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Conserved domains on  [gi|1860299462|ref|NP_001138329|]
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pleckstrin homology domain-containing family G member 6 isoform b [Homo sapiens]

Protein Classification

pleckstrin homology domain-containing family G member 6( domain architecture ID 10457356)

pleckstrin homology domain-containing family G member 6 (PLEKHG6) acts as a guanine nucleotide exchange factor activating the small GTPase RHOA, which, in turn, induces myosin filament formation. Also activates RHOG

Gene Symbol:  PLEKHG6
Gene Ontology:  GO:0005085|GO:0051056|GO:0005096
PubMed:  11738596

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH_PLEKHG5_G6 cd13244
Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; ...
294-392 1.10e-43

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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: 270064  Cd Length: 100  Bit Score: 152.00  E-value: 1.10e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 294 RQLLLEGPVRVKEGREGKLDVYLFLFSDVLLVTKP-QRKADKAKVIRPPLMLEKLVCQPLRDPNSFLLIHLTEFQCVSSA 372
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPvKRKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80
                          90       100
                  ....*....|....*....|
gi 1860299462 373 LLVHCPSPTDRAQWLEKTQQ 392
Cdd:cd13244    81 YTFQTSSQEDTRRWLDAIRK 100
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
51-237 7.25e-41

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


:

Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 147.06  E-value: 7.25e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462  51 ALWELLTTELIYVRKLKIMTDLLAagllnLQRVGLLMEVSAE--TLFGNVPSLIRTHRSFWdevlgptLEETRASGQPLD 128
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFL-----PPNSKPLSESEEEikTIFSNIEEIYELHRQLL-------LEELLKEWISIQ 68
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 129 PIGlqSGFLTFGQRFHPYVQYCLRVKQTMAYAREQQETNPLFHAFVQWCEKHKRSGRQMLCDLLIKPHQRITKYPLLLHA 208
Cdd:pfam00621  69 RIG--DIFLKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKE 146
                         170       180       190
                  ....*....|....*....|....*....|
gi 1860299462 209 VLKRSPEARA-QEALNAMIEAVESFLRHIN 237
Cdd:pfam00621 147 LLKHTPPDHPdYEDLKKALEAIKEVAKQIN 176
 
Name Accession Description Interval E-value
PH_PLEKHG5_G6 cd13244
Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; ...
294-392 1.10e-43

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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: 270064  Cd Length: 100  Bit Score: 152.00  E-value: 1.10e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 294 RQLLLEGPVRVKEGREGKLDVYLFLFSDVLLVTKP-QRKADKAKVIRPPLMLEKLVCQPLRDPNSFLLIHLTEFQCVSSA 372
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPvKRKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80
                          90       100
                  ....*....|....*....|
gi 1860299462 373 LLVHCPSPTDRAQWLEKTQQ 392
Cdd:cd13244    81 YTFQTSSQEDTRRWLDAIRK 100
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
51-237 7.25e-41

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


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 147.06  E-value: 7.25e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462  51 ALWELLTTELIYVRKLKIMTDLLAagllnLQRVGLLMEVSAE--TLFGNVPSLIRTHRSFWdevlgptLEETRASGQPLD 128
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFL-----PPNSKPLSESEEEikTIFSNIEEIYELHRQLL-------LEELLKEWISIQ 68
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 129 PIGlqSGFLTFGQRFHPYVQYCLRVKQTMAYAREQQETNPLFHAFVQWCEKHKRSGRQMLCDLLIKPHQRITKYPLLLHA 208
Cdd:pfam00621  69 RIG--DIFLKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKE 146
                         170       180       190
                  ....*....|....*....|....*....|
gi 1860299462 209 VLKRSPEARA-QEALNAMIEAVESFLRHIN 237
Cdd:pfam00621 147 LLKHTPPDHPdYEDLKKALEAIKEVAKQIN 176
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
51-237 9.39e-37

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


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 135.89  E-value: 9.39e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462   51 ALWELLTTELIYVRKLKIMTDLLAAGLLnlQRVGLLMEVSAETLFGNVPSLIRTHRSFWDEvlgptLEETRA-SGQPLDP 129
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLK--KELKLLSPNELETLFGNIEEIYEFHRDFLDE-----LEERIEeWDDSVER 73
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462  130 IGlqSGFLTFGQRFHPYVQYCLRVKQTMAYaREQQETNPLFHAFVQWCEKHKRSGRQMLCDLLIKPHQRITKYPLLLHAV 209
Cdd:smart00325  74 IG--DVFLKLEEFFKIYSEYCSNHPDALEL-LKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKEL 150
                          170       180
                   ....*....|....*....|....*....
gi 1860299462  210 LKRSPEA-RAQEALNAMIEAVESFLRHIN 237
Cdd:smart00325 151 LKHTPEDhEDREDLKKALKAIKELANQVN 179
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
48-237 5.02e-35

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


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 130.88  E-value: 5.02e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462  48 QQEALWELLTTELIYVRKLKIMTDLLAAGLLnlQRVGLLMEVSAETLFGNVPSLIRTHRSFWDEvLGPTLEETRASGQpl 127
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLD--KELLPLSPEEVELLFGNIEEIYEFHRIFLKS-LEERVEEWDKSGP-- 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 128 dpiGLQSGFLTFGQRFHPYVQYCLRVKQTMAYAREQQETNPLFHAFVQWCEKhkRSGRQMLCDLLIKPHQRITKYPLLLH 207
Cdd:cd00160    76 ---RIGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAES--ECGRLKLESLLLKPVQRLTKYPLLLK 150
                         170       180       190
                  ....*....|....*....|....*....|.
gi 1860299462 208 AVLKRSPEA-RAQEALNAMIEAVESFLRHIN 237
Cdd:cd00160   151 ELLKHTPDGhEDREDLKKALEAIKEVASQVN 181
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
6-399 1.71e-11

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 67.61  E-value: 1.71e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462    6 RLPPEDRRHWEIG---EGGDSGLTIE-----KSWRELVPghKEMSQELCHQ----QEALWELLTTELIYVRKLKIMTDLL 73
Cdd:COG5422    433 RLEQQARLHLKLMgglKRNSSLALDKfdeekNLWTLSVP--KEVWESLPKQeikrQEAIYEVIYTERDFVKDLEYLRDTW 510
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462   74 aagllnlqrVGLLMEVSAetlfgnVPS-----LIRTHRSFWDEVLGPT--LEETRASGQPLDPI--GLQSGFLTFGQRFH 144
Cdd:COG5422    511 ---------IKPLEESNI------IPEnarrnFIKHVFANINEIYAVNskLLKALTNRQCLSPIvnGIADIFLDYVPKFE 575
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462  145 PYVQYclrVKQTMAYARE---QQETNPLFHAFVQWCEKHKRSGRQMLCDLLIKPHQRITKYPLLLHAVLKRS-PEARAQE 220
Cdd:COG5422    576 PFIKY---GASQPYAKYEferEKSVNPNFARFDHEVERLDESRKLELDGYLTKPTTRLARYPLLLEEVLKFTdPDNPDTE 652
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462  221 ALNAMIEAVESFLRHINgqvrqgeeQESLAAAAQrigpYEVLEPPSDEVEKNLRPFSTLDltspmlgvasEHTRQLLLEG 300
Cdd:COG5422    653 DIPKVIDMLREFLSRLN--------FESGKAENR----GDLFHLNQQLLFKPEYVNLGLN----------DEYRKIIFKG 710
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462  301 PVRVKEGR----EGKLDVYLFLFSDVLLVTKP--QRKADKAKVIRPPLMLEKLVCQP----------LRDPNSFLLI--- 361
Cdd:COG5422    711 VLKRKAKSktdgSLRGDIQFFLLDNMLLFCKAkaVNKWRQHKVFQRPIPLELLFISPdedspdraeyLKPAPSADVLdpa 790
                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*....
gi 1860299462  362 ---------HLTEFQCVSSALLV--HCPSPTDRAQWLEKTQQAQAALQK 399
Cdd:COG5422    791 yntkppknaYGFELYGNGQRYQItlYAETHAGRDTWLEHIKNQQDILRT 839
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
296-395 2.73e-06

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 46.39  E-value: 2.73e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462  296 LLLEGPVRVKE--GREGKLDVYLFLFSDVLLVTKpQRKADKAKVIRPPLMLEKLVCQPLRD------PNSFLLIHLTEFQ 367
Cdd:smart00233   1 VIKEGWLYKKSggGKKSWKKRYFVLFNSTLLYYK-SKKDKKSYKPKGSIDLSGCTVREAPDpdsskkPHCFEIKTSDRKT 79
                           90       100
                   ....*....|....*....|....*...
gi 1860299462  368 cvssaLLVHCPSPTDRAQWLEKTQQAQA 395
Cdd:smart00233  80 -----LLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
296-393 4.64e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 40.24  E-value: 4.64e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 296 LLLEGPVRVKEGREGKL--DVYLFLFSDVLLVTKPqRKADKAKVIRPPLMLEKLVCQPLRD------PNSFLLIHLTefQ 367
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSwkKRYFVLFDGSLLYYKD-DKSGKSKEPKGSISLSGCEVVEVVAsdspkrKFCFELRTGE--R 77
                          90       100
                  ....*....|....*....|....*.
gi 1860299462 368 CVSSALLVHCPSPTDRAQWLEKTQQA 393
Cdd:pfam00169  78 TGKRTYLLQAESEEERKDWIKAIQSA 103
 
Name Accession Description Interval E-value
PH_PLEKHG5_G6 cd13244
Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; ...
294-392 1.10e-43

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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: 270064  Cd Length: 100  Bit Score: 152.00  E-value: 1.10e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 294 RQLLLEGPVRVKEGREGKLDVYLFLFSDVLLVTKP-QRKADKAKVIRPPLMLEKLVCQPLRDPNSFLLIHLTEFQCVSSA 372
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPvKRKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80
                          90       100
                  ....*....|....*....|
gi 1860299462 373 LLVHCPSPTDRAQWLEKTQQ 392
Cdd:cd13244    81 YTFQTSSQEDTRRWLDAIRK 100
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
51-237 7.25e-41

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


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 147.06  E-value: 7.25e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462  51 ALWELLTTELIYVRKLKIMTDLLAagllnLQRVGLLMEVSAE--TLFGNVPSLIRTHRSFWdevlgptLEETRASGQPLD 128
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFL-----PPNSKPLSESEEEikTIFSNIEEIYELHRQLL-------LEELLKEWISIQ 68
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 129 PIGlqSGFLTFGQRFHPYVQYCLRVKQTMAYAREQQETNPLFHAFVQWCEKHKRSGRQMLCDLLIKPHQRITKYPLLLHA 208
Cdd:pfam00621  69 RIG--DIFLKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKE 146
                         170       180       190
                  ....*....|....*....|....*....|
gi 1860299462 209 VLKRSPEARA-QEALNAMIEAVESFLRHIN 237
Cdd:pfam00621 147 LLKHTPPDHPdYEDLKKALEAIKEVAKQIN 176
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
51-237 9.39e-37

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


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 135.89  E-value: 9.39e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462   51 ALWELLTTELIYVRKLKIMTDLLAAGLLnlQRVGLLMEVSAETLFGNVPSLIRTHRSFWDEvlgptLEETRA-SGQPLDP 129
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLK--KELKLLSPNELETLFGNIEEIYEFHRDFLDE-----LEERIEeWDDSVER 73
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462  130 IGlqSGFLTFGQRFHPYVQYCLRVKQTMAYaREQQETNPLFHAFVQWCEKHKRSGRQMLCDLLIKPHQRITKYPLLLHAV 209
Cdd:smart00325  74 IG--DVFLKLEEFFKIYSEYCSNHPDALEL-LKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKEL 150
                          170       180
                   ....*....|....*....|....*....
gi 1860299462  210 LKRSPEA-RAQEALNAMIEAVESFLRHIN 237
Cdd:smart00325 151 LKHTPEDhEDREDLKKALKAIKELANQVN 179
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
48-237 5.02e-35

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


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 130.88  E-value: 5.02e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462  48 QQEALWELLTTELIYVRKLKIMTDLLAAGLLnlQRVGLLMEVSAETLFGNVPSLIRTHRSFWDEvLGPTLEETRASGQpl 127
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLD--KELLPLSPEEVELLFGNIEEIYEFHRIFLKS-LEERVEEWDKSGP-- 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 128 dpiGLQSGFLTFGQRFHPYVQYCLRVKQTMAYAREQQETNPLFHAFVQWCEKhkRSGRQMLCDLLIKPHQRITKYPLLLH 207
Cdd:cd00160    76 ---RIGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAES--ECGRLKLESLLLKPVQRLTKYPLLLK 150
                         170       180       190
                  ....*....|....*....|....*....|.
gi 1860299462 208 AVLKRSPEA-RAQEALNAMIEAVESFLRHIN 237
Cdd:cd00160   151 ELLKHTPDGhEDREDLKKALEAIKEVASQVN 181
PH_PLEKHG7 cd13245
Pleckstrin homology domain-containing family G member 7 pleckstrin homology (PH) domain; ...
295-391 8.88e-16

Pleckstrin homology domain-containing family G member 7 pleckstrin homology (PH) domain; PLEKHG7 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG7 is proposed to functions as a guanine nucleotide exchange factor (GEF) and is involved in the regulation of Rho protein signal transduction. 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: 270065  Cd Length: 128  Bit Score: 74.23  E-value: 8.88e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 295 QLLLEGPVRVKEGreGK-LDVYLFLFSDVLLVTKPQRKADKAK------------------------VIRPPLMLEKLV- 348
Cdd:cd13245     1 QLLHEGPLTLIES--GKtLDVYLFLFDDMLLITKMKKNLKKKKssdsensmpsleltplikeggsytVYKQPIPLDRLCl 78
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1860299462 349 -------CQPLRDPNSFLLIHLTEFQCVSSALLVHCPSPTDRAQWLEKTQ 391
Cdd:cd13245    79 hdvdpneATANGLKHAFVLVHLNRYQQVIGVYTLQASSENTKQTWMSKLR 128
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
6-399 1.71e-11

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 67.61  E-value: 1.71e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462    6 RLPPEDRRHWEIG---EGGDSGLTIE-----KSWRELVPghKEMSQELCHQ----QEALWELLTTELIYVRKLKIMTDLL 73
Cdd:COG5422    433 RLEQQARLHLKLMgglKRNSSLALDKfdeekNLWTLSVP--KEVWESLPKQeikrQEAIYEVIYTERDFVKDLEYLRDTW 510
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462   74 aagllnlqrVGLLMEVSAetlfgnVPS-----LIRTHRSFWDEVLGPT--LEETRASGQPLDPI--GLQSGFLTFGQRFH 144
Cdd:COG5422    511 ---------IKPLEESNI------IPEnarrnFIKHVFANINEIYAVNskLLKALTNRQCLSPIvnGIADIFLDYVPKFE 575
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462  145 PYVQYclrVKQTMAYARE---QQETNPLFHAFVQWCEKHKRSGRQMLCDLLIKPHQRITKYPLLLHAVLKRS-PEARAQE 220
Cdd:COG5422    576 PFIKY---GASQPYAKYEferEKSVNPNFARFDHEVERLDESRKLELDGYLTKPTTRLARYPLLLEEVLKFTdPDNPDTE 652
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462  221 ALNAMIEAVESFLRHINgqvrqgeeQESLAAAAQrigpYEVLEPPSDEVEKNLRPFSTLDltspmlgvasEHTRQLLLEG 300
Cdd:COG5422    653 DIPKVIDMLREFLSRLN--------FESGKAENR----GDLFHLNQQLLFKPEYVNLGLN----------DEYRKIIFKG 710
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462  301 PVRVKEGR----EGKLDVYLFLFSDVLLVTKP--QRKADKAKVIRPPLMLEKLVCQP----------LRDPNSFLLI--- 361
Cdd:COG5422    711 VLKRKAKSktdgSLRGDIQFFLLDNMLLFCKAkaVNKWRQHKVFQRPIPLELLFISPdedspdraeyLKPAPSADVLdpa 790
                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*....
gi 1860299462  362 ---------HLTEFQCVSSALLV--HCPSPTDRAQWLEKTQQAQAALQK 399
Cdd:COG5422    791 yntkppknaYGFELYGNGQRYQItlYAETHAGRDTWLEHIKNQQDILRT 839
PH_ephexin cd01221
Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine ...
292-388 1.28e-07

Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine nucleotide exchange factor) plays a role in the homeostatic modulation of presynaptic neurotransmitter release. Specific functions are still unknown for Ephexin-2 (also called RhoGEF19) and Ephexin-3 (also called Rho guanine nucleotide exchange factor 5/RhoGEF5, Transforming immortalized mammary oncogene/p60 TIM, and NGEF/neuronalGEF). Ephexin-4 (also called RhoGEF16) acts downstream of EphA2 to promote ligand-independent breast cancer cell migration and invasion toward epidermal growth factor through activation of RhoG. This in turn results in the activation of RhoG which recruits ELMO2 and Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. Ephexin-5 is the specific GEF for RhoA activation and the regulation of vascular smooth muscle contractility. It interacts with EPHA4 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. The members of the Ephexin family contains a RhoGEF (DH) followed by a PH domain and an SH3 domain. The ephexin PH domain is believed to act with the DH domain in mediating protein-protein interactions. 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: 269929  Cd Length: 131  Bit Score: 50.72  E-value: 1.28e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 292 HTRQLLLEGPVRVKEGREGKL---------DVYLFLFSDVLLVTKP------------QRKADKAKVIRPPLMLEKLVCq 350
Cdd:cd01221    10 SSRWLVKRGELTELVEDGGSLtfrkkfsktPVYLFLFNDLLLITKKkseerylvldyaPRNLVQVEEVEDPLQLPQPLG- 88
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1860299462 351 plrdPNSFLLIHLTEFQCVSSALLVHCPSPTDRAQWLE 388
Cdd:cd01221    89 ----KNLFLLTLLENHEGKTVELLLSAESESDRERWLS 122
PH1_FGD5_FGD6 cd13389
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal ...
294-402 1.87e-06

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275424  Cd Length: 124  Bit Score: 47.26  E-value: 1.87e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 294 RQLLLEGPVrVKEGREGKLDVYLFLFSDVLLVTKPQRKADKAKVIRP-PLMLEKlVCQPLRD--PNSFLLIHLTefqcvS 370
Cdd:cd13389    12 RKLIKEGEL-MKVSRKEMQPRYFFLFNDCLLYTTPVQSSGMLKLNNElPLSGMK-VKLPEDEeySNEFQIISTK-----R 84
                          90       100       110
                  ....*....|....*....|....*....|..
gi 1860299462 371 SALLVhCPSPTDRAQWLEKTQQAQAALQKLKA 402
Cdd:cd13389    85 SFTLI-ASSEEERDEWVKALSRAIEEHTKKQR 115
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
296-395 2.73e-06

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 46.39  E-value: 2.73e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462  296 LLLEGPVRVKE--GREGKLDVYLFLFSDVLLVTKpQRKADKAKVIRPPLMLEKLVCQPLRD------PNSFLLIHLTEFQ 367
Cdd:smart00233   1 VIKEGWLYKKSggGKKSWKKRYFVLFNSTLLYYK-SKKDKKSYKPKGSIDLSGCTVREAPDpdsskkPHCFEIKTSDRKT 79
                           90       100
                   ....*....|....*....|....*...
gi 1860299462  368 cvssaLLVHCPSPTDRAQWLEKTQQAQA 395
Cdd:smart00233  80 -----LLLQAESEEEREKWVEALRKAIA 102
PH_RARhoGAP cd13319
RA and RhoGAP domain-containing protein Pleckstrin homology PH domain; RARhoGAP (also called ...
294-328 3.98e-06

RA and RhoGAP domain-containing protein Pleckstrin homology PH domain; RARhoGAP (also called Rho GTPase-activating protein 20 and ARHGAP20 ) is thought to function in rearrangements of the cytoskeleton and cell signaling events that occur during spermatogenesis. RARhoGAP was also shown to be activated by Rap1 and to induce inactivation of Rho, resulting in the neurite outgrowth. Recent findings show that ARHGAP20, even although it is located in the middle of the MDR on 11q22-23, is expressed at higher levels in chronic lymphocytic leukemia patients with 11q22-23 and/or 13q14 deletions and its expression pattern suggests a functional link between cases with 11q22-23 and 13q14 deletions. The mechanism needs to be further studied. RARhoGAP contains a PH domain, a Ras-associating domain, a Rho-GAP domain, and ANXL repeats. 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: 270129  Cd Length: 97  Bit Score: 45.69  E-value: 3.98e-06
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1860299462 294 RQLLLEGPVRVKEGREGKlDVYLFLFSDVLLVTKP 328
Cdd:cd13319     1 RTFLLEGPVQLTRGLQTQ-ERHLFLFSDVLVVAKP 34
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
298-388 1.46e-05

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


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 44.07  E-value: 1.46e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 298 LEGPVRVKEGREGKL--DVYLFLFSDVLLVTKPQRKADKA--KVIRPPLMLEKLVCQPLRDPNSFLLIHLTEfqcvsSAL 373
Cdd:cd00821     1 KEGYLLKRGGGGLKSwkKRWFVLFEGVLLYYKSKKDSSYKpkGSIPLSGILEVEEVSPKERPHCFELVTPDG-----RTY 75
                          90
                  ....*....|....*
gi 1860299462 374 LVHCPSPTDRAQWLE 388
Cdd:cd00821    76 YLQADSEEERQEWLK 90
PH_RalBD_exo84 cd01226
Exocyst complex 84-kDa subunit Ral-binding domain/Pleckstrin Homology (PH) domain; The Sec6/8 ...
293-399 4.30e-05

Exocyst complex 84-kDa subunit Ral-binding domain/Pleckstrin Homology (PH) domain; The Sec6/8 complex, also called the exocyst complex, forms an octameric protein (Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84) involved in the tethering of secretory vesicles to specific regions on the plasma membrane. The regulation of Sec6/8 complex differs between mammals and yeast. Mamalian Exo84 and Sec5 are effector targets for active Ral GTPases which are not present in yeast. Ral GTPases are members of the Ras superfamily, and as such cycle between an active GTP-bound state and an inactive GDP-bound state. The Exo84 Ral-binding domain adopts a PH domain fold. Mammalian Exo84 and Sec5 competitively bind to active RalA. 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: 269933  Cd Length: 115  Bit Score: 43.41  E-value: 4.30e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 293 TRQLLLEGPVRVKEGREGKL--DVYLFLFSDVLLVTKPqrKADKakviRPPLMLEKLVCQPLRD------------PNSF 358
Cdd:cd01226     5 GRYLLHEGDLLELDPDDYKPiqKVHLFLLNDVLLIASW--LPNR----RGPVRYKFQALYPLEDlavvnvkdlgpvKNAF 78
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1860299462 359 LLIHLTE---FQCVSSAllvhcpsptDRAQWLEKTQQA-QAALQK 399
Cdd:cd01226    79 KLLTFPEtrvFQCENAK---------IKKEWLEKFEQAkRAKLAK 114
PH_Net1 cd13224
Neuroepithelial cell transforming 1 Pleckstrin homology (PH) domain; Net1 (also called ArhGEF8) ...
291-354 2.33e-04

Neuroepithelial cell transforming 1 Pleckstrin homology (PH) domain; Net1 (also called ArhGEF8) is part of the family of Rho guanine nucleotide exchange factors. Members of this family activate Rho proteins by catalyzing the exchange of GDP for GTP. The protein encoded by this gene interacts with RhoA within the cell nucleus and may play a role in repairing DNA damage after ionizing radiation. Net1 binds to caspase activation and recruitment domain (CARD)- and membrane-associated guanylate kinase-like domain-containing (CARMA) proteins and regulates nuclear factor kB activation. Net1 contains a RhoGEF domain N-terminal to a single PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270044  Cd Length: 135  Bit Score: 41.81  E-value: 2.33e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1860299462 291 EHTRQLLLEGPVRVKEGREgkldVYLFLFSDVLLVTKPQRKADKA--KVIRPPLMLEKLVCQPLRD 354
Cdd:cd13224    15 ENSKALLCHGELRNKSGHK----LYVFLFQDILVLTRPVTRNERQsfQVYRQPIPVQELVLEDLQD 76
PH pfam00169
PH domain; PH stands for pleckstrin homology.
296-393 4.64e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 40.24  E-value: 4.64e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 296 LLLEGPVRVKEGREGKL--DVYLFLFSDVLLVTKPqRKADKAKVIRPPLMLEKLVCQPLRD------PNSFLLIHLTefQ 367
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSwkKRYFVLFDGSLLYYKD-DKSGKSKEPKGSISLSGCEVVEVVAsdspkrKFCFELRTGE--R 77
                          90       100
                  ....*....|....*....|....*.
gi 1860299462 368 CVSSALLVHCPSPTDRAQWLEKTQQA 393
Cdd:pfam00169  78 TGKRTYLLQAESEEERKDWIKAIQSA 103
PH_ITSN cd13264
Intersectin Pleckstrin homology (PH) domain; ITSNs, an adaptor protein family, play a role in ...
294-393 4.73e-04

Intersectin Pleckstrin homology (PH) domain; ITSNs, an adaptor protein family, play a role in endo- and exocytosis, actin cytoskeleton rearrangement and signal transduction. There are two human ITSN genes: ITSN1 and ITSN2. They share significant sequence identity and a similar domain structure having both short and long isoforms produced by alternative splicing. The short isoform (ITSN-S) consists of two Eps15 homology domains (EH1 and EH2), a coiled-coil region (CCR) and five Src homology 3 domains (SH3A-E). The EH domains bind to Asn-Pro-Phe motifs and are implicated in endocytosis and vesicle transport. The SH3 domains bind to proline-rich sequences and are commonly found in proteins implicated in cell signalling pathways, cytoskeletal organization and membrane traffic. The long isoform (ITSN-L) contains three additional C-terminal domains, a Dbl homology domain (DH), a Pleckstrin homology domain (PH) and a C2 domain. The tandem DH-PH domains are present in all Dbl family of GEFs. ITSN acts specifically on Cdc42 through its DH domain with no portion of the PH domain making contact with Cdc42. This is in contrast to Dbs which requires the PH domain for full catalytic activity. The ITSN PH domain binds phosphoinositides. C2 domains are usually involved in Ca2+-dependent and Ca2+-independent phospholipid binding. There are more than 30 proteins that interact with ITSNs. ITSN-S is present in mammals, frogs, flies and nematodes, while ITSN-L is present only in vertebrates. 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: 270084  Cd Length: 132  Bit Score: 40.52  E-value: 4.73e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 294 RQLLLEGP-VRVKEGREgkldVYLFLFSDVLLVTKPQR---------KADKAKVI-----RPPLMLEKLVCQPLRDPNS- 357
Cdd:cd13264    14 RKFLHSGKlYKAKSNKE----LYGFLFNDFLLLTQPIKplgssgndfVFDNKANIqykmyKTPIFLNEVLVKLPTDPSGd 89
                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1860299462 358 ---FLLIHLTEFQCVSSAllvhcpSPTDRAQWLEKTQQA 393
Cdd:cd13264    90 epiFHISHIDRVYTLRAE------SINERTAWVQKIKAA 122
PH_16 pfam17838
PH domain;
271-393 5.33e-04

PH domain;


Pssm-ID: 436083  Cd Length: 127  Bit Score: 40.46  E-value: 5.33e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860299462 271 KNLRPFSTLDLTspmlgvasehTRQLLLEGPVRVKEGREGKLDVYLFLFSD--VLLVTKPQRKA----------DKAKVI 338
Cdd:pfam17838   2 PLGEEFKKLDLT----------TRKLIHEGPLTWRNSKGKLVEVHALLLEDilVLLQEKDQKLVlaclstgsenVDQKTQ 71
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1860299462 339 RPPLMLEKL-VCQPLRDPNSFLLIHLTEFQcvSSALLVHCPSPTDRAQWLEKTQQA 393
Cdd:pfam17838  72 SPIISLKKLiVREVATDKKAFFLISTSPSD--PQMYELHASTKSERNTWTKLIQDA 125
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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