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Conserved domains on  [gi|172088110|ref|NP_036008|]
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T-lymphoma invasion and metastasis-inducing protein 2 isoform 1 [Mus musculus]

Protein Classification

PH1_Tiam1_2 and PH2_Tiam1_2 domain-containing protein (domain architecture ID 12913508)

protein containing domains PH1_Tiam1_2, RBD, RhoGEF, and PH2_Tiam1_2

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; ...
1315-1487 3.00e-95

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: 304.30  E-value: 3.00e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110 1315 QKIYEDYGMVFDQLVAEQSGTEKEVTELSMGELLMHSTVSWLNPFLSLGKARKDIELTVFVFKRAVILVYKENCKLKKKL 1394
Cdd:cd01255     1 QKIHEEYGAVFDQLIREQSGTKKEVADLSMGDLLLYGTVEWLNPPSSLGKVKKEPELAVFVFKTAVVLVCKERSKQKKKL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110 1395 PSNSRPAHnSADLDPFKFRWLIPISALQVRLGNTAGTENNSTWELIHTKSEIEGRPETIFQLCCSDSENKTSIVKVIRSI 1474
Cdd:cd01255    81 MGSHRKSS-YEERDPFRFRHLIPVSALQVRNSNTADTESRCLWELIHTKSELEGRPEKVFQLCCSTPEFKNAFLKVIRSI 159
                         170
                  ....*....|...
gi 172088110 1475 LRENFRRHIKCEL 1487
Cdd:cd01255   160 LREKVRRQSSKTE 172
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
503-629 2.13e-80

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: 260.08  E-value: 2.13e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  503 GVVRKAGWLFFKPLVTLQKERKLELVARRKWKQYWVTLKGCTLLFYETYGKNSTEQNSAPRCALFAEDSIVQSVPEHPKK 582
Cdd:cd01230     1 GAVRKAGWLSVKNFLVHKKNKKVELATRRKWKKYWVCLKGCTLLFYECDERSGIDENSEPKHALFVEGSIVQAVPEHPKK 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 172088110  583 EHVFCLSNSCGDVYLFQATSQTDLENWVTAIHSACASLFAKKHGKED 629
Cdd:cd01230    81 DFVFCLSNSFGDAYLFQATSQTELENWVTAIHSACASAFARQHGKED 127
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
1124-1313 2.13e-51

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


:

Pssm-ID: 214619  Cd Length: 180  Bit Score: 179.03  E-value: 2.13e-51
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110   1124 VIQELVDTEKSYVKDLSCLFELYLEPLQNE-TFLTQDEMESLFGSLPEMLEFQKVFLETLEDAISASSDFSvletpsqfr 1202
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKElKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSV--------- 71
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110   1203 kllFSLGGSFLYYADHFKLYSGFCANHIKVQRVLERAKTDKAFKAFLDARNPTKQHSS-TLESYLIKPVQRVLKYPLLLK 1281
Cdd:smart00325   72 ---ERIGDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRlTLESLLLKPVQRLTKYPLLLK 148
                           170       180       190
                    ....*....|....*....|....*....|..
gi 172088110   1282 ELVSLTDHESEEHYHLTEALKAMEKVASHINE 1313
Cdd:smart00325  149 ELLKHTPEDHEDREDLKKALKAIKELANQVNE 180
RBD smart00455
Raf-like Ras-binding domain;
832-902 8.17e-21

Raf-like Ras-binding domain;


:

Pssm-ID: 128731  Cd Length: 70  Bit Score: 87.34  E-value: 8.17e-21
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 172088110    832 QTYVHFQDNEGVTVTIKPEHRVEDVLALVCKMRQLEPTHYGLQLRKvVDKSVEWCVPALYEYMQEQVYDEI 902
Cdd:smart00455    1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLRG-EKKPLDLNQPISSLDGQELVVEEL 70
PDZ_signaling cd00992
PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. ...
909-994 1.85e-13

PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) polypeptides and even to lipids has been demonstrated. In this subfamily of PDZ domains an N-terminal beta-strand forms the peptide-binding groove base, a circular permutation with respect to PDZ domains found in proteases.


:

Pssm-ID: 238492 [Multi-domain]  Cd Length: 82  Bit Score: 66.82  E-value: 1.85e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  909 VYDVQLTKTGDmTDFGFAVTVQVDEHQHlnrIFISDVLPDSLAYGGGLRKGNEITSLNGEPVSDLDIQQMEALFSEKSVG 988
Cdd:cd00992     1 VRTVTLRKDPG-GGLGFSLRGGKDSGGG---IFVSRVEPGGPAERGGLRVGDRILEVNGVSVEGLTHEEAVELLKNSGDE 76

                  ....*.
gi 172088110  989 LTLVAR 994
Cdd:cd00992    77 VTLTVR 82
 
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; ...
1315-1487 3.00e-95

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: 304.30  E-value: 3.00e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110 1315 QKIYEDYGMVFDQLVAEQSGTEKEVTELSMGELLMHSTVSWLNPFLSLGKARKDIELTVFVFKRAVILVYKENCKLKKKL 1394
Cdd:cd01255     1 QKIHEEYGAVFDQLIREQSGTKKEVADLSMGDLLLYGTVEWLNPPSSLGKVKKEPELAVFVFKTAVVLVCKERSKQKKKL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110 1395 PSNSRPAHnSADLDPFKFRWLIPISALQVRLGNTAGTENNSTWELIHTKSEIEGRPETIFQLCCSDSENKTSIVKVIRSI 1474
Cdd:cd01255    81 MGSHRKSS-YEERDPFRFRHLIPVSALQVRNSNTADTESRCLWELIHTKSELEGRPEKVFQLCCSTPEFKNAFLKVIRSI 159
                         170
                  ....*....|...
gi 172088110 1475 LRENFRRHIKCEL 1487
Cdd:cd01255   160 LREKVRRQSSKTE 172
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
503-629 2.13e-80

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: 260.08  E-value: 2.13e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  503 GVVRKAGWLFFKPLVTLQKERKLELVARRKWKQYWVTLKGCTLLFYETYGKNSTEQNSAPRCALFAEDSIVQSVPEHPKK 582
Cdd:cd01230     1 GAVRKAGWLSVKNFLVHKKNKKVELATRRKWKKYWVCLKGCTLLFYECDERSGIDENSEPKHALFVEGSIVQAVPEHPKK 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 172088110  583 EHVFCLSNSCGDVYLFQATSQTDLENWVTAIHSACASLFAKKHGKED 629
Cdd:cd01230    81 DFVFCLSNSFGDAYLFQATSQTELENWVTAIHSACASAFARQHGKED 127
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
1124-1313 2.13e-51

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


Pssm-ID: 214619  Cd Length: 180  Bit Score: 179.03  E-value: 2.13e-51
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110   1124 VIQELVDTEKSYVKDLSCLFELYLEPLQNE-TFLTQDEMESLFGSLPEMLEFQKVFLETLEDAISASSDFSvletpsqfr 1202
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKElKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSV--------- 71
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110   1203 kllFSLGGSFLYYADHFKLYSGFCANHIKVQRVLERAKTDKAFKAFLDARNPTKQHSS-TLESYLIKPVQRVLKYPLLLK 1281
Cdd:smart00325   72 ---ERIGDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRlTLESLLLKPVQRLTKYPLLLK 148
                           170       180       190
                    ....*....|....*....|....*....|..
gi 172088110   1282 ELVSLTDHESEEHYHLTEALKAMEKVASHINE 1313
Cdd:smart00325  149 ELLKHTPEDHEDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
1121-1312 5.90e-50

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


Pssm-ID: 238091  Cd Length: 181  Bit Score: 175.18  E-value: 5.90e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110 1121 LRKVIQELVDTEKSYVKDLSCLFELYLEPLQNE-TFLTQDEMESLFGSLPEMLEFQKVFLETLEDAISASsdfsvletps 1199
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKElLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEW---------- 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110 1200 qfRKLLFSLGGSFLYYADHFKLYSGFCANHIKVQRVLE-RAKTDKAFKAFLDARNpTKQHSSTLESYLIKPVQRVLKYPL 1278
Cdd:cd00160    71 --DKSGPRIGDVFLKLAPFFKIYSEYCSNHPDALELLKkLKKFNKFFQEFLEKAE-SECGRLKLESLLLKPVQRLTKYPL 147
                         170       180       190
                  ....*....|....*....|....*....|....
gi 172088110 1279 LLKELVSLTDHESEEHYHLTEALKAMEKVASHIN 1312
Cdd:cd00160   148 LLKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
1124-1312 4.18e-43

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: 306973  Cd Length: 175  Bit Score: 155.13  E-value: 4.18e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  1124 VIQELVDTEKSYVKDLSCLFELYL--EPLQNetflTQDEMESLFGSLPEMLEFQKVFLetledaisassdfsvLETPSQF 1201
Cdd:pfam00621    1 VIKELLTTERSYVRDLEILVEVFLppKPLSE----SPEEIKTIFSNIEEIYELHRQFL---------------LEELLKE 61
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  1202 RKLLFSLGGSFLYYADHFKL-YSGFCANHIKVQRVLERA-KTDKAFKAFLDARNPTKQHSS-TLESYLIKPVQRVLKYPL 1278
Cdd:pfam00621   62 WIVIQRIGDIFLKFAPGFKLvYSTYCSNYPKALELLKKLlKKNPKFAEFLEECEANPECRGlDLNSFLIKPVQRIPRYPL 141
                          170       180       190
                   ....*....|....*....|....*....|....
gi 172088110  1279 LLKELVSLTDHESEEHYHLTEALKAMEKVASHIN 1312
Cdd:pfam00621  142 LLKELLKHTPPDHPDYEDLKKALEAIKEVAKQIN 175
RBD smart00455
Raf-like Ras-binding domain;
832-902 8.17e-21

Raf-like Ras-binding domain;


Pssm-ID: 128731  Cd Length: 70  Bit Score: 87.34  E-value: 8.17e-21
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 172088110    832 QTYVHFQDNEGVTVTIKPEHRVEDVLALVCKMRQLEPTHYGLQLRKvVDKSVEWCVPALYEYMQEQVYDEI 902
Cdd:smart00455    1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLRG-EKKPLDLNQPISSLDGQELVVEEL 70
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
505-618 4.94e-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  Cd Length: 102  Bit Score: 72.20  E-value: 4.94e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110    505 VRKAGWLffkplvtlqkeRKLELVARRKWKQYWVTLKGCTLLFYEtygKNSTEQNSAPRCALFAEDSIVQSVPE--HPKK 582
Cdd:smart00233    1 VIKEGWL-----------YKKSGGGKKSWKKRYFVLFNSTLLYYK---SKKDKKSYKPKGSIDLSGCTVREAPDpdSSKK 66
                            90       100       110
                    ....*....|....*....|....*....|....*.
gi 172088110    583 EHVFCLSNSCGDVYLFQATSQTDLENWVTAIHSACA 618
Cdd:smart00233   67 PHCFEIKTSDRKTLLLQAESEEEREKWVEALRKAIA 102
PDZ_signaling cd00992
PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. ...
909-994 1.85e-13

PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) polypeptides and even to lipids has been demonstrated. In this subfamily of PDZ domains an N-terminal beta-strand forms the peptide-binding groove base, a circular permutation with respect to PDZ domains found in proteases.


Pssm-ID: 238492 [Multi-domain]  Cd Length: 82  Bit Score: 66.82  E-value: 1.85e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  909 VYDVQLTKTGDmTDFGFAVTVQVDEHQHlnrIFISDVLPDSLAYGGGLRKGNEITSLNGEPVSDLDIQQMEALFSEKSVG 988
Cdd:cd00992     1 VRTVTLRKDPG-GGLGFSLRGGKDSGGG---IFVSRVEPGGPAERGGLRVGDRILEVNGVSVEGLTHEEAVELLKNSGDE 76

                  ....*.
gi 172088110  989 LTLVAR 994
Cdd:cd00992    77 VTLTVR 82
PH pfam00169
PH domain; PH stands for pleckstrin homology.
505-616 7.56e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 333896  Cd Length: 103  Bit Score: 63.33  E-value: 7.56e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110   505 VRKAGWLFfkplvtlqkerKLELVARRKWKQYWVTLKGCTLLFYEtygKNSTEQNSAPRCALFAEDSIVQSV--PEHPKK 582
Cdd:pfam00169    1 VIKEGWLL-----------KKGGGKKKSWKKRYFVLFDGSLLYYK---DSSRGKSKEPKGSISLSGCTVVEVvaPDKPKR 66
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 172088110   583 EHVFCL---SNSCGDVYLFQATSQTDLENWVTAIHSA 616
Cdd:pfam00169   67 KFCFELrtgELDGKRTYLLQAESEEERKEWIKAIQSA 103
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
909-995 2.43e-09

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: 55.46  E-value: 2.43e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110    909 VYDVQLTKTGDmtDFGFAVTVQVDEHQHlnrIFISDVLPDSLAYGGGLRKGNEITSLNGEPVSDLDIQQMEALFSEKSVG 988
Cdd:smart00228    2 PRLVELEKGGG--GLGFSLVGGKDEGGG---VVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGK 76

                    ....*...
gi 172088110    989 LTL-VARP 995
Cdd:smart00228   77 VTLtVLRG 84
PDZ pfam00595
PDZ domain (Also known as DHR or GLGF); PDZ domains are found in diverse signaling proteins.
923-978 1.94e-07

PDZ domain (Also known as DHR or GLGF); PDZ domains are found in diverse signaling proteins.


Pssm-ID: 334167 [Multi-domain]  Cd Length: 81  Bit Score: 49.96  E-value: 1.94e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 172088110   923 FGFAVTVQVDehQHLNRIFISDVLPDSLAYGGGLRKGNEITSLNGEPVSD---LDIQQM 978
Cdd:pfam00595   12 LGFSLKGGSD--QGAKGIFVSEVLPGGAAEAAGLQAGDRILSVNGVPIENlshEEAVLA 68
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
1108-1325 1.41e-05

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 49.89  E-value: 1.41e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110 1108 PRPLARHLSDADRLRK-VIQELVDTEKSYVKDLSCLFELYLEPLQNETFLTQDEMEslfgslpemlEFQKVFLETLEDAI 1186
Cdd:COG5422   471 PKEVWESLPKQEIKRQeAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENARR----------NFIKHVFANINEIY 540
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110 1187 SASSDFSVLETPSQ-FRKLLFSLGGSFLYYADHFKLYSGFCANHIKVQRVLERAK-TDKAFKAFLD----ARNPTKQHss 1260
Cdd:COG5422   541 AVNSKLLKALTNRQcLSPIVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFEREKsVNPNFARFDHeverLDESRKLE-- 618
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 172088110 1261 tLESYLIKPVQRVLKYPLLLKELVSLTDHESEEHYHLTEALKAMEKVASHINEMQKIYEDYGMVF 1325
Cdd:COG5422   619 -LDGYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLF 682
CtpA COG0793
C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, ...
924-1000 3.08e-04

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 223864 [Multi-domain]  Cd Length: 406  Bit Score: 45.02  E-value: 3.08e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  924 GFAVTVQVDEHqhlNRIFISDVLPDSLAYGGGLRKGNEITSLNGEPVSDLDIQQMEALFSEK---SVGLTLV------AR 994
Cdd:COG0793   101 GIGIELQMEDI---GGVKVVSPIDGSPAAKAGIKPGDVIIKIDGKSVGGVSLDEAVKLIRGKpgtKVTLTILragggkPF 177

                  ....*.
gi 172088110  995 PVTTRR 1000
Cdd:COG0793   178 TVTLTR 183
 
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; ...
1315-1487 3.00e-95

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: 304.30  E-value: 3.00e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110 1315 QKIYEDYGMVFDQLVAEQSGTEKEVTELSMGELLMHSTVSWLNPFLSLGKARKDIELTVFVFKRAVILVYKENCKLKKKL 1394
Cdd:cd01255     1 QKIHEEYGAVFDQLIREQSGTKKEVADLSMGDLLLYGTVEWLNPPSSLGKVKKEPELAVFVFKTAVVLVCKERSKQKKKL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110 1395 PSNSRPAHnSADLDPFKFRWLIPISALQVRLGNTAGTENNSTWELIHTKSEIEGRPETIFQLCCSDSENKTSIVKVIRSI 1474
Cdd:cd01255    81 MGSHRKSS-YEERDPFRFRHLIPVSALQVRNSNTADTESRCLWELIHTKSELEGRPEKVFQLCCSTPEFKNAFLKVIRSI 159
                         170
                  ....*....|...
gi 172088110 1475 LRENFRRHIKCEL 1487
Cdd:cd01255   160 LREKVRRQSSKTE 172
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
503-629 2.13e-80

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: 260.08  E-value: 2.13e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  503 GVVRKAGWLFFKPLVTLQKERKLELVARRKWKQYWVTLKGCTLLFYETYGKNSTEQNSAPRCALFAEDSIVQSVPEHPKK 582
Cdd:cd01230     1 GAVRKAGWLSVKNFLVHKKNKKVELATRRKWKKYWVCLKGCTLLFYECDERSGIDENSEPKHALFVEGSIVQAVPEHPKK 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 172088110  583 EHVFCLSNSCGDVYLFQATSQTDLENWVTAIHSACASLFAKKHGKED 629
Cdd:cd01230    81 DFVFCLSNSFGDAYLFQATSQTELENWVTAIHSACASAFARQHGKED 127
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
1124-1313 2.13e-51

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


Pssm-ID: 214619  Cd Length: 180  Bit Score: 179.03  E-value: 2.13e-51
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110   1124 VIQELVDTEKSYVKDLSCLFELYLEPLQNE-TFLTQDEMESLFGSLPEMLEFQKVFLETLEDAISASSDFSvletpsqfr 1202
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKElKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSV--------- 71
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110   1203 kllFSLGGSFLYYADHFKLYSGFCANHIKVQRVLERAKTDKAFKAFLDARNPTKQHSS-TLESYLIKPVQRVLKYPLLLK 1281
Cdd:smart00325   72 ---ERIGDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKNPRFQKFLKEIESSPQCRRlTLESLLLKPVQRLTKYPLLLK 148
                           170       180       190
                    ....*....|....*....|....*....|..
gi 172088110   1282 ELVSLTDHESEEHYHLTEALKAMEKVASHINE 1313
Cdd:smart00325  149 ELLKHTPEDHEDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
1121-1312 5.90e-50

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


Pssm-ID: 238091  Cd Length: 181  Bit Score: 175.18  E-value: 5.90e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110 1121 LRKVIQELVDTEKSYVKDLSCLFELYLEPLQNE-TFLTQDEMESLFGSLPEMLEFQKVFLETLEDAISASsdfsvletps 1199
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKElLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEW---------- 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110 1200 qfRKLLFSLGGSFLYYADHFKLYSGFCANHIKVQRVLE-RAKTDKAFKAFLDARNpTKQHSSTLESYLIKPVQRVLKYPL 1278
Cdd:cd00160    71 --DKSGPRIGDVFLKLAPFFKIYSEYCSNHPDALELLKkLKKFNKFFQEFLEKAE-SECGRLKLESLLLKPVQRLTKYPL 147
                         170       180       190
                  ....*....|....*....|....*....|....
gi 172088110 1279 LLKELVSLTDHESEEHYHLTEALKAMEKVASHIN 1312
Cdd:cd00160   148 LLKELLKHTPDGHEDREDLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
1124-1312 4.18e-43

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: 306973  Cd Length: 175  Bit Score: 155.13  E-value: 4.18e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  1124 VIQELVDTEKSYVKDLSCLFELYL--EPLQNetflTQDEMESLFGSLPEMLEFQKVFLetledaisassdfsvLETPSQF 1201
Cdd:pfam00621    1 VIKELLTTERSYVRDLEILVEVFLppKPLSE----SPEEIKTIFSNIEEIYELHRQFL---------------LEELLKE 61
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  1202 RKLLFSLGGSFLYYADHFKL-YSGFCANHIKVQRVLERA-KTDKAFKAFLDARNPTKQHSS-TLESYLIKPVQRVLKYPL 1278
Cdd:pfam00621   62 WIVIQRIGDIFLKFAPGFKLvYSTYCSNYPKALELLKKLlKKNPKFAEFLEECEANPECRGlDLNSFLIKPVQRIPRYPL 141
                          170       180       190
                   ....*....|....*....|....*....|....
gi 172088110  1279 LLKELVSLTDHESEEHYHLTEALKAMEKVASHIN 1312
Cdd:pfam00621  142 LLKELLKHTPPDHPDYEDLKKALEAIKEVAKQIN 175
RBD smart00455
Raf-like Ras-binding domain;
832-902 8.17e-21

Raf-like Ras-binding domain;


Pssm-ID: 128731  Cd Length: 70  Bit Score: 87.34  E-value: 8.17e-21
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 172088110    832 QTYVHFQDNEGVTVTIKPEHRVEDVLALVCKMRQLEPTHYGLQLRKvVDKSVEWCVPALYEYMQEQVYDEI 902
Cdd:smart00455    1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLRG-EKKPLDLNQPISSLDGQELVVEEL 70
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
505-618 4.94e-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  Cd Length: 102  Bit Score: 72.20  E-value: 4.94e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110    505 VRKAGWLffkplvtlqkeRKLELVARRKWKQYWVTLKGCTLLFYEtygKNSTEQNSAPRCALFAEDSIVQSVPE--HPKK 582
Cdd:smart00233    1 VIKEGWL-----------YKKSGGGKKSWKKRYFVLFNSTLLYYK---SKKDKKSYKPKGSIDLSGCTVREAPDpdSSKK 66
                            90       100       110
                    ....*....|....*....|....*....|....*.
gi 172088110    583 EHVFCLSNSCGDVYLFQATSQTDLENWVTAIHSACA 618
Cdd:smart00233   67 PHCFEIKTSDRKTLLLQAESEEEREKWVEALRKAIA 102
PDZ_signaling cd00992
PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. ...
909-994 1.85e-13

PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) polypeptides and even to lipids has been demonstrated. In this subfamily of PDZ domains an N-terminal beta-strand forms the peptide-binding groove base, a circular permutation with respect to PDZ domains found in proteases.


Pssm-ID: 238492 [Multi-domain]  Cd Length: 82  Bit Score: 66.82  E-value: 1.85e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  909 VYDVQLTKTGDmTDFGFAVTVQVDEHQHlnrIFISDVLPDSLAYGGGLRKGNEITSLNGEPVSDLDIQQMEALFSEKSVG 988
Cdd:cd00992     1 VRTVTLRKDPG-GGLGFSLRGGKDSGGG---IFVSRVEPGGPAERGGLRVGDRILEVNGVSVEGLTHEEAVELLKNSGDE 76

                  ....*.
gi 172088110  989 LTLVAR 994
Cdd:cd00992    77 VTLTVR 82
PH_ARHGAP21-like cd01253
ARHGAP21 and related proteins pleckstrin homology (PH) domain; ARHGAP family genes encode Rho ...
506-615 4.50e-13

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: 67.01  E-value: 4.50e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  506 RKAGWLFFKPLVTLQKERklelVARRKWKQYWVTLKGCTLLFY----ETYGKNSTEQNSAPRcaLFAEDSIVQSVPEHPK 581
Cdd:cd01253     1 AREGWLHYKQIVTDKGKR----VSDRSWKQAWAVLRGHSLYLYkdkrEQTPALSIELGSEQR--ISIRGCIVDIAYSYTK 74
                          90       100       110
                  ....*....|....*....|....*....|....
gi 172088110  582 KEHVFCLSNSCGDVYLFQATSQTDLENWVTAIHS 615
Cdd:cd01253    75 RKHVFRLTTSDFSEYLFQAEDRDDMLGWIKAIQE 108
PH pfam00169
PH domain; PH stands for pleckstrin homology.
505-616 7.56e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 333896  Cd Length: 103  Bit Score: 63.33  E-value: 7.56e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110   505 VRKAGWLFfkplvtlqkerKLELVARRKWKQYWVTLKGCTLLFYEtygKNSTEQNSAPRCALFAEDSIVQSV--PEHPKK 582
Cdd:pfam00169    1 VIKEGWLL-----------KKGGGKKKSWKKRYFVLFDGSLLYYK---DSSRGKSKEPKGSISLSGCTVVEVvaPDKPKR 66
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 172088110   583 EHVFCL---SNSCGDVYLFQATSQTDLENWVTAIHSA 616
Cdd:pfam00169   67 KFCFELrtgELDGKRTYLLQAESEEERKEWIKAIQSA 103
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
507-613 8.47e-12

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  Cd Length: 92  Bit Score: 62.56  E-value: 8.47e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  507 KAGWLFfkplvtlqkerKLELVARRKWKQYWVTLKGCTLLFYetygKNSTEQNSAPRCALFAEDSIVQSVPEHPKKEHVF 586
Cdd:cd00821     1 KEGYLL-----------KRGGGGLKSWKKRWFVLFEGVLLYY----KSKKDSSYKPKGSIPLSGILEVEEVSPKERPHCF 65
                          90       100
                  ....*....|....*....|....*..
gi 172088110  587 CLSNSCGDVYLFQATSQTDLENWVTAI 613
Cdd:cd00821    66 ELVTPDGRTYYLQADSEEERQEWLKAL 92
PH_EFA6 cd13295
Exchange Factor for ARF6 Pleckstrin homology (PH) domain; EFA6 (also called PSD/pleckstrin and ...
501-622 3.05e-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: 62.35  E-value: 3.05e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  501 EQGVVRKAGWLFFKplVTLQKERKLELVARRKWKQYWVTLKGCTLLFY-ETYGKNSTEQNSAPRCALFAEDSIVQSVPEH 579
Cdd:cd13295     2 PNAVEYKKGYLMRK--CCADPDGKKTPFGKRGWKMFYATLKGLVLYLHkDEYGCKKALRYESLRNAISVHHSLATKATDY 79
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 172088110  580 PKKEHVFCLSNSCGDVYLFQATSQTDLENWVTAIHSACASLFA 622
Cdd:cd13295    80 TKKPHVFRLRTADWREYLFQASDTKEMQSWIEAINLVAAAFSA 122
PH_beta_spectrin cd10571
Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a ...
522-616 4.10e-10

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: 58.39  E-value: 4.10e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  522 ERKLEL------VARRKWKQYWVTLKGCTLLFY---ETYGKNSTEQNSAPRcalfaedSIVQSVPE----HPKKEHVFCL 588
Cdd:cd10571     6 ERKHEWesggkkASNRSWKNVYTVLRGQELSFYkdqKAAKSGITYAAEPPL-------NLYNAVCEvasdYTKKKHVFRL 78
                          90       100
                  ....*....|....*....|....*...
gi 172088110  589 SNSCGDVYLFQATSQTDLENWVTAIHSA 616
Cdd:cd10571    79 KLSDGAEFLFQAKDEEEMNQWVKKISFA 106
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
505-615 6.87e-10

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: 57.64  E-value: 6.87e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  505 VRKAGWLffkplvtLQKERKlelvaRRKWKQYWVTLKGCTLLFYetygKNSTE---QNSAPRCALFAedsiVQSVPEHpK 581
Cdd:cd13298     6 VLKSGYL-------LKRSRK-----TKNWKKRWVVLRPCQLSYY----KDEKEyklRRVINLSELLA----VAPLKDK-K 64
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 172088110  582 KEHVFCL-SNScgDVYLFQATSQTDLENWVTAIHS 615
Cdd:cd13298    65 RKNVFGIyTPS--KNLHFRATSEKDANEWVEALRE 97
PH_9 pfam15410
Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.
507-618 7.63e-10

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


Pssm-ID: 292052  Cd Length: 118  Bit Score: 57.79  E-value: 7.63e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110   507 KAGWLFFKplVTLQKERKLELVARRKWKQYWVTLKGCTLLFYETYGKNSTEQ-------NSAPRCALFAEDSIVQSVPEH 579
Cdd:pfam15410    2 KKGIVMRK--CCFESDGKKTPFGKRGWKMVYAVLKGLVLYLYKDEHPPESGTpedfvsvKNAPVGKIRLHHALAEPAPDY 79
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 172088110   580 PKKEHVFCLSNSCGDVYLFQATSQTDLENWVTAIHSACA 618
Cdd:pfam15410   80 TKKSHVFRLQTADGAEYLFQTSDPKEVQEWIDTINYVAA 118
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
909-995 2.43e-09

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: 55.46  E-value: 2.43e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110    909 VYDVQLTKTGDmtDFGFAVTVQVDEHQHlnrIFISDVLPDSLAYGGGLRKGNEITSLNGEPVSDLDIQQMEALFSEKSVG 988
Cdd:smart00228    2 PRLVELEKGGG--GLGFSLVGGKDEGGG---VVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGK 76

                    ....*...
gi 172088110    989 LTL-VARP 995
Cdd:smart00228   77 VTLtVLRG 84
PDZ pfam00595
PDZ domain (Also known as DHR or GLGF); PDZ domains are found in diverse signaling proteins.
923-978 1.94e-07

PDZ domain (Also known as DHR or GLGF); PDZ domains are found in diverse signaling proteins.


Pssm-ID: 334167 [Multi-domain]  Cd Length: 81  Bit Score: 49.96  E-value: 1.94e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 172088110   923 FGFAVTVQVDehQHLNRIFISDVLPDSLAYGGGLRKGNEITSLNGEPVSD---LDIQQM 978
Cdd:pfam00595   12 LGFSLKGGSD--QGAKGIFVSEVLPGGAAEAAGLQAGDRILSVNGVPIENlshEEAVLA 68
PH_RalGPS1_2 cd13310
Ral GEF with PH domain and SH3 binding motif 1 and 2 Pleckstrin homology (PH) domain; RalGPS1 ...
502-620 1.98e-07

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: 51.10  E-value: 1.98e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  502 QGVVRKAgwlffkplvTLQKERKLELVARrkWKQYWVTLKGCTLLFYETYGKNSTEQN--SAPRCALFAEDSIVQSVPEH 579
Cdd:cd13310     3 QGCLRRK---------TVLKEGRKPTVSS--WQRYWVQLWGTSLVYYAPKSLKGTERSdfKSEPCKIVSISGWMVVLGDD 71
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 172088110  580 PKKEHVFCLSNS-CGDVYLFQATSQTDLENWVTAIHSACASL 620
Cdd:cd13310    72 PEHPDSFQLTDPeKGNVYKFRAGSRSNALLWLKHLKDACKGN 113
PH_RhoGAP2 cd13378
Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 ...
503-613 3.14e-07

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241529  Cd Length: 116  Bit Score: 50.33  E-value: 3.14e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  503 GVVRKAGWLffkplvtlQKERKLelvaRRKWKQYWVTLKGCTLLFYETygknstEQNSAPRCALFAEDSIVQSVPEHPKK 582
Cdd:cd13378     1 EGVLKAGWL--------KKQRSI----MKNWQQRWFVLRGDQLFYYKD------EEETKPQGCISLQGSQVNELPPNPEE 62
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 172088110  583 --EHVFCLS-NSCGD---------VYLFQATSQTDLENWVTAI 613
Cdd:cd13378    63 pgKHLFEILpGGAGDrekvpmnheAFLLMANSQSDMEDWVKAI 105
PDZ cd00136
PDZ domain, also called DHR (Dlg homologous region) or GLGF (after a conserved sequence motif). ...
923-992 7.11e-07

PDZ domain, also called DHR (Dlg homologous region) or GLGF (after a conserved sequence motif). Many PDZ domains bind C-terminal polypeptides, though binding to internal (non-C-terminal) polypeptides and even to lipids has been demonstrated. Heterodimerization through PDZ-PDZ domain interactions adds to the domain's versatility, and PDZ domain-mediated interactions may be modulated dynamically through target phosphorylation. Some PDZ domains play a role in scaffolding supramolecular complexes. PDZ domains are found in diverse signaling proteins in bacteria, archebacteria, and eurkayotes. This CD contains two distinct structural subgroups with either a N- or C-terminal beta-strand forming the peptide-binding groove base. The circular permutation placing the strand on the N-terminus appears to be found in Eumetazoa only, while the C-terminal variant is found in all three kingdoms of life, and seems to co-occur with protease domains. PDZ domains have been named after PSD95(post synaptic density protein), DlgA (Drosophila disc large tumor suppressor), and ZO1, a mammalian tight junction protein.


Pssm-ID: 238080 [Multi-domain]  Cd Length: 70  Bit Score: 48.07  E-value: 7.11e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 172088110  923 FGFAVTvQVDEhqhlNRIFISDVLPDSLAYGGGLRKGNEITSLNGEPVSDLDIQQ-MEALfsEKSVGLTLV 992
Cdd:cd00136     3 LGFSIR-GGTE----GGVVVLSVEPGSPAERAGLQAGDVILAVNGTDVKNLTLEDvAELL--KKEVGEKVT 66
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
530-625 2.44e-06

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: 47.75  E-value: 2.44e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  530 RRKWKQYWVTLKGCTLLFYEtygknSTEQNSAPRCALFAEDSIVQSVPEHPKKEHVFCLSNSCGDVYLFQATSQTDLENW 609
Cdd:cd13301    16 VNNWKARWFVLKEDGLEYYK-----KKTDSSPKGMIPLKGCTITSPCLEYGKRPLVFKLTTAKGQEHFFQACSREERDAW 90
                          90
                  ....*....|....*.
gi 172088110  610 VTAIHSACASLFAKKH 625
Cdd:cd13301    91 AKDITKAITCLEGGKR 106
PDZ_CTP_protease cd00988
PDZ domain of C-terminal processing-, tail-specific-, and tricorn proteases, which function in ...
924-1000 8.63e-06

PDZ domain of C-terminal processing-, tail-specific-, and tricorn proteases, which function in posttranslational protein processing, maturation, and disassembly or degradation, in Bacteria, Archaea, and plant chloroplasts. May be responsible for substrate recognition and/or binding, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) polypeptides and even to lipids has been demonstrated. In this subfamily of protease-associated PDZ domains a C-terminal beta-strand forms the peptide-binding groove base, a circular permutation with respect to PDZ domains found in Eumetazoan signaling proteins.


Pssm-ID: 238488 [Multi-domain]  Cd Length: 85  Bit Score: 45.29  E-value: 8.63e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  924 GFAVTVQVDEHqhlnRIFISDVLPDSLAYGGGLRKGNEITSLNGEPVSDLDIQQMEALFSEK---SVGLTLV-----ARP 995
Cdd:cd00988     3 GIGLELKYDDG----GLVITSVLPGSPAAKAGIKAGDIIVAIDGEPVDGLSLEDVVKLLRGKagtKVRLTLKrgdgePRE 78

                  ....*
gi 172088110  996 VTTRR 1000
Cdd:cd00988    79 VTLTR 83
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
1108-1325 1.41e-05

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 49.89  E-value: 1.41e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110 1108 PRPLARHLSDADRLRK-VIQELVDTEKSYVKDLSCLFELYLEPLQNETFLTQDEMEslfgslpemlEFQKVFLETLEDAI 1186
Cdd:COG5422   471 PKEVWESLPKQEIKRQeAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENARR----------NFIKHVFANINEIY 540
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110 1187 SASSDFSVLETPSQ-FRKLLFSLGGSFLYYADHFKLYSGFCANHIKVQRVLERAK-TDKAFKAFLD----ARNPTKQHss 1260
Cdd:COG5422   541 AVNSKLLKALTNRQcLSPIVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFEREKsVNPNFARFDHeverLDESRKLE-- 618
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 172088110 1261 tLESYLIKPVQRVLKYPLLLKELVSLTDHESEEHYHLTEALKAMEKVASHINEMQKIYEDYGMVF 1325
Cdd:COG5422   619 -LDGYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLF 682
PH_PLEKHJ1 cd13258
Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; ...
534-616 1.71e-05

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270078  Cd Length: 123  Bit Score: 45.78  E-value: 1.71e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  534 KQYWVTLKGcTLLFYetYGKNSTEQNSAPRCALFAEDSIVQSVPEHPKKeHVFCLSNScGDV---YLFQATSQTDLENWV 610
Cdd:cd13258    37 KERWFKLKG-NLLFY--FRTNEFGDCSEPIGAIVLENCRVQMEEITEKP-FAFSIVFN-DEPekkYIFSCRSEEQCEQWI 111

                  ....*.
gi 172088110  611 TAIHSA 616
Cdd:cd13258   112 EALRQA 117
PH_ARHGAP9-like cd13233
Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like ...
530-616 2.38e-05

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: 44.96  E-value: 2.38e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  530 RRKWKQYWVTLKGCTLLFYETygKNSTEQNSAPRCAlfAEDSI------VQSVPEHPKKEHVFCLSNSCGDVYLFQATSQ 603
Cdd:cd13233    19 RKNWSTSWVVLTSSHLLFYKD--AKSAAKSGNPYSK--PESSVdlrgasIEWAKEKSSRKNVFQISTVTGTEFLLQSDND 94
                          90
                  ....*....|...
gi 172088110  604 TDLENWVTAIHSA 616
Cdd:cd13233    95 TEIREWFDAIKAV 107
PDZ_serine_protease cd00987
PDZ domain of trypsin-like serine proteases, such as DegP/HtrA, which are oligomeric proteins ...
940-988 4.59e-05

PDZ domain of trypsin-like serine proteases, such as DegP/HtrA, which are oligomeric proteins involved in heat-shock response, chaperone function, and apoptosis. May be responsible for substrate recognition and/or binding, as most PDZ domains bind C-terminal polypeptides, though binding to internal (non-C-terminal) polypeptides and even to lipids has been demonstrated. In this subfamily of protease-associated PDZ domains a C-terminal beta-strand forms the peptide-binding groove base, a circular permutation with respect to PDZ domains found in Eumetazoan signaling proteins.


Pssm-ID: 238487 [Multi-domain]  Cd Length: 90  Bit Score: 43.40  E-value: 4.59e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 172088110  940 IFISDVLPDSLAYGGGLRKGNEITSLNGEPVSDLDiqQMEALFSEKSVG 988
Cdd:cd00987    26 VLVASVDPGSPAAKAGLKPGDVILAVNGKPVKSVA--DLRRALAELKPG 72
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
500-616 4.66e-05

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


Pssm-ID: 269962  Cd Length: 114  Bit Score: 44.32  E-value: 4.66e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  500 KEQGVVRKAGWLFFKplvtlqKERKLELvaRRKWKQYWVTLKGCTLLFYetygkNSTEQNSAPRCALFAEDSIVQSvpEH 579
Cdd:cd01260     8 KDLGRGDCQGWLWKK------KEAKSFF--GQKWKKYWFVLKGSSLYWY-----SNQQDEKAEGFINLPDFKIERA--SE 72
                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 172088110  580 PKKEHVFCLSNSCGDVYLFQATSQTDLENWVTAIHSA 616
Cdd:cd01260    73 CKKKYAFKACHPKIKTFYFAAENLDDMNKWLSKLNMA 109
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
500-613 4.98e-05

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


Pssm-ID: 275402  Cd Length: 116  Bit Score: 44.15  E-value: 4.98e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  500 KEQGVVRKAGWLffkplvtlQKERKLelvaRRKWKQYWVTLKGCTLLFYEtygkNSTEqnsaprcALFAEDSI------- 572
Cdd:cd13215    16 KRSGAVIKSGYL--------SKRSKR----TLRYTRYWFVLKGDTLSWYN----SSTD-------LYFPAGTIdlryats 72
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 172088110  573 VQSVPEHPKKEHVFCLSNScGDVYLFQATSQTDLENWVTAI 613
Cdd:cd13215    73 IELSKSNGEATTSFKIVTN-SRTYKFKADSETSADEWVKAL 112
CtpA COG0793
C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, ...
924-1000 3.08e-04

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 223864 [Multi-domain]  Cd Length: 406  Bit Score: 45.02  E-value: 3.08e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  924 GFAVTVQVDEHqhlNRIFISDVLPDSLAYGGGLRKGNEITSLNGEPVSDLDIQQMEALFSEK---SVGLTLV------AR 994
Cdd:COG0793   101 GIGIELQMEDI---GGVKVVSPIDGSPAAKAGIKPGDVIIKIDGKSVGGVSLDEAVKLIRGKpgtKVTLTILragggkPF 177

                  ....*.
gi 172088110  995 PVTTRR 1000
Cdd:COG0793   178 TVTLTR 183
PH_CNK_insect-like cd13326
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
509-613 4.27e-04

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


Pssm-ID: 270135  Cd Length: 91  Bit Score: 40.79  E-value: 4.27e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  509 GWLFfkplvtlqkERKLELVARRKWKQYWVTLKGCTLlfyetYGKNSTEQNSApRCALFAEDSIVQSVPEHPKKEHVFCL 588
Cdd:cd13326     3 GWLY---------QRRRKGKGGGKWAKRWFVLKGSNL-----YGFRSQESTKA-DCVIFLPGFTVSPAPEVKSRKYAFKV 67
                          90       100
                  ....*....|....*....|....*
gi 172088110  589 SNScGDVYLFQATSQTDLENWVTAI 613
Cdd:cd13326    68 YHT-GTVFYFAAESQEDMKKWLDLL 91
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
507-615 4.99e-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: 40.91  E-value: 4.99e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  507 KAGWLFfkplvtlQKERKLELVARRKWKQYWVTLKGCTLLFYEtygknsTEQNSAPRCALFAEDSIVQSVPEHPkKEHVF 586
Cdd:cd13296     1 KSGWLT-------KKGGGSSTLSRRNWKSRWFVLRDTVLKYYE------NDQEGEKLLGTIDIRSAKEIVDNDP-KENRL 66
                          90       100
                  ....*....|....*....|....*....
gi 172088110  587 CLSNScGDVYLFQATSQTDLENWVTAIHS 615
Cdd:cd13296    67 SITTE-ERTYHLVAESPEDASQWVNVLTR 94
PDZ_metalloprotease cd00989
PDZ domain of bacterial and plant zinc metalloprotases, presumably membrane-associated or ...
934-990 5.69e-04

PDZ domain of bacterial and plant zinc metalloprotases, presumably membrane-associated or integral membrane proteases, which may be involved in signalling and regulatory mechanisms. May be responsible for substrate recognition and/or binding, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) polypeptides and even to lipids has been demonstrated. In this subfamily of protease-associated PDZ domains a C-terminal beta-strand forms the peptide-binding groove base, a circular permutation with respect to PDZ domains found in Eumetazoan signaling proteins.


Pssm-ID: 238489 [Multi-domain]  Cd Length: 79  Bit Score: 39.91  E-value: 5.69e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 172088110  934 HQHLNRIFISDVLPDSLAYGGGLRKGNEITSLNGEPVSD-LDIQQMEALFSEKSVGLT 990
Cdd:cd00989     8 GGPPIEPVIGEVVPGSPAAKAGLKAGDRILAINGQKIKSwEDLVDAVQENPGKPLTLT 65
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
501-620 1.01e-03

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


Pssm-ID: 270075  Cd Length: 110  Bit Score: 40.09  E-value: 1.01e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  501 EQGVVRKAGWLffkplvtlqkERKLElvaRRK-WKQYWVTLKGCTLLFYetygKNSTEQnsapRCALFAEDSIVQSVPEH 579
Cdd:cd13255     2 ISEAVLKAGYL----------EKKGE---RRKtWKKRWFVLRPTKLAYY----KNDKEY----RLLRLIDLTDIHTCTEV 60
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 172088110  580 PKKEHVfclsNSCGDV-----YLFQATSQTDLENWVTAIHSACASL 620
Cdd:cd13255    61 QLKKHD----NTFGIVtpartFYVQADSKAEMESWISAINLARQAL 102
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
507-613 1.16e-03

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


Pssm-ID: 270083  Cd Length: 114  Bit Score: 40.06  E-value: 1.16e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  507 KAGWLffkplvtlQKERKlelvARRKWKQYWVTLKGCTLLFYetygKNstEQNSAPRCALFAEDSIVQSVPEHPKKEHVF 586
Cdd:cd13263     5 KSGWL--------KKQGS----IVKNWQQRWFVLRGDQLYYY----KD--EDDTKPQGTIPLPGNKVKEVPFNPEEPGKF 66
                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 172088110  587 CL----------SNSCGDVYLFQATSQTDLENWVTAI 613
Cdd:cd13263    67 LFeiipggggdrMTSNHDSYLLMANSQAEMEEWVKVI 103
PH_RasGRF1_2 cd13261
Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; ...
532-616 3.22e-03

Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; RasGRF1 (also called GRF1; CDC25Mm/Ras-specific nucleotide exchange factor CDC25; GNRP/Guanine nucleotide-releasing protein) and RasGRF2 (also called GRF2; Ras guanine nucleotide exchange factor 2) are a family of guanine nucleotide exchange factors (GEFs). They both promote the exchange of Ras-bound GDP by GTP, thereby regulating the RAS signaling pathway. RasGRF1 and RasGRF2 form homooligomers and heterooligomers. GRF1 has 3 isoforms and GRF2 has 2 isoforms. The longest isoforms of RasGRF1 and RasGRF2 contain the following domains: a Rho-GEF domain sandwiched between 2 PH domains, IQ domains, a REM (Ras exchanger motif) domain, and a Ras-GEF domainwhich gives them the capacity to activate both Ras and Rac GTPases in response to signals from a variety of neurotransmitter receptors. Their IQ domains allow them to act as calcium sensors to mediate the actions of NMDA-type and calcium-permeable AMPA-type glutamate receptors. GRF1 also mediates the action of dopamine receptors that signal through cAMP. GRF1 and GRF2 play strikingly different roles in regulating MAP kinase family members, neuronal synaptic plasticity, specific forms of learning and memory, and behavioral responses to psychoactive drugs. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270081  Cd Length: 136  Bit Score: 39.33  E-value: 3.22e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  532 KWKQYWVTLKGCTLLFYETygknstEQNSAPRCALFAEDSIVQSVP---------EHPKKEHVFCLS--NSCGDVYLFQA 600
Cdd:cd13261    20 KWHERWFALYQNLLFYFEN------ESSSRPSGLYLLEGCYCERLPtpkgalkgkDHLEKQHYFTISfrHENQRQYELRA 93
                          90
                  ....*....|....*.
gi 172088110  601 TSQTDLENWVTAIHSA 616
Cdd:cd13261    94 ETESDCDEWVEAIKQA 109
PH_PLEKHG1_G2_G3 cd13243
Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) ...
1299-1394 5.68e-03

Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. 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: 270063  Cd Length: 147  Bit Score: 38.87  E-value: 5.68e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110 1299 EALKAMEKVASHINEMQKIYEDygMVFDQLVAEQSGTEKEVTELSMGELLMHSTvswlnpflsLGKARKDIELTVFVFKR 1378
Cdd:cd13243     6 EALDTMTQVAWHINDMKRKHEH--AVRVQEIQSLLDGWEGPELTTYGDLVLEGT---------FRMAGAKNERLLFLFDK 74
                          90
                  ....*....|....*..
gi 172088110 1379 AVILV-YKENCKLKKKL 1394
Cdd:cd13243    75 MLLITkKREDGILQYKT 91
PH2_FARP1-like cd13235
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
533-616 6.15e-03

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 2; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the 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: 270055  Cd Length: 98  Bit Score: 37.68  E-value: 6.15e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  533 WKQYWVTLKGCTLLFYETYgknsteQNSAPRCALFAEDSIVQ--SVPEHPKKEHVFCLSNScGDVYLFQATSQTDLENWV 610
Cdd:cd13235    19 WQKLWVVFTNFCLFFYKSH------QDEFPLASLPLLGYSVGlpSEADNIDKDYVFKLQFK-SHVYFFRAESEYTFERWM 91

                  ....*.
gi 172088110  611 TAIHSA 616
Cdd:cd13235    92 EVIRSA 97
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
507-627 8.73e-03

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


Pssm-ID: 270095  Cd Length: 106  Bit Score: 37.30  E-value: 8.73e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 172088110  507 KAGWLffkplvtlQKERKLelvaRRKWKQYWVTLKGCTLLFYETygkNSTEQNSAPRCALFAED-SIVQSVPEHPKKEHV 585
Cdd:cd13276     1 KAGWL--------EKQGEF----IKTWRRRWFVLKQGKLFWFKE---PDVTPYSKPRGVIDLSKcLTVKSAEDATNKENA 65
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 172088110  586 FCLSNScGDVYLFQATSQTDLENWVTAIHSACASLFAKKHGK 627
Cdd:cd13276    66 FELSTP-EETFYFIADNEKEKEEWIGAIGRAIVKHSRSVTDD 106
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.17
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
  • Marchler-Bauer A et al. (2015), "CDD: NCBI's conserved domain database.", Nucleic Acids Res.43(D)222-6.
  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
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