWREYLFQASDTKEMQSWIEAINLVAAA 119
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 452-542 1.51e-10

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: 59.09  E-value: 1.51e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  452 KKVESATRRKWKHYWVSLKGCTLFFYESDGrsgiDHNSIPKHAVWVENSIVQAVPEHPKKDFVFCLSNSLGDAFLFQTTS 531
Cdd:cd00821      6 LKRGGGGLKSWKKRWFVLFEGVLLYYKSKK----DSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTPDGRTYYLQADS 81

                           90
                   ....*....|.
gi 2217338151  532 QTELENWITAI 542
Cdd:cd00821     82 EEERQEWLKAL 92
PH_beta_spectrin cd10571
Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a ...
 450-545 1.23e-08

Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a major component of the cytoskeleton underlying cellular membranes. Beta spectrin consists of multiple spectrin repeats followed by a PH domain, which binds to inositol-1,4,5-trisphosphate. The PH domain of beta-spectrin is thought to play a role in the association of spectrin with the plasma membrane of cells. 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: 269975  Cd Length: 106  Bit Score: 54.16  E-value: 1.23e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  450 KNKKvesATRRKWKHYWVSLKGCTLFFYEsDGRSGidHNSIPKHAvWVENSIVQAVPE----HPKKDFVFCLSNSLGDAF 525
Cdd:cd10571     14 GGKK---ASNRSWKNVYTVLRGQELSFYK-DQKAA--KSGITYAA-EPPLNLYNAVCEvasdYTKKKHVFRLKLSDGAEF 86

                           90       100
                   ....*....|....*....|
gi 2217338151  526 LFQTTSQTELENWITAIHSA 545
Cdd:cd10571     87 LFQAKDEEEMNQWVKKISFA 106
PH_ARHGAP21-like cd01253
ARHGAP21 and related proteins pleckstrin homology (PH) domain; ARHGAP family genes encode Rho ...
 435-544 1.43e-08

ARHGAP21 and related proteins pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with a RhoGAP domain. These proteins functions as a GTPase-activating protein (GAP) for RHOA and CDC42. ARHGAP21 controls the Arp2/3 complex and F-actin dynamics at the Golgi complex by regulating the activity of the small GTPase Cdc42. It is recruited to the Golgi by to GTPase, ARF1, through its PH domain and its helical motif. It is also required for CTNNA1 recruitment to adherens junctions. ARHGAP21 and it related proteins all contains a PH domain and a RhoGAP domain. Some of the members have additional N-terminal domains including PDZ, SH3, and SPEC. The ARHGAP21 PH domain interacts with the GTPbound forms of both ARF1 and ARF6 ARF-binding domain/ArfBD. The members here include: ARHGAP15, ARHGAP21, and ARHGAP23. 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: 269955  Cd Length: 113  Bit Score: 54.30  E-value: 1.43e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  435 RKAGALAVKNFLVHKKNKkvesATRRKWKHYWVSLKGCTLFFYeSDGRSGIDHNSIPKHA---VWVENSIVQAVPEHPKK 511
Cdd:cd01253      1 AREGWLHYKQIVTDKGKR----VSDRSWKQAWAVLRGHSLYLY-KDKREQTPALSIELGSeqrISIRGCIVDIAYSYTKR 75

                           90       100       110
                   ....*....|....*....|....*....|...
gi 2217338151  512 DFVFCLSNSLGDAFLFQTTSQTELENWITAIHS 544
Cdd:cd01253     76 KHVFRLTTSDFSEYLFQAEDRDDMLGWIKAIQE 108
PH_9 pfam15410
Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.
 459-547 1.63e-07

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


Pssm-ID: 434701  Cd Length: 118  Bit Score: 51.27  E-value: 1.63e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  459 RRKWKHYWVSLKGCTLFFYESDGRS--------GIDHNSiPKHAVWVENSIVQAVPEHPKKDFVFCLSNSLGDAFLFQTT 530
Cdd:pfam15410   23 KRSWKMVYAVLKDLVLYLYKDEHPPessqfedkKSLKNA-PVGKIRLHHALATPAPDYTKKSHVFRLQTADGAEYLFQTG 101

                           90
                   ....*....|....*..
gi 2217338151  531 SQTELENWITAIHSACA 547
Cdd:pfam15410  102 SPKELQEWVDTLNYWAA 118
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
 858-901 3.55e-07

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.


Pssm-ID: 214570 [Multi-domain]  Cd Length: 85  Bit Score: 49.30  E-value: 3.55e-07
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....
gi 2217338151   858 YGFSLSSVEEDGiRRLYVNSVKETGLASKKGLKAGDEILEINNR 901
Cdd:smart00228   14 LGFSLVGGKDEG-GGVVVSSVVPGSPAAKAGLRVGDVILEVNGT 56
PDZ pfam00595
PDZ domain; PDZ domains are found in diverse signaling proteins.
 859-901 1.08e-06

PDZ domain; PDZ domains are found in diverse signaling proteins.


Pssm-ID: 395476 [Multi-domain]  Cd Length: 81  Bit Score: 48.05  E-value: 1.08e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2217338151  859 GFSLSSVEEDGIRRLYVNSVKETGLASKKGLKAGDEILEINNR 901
Cdd:pfam00595   13 GFSLKGGSDQGDPGIFVSEVLPGGAAEAGGLKVGDRILSINGQ 55
PDZ3_DLG5-like cd06767
PDZ domain 3 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density ...
 843-903 1.34e-06

PDZ domain 3 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467248 [Multi-domain]  Cd Length: 82  Bit Score: 47.71  E-value: 1.34e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217338151  843 TQSIHIEKSDtaaDTYGFSLSSVEEDGIrrlYVNSVKETGLASKKGLKAGDEILE---INNRAA 903
Cdd:cd06767      3 PRHVSIEKGS---EPLGISIVSGENGGI---FVSSVTEGSLAHQAGLEYGDQLLEvngINLRNA 60
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 447-544 3.60e-06

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: 47.24  E-value: 3.60e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  447 VHKKNKKvesatRRKWKHYWVSLKGCTLFFYESDGRSGIdHNSIPK---HAVwvensivqAVPEHPKKDFVFCL-SNSlg 522
Cdd:cd13298     12 LLKRSRK-----TKNWKKRWVVLRPCQLSYYKDEKEYKL-RRVINLselLAV--------APLKDKKRKNVFGIyTPS-- 75

                           90       100
                   ....*....|....*....|..
gi 2217338151  523 DAFLFQTTSQTELENWITAIHS 544
Cdd:cd13298     76 KNLHFRATSEKDANEWVEALRE 97
PDZ2_ZO1-like_ds cd06728
PDZ domain 2 of Zonula Occludens-1 (ZO-1), ZO-2 and ZO-3, and related domains; form ...
 856-906 4.21e-06

PDZ domain 2 of Zonula Occludens-1 (ZO-1), ZO-2 and ZO-3, and related domains; form domain-swapping dimers; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins , and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467210 [Multi-domain]  Cd Length: 79  Bit Score: 46.06  E-value: 4.21e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2217338151  856 DTYGFSLSSveedgirRLYVNSVKETGLASK-KGLKAGDEILEINNRAADAL 906
Cdd:cd06728     12 DEYGLRLGS-------RIFVKEITPDSLAAKdGNLQEGDIILKINGTPVENL 56
PDZ_NHERF-like cd06768
PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related ...
 847-899 1.29e-05

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This NHERF-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467249 [Multi-domain]  Cd Length: 80  Bit Score: 44.74  E-value: 1.29e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2217338151  847 HIEKSDtaaDTYGFSLSSveEDGIRRLYVNSVKETGLASKKGLKAGDEILEIN 899
Cdd:cd06768      4 HLVKGP---EGYGFNLHA--EKGRPGHFIREVDPGSPAERAGLKDGDRLVEVN 51
PDZ_canonical cd00136
canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs ...
 846-901 1.98e-05

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467153 [Multi-domain]  Cd Length: 81  Bit Score: 44.46  E-value: 1.98e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2217338151  846 IHIEKSDTaaDTYGFSLSSvEEDGIRRLYVNSVKETGLASKKG-LKAGDEILEINNR 901
Cdd:cd00136      2 VTLEKDPG--GGLGFSIRG-GKDGGGGIFVSRVEPGGPAARDGrLRVGDRILEVNGV 55
cpPDZ2_DegP-like cd23084
circularly permuted second PDZ domain (PDZ2) of Escherichia coli periplasmic serine ...
 855-902 2.90e-05

circularly permuted second PDZ domain (PDZ2) of Escherichia coli periplasmic serine endoprotease DegP and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Escherichia coli DegP (also known as heat shock protein DegP and Protease Do), and related domains. DegP belongs to the HtrA family of housekeeping proteases. It acts as a protease, degrading transiently denatured and unfolded or misfolded proteins which accumulate in the periplasm following heat shock or other stress conditions, and as a molecular chaperone at low temperatures. DegP has two PDZ domains in addition to the protease domain; its PDZ1 domain is responsible for the identifying the distinct substrate sequences that affect degradation (degron) of the substrate sequence, and its PDZ2 domain is responsible for the combining with other DegP monomers to form a stable oligomer structure. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This DegP family PDZ domain 2 is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.


Pssm-ID: 467631 [Multi-domain]  Cd Length: 83  Bit Score: 43.77  E-value: 2.90e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2217338151  855 ADTYGFSLSSVEEDGIRR-LYVNSVKETGLASKKGLKAGDEILEINNRA 902
Cdd:cd23084      1 LALEGATVSNVTDEDGGKgVVVTEVDPGSPAAQSGLKKGDVIIGVNRQP 49
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 1033-1266 3.97e-05

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 48.73  E-value: 3.97e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1033 RQLSDADKLRK-VICELLETERTYVKDLNCLMERYLKPLQKETFLTQDE----LDVLFGNLTEMVEFQVEFLKTLEDGVR 1107
Cdd:COG5422    476 ESLPKQEIKRQeAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENArrnfIKHVFANINEIYAVNSKLLKALTNRQC 555

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1108 LVPdleklekvdqfkkVLFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVKAK-TDTAFKAFLD---AQNPKQQHSstLE 1183
Cdd:COG5422    556 LSP-------------IVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFEREKsVNPNFARFDHeveRLDESRKLE--LD 620

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1184 SYLIKPIQRILKYPLLLRELFALTDAESEEHYHLDVAIKTMNKVASHINEMQKIHEEFGAVFdqLIAEQTGEKKEVADLS 1263
Cdd:COG5422    621 GYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLF--HLNQQLLFKPEYVNLG 698


                   ...
gi 2217338151 1264 MGD 1266
Cdd:COG5422    699 LND 701
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
 450-545 1.21e-04

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: 43.17  E-value: 1.21e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  450 KNKKVESATRRKWKHYWVSLKGCTLFFYESDGRSGID-HNSIPkhavwvENSIVQAvpEHPKKDFVFCLSNSLGDAFLFQ 528
Cdd:cd01260     21 KKKEAKSFFGQKWKKYWFVLKGSSLYWYSNQQDEKAEgFINLP------DFKIERA--SECKKKYAFKACHPKIKTFYFA 92

                           90
                   ....*....|....*..
gi 2217338151  529 TTSQTELENWITAIHSA 545
Cdd:cd01260     93 AENLDDMNKWLSKLNMA 109
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
 445-545 1.23e-04

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: 42.74  E-value: 1.23e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  445 FLVHKKNKkvesatRRKWKHYWVSLKGCTLFFYESDgrsgidHNSIPKHAVWVENS-IVQAVPEHPKKDFVFCLSNSLGD 523
Cdd:cd13301      8 YLVKKGHV------VNNWKARWFVLKEDGLEYYKKK------TDSSPKGMIPLKGCtITSPCLEYGKRPLVFKLTTAKGQ 75

                           90       100
                   ....*....|....*....|..
gi 2217338151  524 AFLFQTTSQTELENWITAIHSA 545
Cdd:cd13301     76 EHFFQACSREERDAWAKDITKA 97
PH_RhoGAP2 cd13378
Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 ...
 453-542 6.21e-04

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: 41.09  E-value: 6.21e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  453 KVESATRRKWKHYWVSLKGCTLFFYESDgrsgidHNSIPKHAVWVENSIVQAV---PEHPKKDFVFCLSNSLGD------ 523
Cdd:cd13378     10 KKQRSIMKNWQQRWFVLRGDQLFYYKDE------EETKPQGCISLQGSQVNELppnPEEPGKHLFEILPGGAGDrekvpm 83

                           90       100
                   ....*....|....*....|..
gi 2217338151  524 ---AFLFQTTSQTELENWITAI 542
Cdd:cd13378     84 nheAFLLMANSQSDMEDWVKAI 105
PH_PLEKHJ1 cd13258
Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; ...
 452-545 8.01e-04

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: 40.77  E-value: 8.01e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  452 KKVESATRRkwkhyWVSLKGCTLFFYESDGRSGIDHnsiPKHAVWVENSIVQAVPEHPKKdFVFCLSNS--LGDAFLFQT 529
Cdd:cd13258     31 KKSEVFKER-----WFKLKGNLLFYFRTNEFGDCSE---PIGAIVLENCRVQMEEITEKP-FAFSIVFNdePEKKYIFSC 101

                           90
                   ....*....|....*.
gi 2217338151  530 TSQTELENWITAIHSA 545
Cdd:cd13258    102 RSEEQCEQWIEALRQA 117
PDZ_ARHGEF11-12-like cd23069
PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density ...
 858-899 8.06e-04

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467282 [Multi-domain]  Cd Length: 76  Bit Score: 39.68  E-value: 8.06e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2217338151  858 YGFSLSsveedGIRRLYVNSVKETGLASKKGLKAGDEILEIN 899
Cdd:cd23069     13 YGLTVS-----GDNPVFVQSVKEGGAAYRAGVQEGDRIIKVN 49
PDZ7_GRIP1-2-like cd06685
PDZ domain 7 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 852-900 8.60e-04

PDZ domain 7 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ7 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467173 [Multi-domain]  Cd Length: 85  Bit Score: 39.93  E-value: 8.60e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2217338151  852 DTAADTYGFSLSsveeDGI--RRLYVNSVKETGLASKKGLKAGDEILEINN 900
Cdd:cd06685     11 DSDTEDFGFSVS----DGLyeKGVYVNAIRPGGPADLSGLQPYDRILQVNH 57
PDZ1_PDZD7-like cd10833
PDZ domain 1 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related ...
 845-925 9.02e-04

PDZ domain 1 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the first PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467269 [Multi-domain]  Cd Length: 84  Bit Score: 39.72  E-value: 9.02e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  845 SIHIEKSdtAADTYGFSLSSVEEDGIRrLYVNSVKETGLASKKGLKAGDEILEINNRAADALN-SSMLKDFLSQPSLGLL 923
Cdd:cd10833      3 TVTVEKS--PDGSLGFSVRGGSEHGLG-IFVSKVEEGSAAERAGLCVGDKITEVNGVSLENITmSSAVKVLTGSNRLRMV 79


                   ..
gi 2217338151  924 VR 925
Cdd:cd10833     80 VR 81
PH_RalGPS1_2 cd13310
Ral GEF with PH domain and SH3 binding motif 1 and 2 Pleckstrin homology (PH) domain; RalGPS1 ...
 462-550 1.07e-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: 40.32  E-value: 1.07e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  462 WKHYWVSLKGCTLFFYESDGRSGIDHN---SIPKHAVWVENSIVqAVPEHPKKDFVFCLSNS-LGDAFLFQTTSQTELEN 537
Cdd:cd13310     23 WQRYWVQLWGTSLVYYAPKSLKGTERSdfkSEPCKIVSISGWMV-VLGDDPEHPDSFQLTDPeKGNVYKFRAGSRSNALL 101

                           90
                   ....*....|...
gi 2217338151  538 WITAIHSACATAV 550
Cdd:cd13310    102 WLKHLKDACKGNR 114
PDZ1_harmonin cd06737
PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic ...
 853-899 1.46e-03

PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467219 [Multi-domain]  Cd Length: 85  Bit Score: 39.16  E-value: 1.46e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2217338151  853 TAADTYGFSLSSVEEDGIRrLYVNSVKETGLASKKGLKAGDEILEIN 899
Cdd:cd06737     10 RGPESLGFSVRGGLEHGCG-LFVSHVSPGSQADNKGLRVGDEIVRIN 55
PDZ_SNX27-like cd23070
PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density ...
 846-917 1.48e-03

PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SNX27, and related domains. SNX27 is involved in retrograde transport from endosome to plasma membrane. The PDZ domain of SNX27 links cargo identification to retromer-mediated transport. SNX27 binds to the retromer complex (vacuolar protein sorting 26(VPS26)-VPS29-VPS35), via its PDZ domain binding to VPS26. The SNX27 PDZ domain also binds to cargo including the G-protein-coupled receptors (GPCRs): beta2-adrenergic receptor (beta2AR), beta1AR, parathyroid hormone receptor (PTHR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), NMDA receptors, 5-hydroxytryptamine 4a receptors, frizzled receptors, and somatostatin receptor subtype 5 (SSTR5). Additional binding partners of the SNX27 PDZ domain include G protein-gated inwardly rectifying potassium (Kir3) channels, angiotensin-converting enzyme 2 (ACE2), and PTEN (phosphatase and tensin homolog deleted on chromosome 10); PTEN binding to SNX27 prevents SNX27's association with the retromer complex. SNX27 has been reported to be a host factor needed for efficient entry of an engineered SARS-CoV-2 variant, the spike protein of which contains a deletion at the S1/S2 subunit cleavage site; the PDZ domain of SNX27 binds angiotensin-converting enzyme 2 (ACE2), and may be involved in recycling ACE2 to the plasma membrane, thereby promoting viral entry. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SNX27-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467283 [Multi-domain]  Cd Length: 93  Bit Score: 39.31  E-value: 1.48e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  846 IHIEKSDTAadtYGFSL-SSVEEDGIRR-----LY-----VNSVKETGLASKKGLKAGDEILEINNRAADALNSSMLKDF 914
Cdd:cd23070      3 VTIVKSETG---FGFNVrGQVSEGGQLRsingeLYaplqhVSAVLEGGAADKAGVRKGDRILEVNGVNVEGATHKQVVDL 79


                   ...
gi 2217338151  915 LSQ 917
Cdd:cd23070     80 IKS 82
PDZ_2 pfam13180
PDZ domain;
872-902 1.74e-03

PDZ domain;


Pssm-ID: 433015 [Multi-domain]  Cd Length: 74  Bit Score: 38.41  E-value: 1.74e-03
                           10        20        30
                   ....*....|....*....|....*....|.
gi 2217338151  872 RLYVNSVKETGLASKKGLKAGDEILEINNRA 902
Cdd:pfam13180    7 GVVVVSVKSSGPAAKAGLKAGDVILSIDGRK 37
PDZ_SHANK1_3-like cd06746
PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and ...
 874-900 1.79e-03

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SHANK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.


Pssm-ID: 467228 [Multi-domain]  Cd Length: 101  Bit Score: 39.50  E-value: 1.79e-03
                           10        20
                   ....*....|....*....|....*..
gi 2217338151  874 YVNSVKETGLASKKGLKAGDEILEINN 900
Cdd:cd06746     45 YLESVDPGGVADKAGLKKGDFLLEING 71
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
 431-542 1.83e-03

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


Pssm-ID: 275402  Cd Length: 116  Bit Score: 39.91  E-value: 1.83e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  431 QGTVRKAGALavknflvHKKNKKvesatRRKWKHYWVSLKGCTLFFYESDG-----RSGIDHNSIPKhavwvensiVQAV 505
Cdd:cd13215     18 SGAVIKSGYL-------SKRSKR-----TLRYTRYWFVLKGDTLSWYNSSTdlyfpAGTIDLRYATS---------IELS 76

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 2217338151  506 PEHPKKDFVFCLSNSlGDAFLFQTTSQTELENWITAI 542
Cdd:cd13215     77 KSNGEATTSFKIVTN-SRTYKFKADSETSADEWVKAL 112
PDZ_ZASP52-like cd23068
PDZ domain of Drosophila melanogaster PDZ and LIM domain protein Zasp52 (also known as Zasp), ...
 873-906 2.04e-03

PDZ domain of Drosophila melanogaster PDZ and LIM domain protein Zasp52 (also known as Zasp), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Drosophila melanogaster Zasp52 and related domains. Drosophila melanogaster Zasp52 (also known as Z band alternatively spliced PDZ-motif protein or Zasp) colocalizes with integrins at myotendinous junctions and with alpha-actinin at Z-disks and is required for muscle attachment as well as Z-disk assembly and maintenance. The Zasp52 actin-binding site includes the extended PDZ domain and the ZM region. The Zasp52-PDZ domain is required for myofibril assembly. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Zasp52-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467281 [Multi-domain]  Cd Length: 82  Bit Score: 38.66  E-value: 2.04e-03
                           10        20        30
                   ....*....|....*....|....*....|....
gi 2217338151  873 LYVNSVKETGLASKKGLKAGDEILEINNRAADAL 906
Cdd:cd23068     27 LSIQKVNPGSPADKAGLRRGDVILRINGTDTSNL 60
cpPDZ_BsHtra-like cd06781
circularly permuted PDZ domain of Bacillus subtilis HtrA-type serine proteases HtrA, HtrB, and ...
 858-917 2.09e-03

circularly permuted PDZ domain of Bacillus subtilis HtrA-type serine proteases HtrA, HtrB, and YyxA and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Bacillus subtilis HtrA/YkdA, HtrB/YvtA and YyxA/YycK, and related domains. HtrA-type serine proteases participate in folding and degradation of aberrant proteins, and in processing and maturation of native proteins. HtrA, HtrB, and YyxA have a single transmembrane domain at the N-terminus and a PDZ domain at the C-terminus. Expression of htrA and htrB genes is induced both by heat shock and by secretion stress (by a common) mechanism; yyxA is neither heat shock nor secretion stress inducible. HtrA and HtrB may have overlapping cellular functions; YyxA may have a cellular function distinct from the other two proteases or have the same function but under different conditions. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This BsHtrA-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.


Pssm-ID: 467622 [Multi-domain]  Cd Length: 98  Bit Score: 39.16  E-value: 2.09e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  858 YGFSLSSVEEDGIRRL----------YVNSVKETGLASKKGLKAGDEILEINNRAADalNSSMLKDFLSQ 917
Cdd:cd06781      7 SMVDLSDVPEYEQQSLklpsnvnkgvYVAQVQSNSPAEKAGLKKGDVITKLDGKKVE--SSSDLRQILYS 74
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 451-570 2.14e-03

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: 39.53  E-value: 2.14e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  451 NKKVESAT---RRkwkhyWVSLKGCTLFFYESDGrsgiDHNsiPKHAVWVENSIVQAVPEHPKKDFVFCLSNSLGDAFLF 527
Cdd:cd13288     15 WKKGERNTsyqKR-----WFVLKGNLLFYFEKKG----DRE--PLGVIVLEGCTVELAEDAEPYAFAIRFDGPGARSYVL 83

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2217338151  528 QTTSQTELENWITAIhsACATavarHHHKEDTLRLLKSEIKKL 570
Cdd:cd13288     84 AAENQEDMESWMKAL--SRAS----YDYLRLTVEELEKQLEEL 120
PDZ1_FL-whirlin cd06740
PDZ domain 1 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 ...
 850-925 2.62e-03

PDZ domain 1 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the full-length isoform of whirlin and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This whirlin family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467222 [Multi-domain]  Cd Length: 82  Bit Score: 38.50  E-value: 2.62e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217338151  850 KSDTAADTYGFSLSSVEEDGIRrLYVNSVKETGLASKKGLKAGDEILEINNRAADAL-NSSMLKDFLSQPSLGLLVR 925
Cdd:cd06740      7 KRSKSHEGLGFSIRGGAEHGVG-IYVSLVEPGSLAEKEGLRVGDQILRVNDVSFEKVtHAEAVKILRVSKKLVLSVR 82
PH_ARHGAP9-like cd13233
Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like ...
 451-545 2.74e-03

Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with RhoGAP domain. The ARHGAP members here all have a PH domain upstream of their C-terminal RhoGAP domain. Some have additional N-terminal SH3 and WW domains. The members here include: ARHGAP9, ARHGAP12, ARHGAP15, and ARHGAP27. ARHGAP27 and ARHGAP12 shared the common-domain structure, consisting of SH3, WW, PH, and RhoGAP domains. The PH domain of ArhGAP9 employs a non-canonical phosphoinositide binding mechanism, a variation of the spectrin- Ins(4,5)P2-binding mode, that gives rise to a unique PI binding profile, namely a preference for both PI(4,5)P2 and the PI 3-kinase products PI(3,4,5)P3 and PI(3,4)P2. This lipid binding mechanism is also employed by the PH domain of Tiam1 and Slm1. 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: 270053  Cd Length: 110  Bit Score: 39.19  E-value: 2.74e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  451 NKKVesatRRKWKHYWVSLKGCTLFFYEsDGRSGIDHNSIPKHAvwvENSI------VQAVPEHPKKDFVFCLSNSLGDA 524
Cdd:cd13233     15 GKKL----RKNWSTSWVVLTSSHLLFYK-DAKSAAKSGNPYSKP---ESSVdlrgasIEWAKEKSSRKNVFQISTVTGTE 86

                           90       100
                   ....*....|....*....|.
gi 2217338151  525 FLFQTTSQTELENWITAIHSA 545
Cdd:cd13233     87 FLLQSDNDTEIREWFDAIKAV 107
PDZ5_MAGI-1_3-like cd06735
PDZ domain 5 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, ...
 858-900 2.89e-03

PDZ domain 5 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5, and belongs to this MAGI1,2,3-like family. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ5 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467217 [Multi-domain]  Cd Length: 84  Bit Score: 38.33  E-value: 2.89e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2217338151  858 YGFSLSSVEEDGIRRLYVNSVKETGLASKKG-LKAGDEILEINN 900
Cdd:cd06735     13 FGFSIRGGREYNNMPLYVLRLAEDGPAQRDGrLRVGDQILEING 56
PDZ2_L-delphilin-like cd06744
PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 ...
 845-920 6.50e-03

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467226 [Multi-domain]  Cd Length: 75  Bit Score: 36.87  E-value: 6.50e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151  845 SIHIEKSDTaadTYGFSLSsveedGIRRLYVNSVKETGLASKKGLKAGDEILEINNraADALNSS------MLKDFLSQP 918
Cdd:cd06744      1 TVRVYRGNG---SFGFTLR-----GHAPVYIESVDPGSAAERAGLKPGDRILFLNG--LDVRNCShdkvvsLLQGSGSMP 70


                   ..
gi 2217338151  919 SL 920
Cdd:cd06744     71 TL 72
PDZ3_PDZD2-PDZ1_hPro-IL-16-like cd06759
PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 of human pro-interleukin-16 ...
 873-899 7.37e-03

PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family also includes the first PDZ domain (PDZ1) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467240 [Multi-domain]  Cd Length: 87  Bit Score: 37.25  E-value: 7.37e-03
                           10        20
                   ....*....|....*....|....*...
gi 2217338151  873 LYVNSVKETGLASKKG-LKAGDEILEIN 899
Cdd:cd06759     31 IYVKTIFPGGAAAEDGrLKEGDEILEVN 58
PDZ_6 pfam17820
PDZ domain; This entry represents the PDZ domain from a wide variety of proteins.
 874-902 8.00e-03

PDZ domain; This entry represents the PDZ domain from a wide variety of proteins.


Pssm-ID: 436067 [Multi-domain]  Cd Length: 54  Bit Score: 35.97  E-value: 8.00e-03
                           10        20
                   ....*....|....*....|....*....
gi 2217338151  874 YVNSVKETGLASKKGLKAGDEILEINNRA 902
Cdd:pfam17820    1 VVTAVVPGSPAERAGLRVGDVILAVNGKP 29
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1283-1395 8.13e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 37.54  E-value: 8.13e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217338151 1283 GKWKKepelAAFVFKTAVVLVYKDGSKQKKKlvgshrlsiyedwdpfRFRHMIPTEALQV-RALASADAEANAVCEIVHv 1361
Cdd:pfam00169   16 KSWKK----RYFVLFDGSLLYYKDDKSGKSK----------------EPKGSISLSGCEVvEVVASDSPKRKFCFELRT- 74

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2217338151 1362 kseSEGRPERVFHLCCSSPESRKDFLKAVHSILR 1395
Cdd:pfam00169   75 ---GERTGKRTYLLQAESEEERKDWIKAIQSAIR 105
PDZ2_FL-whirlin cd06741
PDZ domain 2 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 ...
 873-901 9.01e-03

PDZ domain 2 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the full-length isoform of whirlin and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This whirlin family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467223 [Multi-domain]  Cd Length: 84  Bit Score: 36.86  E-value: 9.01e-03
                           10        20
                   ....*....|....*....|....*....
gi 2217338151  873 LYVNSVKETGLASKKGLKAGDEILEINNR 901
Cdd:cd06741     28 IYVTGVDPGSVAENAGLKVGDQILEVNGR 56
PDZ2_harmonin cd06738
PDZ domain 2 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic ...
 859-899 9.29e-03

PDZ domain 2 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467220 [Multi-domain]  Cd Length: 82  Bit Score: 36.91  E-value: 9.29e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2217338151  859 GFSLSS--VEEDGIrrlYVNSVKETGLASKKGLKAGDEILEIN 899
Cdd:cd06738     16 GCSISSgpTQKPGI---FISNVKPGSLAEEVGLEVGDQIVEVN 55
PDZ3_Scribble-like cd06702
PDZ domain 3 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 ...
 865-925 9.33e-03

PDZ domain 3 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467186 [Multi-domain]  Cd Length: 89  Bit Score: 36.85  E-value: 9.33e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2217338151  865 VEEDGIrrlYVNSVKETGLASKKGLKAGDEILEINN---RAA---DALNSsmlkdfLSQPS--LGLLVR 925
Cdd:cd06702     29 VDEPGI---FISKVIPDGAAAKSGLRIGDRILSVNGkdlRHAthqEAVSA------LLSPGqeIKLLVR 88
 
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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