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Conserved domains on  [gi|45552947|ref|NP_996000|]
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still life, isoform C [Drosophila melanogaster]

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; ...
 1620-1793 1.37e-96

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: 308.54  E-value: 1.37e-96
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1620 QRIHEEYGAIFDHLFRQHQKSCKQPIDLSPGDLLYYGGVEWLNISDFLGKIKKglELHAMCFVFKSAVVFLCKERLRQKK 1699
Cdd:cd01255    1 QKIHEEYGAVFDQLIREQSGTKKEVADLSMGDLLLYGTVEWLNPPSSLGKVKK--EPELAVFVFKTAVVLVCKERSKQKK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1700 KLMGVSSKNATNEVEIIRYQVLIPVTEVQVRASSAKDMDSHFLWELIHLRSQLQRRSEKVYVLSNSTADFRNAFLKTIRQ 1779
Cdd:cd01255   79 KLMGSHRKSSYEERDPFRFRHLIPVSALQVRNSNTADTESRCLWELIHTKSELEGRPEKVFQLCCSTPEFKNAFLKVIRS 158

                        170
                 ....*....|....
gi 45552947 1780 IIRESVRNMSIPMK 1793
Cdd:cd01255  159 ILREKVRRQSSKTE 172
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
 821-946 6.52e-79

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: 256.23  E-value: 6.52e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947  821 GAVRKAGFLSVKKWLLRKKH-QIELARKRGWKGYWVCLKGTTLLFYPCDSREGRSVEAAPKHLIIVDGAIMQPIPEHPKR 899
Cdd:cd01230    1 GAVRKAGWLSVKNFLVHKKNkKVELATRRKWKKYWVCLKGCTLLFYECDERSGIDENSEPKHALFVEGSIVQAVPEHPKK 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 45552947  900 DYIFCLSTAFGDAYLFQAPCQVELENWVNSIHSACAAAFARHRGKTG 946
Cdd:cd01230   81 DFVFCLSNSFGDAYLFQATSQTELENWVTAIHSACASAFARQHGKED 127
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 1426-1617 3.16e-55

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: 190.59  E-value: 3.16e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1426 LRKVVMELVDTERTYVKHLNNLLEHYLEPM-KRETFLSNAEINALFGNIHEIVTFQRQFLQNLEESLDLEPDFnkfehcg 1504
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLdKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKS------- 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1505 qfrnvLFAIGSAFLYYVNHFKLYSSFCASHSKAQKVL-HPNEGNHALQEFLAARNpKQQHSSTLESYLIKPIQRILKYPL 1583
Cdd:cd00160   74 -----GPRIGDVFLKLAPFFKIYSEYCSNHPDALELLkKLKKFNKFFQEFLEKAE-SECGRLKLESLLLKPVQRLTKYPL 147

                        170       180       190
                 ....*....|....*....|....*....|....
gi 45552947 1584 LLQQMRNLTDTRADEHVHLCEALKGMEKVAEHIN 1617
Cdd:cd00160  148 LLKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181
RBD smart00455
Raf-like Ras-binding domain;
1102-1168 8.74e-20

Raf-like Ras-binding domain;


:

Pssm-ID: 128731  Cd Length: 70  Bit Score: 85.03  E-value: 8.74e-20
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    1102 TFKVAMPDNAYSTVYLRDAMSVEEFLASACARRNLNPMEHFVR---VKKRRDMEDHNYFVPHRNDLIENY 1168
Cdd:smart00455    1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRlrgEKKPLDLNQPISSLDGQELVVEEL 70
Tiam_CC_Ex super family cl39723
T-lymphoma invasion and metastasis CC-Ex domain; This is the CC and Ex subdomains found in ...
 960-1057 1.75e-12

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: 65.16  E-value: 1.75e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    960 KAIESDHKLKHMAELQQSVVTDQETRHQIQTQILQWEENLERLHCEQFRLRCYMASLQSGELPNPKSLLTHVSRPTKNTL 1039
Cdd:pfam18385    1 QKIDMDEKMKKMGEMQLSSVTDAKKKKTILDQVFLWGENTEQERLSLFLFAQYLAECQGAELPCPTYMLIYASETDKLAS 80

                           90
                   ....*....|....*...
gi 45552947   1040 NKLGVFTVSSFHAFICAR 1057
Cdd:pfam18385   81 GTLGVARVGTYQSQVAAR 98
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
 1181-1260 5.81e-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: 46.22  E-value: 5.81e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    1181 ILYQVELQRTTLEqmWGFSVEAElienaeRQDELCCYVSRVEDKSVAMHNGIIKGDEIMVINGAIVSDLDMMYLESVLQE 1260
Cdd:smart00228    1 EPRLVELEKGGGG--LGFSLVGG------KDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKK 72
 
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; ...
 1620-1793 1.37e-96

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: 308.54  E-value: 1.37e-96
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1620 QRIHEEYGAIFDHLFRQHQKSCKQPIDLSPGDLLYYGGVEWLNISDFLGKIKKglELHAMCFVFKSAVVFLCKERLRQKK 1699
Cdd:cd01255    1 QKIHEEYGAVFDQLIREQSGTKKEVADLSMGDLLLYGTVEWLNPPSSLGKVKK--EPELAVFVFKTAVVLVCKERSKQKK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1700 KLMGVSSKNATNEVEIIRYQVLIPVTEVQVRASSAKDMDSHFLWELIHLRSQLQRRSEKVYVLSNSTADFRNAFLKTIRQ 1779
Cdd:cd01255   79 KLMGSHRKSSYEERDPFRFRHLIPVSALQVRNSNTADTESRCLWELIHTKSELEGRPEKVFQLCCSTPEFKNAFLKVIRS 158

                        170
                 ....*....|....
gi 45552947 1780 IIRESVRNMSIPMK 1793
Cdd:cd01255  159 ILREKVRRQSSKTE 172
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
 821-946 6.52e-79

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: 256.23  E-value: 6.52e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947  821 GAVRKAGFLSVKKWLLRKKH-QIELARKRGWKGYWVCLKGTTLLFYPCDSREGRSVEAAPKHLIIVDGAIMQPIPEHPKR 899
Cdd:cd01230    1 GAVRKAGWLSVKNFLVHKKNkKVELATRRKWKKYWVCLKGCTLLFYECDERSGIDENSEPKHALFVEGSIVQAVPEHPKK 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 45552947  900 DYIFCLSTAFGDAYLFQAPCQVELENWVNSIHSACAAAFARHRGKTG 946
Cdd:cd01230   81 DFVFCLSNSFGDAYLFQATSQTELENWVTAIHSACASAFARQHGKED 127
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 1426-1617 3.16e-55

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: 190.59  E-value: 3.16e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1426 LRKVVMELVDTERTYVKHLNNLLEHYLEPM-KRETFLSNAEINALFGNIHEIVTFQRQFLQNLEESLDLEPDFnkfehcg 1504
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLdKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKS------- 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1505 qfrnvLFAIGSAFLYYVNHFKLYSSFCASHSKAQKVL-HPNEGNHALQEFLAARNpKQQHSSTLESYLIKPIQRILKYPL 1583
Cdd:cd00160   74 -----GPRIGDVFLKLAPFFKIYSEYCSNHPDALELLkKLKKFNKFFQEFLEKAE-SECGRLKLESLLLKPVQRLTKYPL 147

                        170       180       190
                 ....*....|....*....|....*....|....
gi 45552947 1584 LLQQMRNLTDTRADEHVHLCEALKGMEKVAEHIN 1617
Cdd:cd00160  148 LLKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 1429-1618 2.65e-53

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: 185.20  E-value: 2.65e-53
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    1429 VVMELVDTERTYVKHLNNLLEHYLEPM-KRETFLSNAEINALFGNIHEIVTFQRQFLQNLEESLDLEPDFNKFehcgqfr 1507
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLkKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSVER------- 73

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    1508 nvlfaIGSAFLYYVNHFKLYSSFCASHSKAQKVLHPNEGNHALQEFLAARNPKQQHSS-TLESYLIKPIQRILKYPLLLQ 1586
Cdd:smart00325   74 -----IGDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRlTLESLLLKPVQRLTKYPLLLK 148

                           170       180       190
                    ....*....|....*....|....*....|..
gi 45552947    1587 QMRNLTDTRADEHVHLCEALKGMEKVAEHINE 1618
Cdd:smart00325  149 ELLKHTPEDHEDREDLKKALKAIKELANQVNE 180
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 1429-1617 1.81e-45

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: 162.47  E-value: 1.81e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947   1429 VVMELVDTERTYVKHLNNLLEHYLEPMKRETFLSNAEINALFGNIHEIVTFQRQFLqnleesldlepdfnkFEHCGQFRN 1508
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL---------------LEELLKEWI 65

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947   1509 VLFAIGSAFLYYVNHFKLYSSFCASHSKAQKVL-HPNEGNHALQEFLAARNPKQQHSS-TLESYLIKPIQRILKYPLLLQ 1586
Cdd:pfam00621   66 SIQRIGDIFLKFAPGFKVYSTYCSNYPKALKLLkKLLKKNPKFRAFLEELEANPECRGlDLNSFLIKPVQRIPRYPLLLK 145

                          170       180       190
                   ....*....|....*....|....*....|.
gi 45552947   1587 QMRNLTDTRADEHVHLCEALKGMEKVAEHIN 1617
Cdd:pfam00621  146 ELLKHTPPDHPDYEDLKKALEAIKEVAKQIN 176
RBD smart00455
Raf-like Ras-binding domain;
1102-1168 8.74e-20

Raf-like Ras-binding domain;


Pssm-ID: 128731  Cd Length: 70  Bit Score: 85.03  E-value: 8.74e-20
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    1102 TFKVAMPDNAYSTVYLRDAMSVEEFLASACARRNLNPMEHFVR---VKKRRDMEDHNYFVPHRNDLIENY 1168
Cdd:smart00455    1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRlrgEKKPLDLNQPISSLDGQELVVEEL 70
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 823-935 3.54e-15

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: 72.97  E-value: 3.54e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947     823 VRKAGFLSVKKWllrkkhqielARKRGWKGYWVCLKGTTLLFYPCDSREGRSveaAPKHLIIVDGAIMQPIPE--HPKRD 900
Cdd:smart00233    1 VIKEGWLYKKSG----------GGKKSWKKRYFVLFNSTLLYYKSKKDKKSY---KPKGSIDLSGCTVREAPDpdSSKKP 67

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 45552947     901 YIFCLSTAFGDAYLFQAPCQVELENWVNSIHSACA 935
Cdd:smart00233   68 HCFEIKTSDRKTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 834-935 5.97e-15

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 72.60  E-value: 5.97e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    834 WLLRKKHQielaRKRGWKGYWVCLKGTTLLFYpcdSREGRSVEAAPKHLIIVDGAIMQPI--PEHPKRDYIFCLSTA--- 908
Cdd:pfam00169    6 WLLKKGGG----KKKSWKKRYFVLFDGSLLYY---KDDKSGKSKEPKGSISLSGCEVVEVvaSDSPKRKFCFELRTGert 78

                           90       100
                   ....*....|....*....|....*..
gi 45552947    909 FGDAYLFQAPCQVELENWVNSIHSACA 935
Cdd:pfam00169   79 GKRTYLLQAESEEERKDWIKAIQSAIR 105
Tiam_CC_Ex pfam18385
T-lymphoma invasion and metastasis CC-Ex domain; This is the CC and Ex subdomains found in ...
 960-1057 1.75e-12

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: 65.16  E-value: 1.75e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    960 KAIESDHKLKHMAELQQSVVTDQETRHQIQTQILQWEENLERLHCEQFRLRCYMASLQSGELPNPKSLLTHVSRPTKNTL 1039
Cdd:pfam18385    1 QKIDMDEKMKKMGEMQLSSVTDAKKKKTILDQVFLWGENTEQERLSLFLFAQYLAECQGAELPCPTYMLIYASETDKLAS 80

                           90
                   ....*....|....*...
gi 45552947   1040 NKLGVFTVSSFHAFICAR 1057
Cdd:pfam18385   81 GTLGVARVGTYQSQVAAR 98
RBD pfam02196
Raf-like Ras-binding domain;
1102-1178 3.25e-12

Raf-like Ras-binding domain;


Pssm-ID: 460485  Cd Length: 69  Bit Score: 63.31  E-value: 3.25e-12
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 45552947   1102 TFKVAMPDNAYSTVYLRDAMSVEEFLASACARRNLNPMEHFVRVKKRrdmedHNYFVPHRNDLIenYLHNHEfVEVC 1178
Cdd:pfam02196    1 LCRVYLPDGQRTVVQVRPGETVRDALSKLCKKRGLNPEACDVYLVGG-----DKYPLDLDTDSS--TLEGEE-VRVE 69
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
 1181-1260 5.81e-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: 46.22  E-value: 5.81e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    1181 ILYQVELQRTTLEqmWGFSVEAElienaeRQDELCCYVSRVEDKSVAMHNGIIKGDEIMVINGAIVSDLDMMYLESVLQE 1260
Cdd:smart00228    1 EPRLVELEKGGGG--LGFSLVGG------KDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKK 72
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 1416-1642 2.19e-04

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 46.42  E-value: 2.19e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1416 PSRQLtdaeKLRKVVMELVDTERTYVKHLNNLLEHYLEPM---------KRETFlsnaeINALFGNIHEIVTFQRQFLQN 1486
Cdd:COG5422  479 PKQEI----KRQEAIYEVIYTERDFVKDLEYLRDTWIKPLeesniipenARRNF-----IKHVFANINEIYAVNSKLLKA 549

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1487 LEESLDLEPdfnkfehcgqfrnVLFAIGSAFLYYVNHFKLYSSFCASH------SKAQKVLHPNEGNHAlQEFLAARNPk 1560
Cdd:COG5422  550 LTNRQCLSP-------------IVNGIADIFLDYVPKFEPFIKYGASQpyakyeFEREKSVNPNFARFD-HEVERLDES- 614

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1561 QQHSstLESYLIKPIQRILKYPLLLQQMRNLTDTRADEhvhlceaLKGMEKVAEHINE-MQRIHEEYGAI---FDHLFRQ 1636
Cdd:COG5422  615 RKLE--LDGYLTKPTTRLARYPLLLEEVLKFTDPDNPD-------TEDIPKVIDMLREfLSRLNFESGKAenrGDLFHLN 685


                 ....*.
gi 45552947 1637 HQKSCK 1642
Cdd:COG5422  686 QQLLFK 691
PDZ_canonical cd00136
canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs ...
 1185-1269 3.09e-04

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: 41.37  E-value: 3.09e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1185 VELQRTTLEQmWGFSVEAElienaeRQDELCCYVSRVEDKSVAMHNGIIK-GDEIMVINGAIVSDLDMMYLESVLQE-EQ 1262
Cdd:cd00136    2 VTLEKDPGGG-LGFSIRGG------KDGGGGIFVSRVEPGGPAARDGRLRvGDRILEVNGVSLEGLTHEEAVELLKSaGG 74


                 ....*..
gi 45552947 1263 SLSMMMR 1269
Cdd:cd00136   75 EVTLTVR 81
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1663-1782 5.87e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 38.31  E-value: 5.87e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947   1663 ISDFLGKIKKGLE--LHAMCFVFKSAVVFLCKERLRQKKKlmgvssknatneveiiRYQVLIPVTEVQVRASSAKDMDSH 1740
Cdd:pfam00169    3 KEGWLLKKGGGKKksWKKRYFVLFDGSLLYYKDDKSGKSK----------------EPKGSISLSGCEVVEVVASDSPKR 66

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 45552947   1741 -FLWELIHLrsqlQRRSEKVYVLSNSTADFRNAFLKTIRQIIR 1782
Cdd:pfam00169   67 kFCFELRTG----ERTGKRTYLLQAESEEERKDWIKAIQSAIR 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; ...
 1620-1793 1.37e-96

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: 308.54  E-value: 1.37e-96
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1620 QRIHEEYGAIFDHLFRQHQKSCKQPIDLSPGDLLYYGGVEWLNISDFLGKIKKglELHAMCFVFKSAVVFLCKERLRQKK 1699
Cdd:cd01255    1 QKIHEEYGAVFDQLIREQSGTKKEVADLSMGDLLLYGTVEWLNPPSSLGKVKK--EPELAVFVFKTAVVLVCKERSKQKK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1700 KLMGVSSKNATNEVEIIRYQVLIPVTEVQVRASSAKDMDSHFLWELIHLRSQLQRRSEKVYVLSNSTADFRNAFLKTIRQ 1779
Cdd:cd01255   79 KLMGSHRKSSYEERDPFRFRHLIPVSALQVRNSNTADTESRCLWELIHTKSELEGRPEKVFQLCCSTPEFKNAFLKVIRS 158

                        170
                 ....*....|....
gi 45552947 1780 IIRESVRNMSIPMK 1793
Cdd:cd01255  159 ILREKVRRQSSKTE 172
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
 821-946 6.52e-79

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: 256.23  E-value: 6.52e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947  821 GAVRKAGFLSVKKWLLRKKH-QIELARKRGWKGYWVCLKGTTLLFYPCDSREGRSVEAAPKHLIIVDGAIMQPIPEHPKR 899
Cdd:cd01230    1 GAVRKAGWLSVKNFLVHKKNkKVELATRRKWKKYWVCLKGCTLLFYECDERSGIDENSEPKHALFVEGSIVQAVPEHPKK 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 45552947  900 DYIFCLSTAFGDAYLFQAPCQVELENWVNSIHSACAAAFARHRGKTG 946
Cdd:cd01230   81 DFVFCLSNSFGDAYLFQATSQTELENWVTAIHSACASAFARQHGKED 127
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 1426-1617 3.16e-55

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: 190.59  E-value: 3.16e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1426 LRKVVMELVDTERTYVKHLNNLLEHYLEPM-KRETFLSNAEINALFGNIHEIVTFQRQFLQNLEESLDLEPDFnkfehcg 1504
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLdKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKS------- 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1505 qfrnvLFAIGSAFLYYVNHFKLYSSFCASHSKAQKVL-HPNEGNHALQEFLAARNpKQQHSSTLESYLIKPIQRILKYPL 1583
Cdd:cd00160   74 -----GPRIGDVFLKLAPFFKIYSEYCSNHPDALELLkKLKKFNKFFQEFLEKAE-SECGRLKLESLLLKPVQRLTKYPL 147

                        170       180       190
                 ....*....|....*....|....*....|....
gi 45552947 1584 LLQQMRNLTDTRADEHVHLCEALKGMEKVAEHIN 1617
Cdd:cd00160  148 LLKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 1429-1618 2.65e-53

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: 185.20  E-value: 2.65e-53
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    1429 VVMELVDTERTYVKHLNNLLEHYLEPM-KRETFLSNAEINALFGNIHEIVTFQRQFLQNLEESLDLEPDFNKFehcgqfr 1507
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLkKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSVER------- 73

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    1508 nvlfaIGSAFLYYVNHFKLYSSFCASHSKAQKVLHPNEGNHALQEFLAARNPKQQHSS-TLESYLIKPIQRILKYPLLLQ 1586
Cdd:smart00325   74 -----IGDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRlTLESLLLKPVQRLTKYPLLLK 148

                           170       180       190
                    ....*....|....*....|....*....|..
gi 45552947    1587 QMRNLTDTRADEHVHLCEALKGMEKVAEHINE 1618
Cdd:smart00325  149 ELLKHTPEDHEDREDLKKALKAIKELANQVNE 180
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 1429-1617 1.81e-45

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: 162.47  E-value: 1.81e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947   1429 VVMELVDTERTYVKHLNNLLEHYLEPMKRETFLSNAEINALFGNIHEIVTFQRQFLqnleesldlepdfnkFEHCGQFRN 1508
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL---------------LEELLKEWI 65

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947   1509 VLFAIGSAFLYYVNHFKLYSSFCASHSKAQKVL-HPNEGNHALQEFLAARNPKQQHSS-TLESYLIKPIQRILKYPLLLQ 1586
Cdd:pfam00621   66 SIQRIGDIFLKFAPGFKVYSTYCSNYPKALKLLkKLLKKNPKFRAFLEELEANPECRGlDLNSFLIKPVQRIPRYPLLLK 145

                          170       180       190
                   ....*....|....*....|....*....|.
gi 45552947   1587 QMRNLTDTRADEHVHLCEALKGMEKVAEHIN 1617
Cdd:pfam00621  146 ELLKHTPPDHPDYEDLKKALEAIKEVAKQIN 176
RBD smart00455
Raf-like Ras-binding domain;
1102-1168 8.74e-20

Raf-like Ras-binding domain;


Pssm-ID: 128731  Cd Length: 70  Bit Score: 85.03  E-value: 8.74e-20
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    1102 TFKVAMPDNAYSTVYLRDAMSVEEFLASACARRNLNPMEHFVR---VKKRRDMEDHNYFVPHRNDLIENY 1168
Cdd:smart00455    1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRlrgEKKPLDLNQPISSLDGQELVVEEL 70
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 823-935 3.54e-15

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: 72.97  E-value: 3.54e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947     823 VRKAGFLSVKKWllrkkhqielARKRGWKGYWVCLKGTTLLFYPCDSREGRSveaAPKHLIIVDGAIMQPIPE--HPKRD 900
Cdd:smart00233    1 VIKEGWLYKKSG----------GGKKSWKKRYFVLFNSTLLYYKSKKDKKSY---KPKGSIDLSGCTVREAPDpdSSKKP 67

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 45552947     901 YIFCLSTAFGDAYLFQAPCQVELENWVNSIHSACA 935
Cdd:smart00233   68 HCFEIKTSDRKTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 834-935 5.97e-15

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 72.60  E-value: 5.97e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    834 WLLRKKHQielaRKRGWKGYWVCLKGTTLLFYpcdSREGRSVEAAPKHLIIVDGAIMQPI--PEHPKRDYIFCLSTA--- 908
Cdd:pfam00169    6 WLLKKGGG----KKKSWKKRYFVLFDGSLLYY---KDDKSGKSKEPKGSISLSGCEVVEVvaSDSPKRKFCFELRTGert 78

                           90       100
                   ....*....|....*....|....*..
gi 45552947    909 FGDAYLFQAPCQVELENWVNSIHSACA 935
Cdd:pfam00169   79 GKRTYLLQAESEEERKDWIKAIQSAIR 105
Tiam_CC_Ex pfam18385
T-lymphoma invasion and metastasis CC-Ex domain; This is the CC and Ex subdomains found in ...
 960-1057 1.75e-12

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: 65.16  E-value: 1.75e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    960 KAIESDHKLKHMAELQQSVVTDQETRHQIQTQILQWEENLERLHCEQFRLRCYMASLQSGELPNPKSLLTHVSRPTKNTL 1039
Cdd:pfam18385    1 QKIDMDEKMKKMGEMQLSSVTDAKKKKTILDQVFLWGENTEQERLSLFLFAQYLAECQGAELPCPTYMLIYASETDKLAS 80

                           90
                   ....*....|....*...
gi 45552947   1040 NKLGVFTVSSFHAFICAR 1057
Cdd:pfam18385   81 GTLGVARVGTYQSQVAAR 98
RBD pfam02196
Raf-like Ras-binding domain;
1102-1178 3.25e-12

Raf-like Ras-binding domain;


Pssm-ID: 460485  Cd Length: 69  Bit Score: 63.31  E-value: 3.25e-12
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 45552947   1102 TFKVAMPDNAYSTVYLRDAMSVEEFLASACARRNLNPMEHFVRVKKRrdmedHNYFVPHRNDLIenYLHNHEfVEVC 1178
Cdd:pfam02196    1 LCRVYLPDGQRTVVQVRPGETVRDALSKLCKKRGLNPEACDVYLVGG-----DKYPLDLDTDSS--TLEGEE-VRVE 69
PH_EFA6 cd13295
Exchange Factor for ARF6 Pleckstrin homology (PH) domain; EFA6 (also called PSD/pleckstrin and ...
 832-936 1.00e-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: 63.89  E-value: 1.00e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947  832 KKWLLRKKHQIELAR-----KRGWKGYWVCLKGTTLLF----YPCdsrEGRSVEAAPKHLIIVDGAIMQPIPEHPKRDYI 902
Cdd:cd13295    9 KGYLMRKCCADPDGKktpfgKRGWKMFYATLKGLVLYLhkdeYGC---KKALRYESLRNAISVHHSLATKATDYTKKPHV 85

                         90       100       110
                 ....*....|....*....|....*....|....
gi 45552947  903 FCLSTAFGDAYLFQAPCQVELENWVNSIHSACAA 936
Cdd:cd13295   86 FRLRTADWREYLFQASDTKEMQSWIEAINLVAAA 119
PH_9 pfam15410
Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.
 825-935 1.85e-11

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


Pssm-ID: 434701  Cd Length: 118  Bit Score: 62.83  E-value: 1.85e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    825 KAGFLsVKKWLLRKKHQIELARKRGWKGYWVCLKGTTLLFY-------PCDSREGRSVEAAPKHLIIVDGAIMQPIPEHP 897
Cdd:pfam15410    2 KKGIV-MRKCCFESKGKKTPRGKRSWKMVYAVLKDLVLYLYkdehppeSSQFEDKKSLKNAPVGKIRLHHALATPAPDYT 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 45552947    898 KRDYIFCLSTAFGDAYLFQAPCQVELENWVNSIHSACA 935
Cdd:pfam15410   81 KKSHVFRLQTADGAEYLFQTGSPKELQEWVDTLNYWAA 118
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
 825-933 3.12e-09

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: 56.23  E-value: 3.12e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947  825 KAGFLsVKKWLLRKKhqielarkrgWKGYWVCLKGTTLLFYpcdsrEGRSvEAAPKHLIIVDGA-IMQPIPEHPKRDYIF 903
Cdd:cd13301    5 KEGYL-VKKGHVVNN----------WKARWFVLKEDGLEYY-----KKKT-DSSPKGMIPLKGCtITSPCLEYGKRPLVF 67

                         90       100       110
                 ....*....|....*....|....*....|
gi 45552947  904 CLSTAFGDAYLFQAPCQVELENWVNSIHSA 933
Cdd:cd13301   68 KLTTAKGQEHFFQACSREERDAWAKDITKA 97
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 825-930 6.51e-09

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: 54.86  E-value: 6.51e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947  825 KAGFLSVKKWLLRKKhqielarkrgWKGYWVCLKGTTLLFYpcdsREGRSVEAAPKHLIIVDGAIMQPIPEHPKRDYIFC 904
Cdd:cd00821    1 KEGYLLKRGGGGLKS----------WKKRWFVLFEGVLLYY----KSKKDSSYKPKGSIPLSGILEVEEVSPKERPHCFE 66

                         90       100
                 ....*....|....*....|....*.
gi 45552947  905 LSTAFGDAYLFQAPCQVELENWVNSI 930
Cdd:cd00821   67 LVTPDGRTYYLQADSEEERQEWLKAL 92
PH_beta_spectrin cd10571
Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a ...
 835-933 1.89e-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: 1.89e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947  835 LLRKkHQIELARKRG----WKGYWVCLKGTTLLFYPcDSREGRSVE----AAPkhlIIVDGAIMQPIPEHPKRDYIFCLS 906
Cdd:cd10571    5 LERK-HEWESGGKKAsnrsWKNVYTVLRGQELSFYK-DQKAAKSGItyaaEPP---LNLYNAVCEVASDYTKKKHVFRLK 79

                         90       100
                 ....*....|....*....|....*..
gi 45552947  907 TAFGDAYLFQAPCQVELENWVNSIHSA 933
Cdd:cd10571   80 LSDGAEFLFQAKDEEEMNQWVKKISFA 106
PH_ARHGAP21-like cd01253
ARHGAP21 and related proteins pleckstrin homology (PH) domain; ARHGAP family genes encode Rho ...
 834-932 4.57e-07

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: 50.45  E-value: 4.57e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947  834 WLLRKKHQIELARK---RGWKGYWVCLKGTTLLFYPcDSRE---GRSVEAAPKHLIIVDGAIMQPIPEHPKRDYIFCLST 907
Cdd:cd01253    5 WLHYKQIVTDKGKRvsdRSWKQAWAVLRGHSLYLYK-DKREqtpALSIELGSEQRISIRGCIVDIAYSYTKRKHVFRLTT 83

                         90       100
                 ....*....|....*....|....*
gi 45552947  908 AFGDAYLFQAPCQVELENWVNSIHS 932
Cdd:cd01253   84 SDFSEYLFQAEDRDDMLGWIKAIQE 108
PH_ARHGAP9-like cd13233
Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like ...
 825-933 3.98e-06

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: 47.66  E-value: 3.98e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947  825 KAGFLSVKKWLLRKKHQielarKRGWKGYWVCLKGTTLLFYpcdsREGRSVEAAPKH----LIIVD--GAIMQPIPEHPK 898
Cdd:cd13233    2 KQGLLNKTKIAENGKKL-----RKNWSTSWVVLTSSHLLFY----KDAKSAAKSGNPyskpESSVDlrGASIEWAKEKSS 72

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 45552947  899 RDYIFCLSTAFGDAYLFQAPCQVELENWVNSIHSA 933
Cdd:cd13233   73 RKNVFQISTVTGTEFLLQSDNDTEIREWFDAIKAV 107
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
 1181-1260 5.81e-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: 46.22  E-value: 5.81e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947    1181 ILYQVELQRTTLEqmWGFSVEAElienaeRQDELCCYVSRVEDKSVAMHNGIIKGDEIMVINGAIVSDLDMMYLESVLQE 1260
Cdd:smart00228    1 EPRLVELEKGGGG--LGFSLVGG------KDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKK 72
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
 834-937 1.38e-04

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


Pssm-ID: 270108  Cd Length: 103  Bit Score: 42.84  E-value: 1.38e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947  834 WLLRKKHQIELARKRGWKGYWVCLKGTTLLFYPCDSrEGrsveAAPKHLIIVdGAIMQPIPEHPKrDYIFCLSTAfGDAY 913
Cdd:cd13296    4 WLTKKGGGSSTLSRRNWKSRWFVLRDTVLKYYENDQ-EG----EKLLGTIDI-RSAKEIVDNDPK-ENRLSITTE-ERTY 75

                         90       100
                 ....*....|....*....|....
gi 45552947  914 LFQAPCQVELENWVNSIHSACAAA 937
Cdd:cd13296   76 HLVAESPEDASQWVNVLTRVISAT 99
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 1416-1642 2.19e-04

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 46.42  E-value: 2.19e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1416 PSRQLtdaeKLRKVVMELVDTERTYVKHLNNLLEHYLEPM---------KRETFlsnaeINALFGNIHEIVTFQRQFLQN 1486
Cdd:COG5422  479 PKQEI----KRQEAIYEVIYTERDFVKDLEYLRDTWIKPLeesniipenARRNF-----IKHVFANINEIYAVNSKLLKA 549

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1487 LEESLDLEPdfnkfehcgqfrnVLFAIGSAFLYYVNHFKLYSSFCASH------SKAQKVLHPNEGNHAlQEFLAARNPk 1560
Cdd:COG5422  550 LTNRQCLSP-------------IVNGIADIFLDYVPKFEPFIKYGASQpyakyeFEREKSVNPNFARFD-HEVERLDES- 614

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1561 QQHSstLESYLIKPIQRILKYPLLLQQMRNLTDTRADEhvhlceaLKGMEKVAEHINE-MQRIHEEYGAI---FDHLFRQ 1636
Cdd:COG5422  615 RKLE--LDGYLTKPTTRLARYPLLLEEVLKFTDPDNPD-------TEDIPKVIDMLREfLSRLNFESGKAenrGDLFHLN 685


                 ....*.
gi 45552947 1637 HQKSCK 1642
Cdd:COG5422  686 QQLLFK 691
PDZ_canonical cd00136
canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs ...
 1185-1269 3.09e-04

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: 41.37  E-value: 3.09e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947 1185 VELQRTTLEQmWGFSVEAElienaeRQDELCCYVSRVEDKSVAMHNGIIK-GDEIMVINGAIVSDLDMMYLESVLQE-EQ 1262
Cdd:cd00136    2 VTLEKDPGGG-LGFSIRGG------KDGGGGIFVSRVEPGGPAARDGRLRvGDRILEVNGVSLEGLTHEEAVELLKSaGG 74


                 ....*..
gi 45552947 1263 SLSMMMR 1269
Cdd:cd00136   75 EVTLTVR 81
PDZ1_PDZD7-like cd10833
PDZ domain 1 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related ...
 1217-1269 3.85e-04

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


Pssm-ID: 467269 [Multi-domain]  Cd Length: 84  Bit Score: 41.27  E-value: 3.85e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 45552947 1217 YVSRVEDKSVAMHNGIIKGDEIMVINGAIVSDLDMMYLESVLQEEQSLSMMMR 1269
Cdd:cd10833   29 FVSKVEEGSAAERAGLCVGDKITEVNGVSLENITMSSAVKVLTGSNRLRMVVR 81
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 817-935 5.53e-04

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: 41.84  E-value: 5.53e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947  817 FNCTGAVRKAGFLSvKKWLLRKKHQielarKRgwkgyWVCLKGtTLLFYpCDSREGRSveaaPKHLIIVDGAIMQPIPEH 896
Cdd:cd13288    2 ATCNSPVDKEGYLW-KKGERNTSYQ-----KR-----WFVLKG-NLLFY-FEKKGDRE----PLGVIVLEGCTVELAEDA 64

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 45552947  897 PKrdYIFCLSTAFGDA--YLFQAPCQVELENWVNSIhsACA 935
Cdd:cd13288   65 EP--YAFAIRFDGPGArsYVLAAENQEDMESWMKAL--SRA 101
PDZ_tamalin_CYTIP-like cd06713
PDZ domain of tamalin, cytohesin-1-interacting protein (CYTIP), and related domains; PDZ ...
 1185-1250 6.68e-04

PDZ domain of tamalin, cytohesin-1-interacting protein (CYTIP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of tamalin, cytohesin-1-interacting protein, and related domains. Tamalin (trafficking regulator and scaffold protein tamalin, also known as general receptor for phosphoinositides 1-associated scaffold protein, GRASP) functions to link receptors, including group 1 metabotropic glutamate receptors (mGluRs), to neuronal proteins. The tamalin PDZ domain binds the C-terminal domains of group I mGluRs; it also binds potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2), neurotrophin-3 (NT3) TrkCT1-truncated receptor, SAP90/PSD-95-associated protein, and tamalin itself. CYTIP (cytohesin-1-interacting protein, also known as Pleckstrin homology Sec7 and coiled-coil domain-binding protein) sequesters cytohesin-1 in the cytoplasm, limiting its interaction with beta2 integrins; cytohesin-1 binds the CYTIP coiled coil domain. The CYTIP PDZ domain can bind the C-terminal peptide of protocadherin alpha-1 (PCDHA1), indicating a possible interaction between the two. 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 tamalin-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: 467197 [Multi-domain]  Cd Length: 91  Bit Score: 40.68  E-value: 6.68e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 45552947 1185 VELQRTTlEQMWGFSVEAELIENAERQD-ELCCYVSRVEDKSVAMHNGIIKGDEIMVINGAIVSDLD 1250
Cdd:cd06713    6 IILEKQD-NETFGFEIQTYGLHHKNSNEvEMCTYVCRVHEDSPAYLAGLTAGDVILSVNGVSVEGAS 71
PH_Skap_family cd13266
Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...
 825-930 9.19e-04

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


Pssm-ID: 270086  Cd Length: 106  Bit Score: 40.58  E-value: 9.19e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947  825 KAGFLSVKkwllRKKHQIELARkrgWKGYWVCLKGTTLLFYpcdsreGRSVEAAPKHLIIVDGAIMQPIPE---HPKRDY 901
Cdd:cd13266    3 KAGYLEKR----RKDHSFFGSE---WQKRWCAISKNVFYYY------GSDKDKQQKGEFAINGYDVRMNPTlrkDGKKDC 69

                         90       100
                 ....*....|....*....|....*....
gi 45552947  902 IFCLSTAFGDAYLFQAPCQVELENWVNSI 930
Cdd:cd13266   70 CFELVCPDKRTYQFTAASPEDAEDWVDQI 98
PH_RalGPS1_2 cd13310
Ral GEF with PH domain and SH3 binding motif 1 and 2 Pleckstrin homology (PH) domain; RalGPS1 ...
 836-935 9.88e-04

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: 40.70  E-value: 9.88e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947  836 LRKKHQIELARKRG---WKGYWVCLKGTTLLFYPCDSREG--RS-VEAAPKHLIIVDGAIMQPiPEHPKRDYIFCLS-TA 908
Cdd:cd13310    6 LRRKTVLKEGRKPTvssWQRYWVQLWGTSLVYYAPKSLKGteRSdFKSEPCKIVSISGWMVVL-GDDPEHPDSFQLTdPE 84

                         90       100
                 ....*....|....*....|....*..
gi 45552947  909 FGDAYLFQAPCQVELENWVNSIHSACA 935
Cdd:cd13310   85 KGNVYKFRAGSRSNALLWLKHLKDACK 111
PDZ3_harmonin cd06739
PDZ domain 3 of harmonin isoforms a and b, and related domains; PDZ (PSD-95 (Postsynaptic ...
 1216-1260 2.16e-03

PDZ domain 3 of harmonin isoforms a and b, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of harmonin isoforms a and b, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family 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: 467221 [Multi-domain]  Cd Length: 94  Bit Score: 39.21  E-value: 2.16e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 45552947 1216 CYVSRV-EDKSVAMHNGIIKGDEIMVINGAIVSDLDMMYLESVLQE 1260
Cdd:cd06739   30 IVVSAVyEGGAADKHGGIVKGDQIMMVNGKSLTDVTLAEAEAALQR 75
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 823-932 2.81e-03

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


Pssm-ID: 270110  Cd Length: 106  Bit Score: 39.15  E-value: 2.81e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947  823 VRKAGflsvkkWLLRKKHqielaRKRGWKGYWVCLKGTTLLFYPcDSREGRsveaaPKHLI-IVDGAIMQPIPEHpKRDY 901
Cdd:cd13298    6 VLKSG------YLLKRSR-----KTKNWKKRWVVLRPCQLSYYK-DEKEYK-----LRRVInLSELLAVAPLKDK-KRKN 67

                         90       100       110
                 ....*....|....*....|....*....|.
gi 45552947  902 IFCLSTAfGDAYLFQAPCQVELENWVNSIHS 932
Cdd:cd13298   68 VFGIYTP-SKNLHFRATSEKDANEWVEALRE 97
PDZ_Par6-like cd06718
PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F ...
 1217-1272 3.34e-03

PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F (RhoGAP100F), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Par6 (also known as PAR6 or Par-6), RhoGAP100F, and related domains. Par6 is part of a conserved machinery that directs metazoan cell polarity, a process necessary for the function of diverse cell types. Par6 forms a cell polarity-regulatory complex with atypical protein kinase C (aPKC) and Par3. Par6 can also directly associate with PALS1 (proteins associated with Lin7, also known as Stardust) providing a link between the Par3/aPKC/Par6 complex and the PALS1-PATJ (protein-associated TJ) complex. Binding partners of the Par6-PDZ domain include Par3, PALS1/Stardust; leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2), human crumbs (CRB3) involve in the morphogenesis of the tight junctions in mammalian epithelial cells, and PAR-6 co-operates with the Par6 semi-CRIB domain to bind CDC42. CDC42 regulates the Par6 PDZ domain through an allosteric CRIB-PDZ transition. Drosophila RhoGAP100F, also known as synapse defective protein 1 homolog (syd-1 homolog), is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound form. The RhoGAP100F-PDZ domain binds the neurexin C terminus to control synapse formation at the Drosophila neuromuscular junction. 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 Par6-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: 467202 [Multi-domain]  Cd Length: 84  Bit Score: 38.32  E-value: 3.34e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 45552947 1217 YVSRVEDKSVAMHNGIIK-GDEIMVINGAIVSDLDMmylesvlqeEQSLSMMMRSSR 1272
Cdd:cd06718   30 FISRLVLGSLADSTGLLAvGDEILEVNGVEVTGKSL---------DDVTDMMVAPTR 77
PDZ2_FL-whirlin cd06741
PDZ domain 2 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 ...
 1217-1269 5.85e-03

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


Pssm-ID: 467223 [Multi-domain]  Cd Length: 84  Bit Score: 37.63  E-value: 5.85e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 45552947 1217 YVSRVEDKSVAMHNGIIKGDEIMVINGaiVSDLDMMYLESVLQEEQSLSMMMR 1269
Cdd:cd06741   29 YVTGVDPGSVAENAGLKVGDQILEVNG--RSFLDITHDEAVKILKSSKHLIMT 79
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1663-1782 5.87e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 38.31  E-value: 5.87e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552947   1663 ISDFLGKIKKGLE--LHAMCFVFKSAVVFLCKERLRQKKKlmgvssknatneveiiRYQVLIPVTEVQVRASSAKDMDSH 1740
Cdd:pfam00169    3 KEGWLLKKGGGKKksWKKRYFVLFDGSLLYYKDDKSGKSK----------------EPKGSISLSGCEVVEVVASDSPKR 66

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 45552947   1741 -FLWELIHLrsqlQRRSEKVYVLSNSTADFRNAFLKTIRQIIR 1782
Cdd:pfam00169   67 kFCFELRTG----ERTGKRTYLLQAESEEERKDWIKAIQSAIR 105
PDZ1_L-delphilin-like cd06743
PDZ domain 1 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 ...
 1216-1279 6.25e-03

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


Pssm-ID: 467225 [Multi-domain]  Cd Length: 76  Bit Score: 37.26  E-value: 6.25e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 45552947 1216 CYVSRVEDKSVAMHNGIIKGDEIMVINGAIVSDLDMmylesvlqeeQSLSMMMRSSRTEPPDLV 1279
Cdd:cd06743   21 CYILSVEEGSSAHAAGLQPGDQILELDGQDVSSLSC----------EAIIALARRCPSVPPSLG 74
 
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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