NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|1720357746|ref|XP_030099522|]
View 

ras-specific guanine nucleotide-releasing factor RalGPS2 isoform X3 [Mus musculus]

Protein Classification

RasGEF and PH_RalGPS1_2 domain-containing protein( domain architecture ID 10242552)

RasGEF and PH_RalGPS1_2 domain-containing protein

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
PH_RalGPS1_2 cd13310
Ral GEF with PH domain and SH3 binding motif 1 and 2 Pleckstrin homology (PH) domain; RalGPS1 ...
 326-441 1.34e-68

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: 213.66  E-value: 1.34e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720357746 326 TIQGVLRRKTLLKEGKKPTVASWTKYWAALCGTQLFYYAAKSLKATERKHFKSTSNKNVSVVGWMVMMADDPEHPDLFLL 405
Cdd:cd13310     1 TMQGCLRRKTVLKEGRKPTVSSWQRYWVQLWGTSLVYYAPKSLKGTERSDFKSEPCKIVSISGWMVVLGDDPEHPDSFQL 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1720357746 406 TDSEKGNSYKFQAGSRMNAMLWFKHLSAACQSNKQQ 441
Cdd:cd13310    81 TDPEKGNVYKFRAGSRSNALLWLKHLKDACKGNRPP 116
RasGEF super family cl02485
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 1-146 1.16e-40

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.


The actual alignment was detected with superfamily member smart00147:

Pssm-ID: 470590  Cd Length: 242  Bit Score: 145.47  E-value: 1.16e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720357746    1 MAVVSGLQSAPIFRLTKTWALLSRKDKTTFEKLEYVMSKEDNYKRLRDYISSLKMTPCIPYLGIYLSDLTYIDSAYPS-T 79
Cdd:smart00147  98 MAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSCNLPPCIPFLGVLLKDLTFIDEGNPDfL 177

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720357746   80 GSILENEQRSNLMNNILRIISDLQQScEYDI-PILPHVQKYLNSVqyIEELQKfvEDDNYKLSLKIEP 146
Cdd:smart00147 178 ENGLVNFEKRRQIAEILREIRQLQSQ-PYNLrPNRSDIQSLLQQL--LDHLDE--EEELYQLSLKIEP 240
 
Name Accession Description Interval E-value
PH_RalGPS1_2 cd13310
Ral GEF with PH domain and SH3 binding motif 1 and 2 Pleckstrin homology (PH) domain; RalGPS1 ...
 326-441 1.34e-68

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: 213.66  E-value: 1.34e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720357746 326 TIQGVLRRKTLLKEGKKPTVASWTKYWAALCGTQLFYYAAKSLKATERKHFKSTSNKNVSVVGWMVMMADDPEHPDLFLL 405
Cdd:cd13310     1 TMQGCLRRKTVLKEGRKPTVSSWQRYWVQLWGTSLVYYAPKSLKGTERSDFKSEPCKIVSISGWMVVLGDDPEHPDSFQL 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1720357746 406 TDSEKGNSYKFQAGSRMNAMLWFKHLSAACQSNKQQ 441
Cdd:cd13310    81 TDPEKGNVYKFRAGSRSNALLWLKHLKDACKGNRPP 116
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
1-146 1.16e-40

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 145.47  E-value: 1.16e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720357746    1 MAVVSGLQSAPIFRLTKTWALLSRKDKTTFEKLEYVMSKEDNYKRLRDYISSLKMTPCIPYLGIYLSDLTYIDSAYPS-T 79
Cdd:smart00147  98 MAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSCNLPPCIPFLGVLLKDLTFIDEGNPDfL 177

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720357746   80 GSILENEQRSNLMNNILRIISDLQQScEYDI-PILPHVQKYLNSVqyIEELQKfvEDDNYKLSLKIEP 146
Cdd:smart00147 178 ENGLVNFEKRRQIAEILREIRQLQSQ-PYNLrPNRSDIQSLLQQL--LDHLDE--EEELYQLSLKIEP 240
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
 1-79 2.06e-29

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


Pssm-ID: 459872  Cd Length: 179  Bit Score: 113.07  E-value: 2.06e-29
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720357746   1 MAVVSGLQSAPIFRLTKTWALLSRKDKTTFEKLEYVMSKEDNYKRLRDYISSLKmTPCIPYLGIYLSDLTYIDSAYPST 79
Cdd:pfam00617  90 MAILSGLNSSPISRLKKTWELVSKKYKKTLEELEKLMSPSRNFKNYREALSSAS-PPCIPFLGLYLTDLTFIEEGNPDF 167
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 1-143 8.25e-29

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: 113.12  E-value: 8.25e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720357746   1 MAVVSGLQSAPIFRLTKTWALLSRKDKTTFEKLEYVMSKEDNYKRLRDYISSLKMT-PCIPYLGIYLSDLTYIDSAYPst 79
Cdd:cd00155    98 MAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVGPNpPCVPFLGVYLKDLTFLHEGNP-- 175

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720357746  80 gSILENEQRS-NLMNNILRIISDLQ--QSCEYDIPILPHVQKYLNSVQYIEELqkfvEDDNYKLSLK 143
Cdd:cd00155   176 -DFLEGNLVNfEKRRKIAEILREIRqlQSNSYELNRDEDILAFLWKLLELILN----EDELYELSLE 237
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 325-436 1.01e-08

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: 52.55  E-value: 1.01e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720357746  325 VTIQGVLRRKTllKEGKKptvaSWTKYWAALCGTQLFYYaaKSLKATERKHFKSTsnknVSVVGWMVMMADDPEHPD--- 401
Cdd:smart00233   1 VIKEGWLYKKS--GGGKK----SWKKRYFVLFNSTLLYY--KSKKDKKSYKPKGS----IDLSGCTVREAPDPDSSKkph 68

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1720357746  402 LFLLTdSEKGNSYKFQAGSRMNAMLWFKHLSAACQ 436
Cdd:smart00233  69 CFEIK-TSDRKTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 325-435 5.65e-07

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 47.94  E-value: 5.65e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720357746 325 VTIQGVLRRKTLLKEGkkptvaSWTKYWAALCGTQLFYYAAKSlKATERKHFKSTSNKNVSVVgwMVMMADDPEHPDLFL 404
Cdd:pfam00169   1 VVKEGWLLKKGGGKKK------SWKKRYFVLFDGSLLYYKDDK-SGKSKEPKGSISLSGCEVV--EVVASDSPKRKFCFE 71

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1720357746 405 L--TDSEKGNSYKFQAGSRMNAMLWFKHLSAAC 435
Cdd:pfam00169  72 LrtGERTGKRTYLLQAESEEERKDWIKAIQSAI 104
 
Name Accession Description Interval E-value
PH_RalGPS1_2 cd13310
Ral GEF with PH domain and SH3 binding motif 1 and 2 Pleckstrin homology (PH) domain; RalGPS1 ...
 326-441 1.34e-68

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: 213.66  E-value: 1.34e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720357746 326 TIQGVLRRKTLLKEGKKPTVASWTKYWAALCGTQLFYYAAKSLKATERKHFKSTSNKNVSVVGWMVMMADDPEHPDLFLL 405
Cdd:cd13310     1 TMQGCLRRKTVLKEGRKPTVSSWQRYWVQLWGTSLVYYAPKSLKGTERSDFKSEPCKIVSISGWMVVLGDDPEHPDSFQL 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1720357746 406 TDSEKGNSYKFQAGSRMNAMLWFKHLSAACQSNKQQ 441
Cdd:cd13310    81 TDPEKGNVYKFRAGSRSNALLWLKHLKDACKGNRPP 116
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
1-146 1.16e-40

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 145.47  E-value: 1.16e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720357746    1 MAVVSGLQSAPIFRLTKTWALLSRKDKTTFEKLEYVMSKEDNYKRLRDYISSLKMTPCIPYLGIYLSDLTYIDSAYPS-T 79
Cdd:smart00147  98 MAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSCNLPPCIPFLGVLLKDLTFIDEGNPDfL 177

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720357746   80 GSILENEQRSNLMNNILRIISDLQQScEYDI-PILPHVQKYLNSVqyIEELQKfvEDDNYKLSLKIEP 146
Cdd:smart00147 178 ENGLVNFEKRRQIAEILREIRQLQSQ-PYNLrPNRSDIQSLLQQL--LDHLDE--EEELYQLSLKIEP 240
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
 1-79 2.06e-29

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


Pssm-ID: 459872  Cd Length: 179  Bit Score: 113.07  E-value: 2.06e-29
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720357746   1 MAVVSGLQSAPIFRLTKTWALLSRKDKTTFEKLEYVMSKEDNYKRLRDYISSLKmTPCIPYLGIYLSDLTYIDSAYPST 79
Cdd:pfam00617  90 MAILSGLNSSPISRLKKTWELVSKKYKKTLEELEKLMSPSRNFKNYREALSSAS-PPCIPFLGLYLTDLTFIEEGNPDF 167
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 1-143 8.25e-29

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: 113.12  E-value: 8.25e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720357746   1 MAVVSGLQSAPIFRLTKTWALLSRKDKTTFEKLEYVMSKEDNYKRLRDYISSLKMT-PCIPYLGIYLSDLTYIDSAYPst 79
Cdd:cd00155    98 MAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVGPNpPCVPFLGVYLKDLTFLHEGNP-- 175

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720357746  80 gSILENEQRS-NLMNNILRIISDLQ--QSCEYDIPILPHVQKYLNSVQYIEELqkfvEDDNYKLSLK 143
Cdd:cd00155   176 -DFLEGNLVNfEKRRKIAEILREIRqlQSNSYELNRDEDILAFLWKLLELILN----EDELYELSLE 237
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 325-436 1.01e-08

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: 52.55  E-value: 1.01e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720357746  325 VTIQGVLRRKTllKEGKKptvaSWTKYWAALCGTQLFYYaaKSLKATERKHFKSTsnknVSVVGWMVMMADDPEHPD--- 401
Cdd:smart00233   1 VIKEGWLYKKS--GGGKK----SWKKRYFVLFNSTLLYY--KSKKDKKSYKPKGS----IDLSGCTVREAPDPDSSKkph 68

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1720357746  402 LFLLTdSEKGNSYKFQAGSRMNAMLWFKHLSAACQ 436
Cdd:smart00233  69 CFEIK-TSDRKTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 325-435 5.65e-07

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 47.94  E-value: 5.65e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720357746 325 VTIQGVLRRKTLLKEGkkptvaSWTKYWAALCGTQLFYYAAKSlKATERKHFKSTSNKNVSVVgwMVMMADDPEHPDLFL 404
Cdd:pfam00169   1 VVKEGWLLKKGGGKKK------SWKKRYFVLFDGSLLYYKDDK-SGKSKEPKGSISLSGCEVV--EVVASDSPKRKFCFE 71

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1720357746 405 L--TDSEKGNSYKFQAGSRMNAMLWFKHLSAAC 435
Cdd:pfam00169  72 LrtGERTGKRTYLLQAESEEERKDWIKAIQSAI 104
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 336-431 3.95e-06

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: 45.23  E-value: 3.95e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720357746 336 LLKEGKKpTVASWTKYWAALCGTQLFYYAAKSLKATERKHFkstsnknVSVVGWM-VMMADDPEHPDLFLLTdSEKGNSY 414
Cdd:cd00821     5 LLKRGGG-GLKSWKKRWFVLFEGVLLYYKSKKDSSYKPKGS-------IPLSGILeVEEVSPKERPHCFELV-TPDGRTY 75

                          90
                  ....*....|....*..
gi 1720357746 415 KFQAGSRMNAMLWFKHL 431
Cdd:cd00821    76 YLQADSEEERQEWLKAL 92
PH1_Tiam1_2 cd01230
T-lymphoma invasion and metastasis 1 and 2 Pleckstrin Homology (PH) domain, N-terminal domain; ...
 323-437 1.69e-05

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: 43.99  E-value: 1.69e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720357746 323 GAVTIQGVLRRKTLLKEGKKPTVA-----SWTKYWAALCGTQLFYYAAKSLKATErkhfKSTSNKNVSVVGWMVMMAdDP 397
Cdd:cd01230     1 GAVRKAGWLSVKNFLVHKKNKKVElatrrKWKKYWVCLKGCTLLFYECDERSGID----ENSEPKHALFVEGSIVQA-VP 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1720357746 398 EHPDL---FLLTDSeKGNSYKFQAGSRMNAMLWFKHLSAACQS 437
Cdd:cd01230    76 EHPKKdfvFCLSNS-FGDAYLFQATSQTELENWVTAIHSACAS 117
PH_beta_spectrin cd10571
Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a ...
 327-434 2.35e-05

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: 43.37  E-value: 2.35e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720357746 327 IQGVLRRKTLLKE-GKKPTVASWTKYWAALCGTQL-FYYAAKSLKATERKHFKSTsnknVSVVGWMVMMADD---PEHPD 401
Cdd:cd10571     1 MEGFLERKHEWESgGKKASNRSWKNVYTVLRGQELsFYKDQKAAKSGITYAAEPP----LNLYNAVCEVASDytkKKHVF 76

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1720357746 402 LFLLTDsekGNSYKFQAGSR--MNAmlWFKHLSAA 434
Cdd:cd10571    77 RLKLSD---GAEFLFQAKDEeeMNQ--WVKKISFA 106
 
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