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Conserved domains on  [gi|1958665702|ref|XP_038944357|]
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rho guanine nucleotide exchange factor TIAM1 isoform X1 [Rattus norvegicus]

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; ...
 1253-1424 4.01e-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: 337.82  E-value: 4.01e-107
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1253 QKIHEEFGAVFDQLIAEQTGEKKEVADLSMGDLLLHTSVIWLNPPASLGKWKKEPELAAFVFKTAVVLVYKDGSKQKKKL 1332
Cdd:cd01255      1 QKIHEEYGAVFDQLIREQSGTKKEVADLSMGDLLLYGTVEWLNPPSSLGKVKKEPELAVFVFKTAVVLVCKERSKQKKKL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1333 VGSHRLSIYEEWDPFRFRHMIPTEALQVRALPSADAEANAVCEIVHVKSESEGRPERVFHLCCSSPESRKDFLKSVHSIL 1412
Cdd:cd01255     81 MGSHRKSSYEERDPFRFRHLIPVSALQVRNSNTADTESRCLWELIHTKSELEGRPEKVFQLCCSTPEFKNAFLKVIRSIL 160

                          170
                   ....*....|..
gi 1958665702 1413 RDKHRRQLLKTE 1424
Cdd:cd01255    161 REKVRRQSSKTE 172
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
 450-576 2.07e-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: 265.86  E-value: 2.07e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  450 GTVRKAGALAVKNFLVHKKNKKVESATRRKWKHYWVSLKGCTLFFYESDGRSGIDHNSVPKHAVWVENSIVQAVPEHPKK 529
Cdd:cd01230      1 GAVRKAGWLSVKNFLVHKKNKKVELATRRKWKKYWVCLKGCTLLFYECDERSGIDENSEPKHALFVEGSIVQAVPEHPKK 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1958665702  530 DFVFCLSNSLGDAFLFQTTSQTELENWITAIHSACAAAVARHHHKED 576
Cdd:cd01230     81 DFVFCLSNSFGDAYLFQATSQTELENWVTAIHSACASAFARQHGKED 127
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 1062-1251 2.93e-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: 179.03  E-value: 2.93e-51
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  1062 VICELLETERTYVKDLNCLMERYLKPLQKE-TFLTQDELDVLFGNLTEMVEFQVEFLKTLEdgvrlvpdleklEKVDQFK 1140
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKElKLLSPNELETLFGNIEEIYEFHRDFLDELE------------ERIEEWD 68

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  1141 KVLFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVKAKTDTAFKAFLDAQNPRQQHSS-TLESYLIKPIQRVLKYPLLLR 1219
Cdd:smart00325   69 DSVERIGDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRlTLESLLLKPVQRLTKYPLLLK 148

                           170       180       190
                    ....*....|....*....|....*....|..
gi 1958665702  1220 ELFALTDAESEEHYHLDVAIKTMNKVASHINE 1251
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 ...
 590-687 9.36e-35

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: 9.36e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  590 QKIDMDEKMKKMGEMQLSSVTDAKKKKTILDQIFVWEQNLEQFQMDLFRFRCYLASLQGGELPNPKRLLGFASRPTKVAM 669
Cdd:pfam18385    1 QKIDMDEKMKKMGEMQLSSVTDAKKKKTILDQVFLWGENTEQERLSLFLFAQYLAECQGAELPCPTYMLIYASETDKLAS 80

                           90
                   ....*....|....*...
gi 1958665702  670 GRLGIFSVSSFHALVAAR 687
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 ...
 784-850 4.56e-17

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: 76.94  E-value: 4.56e-17
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958665702   784 PSWFCLPNNQPALTVVRPGDTARDTLELICKAHQLDHSAHYLRL----KFLMENKMQFYVPQpEEDIYELL 850
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 ...
 860-919 3.14e-06

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: 46.60  E-value: 3.14e-06
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702   860 VTQNIHIEKSDAaadNYGFLLSSVDEDGvRRLYVNSVKETGLASKKGLKAGDEILQINNR 919
Cdd:smart00228    1 EPRLVELEKGGG---GLGFSLVGGKDEG-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; ...
 1253-1424 4.01e-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: 337.82  E-value: 4.01e-107
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1253 QKIHEEFGAVFDQLIAEQTGEKKEVADLSMGDLLLHTSVIWLNPPASLGKWKKEPELAAFVFKTAVVLVYKDGSKQKKKL 1332
Cdd:cd01255      1 QKIHEEYGAVFDQLIREQSGTKKEVADLSMGDLLLYGTVEWLNPPSSLGKVKKEPELAVFVFKTAVVLVCKERSKQKKKL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1333 VGSHRLSIYEEWDPFRFRHMIPTEALQVRALPSADAEANAVCEIVHVKSESEGRPERVFHLCCSSPESRKDFLKSVHSIL 1412
Cdd:cd01255     81 MGSHRKSSYEERDPFRFRHLIPVSALQVRNSNTADTESRCLWELIHTKSELEGRPEKVFQLCCSTPEFKNAFLKVIRSIL 160

                          170
                   ....*....|..
gi 1958665702 1413 RDKHRRQLLKTE 1424
Cdd:cd01255    161 REKVRRQSSKTE 172
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
 450-576 2.07e-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: 265.86  E-value: 2.07e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  450 GTVRKAGALAVKNFLVHKKNKKVESATRRKWKHYWVSLKGCTLFFYESDGRSGIDHNSVPKHAVWVENSIVQAVPEHPKK 529
Cdd:cd01230      1 GAVRKAGWLSVKNFLVHKKNKKVELATRRKWKKYWVCLKGCTLLFYECDERSGIDENSEPKHALFVEGSIVQAVPEHPKK 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1958665702  530 DFVFCLSNSLGDAFLFQTTSQTELENWITAIHSACAAAVARHHHKED 576
Cdd:cd01230     81 DFVFCLSNSFGDAYLFQATSQTELENWVTAIHSACASAFARQHGKED 127
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 1062-1251 2.93e-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: 179.03  E-value: 2.93e-51
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  1062 VICELLETERTYVKDLNCLMERYLKPLQKE-TFLTQDELDVLFGNLTEMVEFQVEFLKTLEdgvrlvpdleklEKVDQFK 1140
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKElKLLSPNELETLFGNIEEIYEFHRDFLDELE------------ERIEEWD 68

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  1141 KVLFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVKAKTDTAFKAFLDAQNPRQQHSS-TLESYLIKPIQRVLKYPLLLR 1219
Cdd:smart00325   69 DSVERIGDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRlTLESLLLKPVQRLTKYPLLLK 148

                           170       180       190
                    ....*....|....*....|....*....|..
gi 1958665702  1220 ELFALTDAESEEHYHLDVAIKTMNKVASHINE 1251
Cdd:smart00325  149 ELLKHTPEDHEDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 1059-1250 2.32e-50

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: 176.33  E-value: 2.32e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1059 LRKVICELLETERTYVKDLNCLMERYLKPLQKE-TFLTQDELDVLFGNLTEMVEFQVEFLKTLEdgvrlvpdlEKLEKVD 1137
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKElLPLSPEEVELLFGNIEEIYEFHRIFLKSLE---------ERVEEWD 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1138 QFKkvlFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVK-AKTDTAFKAFLDAQNpRQQHSSTLESYLIKPIQRVLKYPL 1216
Cdd:cd00160     72 KSG---PRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKlKKFNKFFQEFLEKAE-SECGRLKLESLLLKPVQRLTKYPL 147

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1958665702 1217 LLRELFALTDAESEEHYHLDVAIKTMNKVASHIN 1250
Cdd:cd00160    148 LLKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 1062-1250 9.17e-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: 151.68  E-value: 9.17e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1062 VICELLETERTYVKDLNCLMERYLKPLQKETFLTQDELDVLFGNLTEMVEFQVEFLktledgvrlvpdlekLEKVDQFKK 1141
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL---------------LEELLKEWI 65

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1142 VLFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVKAK-TDTAFKAFLDAQNPRQQHSS-TLESYLIKPIQRVLKYPLLLR 1219
Cdd:pfam00621   66 SIQRIGDIFLKFAPGFKVYSTYCSNYPKALKLLKKLLkKNPKFRAFLEELEANPECRGlDLNSFLIKPVQRIPRYPLLLK 145

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1958665702 1220 ELFALTDAESEEHYHLDVAIKTMNKVASHIN 1250
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 ...
 590-687 9.36e-35

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: 9.36e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  590 QKIDMDEKMKKMGEMQLSSVTDAKKKKTILDQIFVWEQNLEQFQMDLFRFRCYLASLQGGELPNPKRLLGFASRPTKVAM 669
Cdd:pfam18385    1 QKIDMDEKMKKMGEMQLSSVTDAKKKKTILDQVFLWGENTEQERLSLFLFAQYLAECQGAELPCPTYMLIYASETDKLAS 80

                           90
                   ....*....|....*...
gi 1958665702  670 GRLGIFSVSSFHALVAAR 687
Cdd:pfam18385   81 GTLGVARVGTYQSQVAAR 98
RBD smart00455
Raf-like Ras-binding domain;
784-850 4.56e-17

Raf-like Ras-binding domain;


Pssm-ID: 128731  Cd Length: 70  Bit Score: 76.94  E-value: 4.56e-17
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958665702   784 PSWFCLPNNQPALTVVRPGDTARDTLELICKAHQLDHSAHYLRL----KFLMENKMQFYVPQpEEDIYELL 850
Cdd:smart00455    1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLrgekKPLDLNQPISSLDG-QELVVEEL 70
RBD pfam02196
Raf-like Ras-binding domain;
784-857 6.72e-17

Raf-like Ras-binding domain;


Pssm-ID: 460485  Cd Length: 69  Bit Score: 76.40  E-value: 6.72e-17
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958665702  784 PSWFCLPNNQPALTVVRPGDTARDTLELICKAHQLDHSAHYLRLKFLmenkmQFYVPQPEEDIYELLYKEIEIC 857
Cdd:pfam02196    1 LCRVYLPDGQRTVVQVRPGETVRDALSKLCKKRGLNPEACDVYLVGG-----DKYPLDLDTDSSTLEGEEVRVE 69
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 470-565 3.25e-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: 69.88  E-value: 3.25e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702   470 KKVESATRRKWKHYWVSLKGCTLFFYESDGRSGIdhnSVPKHAVWVENSIVQAVPE--HPKKDFVFCLSNSLGDAFLFQT 547
Cdd:smart00233    8 YKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKS---YKPKGSIDLSGCTVREAPDpdSSKKPHCFEIKTSDRKTLLLQA 84

                            90
                    ....*....|....*...
gi 1958665702   548 TSQTELENWITAIHSACA 565
Cdd:smart00233   85 ESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 470-565 2.86e-13

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 67.59  E-value: 2.86e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  470 KKVESATRRKWKHYWVSLKGCTLFFYESDGRsgiDHNSVPKHAVWVENSIVQAV--PEHPKKDFVFCLSNSL---GDAFL 544
Cdd:pfam00169    8 LKKGGGKKKSWKKRYFVLFDGSLLYYKDDKS---GKSKEPKGSISLSGCEVVEVvaSDSPKRKFCFELRTGErtgKRTYL 84

                           90       100
                   ....*....|....*....|.
gi 1958665702  545 FQTTSQTELENWITAIHSACA 565
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 ...
 860-919 3.14e-06

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: 46.60  E-value: 3.14e-06
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702   860 VTQNIHIEKSDAaadNYGFLLSSVDEDGvRRLYVNSVKETGLASKKGLKAGDEILQINNR 919
Cdd:smart00228    1 EPRLVELEKGGG---GLGFSLVGGKDEG-GGVVVSSVVPGSPAAKAGLRVGDVILEVNGT 56
PDZ pfam00595
PDZ domain; PDZ domains are found in diverse signaling proteins.
 877-919 1.60e-05

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


Pssm-ID: 395476 [Multi-domain]  Cd Length: 81  Bit Score: 44.58  E-value: 1.60e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1958665702  877 GFLLSSVDEDGVRRLYVNSVKETGLASKKGLKAGDEILQINNR 919
Cdd:pfam00595   13 GFSLKGGSDQGDPGIFVSEVLPGGAAEAGGLKVGDRILSINGQ 55
cpPDZ2_DegP-like cd23084
circularly permuted second PDZ domain (PDZ2) of Escherichia coli periplasmic serine ...
 873-920 2.30e-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: 44.16  E-value: 2.30e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1958665702  873 ADNYGFLLSSV-DEDGVRRLYVNSVKETGLASKKGLKAGDEILQINNRA 920
Cdd:cd23084      1 LALEGATVSNVtDEDGGKGVVVTEVDPGSPAAQSGLKKGDVIIGVNRQP 49
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 1051-1284 3.60e-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: 3.60e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1051 RQLSDADKLRK-VICELLETERTYVKDLNCLMERYLKPLQKETFLTQDE----LDVLFGNLTEMVEFQVEFLKTLEDGVR 1125
Cdd:COG5422    476 ESLPKQEIKRQeAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENArrnfIKHVFANINEIYAVNSKLLKALTNRQC 555

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1126 LVPdleklekvdqfkkVLFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVKAKTDTAFKAFLDAQNPRQQHSSTLE--SY 1203
Cdd:COG5422    556 LSP-------------IVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLEldGY 622

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1204 LIKPIQRVLKYPLLLRELFALTDAESEEHYHLDVAIKTMNKVASHINEMQKIHEEFGAVFdqLIAEQTGEKKEVADLSMG 1283
Cdd:COG5422    623 LTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLF--HLNQQLLFKPEYVNLGLN 700


                   .
gi 1958665702 1284 D 1284
Cdd:COG5422    701 D 701
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1301-1413 9.70e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 37.54  E-value: 9.70e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1301 GKWKKepelAAFVFKTAVVLVYKDGSKQKKKlvgshrlsiyeewdpfRFRHMIPTEALQVRALPSADAEANAVC-EIVHv 1379
Cdd:pfam00169   16 KSWKK----RYFVLFDGSLLYYKDDKSGKSK----------------EPKGSISLSGCEVVEVVASDSPKRKFCfELRT- 74

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1958665702 1380 kseSEGRPERVFHLCCSSPESRKDFLKSVHSILR 1413
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; ...
 1253-1424 4.01e-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: 337.82  E-value: 4.01e-107
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1253 QKIHEEFGAVFDQLIAEQTGEKKEVADLSMGDLLLHTSVIWLNPPASLGKWKKEPELAAFVFKTAVVLVYKDGSKQKKKL 1332
Cdd:cd01255      1 QKIHEEYGAVFDQLIREQSGTKKEVADLSMGDLLLYGTVEWLNPPSSLGKVKKEPELAVFVFKTAVVLVCKERSKQKKKL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1333 VGSHRLSIYEEWDPFRFRHMIPTEALQVRALPSADAEANAVCEIVHVKSESEGRPERVFHLCCSSPESRKDFLKSVHSIL 1412
Cdd:cd01255     81 MGSHRKSSYEERDPFRFRHLIPVSALQVRNSNTADTESRCLWELIHTKSELEGRPEKVFQLCCSTPEFKNAFLKVIRSIL 160

                          170
                   ....*....|..
gi 1958665702 1413 RDKHRRQLLKTE 1424
Cdd:cd01255    161 REKVRRQSSKTE 172
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
 450-576 2.07e-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: 265.86  E-value: 2.07e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  450 GTVRKAGALAVKNFLVHKKNKKVESATRRKWKHYWVSLKGCTLFFYESDGRSGIDHNSVPKHAVWVENSIVQAVPEHPKK 529
Cdd:cd01230      1 GAVRKAGWLSVKNFLVHKKNKKVELATRRKWKKYWVCLKGCTLLFYECDERSGIDENSEPKHALFVEGSIVQAVPEHPKK 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1958665702  530 DFVFCLSNSLGDAFLFQTTSQTELENWITAIHSACAAAVARHHHKED 576
Cdd:cd01230     81 DFVFCLSNSFGDAYLFQATSQTELENWVTAIHSACASAFARQHGKED 127
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 1062-1251 2.93e-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: 179.03  E-value: 2.93e-51
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  1062 VICELLETERTYVKDLNCLMERYLKPLQKE-TFLTQDELDVLFGNLTEMVEFQVEFLKTLEdgvrlvpdleklEKVDQFK 1140
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKElKLLSPNELETLFGNIEEIYEFHRDFLDELE------------ERIEEWD 68

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  1141 KVLFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVKAKTDTAFKAFLDAQNPRQQHSS-TLESYLIKPIQRVLKYPLLLR 1219
Cdd:smart00325   69 DSVERIGDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRlTLESLLLKPVQRLTKYPLLLK 148

                           170       180       190
                    ....*....|....*....|....*....|..
gi 1958665702  1220 ELFALTDAESEEHYHLDVAIKTMNKVASHINE 1251
Cdd:smart00325  149 ELLKHTPEDHEDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 1059-1250 2.32e-50

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: 176.33  E-value: 2.32e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1059 LRKVICELLETERTYVKDLNCLMERYLKPLQKE-TFLTQDELDVLFGNLTEMVEFQVEFLKTLEdgvrlvpdlEKLEKVD 1137
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKElLPLSPEEVELLFGNIEEIYEFHRIFLKSLE---------ERVEEWD 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1138 QFKkvlFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVK-AKTDTAFKAFLDAQNpRQQHSSTLESYLIKPIQRVLKYPL 1216
Cdd:cd00160     72 KSG---PRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKlKKFNKFFQEFLEKAE-SECGRLKLESLLLKPVQRLTKYPL 147

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1958665702 1217 LLRELFALTDAESEEHYHLDVAIKTMNKVASHIN 1250
Cdd:cd00160    148 LLKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 1062-1250 9.17e-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: 151.68  E-value: 9.17e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1062 VICELLETERTYVKDLNCLMERYLKPLQKETFLTQDELDVLFGNLTEMVEFQVEFLktledgvrlvpdlekLEKVDQFKK 1141
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL---------------LEELLKEWI 65

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1142 VLFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVKAK-TDTAFKAFLDAQNPRQQHSS-TLESYLIKPIQRVLKYPLLLR 1219
Cdd:pfam00621   66 SIQRIGDIFLKFAPGFKVYSTYCSNYPKALKLLKKLLkKNPKFRAFLEELEANPECRGlDLNSFLIKPVQRIPRYPLLLK 145

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1958665702 1220 ELFALTDAESEEHYHLDVAIKTMNKVASHIN 1250
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 ...
 590-687 9.36e-35

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: 9.36e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  590 QKIDMDEKMKKMGEMQLSSVTDAKKKKTILDQIFVWEQNLEQFQMDLFRFRCYLASLQGGELPNPKRLLGFASRPTKVAM 669
Cdd:pfam18385    1 QKIDMDEKMKKMGEMQLSSVTDAKKKKTILDQVFLWGENTEQERLSLFLFAQYLAECQGAELPCPTYMLIYASETDKLAS 80

                           90
                   ....*....|....*...
gi 1958665702  670 GRLGIFSVSSFHALVAAR 687
Cdd:pfam18385   81 GTLGVARVGTYQSQVAAR 98
RBD smart00455
Raf-like Ras-binding domain;
784-850 4.56e-17

Raf-like Ras-binding domain;


Pssm-ID: 128731  Cd Length: 70  Bit Score: 76.94  E-value: 4.56e-17
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958665702   784 PSWFCLPNNQPALTVVRPGDTARDTLELICKAHQLDHSAHYLRL----KFLMENKMQFYVPQpEEDIYELL 850
Cdd:smart00455    1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLrgekKPLDLNQPISSLDG-QELVVEEL 70
RBD pfam02196
Raf-like Ras-binding domain;
784-857 6.72e-17

Raf-like Ras-binding domain;


Pssm-ID: 460485  Cd Length: 69  Bit Score: 76.40  E-value: 6.72e-17
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958665702  784 PSWFCLPNNQPALTVVRPGDTARDTLELICKAHQLDHSAHYLRLKFLmenkmQFYVPQPEEDIYELLYKEIEIC 857
Cdd:pfam02196    1 LCRVYLPDGQRTVVQVRPGETVRDALSKLCKKRGLNPEACDVYLVGG-----DKYPLDLDTDSSTLEGEEVRVE 69
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 470-565 3.25e-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: 69.88  E-value: 3.25e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702   470 KKVESATRRKWKHYWVSLKGCTLFFYESDGRSGIdhnSVPKHAVWVENSIVQAVPE--HPKKDFVFCLSNSLGDAFLFQT 547
Cdd:smart00233    8 YKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKS---YKPKGSIDLSGCTVREAPDpdSSKKPHCFEIKTSDRKTLLLQA 84

                            90
                    ....*....|....*...
gi 1958665702   548 TSQTELENWITAIHSACA 565
Cdd:smart00233   85 ESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 470-565 2.86e-13

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 67.59  E-value: 2.86e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  470 KKVESATRRKWKHYWVSLKGCTLFFYESDGRsgiDHNSVPKHAVWVENSIVQAV--PEHPKKDFVFCLSNSL---GDAFL 544
Cdd:pfam00169    8 LKKGGGKKKSWKKRYFVLFDGSLLYYKDDKS---GKSKEPKGSISLSGCEVVEVvaSDSPKRKFCFELRTGErtgKRTYL 84

                           90       100
                   ....*....|....*....|.
gi 1958665702  545 FQTTSQTELENWITAIHSACA 565
Cdd:pfam00169   85 LQAESEEERKDWIKAIQSAIR 105
PH_EFA6 cd13295
Exchange Factor for ARF6 Pleckstrin homology (PH) domain; EFA6 (also called PSD/pleckstrin and ...
 461-566 4.97e-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: 4.97e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  461 KNFLVHK----KNKKVESATRRKWKHYWVSLKGCTLFFYESDGrsGIDHNSV---PKHAVWVENSIVQAVPEHPKKDFVF 533
Cdd:cd13295      9 KGYLMRKccadPDGKKTPFGKRGWKMFYATLKGLVLYLHKDEY--GCKKALRyesLRNAISVHHSLATKATDYTKKPHVF 86

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1958665702  534 CLSNSLGDAFLFQTTSQTELENWITAIHSACAA 566
Cdd:cd13295     87 RLRTADWREYLFQASDTKEMQSWIEAINLVAAA 119
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 470-560 1.00e-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: 59.86  E-value: 1.00e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  470 KKVESATRRKWKHYWVSLKGCTLFFYESDGrsgiDHNSVPKHAVWVENSIVQAVPEHPKKDFVFCLSNSLGDAFLFQTTS 549
Cdd:cd00821      6 LKRGGGGLKSWKKRWFVLFEGVLLYYKSKK----DSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTPDGRTYYLQADS 81

                           90
                   ....*....|.
gi 1958665702  550 QTELENWITAI 560
Cdd:cd00821     82 EEERQEWLKAL 92
PH_beta_spectrin cd10571
Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a ...
 468-563 1.35e-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: 1.35e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  468 KNKKvesATRRKWKHYWVSLKGCTLFFYEsDGRsgiDHNSVPKHAVWVENSIVQAVPE----HPKKDFVFCLSNSLGDAF 543
Cdd:cd10571     14 GGKK---ASNRSWKNVYTVLRGQELSFYK-DQK---AAKSGITYAAEPPLNLYNAVCEvasdYTKKKHVFRLKLSDGAEF 86

                           90       100
                   ....*....|....*....|
gi 1958665702  544 LFQTTSQTELENWITAIHSA 563
Cdd:cd10571     87 LFQAKDEEEMNQWVKKISFA 106
PH_ARHGAP21-like cd01253
ARHGAP21 and related proteins pleckstrin homology (PH) domain; ARHGAP family genes encode Rho ...
 453-562 1.80e-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: 53.91  E-value: 1.80e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  453 RKAGALAVKNFLVHKKNKkvesATRRKWKHYWVSLKGCTLFFYeSDGRSGIDHNSVPKHA---VWVENSIVQAVPEHPKK 529
Cdd:cd01253      1 AREGWLHYKQIVTDKGKR----VSDRSWKQAWAVLRGHSLYLY-KDKREQTPALSIELGSeqrISIRGCIVDIAYSYTKR 75

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1958665702  530 DFVFCLSNSLGDAFLFQTTSQTELENWITAIHS 562
Cdd:cd01253     76 KHVFRLTTSDFSEYLFQAEDRDDMLGWIKAIQE 108
PH_9 pfam15410
Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.
 477-565 1.48e-07

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


Pssm-ID: 434701  Cd Length: 118  Bit Score: 51.66  E-value: 1.48e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  477 RRKWKHYWVSLKGCTLFFYESDGRS--------GIDHNSvPKHAVWVENSIVQAVPEHPKKDFVFCLSNSLGDAFLFQTT 548
Cdd:pfam15410   23 KRSWKMVYAVLKDLVLYLYKDEHPPessqfedkKSLKNA-PVGKIRLHHALATPAPDYTKKSHVFRLQTADGAEYLFQTG 101

                           90
                   ....*....|....*..
gi 1958665702  549 SQTELENWITAIHSACA 565
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 ...
 860-919 3.14e-06

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: 46.60  E-value: 3.14e-06
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702   860 VTQNIHIEKSDAaadNYGFLLSSVDEDGvRRLYVNSVKETGLASKKGLKAGDEILQINNR 919
Cdd:smart00228    1 EPRLVELEKGGG---GLGFSLVGGKDEG-GGVVVSSVVPGSPAAKAGLRVGDVILEVNGT 56
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 465-562 1.46e-05

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: 45.31  E-value: 1.46e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  465 VHKKNKKvesatRRKWKHYWVSLKGCTLFFY----ESDGRSGIDHNSVpkHAVwvensivqAVPEHPKKDFVFCL-SNSl 539
Cdd:cd13298     12 LLKRSRK-----TKNWKKRWVVLRPCQLSYYkdekEYKLRRVINLSEL--LAV--------APLKDKKRKNVFGIyTPS- 75

                           90       100
                   ....*....|....*....|...
gi 1958665702  540 gDAFLFQTTSQTELENWITAIHS 562
Cdd:cd13298     76 -KNLHFRATSEKDANEWVEALRE 97
PDZ pfam00595
PDZ domain; PDZ domains are found in diverse signaling proteins.
 877-919 1.60e-05

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


Pssm-ID: 395476 [Multi-domain]  Cd Length: 81  Bit Score: 44.58  E-value: 1.60e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1958665702  877 GFLLSSVDEDGVRRLYVNSVKETGLASKKGLKAGDEILQINNR 919
Cdd:pfam00595   13 GFSLKGGSDQGDPGIFVSEVLPGGAAEAGGLKVGDRILSINGQ 55
cpPDZ2_DegP-like cd23084
circularly permuted second PDZ domain (PDZ2) of Escherichia coli periplasmic serine ...
 873-920 2.30e-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: 44.16  E-value: 2.30e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1958665702  873 ADNYGFLLSSV-DEDGVRRLYVNSVKETGLASKKGLKAGDEILQINNRA 920
Cdd:cd23084      1 LALEGATVSNVtDEDGGKGVVVTEVDPGSPAAQSGLKKGDVIIGVNRQP 49
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 1051-1284 3.60e-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: 3.60e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1051 RQLSDADKLRK-VICELLETERTYVKDLNCLMERYLKPLQKETFLTQDE----LDVLFGNLTEMVEFQVEFLKTLEDGVR 1125
Cdd:COG5422    476 ESLPKQEIKRQeAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENArrnfIKHVFANINEIYAVNSKLLKALTNRQC 555

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1126 LVPdleklekvdqfkkVLFSLGGSFLYYADRFKLYSAFCASHTKVPKVLVKAKTDTAFKAFLDAQNPRQQHSSTLE--SY 1203
Cdd:COG5422    556 LSP-------------IVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLEldGY 622

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1204 LIKPIQRVLKYPLLLRELFALTDAESEEHYHLDVAIKTMNKVASHINEMQKIHEEFGAVFdqLIAEQTGEKKEVADLSMG 1283
Cdd:COG5422    623 LTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLF--HLNQQLLFKPEYVNLGLN 700


                   .
gi 1958665702 1284 D 1284
Cdd:COG5422    701 D 701
PDZ2_ZO1-like_ds cd06728
PDZ domain 2 of Zonula Occludens-1 (ZO-1), ZO-2 and ZO-3, and related domains; form ...
 874-924 4.05e-05

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: 43.37  E-value: 4.05e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1958665702  874 DNYGFLLSSvdedgvrRLYVNSVKETGLASK-KGLKAGDEILQINNRAAGTL 924
Cdd:cd06728     12 DEYGLRLGS-------RIFVKEITPDSLAAKdGNLQEGDIILKINGTPVENL 56
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
 463-574 9.12e-05

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: 43.13  E-value: 9.12e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  463 FLVHKKNKkvesatRRKWKHYWVSLKGCTLFFYESDgrsgidHNSVPKHAVWVENS-IVQAVPEHPKKDFVFCLSNSLGD 541
Cdd:cd13301      8 YLVKKGHV------VNNWKARWFVLKEDGLEYYKKK------TDSSPKGMIPLKGCtITSPCLEYGKRPLVFKLTTAKGQ 75

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1958665702  542 AFLFQTTSQTELENWITAIHSACAAAVARHHHK 574
Cdd:cd13301     76 EHFFQACSREERDAWAKDITKAITCLEGGKRFA 108
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
 468-563 1.86e-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: 42.40  E-value: 1.86e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  468 KNKKVESATRRKWKHYWVSLKGCTLFFYESDGRSGID-HNSVPkhavwvENSIVQAvpEHPKKDFVFCLSNSLGDAFLFQ 546
Cdd:cd01260     21 KKKEAKSFFGQKWKKYWFVLKGSSLYWYSNQQDEKAEgFINLP------DFKIERA--SECKKKYAFKACHPKIKTFYFA 92

                           90
                   ....*....|....*..
gi 1958665702  547 TTSQTELENWITAIHSA 563
Cdd:cd01260     93 AENLDDMNKWLSKLNMA 109
PDZ_NHERF-like cd06768
PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related ...
 865-917 1.99e-04

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: 41.27  E-value: 1.99e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1958665702  865 HIEKSDaaaDNYGFLLSSvdEDGVRRLYVNSVKETGLASKKGLKAGDEILQIN 917
Cdd:cd06768      4 HLVKGP---EGYGFNLHA--EKGRPGHFIREVDPGSPAERAGLKDGDRLVEVN 51
PDZ_2 pfam13180
PDZ domain;
882-924 5.42e-04

PDZ domain;


Pssm-ID: 433015 [Multi-domain]  Cd Length: 74  Bit Score: 39.95  E-value: 5.42e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1958665702  882 SVDEDGVrrlYVNSVKETGLASKKGLKAGDEILQINNRAAGTL 924
Cdd:pfam13180    2 VDLEGGV---VVVSVKSSGPAAKAGLKAGDVILSIDGRKINDL 41
PH_RhoGAP2 cd13378
Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 ...
 471-560 5.43e-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: 41.47  E-value: 5.43e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  471 KVESATRRKWKHYWVSLKGCTLFFYESDgrsgidHNSVPKHAVWVENSIVQAV---PEHPKKDFVFCLSNSLGD------ 541
Cdd:cd13378     10 KKQRSIMKNWQQRWFVLRGDQLFYYKDE------EETKPQGCISLQGSQVNELppnPEEPGKHLFEILPGGAGDrekvpm 83

                           90       100
                   ....*....|....*....|..
gi 1958665702  542 ---AFLFQTTSQTELENWITAI 560
Cdd:cd13378     84 nheAFLLMANSQSDMEDWVKAI 105
PDZ_ARHGEF11-12-like cd23069
PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density ...
 874-928 5.84e-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: 40.07  E-value: 5.84e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1958665702  874 DNYGFLLSsvdedGVRRLYVNSVKETGLASKKGLKAGDEILQINnraaGTLNSSM 928
Cdd:cd23069     11 NGYGLTVS-----GDNPVFVQSVKEGGAAYRAGVQEGDRIIKVN----GTLVTHS 56
PH_PLEKHJ1 cd13258
Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; ...
 470-563 6.82e-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: 41.16  E-value: 6.82e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  470 KKVESATRRkwkhyWVSLKGCTLFFYESDGRSgidHNSVPKHAVWVENSIVQAVPEHPKKdFVFCLSNS--LGDAFLFQT 547
Cdd:cd13258     31 KKSEVFKER-----WFKLKGNLLFYFRTNEFG---DCSEPIGAIVLENCRVQMEEITEKP-FAFSIVFNdePEKKYIFSC 101

                           90
                   ....*....|....*.
gi 1958665702  548 TSQTELENWITAIHSA 563
Cdd:cd13258    102 RSEEQCEQWIEALRQA 117
PH_RalGPS1_2 cd13310
Ral GEF with PH domain and SH3 binding motif 1 and 2 Pleckstrin homology (PH) domain; RalGPS1 ...
 480-565 1.01e-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: 1.01e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  480 WKHYWVSLKGCTLFFYESDGRSGIDHN---SVPKHAVWVENSIVqAVPEHPKKDFVFCLSNS-LGDAFLFQTTSQTELEN 555
Cdd:cd13310     23 WQRYWVQLWGTSLVYYAPKSLKGTERSdfkSEPCKIVSISGWMV-VLGDDPEHPDSFQLTDPeKGNVYKFRAGSRSNALL 101

                           90
                   ....*....|
gi 1958665702  556 WITAIHSACA 565
Cdd:cd13310    102 WLKHLKDACK 111
PH_ARHGAP9-like cd13233
Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like ...
 469-563 1.04e-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: 40.34  E-value: 1.04e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  469 NKKVesatRRKWKHYWVSLKGCTLFFYEsDGRSGIDHN---SVPKHAVWVENSIVQAVPEHPKKDFVFCLSNSLGDAFLF 545
Cdd:cd13233     15 GKKL----RKNWSTSWVVLTSSHLLFYK-DAKSAAKSGnpySKPESSVDLRGASIEWAKEKSSRKNVFQISTVTGTEFLL 89

                           90
                   ....*....|....*...
gi 1958665702  546 QTTSQTELENWITAIHSA 563
Cdd:cd13233     90 QSDNDTEIREWFDAIKAV 107
PDZ3_DLG5-like cd06767
PDZ domain 3 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density ...
 861-921 1.13e-03

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: 39.23  E-value: 1.13e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958665702  861 TQNIHIEKSDaaaDNYGFLLSSVDEDGVrrlYVNSVKETGLASKKGLKAGDEILQ---INNRAA 921
Cdd:cd06767      3 PRHVSIEKGS---EPLGISIVSGENGGI---FVSSVTEGSLAHQAGLEYGDQLLEvngINLRNA 60
PDZ7_GRIP1-2-like cd06685
PDZ domain 7 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 870-918 1.24e-03

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: 39.55  E-value: 1.24e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1958665702  870 DAAADNYGFLLSS-VDEDGVrrlYVNSVKETGLASKKGLKAGDEILQINN 918
Cdd:cd06685     11 DSDTEDFGFSVSDgLYEKGV---YVNAIRPGGPADLSGLQPYDRILQVNH 57
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
 449-560 1.62e-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: 1.62e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  449 QGTVRKAGALavknflvHKKNKKvesatRRKWKHYWVSLKGCTLFFYESDG-----RSGIDHNSVPKhavwvensiVQAV 523
Cdd:cd13215     18 SGAVIKSGYL-------SKRSKR-----TLRYTRYWFVLKGDTLSWYNSSTdlyfpAGTIDLRYATS---------IELS 76

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1958665702  524 PEHPKKDFVFCLSNSlGDAFLFQTTSQTELENWITAI 560
Cdd:cd13215     77 KSNGEATTSFKIVTN-SRTYKFKADSETSADEWVKAL 112
PDZ_canonical cd00136
canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs ...
 864-919 3.56e-03

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: 37.91  E-value: 3.56e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958665702  864 IHIEKSDAAAdnYGFLLSSvDEDGVRRLYVNSVKETGLASKKG-LKAGDEILQINNR 919
Cdd:cd00136      2 VTLEKDPGGG--LGFSIRG-GKDGGGGIFVSRVEPGGPAARDGrLRVGDRILEVNGV 55
PDZ_6 pfam17820
PDZ domain; This entry represents the PDZ domain from a wide variety of proteins.
 892-925 4.35e-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: 36.74  E-value: 4.35e-03
                           10        20        30
                   ....*....|....*....|....*....|....
gi 1958665702  892 YVNSVKETGLASKKGLKAGDEILQINNRAAGTLN 925
Cdd:pfam17820    1 VVTAVVPGSPAERAGLRVGDVILAVNGKPVRSLE 34
PDZ3_ZO1-like_domain cd06729
PDZ domain 3 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ ...
 892-918 5.57e-03

PDZ domain 3 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 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 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: 467211 [Multi-domain]  Cd Length: 82  Bit Score: 37.55  E-value: 5.57e-03
                           10        20
                   ....*....|....*....|....*..
gi 1958665702  892 YVNSVKETGLASKKGLKAGDEILQINN 918
Cdd:cd06729     26 FVAGVQEGSPAEKQGLQEGDQILKVNG 52
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 469-588 6.57e-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: 38.37  E-value: 6.57e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702  469 NKKVESAT---RRkwkhyWVSLKGCTLFFYESDGrsgiDHNsvPKHAVWVENSIVQAVPEHPKKDFVFCLSNSLGDAFLF 545
Cdd:cd13288     15 WKKGERNTsyqKR-----WFVLKGNLLFYFEKKG----DRE--PLGVIVLEGCTVELAEDAEPYAFAIRFDGPGARSYVL 83

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1958665702  546 QTTSQTELENWITAIhsACAAavarHHHKEDTLRLLKSEIKKL 588
Cdd:cd13288     84 AAENQEDMESWMKAL--SRAS----YDYLRLTVEELEKQLEEL 120
PDZ_ZASP52-like cd23068
PDZ domain of Drosophila melanogaster PDZ and LIM domain protein Zasp52 (also known as Zasp), ...
 891-921 7.54e-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: 37.12  E-value: 7.54e-03
                           10        20        30
                   ....*....|....*....|....*....|.
gi 1958665702  891 LYVNSVKETGLASKKGLKAGDEILQINNRAA 921
Cdd:cd23068     27 LSIQKVNPGSPADKAGLRRGDVILRINGTDT 57
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1301-1413 9.70e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 37.54  E-value: 9.70e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958665702 1301 GKWKKepelAAFVFKTAVVLVYKDGSKQKKKlvgshrlsiyeewdpfRFRHMIPTEALQVRALPSADAEANAVC-EIVHv 1379
Cdd:pfam00169   16 KSWKK----RYFVLFDGSLLYYKDDKSGKSK----------------EPKGSISLSGCEVVEVVASDSPKRKFCfELRT- 74

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1958665702 1380 kseSEGRPERVFHLCCSSPESRKDFLKSVHSILR 1413
Cdd:pfam00169   75 ---GERTGKRTYLLQAESEEERKDWIKAIQSAIR 105
 
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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