NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|299758454|ref|NP_001177658|]
View 

ras-specific guanine nucleotide-releasing factor RalGPS1 isoform 2 [Homo sapiens]

Protein Classification

ras-specific guanine nucleotide-releasing factor RalGPS( domain architecture ID 10639779)

ras-specific guanine nucleotide-releasing factor RalGPS is a guanine nucleotide exchange factor for the small GTPase RALA; similar to RalGPS1 and RalGPS2

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

Name Accession Description Interval E-value
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
46-288 4.91e-86

Guanine nucleotide exchange factor for Ras-like small GTPases;


:

Pssm-ID: 214539  Cd Length: 242  Bit Score: 266.03  E-value: 4.91e-86
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454    46 VLKVTPEEFASQITLMDIPVFKAIQPEELASCGWSKKEKHSLAP-NVVAFTRRFNQVSFWVVREILTAQTLKIRAEILSH 124
Cdd:smart00147   1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPSPlNLEAFIRRFNEVSNWVATEILKQTTPKDRAELLSK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454   125 FVKIAKKLLELNNLHSLMSVVSALQSAPIFRLTKTWALLNRKDKTTFEKLDYLMSKEDNYKRTREYIRSLKMVPSIPYLG 204
Cdd:smart00147  81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSCNLPPCIPFLG 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454   205 IYLLDLIYIDSAYPASGS-IMENEQRSNQMNNILRIIADLQVScSYDHLTTLPHVQKYLKSVryIEELQKfvEDDNYKLS 283
Cdd:smart00147 161 VLLKDLTFIDEGNPDFLEnGLVNFEKRRQIAEILREIRQLQSQ-PYNLRPNRSDIQSLLQQL--LDHLDE--EEELYQLS 235

                   ....*
gi 299758454   284 LRIEP 288
Cdd:smart00147 236 LKIEP 240
PH_RalGPS1_2 cd13310
Ral GEF with PH domain and SH3 binding motif 1 and 2 Pleckstrin homology (PH) domain; RalGPS1 ...
391-506 4.10e-72

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: 225.21  E-value: 4.10e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454 391 TMEGPLRRKTLLKEGRKPALSSWTRYWVILSGSTLLYYGAKSLRGTDRKHYKSTPGKKVSIVGWMVQLPDDPEHPDIFQL 470
Cdd:cd13310    1 TMQGCLRRKTVLKEGRKPTVSSWQRYWVQLWGTSLVYYAPKSLKGTERSDFKSEPCKIVSISGWMVVLGDDPEHPDSFQL 80
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 299758454 471 NNPDKGNVYKFQTGSRFHAILWHKHLDDACKSNRPQ 506
Cdd:cd13310   81 TDPEKGNVYKFRAGSRSNALLWLKHLKDACKGNRPP 116
 
Name Accession Description Interval E-value
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
46-288 4.91e-86

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 266.03  E-value: 4.91e-86
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454    46 VLKVTPEEFASQITLMDIPVFKAIQPEELASCGWSKKEKHSLAP-NVVAFTRRFNQVSFWVVREILTAQTLKIRAEILSH 124
Cdd:smart00147   1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPSPlNLEAFIRRFNEVSNWVATEILKQTTPKDRAELLSK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454   125 FVKIAKKLLELNNLHSLMSVVSALQSAPIFRLTKTWALLNRKDKTTFEKLDYLMSKEDNYKRTREYIRSLKMVPSIPYLG 204
Cdd:smart00147  81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSCNLPPCIPFLG 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454   205 IYLLDLIYIDSAYPASGS-IMENEQRSNQMNNILRIIADLQVScSYDHLTTLPHVQKYLKSVryIEELQKfvEDDNYKLS 283
Cdd:smart00147 161 VLLKDLTFIDEGNPDFLEnGLVNFEKRRQIAEILREIRQLQSQ-PYNLRPNRSDIQSLLQQL--LDHLDE--EEELYQLS 235

                   ....*
gi 299758454   284 LRIEP 288
Cdd:smart00147 236 LKIEP 240
PH_RalGPS1_2 cd13310
Ral GEF with PH domain and SH3 binding motif 1 and 2 Pleckstrin homology (PH) domain; RalGPS1 ...
391-506 4.10e-72

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: 225.21  E-value: 4.10e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454 391 TMEGPLRRKTLLKEGRKPALSSWTRYWVILSGSTLLYYGAKSLRGTDRKHYKSTPGKKVSIVGWMVQLPDDPEHPDIFQL 470
Cdd:cd13310    1 TMQGCLRRKTVLKEGRKPTVSSWQRYWVQLWGTSLVYYAPKSLKGTERSDFKSEPCKIVSISGWMVVLGDDPEHPDSFQL 80
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 299758454 471 NNPDKGNVYKFQTGSRFHAILWHKHLDDACKSNRPQ 506
Cdd:cd13310   81 TDPEKGNVYKFRAGSRSNALLWLKHLKDACKGNRPP 116
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
53-218 1.33e-67

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.


Pssm-ID: 459872  Cd Length: 179  Bit Score: 215.92  E-value: 1.33e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454   53 EFASQITLMDIPVFKAIQPEELASCGWSKKEKHSLAPNVVAFTRRFNQVSFWVVREILTAQTLKIRAEILSHFVKIAKKL 132
Cdd:pfam00617   1 ELARQLTLIEFELFRKIKPRELLGSAWSKKDKKENSPNIEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIAEHC 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454  133 LELNNLHSLMSVVSALQSAPIFRLTKTWALLNRKDKTTFEKLDYLMSKEDNYKRTREYIRSLKmVPSIPYLGIYLLDLIY 212
Cdd:pfam00617  81 RELNNFNSLMAILSGLNSSPISRLKKTWELVSKKYKKTLEELEKLMSPSRNFKNYREALSSAS-PPCIPFLGLYLTDLTF 159

                  ....*.
gi 299758454  213 IDSAYP 218
Cdd:pfam00617 160 IEEGNP 165
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
46-285 1.74e-62

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 204.79  E-value: 1.74e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454  46 VLKVTPEEFASQITLMDIPVFKAIQPEELASCGWSKK-EKHSLAPNVVAFTRRFNQVSFWVVREILTAQTLKIRAEILSH 124
Cdd:cd00155    1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKdKNIHLSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454 125 FVKIAKKLLELNNLHSLMSVVSALQSAPIFRLTKTWALLNRKDKTTFEKLDYLMSKEDNYKRTREYIRSLK-MVPSIPYL 203
Cdd:cd00155   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVGpNPPCVPFL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454 204 GIYLLDLIYIDSAYPasGSIMENEQRSNQMNNILRIIADLQV--SCSYDhLTTLPHVQKYLKSVRYIEELqkfvEDDNYK 281
Cdd:cd00155  161 GVYLKDLTFLHEGNP--DFLEGNLVNFEKRRKIAEILREIRQlqSNSYE-LNRDEDILAFLWKLLELILN----EDELYE 233

                 ....
gi 299758454 282 LSLR 285
Cdd:cd00155  234 LSLE 237
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
390-501 2.82e-12

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: 62.95  E-value: 2.82e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454   390 PTMEGPLRRKTllkegrKPALSSWTRYWVILSGSTLLYYGAKSlrgtdrKHYKSTPGKKVSIVGWMVQLPDDPEHPD--- 466
Cdd:smart00233   1 VIKEGWLYKKS------GGGKKSWKKRYFVLFNSTLLYYKSKK------DKKSYKPKGSIDLSGCTVREAPDPDSSKkph 68
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 299758454   467 IFQLNNPDkGNVYKFQTGSRFHAILWHKHLDDACK 501
Cdd:smart00233  69 CFEIKTSD-RKTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
390-501 1.71e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 57.96  E-value: 1.71e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454  390 PTMEGPLRRKTllkegrKPALSSWTRYWVILSGSTLLYYGAKSlRGTDRKHYKSTPGKKVSIVgwMVQLPDDPEHPDIFQ 469
Cdd:pfam00169   1 VVKEGWLLKKG------GGKKKSWKKRYFVLFDGSLLYYKDDK-SGKSKEPKGSISLSGCEVV--EVVASDSPKRKFCFE 71
                          90       100       110
                  ....*....|....*....|....*....|....
gi 299758454  470 L--NNPDKGNVYKFQTGSRFHAILWHKHLDDACK 501
Cdd:pfam00169  72 LrtGERTGKRTYLLQAESEEERKDWIKAIQSAIR 105
 
Name Accession Description Interval E-value
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
46-288 4.91e-86

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 266.03  E-value: 4.91e-86
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454    46 VLKVTPEEFASQITLMDIPVFKAIQPEELASCGWSKKEKHSLAP-NVVAFTRRFNQVSFWVVREILTAQTLKIRAEILSH 124
Cdd:smart00147   1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPSPlNLEAFIRRFNEVSNWVATEILKQTTPKDRAELLSK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454   125 FVKIAKKLLELNNLHSLMSVVSALQSAPIFRLTKTWALLNRKDKTTFEKLDYLMSKEDNYKRTREYIRSLKMVPSIPYLG 204
Cdd:smart00147  81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSCNLPPCIPFLG 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454   205 IYLLDLIYIDSAYPASGS-IMENEQRSNQMNNILRIIADLQVScSYDHLTTLPHVQKYLKSVryIEELQKfvEDDNYKLS 283
Cdd:smart00147 161 VLLKDLTFIDEGNPDFLEnGLVNFEKRRQIAEILREIRQLQSQ-PYNLRPNRSDIQSLLQQL--LDHLDE--EEELYQLS 235

                   ....*
gi 299758454   284 LRIEP 288
Cdd:smart00147 236 LKIEP 240
PH_RalGPS1_2 cd13310
Ral GEF with PH domain and SH3 binding motif 1 and 2 Pleckstrin homology (PH) domain; RalGPS1 ...
391-506 4.10e-72

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: 225.21  E-value: 4.10e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454 391 TMEGPLRRKTLLKEGRKPALSSWTRYWVILSGSTLLYYGAKSLRGTDRKHYKSTPGKKVSIVGWMVQLPDDPEHPDIFQL 470
Cdd:cd13310    1 TMQGCLRRKTVLKEGRKPTVSSWQRYWVQLWGTSLVYYAPKSLKGTERSDFKSEPCKIVSISGWMVVLGDDPEHPDSFQL 80
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 299758454 471 NNPDKGNVYKFQTGSRFHAILWHKHLDDACKSNRPQ 506
Cdd:cd13310   81 TDPEKGNVYKFRAGSRSNALLWLKHLKDACKGNRPP 116
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
53-218 1.33e-67

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.


Pssm-ID: 459872  Cd Length: 179  Bit Score: 215.92  E-value: 1.33e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454   53 EFASQITLMDIPVFKAIQPEELASCGWSKKEKHSLAPNVVAFTRRFNQVSFWVVREILTAQTLKIRAEILSHFVKIAKKL 132
Cdd:pfam00617   1 ELARQLTLIEFELFRKIKPRELLGSAWSKKDKKENSPNIEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIAEHC 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454  133 LELNNLHSLMSVVSALQSAPIFRLTKTWALLNRKDKTTFEKLDYLMSKEDNYKRTREYIRSLKmVPSIPYLGIYLLDLIY 212
Cdd:pfam00617  81 RELNNFNSLMAILSGLNSSPISRLKKTWELVSKKYKKTLEELEKLMSPSRNFKNYREALSSAS-PPCIPFLGLYLTDLTF 159

                  ....*.
gi 299758454  213 IDSAYP 218
Cdd:pfam00617 160 IEEGNP 165
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
46-285 1.74e-62

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 204.79  E-value: 1.74e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454  46 VLKVTPEEFASQITLMDIPVFKAIQPEELASCGWSKK-EKHSLAPNVVAFTRRFNQVSFWVVREILTAQTLKIRAEILSH 124
Cdd:cd00155    1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKdKNIHLSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454 125 FVKIAKKLLELNNLHSLMSVVSALQSAPIFRLTKTWALLNRKDKTTFEKLDYLMSKEDNYKRTREYIRSLK-MVPSIPYL 203
Cdd:cd00155   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVGpNPPCVPFL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454 204 GIYLLDLIYIDSAYPasGSIMENEQRSNQMNNILRIIADLQV--SCSYDhLTTLPHVQKYLKSVRYIEELqkfvEDDNYK 281
Cdd:cd00155  161 GVYLKDLTFLHEGNP--DFLEGNLVNFEKRRKIAEILREIRQlqSNSYE-LNRDEDILAFLWKLLELILN----EDELYE 233

                 ....
gi 299758454 282 LSLR 285
Cdd:cd00155  234 LSLE 237
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
390-501 2.82e-12

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: 62.95  E-value: 2.82e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454   390 PTMEGPLRRKTllkegrKPALSSWTRYWVILSGSTLLYYGAKSlrgtdrKHYKSTPGKKVSIVGWMVQLPDDPEHPD--- 466
Cdd:smart00233   1 VIKEGWLYKKS------GGGKKSWKKRYFVLFNSTLLYYKSKK------DKKSYKPKGSIDLSGCTVREAPDPDSSKkph 68
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 299758454   467 IFQLNNPDkGNVYKFQTGSRFHAILWHKHLDDACK 501
Cdd:smart00233  69 CFEIKTSD-RKTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
390-501 1.71e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 57.96  E-value: 1.71e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454  390 PTMEGPLRRKTllkegrKPALSSWTRYWVILSGSTLLYYGAKSlRGTDRKHYKSTPGKKVSIVgwMVQLPDDPEHPDIFQ 469
Cdd:pfam00169   1 VVKEGWLLKKG------GGKKKSWKKRYFVLFDGSLLYYKDDK-SGKSKEPKGSISLSGCEVV--EVVASDSPKRKFCFE 71
                          90       100       110
                  ....*....|....*....|....*....|....
gi 299758454  470 L--NNPDKGNVYKFQTGSRFHAILWHKHLDDACK 501
Cdd:pfam00169  72 LrtGERTGKRTYLLQAESEEERKDWIKAIQSAIR 105
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
392-496 1.73e-09

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


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 54.86  E-value: 1.73e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454 392 MEGPLRRKTllkegrKPALSSWTRYWVILSGSTLLYYgakslrgTDRKHYKSTPGKKVSIVGWM-VQLPDDPEHPDIFQL 470
Cdd:cd00821    1 KEGYLLKRG------GGGLKSWKKRWFVLFEGVLLYY-------KSKKDSSYKPKGSIPLSGILeVEEVSPKERPHCFEL 67
                         90       100
                 ....*....|....*....|....*.
gi 299758454 471 NNPDkGNVYKFQTGSRFHAILWHKHL 496
Cdd:cd00821   68 VTPD-GRTYYLQADSEEERQEWLKAL 92
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
401-502 2.39e-06

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: 46.68  E-value: 2.39e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454 401 LLKEGRKPALSS---WTRYWVILSGSTLLYYGAKSLRGTDRkhyKSTPGKKVSIVGWMVQLPddPEHP---DIFQLNNpD 474
Cdd:cd01230   16 VHKKNKKVELATrrkWKKYWVCLKGCTLLFYECDERSGIDE---NSEPKHALFVEGSIVQAV--PEHPkkdFVFCLSN-S 89
                         90       100
                 ....*....|....*....|....*...
gi 299758454 475 KGNVYKFQTGSRFHAILWHKHLDDACKS 502
Cdd:cd01230   90 FGDAYLFQATSQTELENWVTAIHSACAS 117
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
392-496 6.49e-04

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


Pssm-ID: 275402  Cd Length: 116  Bit Score: 39.53  E-value: 6.49e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454 392 MEGPLRRKTLLKegrkpalSSWTRYWVILSGSTLLYY----------GAKSLRgtdrkhykstpgKKVSIvgwmVQLPDD 461
Cdd:cd13215   23 KSGYLSKRSKRT-------LRYTRYWFVLKGDTLSWYnsstdlyfpaGTIDLR------------YATSI----ELSKSN 79
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 299758454 462 PEHPDIFQLNNPDKgnVYKFQTGSRFHAILWHKHL 496
Cdd:cd13215   80 GEATTSFKIVTNSR--TYKFKADSETSADEWVKAL 112
PH_Skap-hom_Skap2 cd13381
Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; ...
411-501 9.37e-04

Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; Adaptor protein Skap-hom, a homolog of Skap55, which interacts with actin and with ADAP (adhesion and degranulation promoting adapter protein) undergoes tyrosine phosphorylation in response to plating of bone marrow-derived macrophages on fibronectin. Skap-hom has an N-terminal coiled-coil conformation that is involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap-hom PH domain regulates intracellular targeting; its interaction with the DM domain inhibits Skap-hom actin-based ruffles in macrophages and its binding to 3'-phosphoinositides reverses this autoinhibition. The Skap-hom PH domain binds PI[3,4]P2 and PI[3,4,5]P3, but not to PI[3]P, PI[5]P, or PI[4,5]P2. Skap2 is a downstream target of Heat shock transcription factor 4 (HSF4) and functions in the regulation of actin reorganization during lens differentiation. It is thought that SKAP2 anchors the complex of tyrosine kinase adaptor protein 2 (NCK20/focal adhesion to fibroblast growth factor receptors at the lamellipodium in lens epithelial cells. Skap2 has an N-terminal coiled-coil conformation which interacts with the SH2 domain of NCK2, a central PH domain and a C-terminal SH3 domain that associates with ADAP (adhesion and degranulation promoting adapter protein)/FYB (the Fyn binding protein). Skap2 PH domain binds to membrane lipids. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-hom have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains 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: 270181  Cd Length: 106  Bit Score: 38.78  E-value: 9.37e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454 411 SSWTRYWVILSGSTLLYYGAKSlrgtdRKHYKStpgkKVSIVGWMVQLPD----DPEHPDIFQLNNPDKgNVYKFQTGSR 486
Cdd:cd13381   19 FEWQKRWCALSNSVFYYYGSDK-----DKQQKG----EFAIDGYDVKMNNtlrkDAKKDCCFEICAPDK-RVYQFTAASP 88
                         90
                 ....*....|....*
gi 299758454 487 FHAILWHKHLDDACK 501
Cdd:cd13381   89 KEAEEWVQQIKFILQ 103
PH_beta_spectrin cd10571
Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a ...
392-485 2.60e-03

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: 37.59  E-value: 2.60e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299758454 392 MEGPLRRKTLLKEGRKPALS-SWTRYWVILSGSTLLYYgaKslrgtDRKHYKSTPGKK----VSIVGWMVQLPDD---PE 463
Cdd:cd10571    1 MEGFLERKHEWESGGKKASNrSWKNVYTVLRGQELSFY--K-----DQKAAKSGITYAaeppLNLYNAVCEVASDytkKK 73
                         90       100
                 ....*....|....*....|..
gi 299758454 464 HpdIFQLNNPDkGNVYKFQTGS 485
Cdd:cd10571   74 H--VFRLKLSD-GAEFLFQAKD 92
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH