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Conserved domains on  [gi|578838539|ref|XP_006724776|]
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insulin receptor substrate 4 isoform X2 [Homo sapiens]

Protein Classification

insulin receptor substrate( domain architecture ID 10100909)

insulin receptor substrate is a key mediator in insulin signaling, acting as a docking protein between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains

Gene Ontology:  GO:0005158|GO:0043548|GO:0008286
PubMed:  15567406|8987385|10610414|15493994|22728242

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PTB_IRS cd01204
Insulin receptor substrate phosphotyrosine-binding domain (PTBi); Insulin receptor substrate ...
 231-334 1.49e-57

Insulin receptor substrate phosphotyrosine-binding domain (PTBi); Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the IRS-like subgroup.


:

Pssm-ID: 269915  Cd Length: 106  Bit Score: 193.62  E-value: 1.49e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539  231 YKDVWQVIVKPRGLGHRKELSGVFRLCLTDEEVVFVRLNTEV--ASVVVQLLSIRRCGHSEQYFFLEVGRSTVIGPGELW 308
Cdd:cd01204     1 FEHVWQVTVKKKGLGQSKNLTGIYRLCLTSKTLSLVKLNSEKnpPSVEIQLMNIRRCGHSENFFFIEVGRSAVTGPGELW 80

                          90       100
                  ....*....|....*....|....*.
gi 578838539  309 MQVDDCVVAQNMHELFLEKMRALCAD 334
Cdd:cd01204    81 MQVDDSVVAQNMHETILEAMKALSEE 106
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 79-202 1.93e-43

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. 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.cytoskeletal associated molecules, and in lipid associated enzymes.


:

Pssm-ID: 269959  Cd Length: 106  Bit Score: 153.21  E-value: 1.93e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539   79 VCKRGYLRKQKHGHRRYFVLKLETADAPARLEYYENARKFRHSVraaaaaaaaaasgaaippliPPRRVITLYQCFSVSQ 158
Cdd:cd01257     3 VRKSGYLKKLKTMRKRYFVLRAESHGGPARLEYYENEKKFRRNA--------------------EPKRVIPLSSCFNINK 62

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 578838539  159 RADARYRHLIALFTQDEYFAMVAENESEQESWYLLLSRLILESK 202
Cdd:cd01257    63 RADAKHKHLIALYTKDECFGLVAESEEEQDEWYQALLELQRPAR 106
 
Name Accession Description Interval E-value
PTB_IRS cd01204
Insulin receptor substrate phosphotyrosine-binding domain (PTBi); Insulin receptor substrate ...
 231-334 1.49e-57

Insulin receptor substrate phosphotyrosine-binding domain (PTBi); Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the IRS-like subgroup.


Pssm-ID: 269915  Cd Length: 106  Bit Score: 193.62  E-value: 1.49e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539  231 YKDVWQVIVKPRGLGHRKELSGVFRLCLTDEEVVFVRLNTEV--ASVVVQLLSIRRCGHSEQYFFLEVGRSTVIGPGELW 308
Cdd:cd01204     1 FEHVWQVTVKKKGLGQSKNLTGIYRLCLTSKTLSLVKLNSEKnpPSVEIQLMNIRRCGHSENFFFIEVGRSAVTGPGELW 80

                          90       100
                  ....*....|....*....|....*.
gi 578838539  309 MQVDDCVVAQNMHELFLEKMRALCAD 334
Cdd:cd01204    81 MQVDDSVVAQNMHETILEAMKALSEE 106
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 79-202 1.93e-43

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. 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.cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269959  Cd Length: 106  Bit Score: 153.21  E-value: 1.93e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539   79 VCKRGYLRKQKHGHRRYFVLKLETADAPARLEYYENARKFRHSVraaaaaaaaaasgaaippliPPRRVITLYQCFSVSQ 158
Cdd:cd01257     3 VRKSGYLKKLKTMRKRYFVLRAESHGGPARLEYYENEKKFRRNA--------------------EPKRVIPLSSCFNINK 62

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 578838539  159 RADARYRHLIALFTQDEYFAMVAENESEQESWYLLLSRLILESK 202
Cdd:cd01257    63 RADAKHKHLIALYTKDECFGLVAESEEEQDEWYQALLELQRPAR 106
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
232-333 4.89e-40

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 143.32  E-value: 4.89e-40
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539    232 KDVWQVIVKPRGLGHRKeLSGVFRLCLTDEEVVFVR-LNTEVASVVVQLLSIRRCGHSEQYFFLEVGRSTVIGPGELWMQ 310
Cdd:smart00310    1 KQFWVTIRKTEGLERCP-LSGSYRLRLTSEELVLWRgLNPRVELVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFTFQ 79

                            90       100
                    ....*....|....*....|...
gi 578838539    311 vddCVVAQNMHELFLEKMRALCA 333
Cdd:smart00310   80 ---TVVAQEIFQLVLEAMQAQKN 99
IRS pfam02174
PTB domain (IRS-1 type);
232-333 5.53e-40

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 143.16  E-value: 5.53e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539   232 KDVWQVIVKPRGLGHRKELSGVFRLCLTDEEVVFVRLNTEVASVVVQLLSIRRCGHSEQYFFLEVGRSTVIGPGELWMQV 311
Cdd:pfam02174    1 VEVFPVTVRRTGASERCGLSGSYRLCLTAEALTLDKLNTRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQT 80

                           90       100
                   ....*....|....*....|..
gi 578838539   312 DDcvvAQNMHELFLEKMRALCA 333
Cdd:pfam02174   81 DD---AEEIFETVLAAMKAQKE 99
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 79-198 1.45e-04

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: 42.15  E-value: 1.45e-04
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539     79 VCKRGYLRKQKHG-----HRRYFVLKletadaPARLEYYENARKFRHSVraaaaaaaaaasgaaipplipPRRVITLYQC 153
Cdd:smart00233    1 VIKEGWLYKKSGGgkkswKKRYFVLF------NSTLLYYKSKKDKKSYK---------------------PKGSIDLSGC 53

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*....
gi 578838539    154 fSVSQRAD---ARYRHLIALFTQDEY-FAMVAENESEQESWYLLLSRLI 198
Cdd:smart00233   54 -TVREAPDpdsSKKPHCFEIKTSDRKtLLLQAESEEEREKWVEALRKAI 101
 
Name Accession Description Interval E-value
PTB_IRS cd01204
Insulin receptor substrate phosphotyrosine-binding domain (PTBi); Insulin receptor substrate ...
 231-334 1.49e-57

Insulin receptor substrate phosphotyrosine-binding domain (PTBi); Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the IRS-like subgroup.


Pssm-ID: 269915  Cd Length: 106  Bit Score: 193.62  E-value: 1.49e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539  231 YKDVWQVIVKPRGLGHRKELSGVFRLCLTDEEVVFVRLNTEV--ASVVVQLLSIRRCGHSEQYFFLEVGRSTVIGPGELW 308
Cdd:cd01204     1 FEHVWQVTVKKKGLGQSKNLTGIYRLCLTSKTLSLVKLNSEKnpPSVEIQLMNIRRCGHSENFFFIEVGRSAVTGPGELW 80

                          90       100
                  ....*....|....*....|....*.
gi 578838539  309 MQVDDCVVAQNMHELFLEKMRALCAD 334
Cdd:cd01204    81 MQVDDSVVAQNMHETILEAMKALSEE 106
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 79-202 1.93e-43

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. 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.cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269959  Cd Length: 106  Bit Score: 153.21  E-value: 1.93e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539   79 VCKRGYLRKQKHGHRRYFVLKLETADAPARLEYYENARKFRHSVraaaaaaaaaasgaaippliPPRRVITLYQCFSVSQ 158
Cdd:cd01257     3 VRKSGYLKKLKTMRKRYFVLRAESHGGPARLEYYENEKKFRRNA--------------------EPKRVIPLSSCFNINK 62

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 578838539  159 RADARYRHLIALFTQDEYFAMVAENESEQESWYLLLSRLILESK 202
Cdd:cd01257    63 RADAKHKHLIALYTKDECFGLVAESEEEQDEWYQALLELQRPAR 106
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
232-333 4.89e-40

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 143.32  E-value: 4.89e-40
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539    232 KDVWQVIVKPRGLGHRKeLSGVFRLCLTDEEVVFVR-LNTEVASVVVQLLSIRRCGHSEQYFFLEVGRSTVIGPGELWMQ 310
Cdd:smart00310    1 KQFWVTIRKTEGLERCP-LSGSYRLRLTSEELVLWRgLNPRVELVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFTFQ 79

                            90       100
                    ....*....|....*....|...
gi 578838539    311 vddCVVAQNMHELFLEKMRALCA 333
Cdd:smart00310   80 ---TVVAQEIFQLVLEAMQAQKN 99
IRS pfam02174
PTB domain (IRS-1 type);
232-333 5.53e-40

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 143.16  E-value: 5.53e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539   232 KDVWQVIVKPRGLGHRKELSGVFRLCLTDEEVVFVRLNTEVASVVVQLLSIRRCGHSEQYFFLEVGRSTVIGPGELWMQV 311
Cdd:pfam02174    1 VEVFPVTVRRTGASERCGLSGSYRLCLTAEALTLDKLNTRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQT 80

                           90       100
                   ....*....|....*....|..
gi 578838539   312 DDcvvAQNMHELFLEKMRALCA 333
Cdd:pfam02174   81 DD---AEEIFETVLAAMKAQKE 99
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 77-190 4.44e-06

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


Pssm-ID: 270110  Cd Length: 106  Bit Score: 46.46  E-value: 4.44e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539   77 EEVCKRGYL----RKQKHGHRRYFVLKletadaPARLEYYENARKFRhsvraaaaaaaaaasgaaipplipPRRVITLYQ 152
Cdd:cd13298     4 DRVLKSGYLlkrsRKTKNWKKRWVVLR------PCQLSYYKDEKEYK------------------------LRRVINLSE 53

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 578838539  153 CFSVSQRADARYRHLIALFTQDEYFAMVAENESEQESW 190
Cdd:cd13298    54 LLAVAPLKDKKRKNVFGIYTPSKNLHFRATSEKDANEW 91
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
 83-190 1.17e-05

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. 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: 270133  Cd Length: 112  Bit Score: 45.48  E-value: 1.17e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539   83 GYLRKQKHGH--------RRYFVLKL-ETADAPARLEYYENarkfRHSVRaaaaaaaaaasgaaipplipPRRVITLYQC 153
Cdd:cd13324     5 GWLTKSPPEKkiwraawrRRWFVLRSgRLSGGQDVLEYYTD----DHCKK--------------------LKGIIDLDQC 60

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 578838539  154 FSVSQ-----RADARYRHLIALFTQDEYFAMVAENESEQESW 190
Cdd:cd13324    61 EQVDAgltfeKKKFKNQFIFDIRTPKRTYYLVAETEEEMNKW 102
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
 81-190 1.17e-04

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


Pssm-ID: 270095  Cd Length: 106  Bit Score: 42.69  E-value: 1.17e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539   81 KRGYLRKQ----KHGHRRYFVLKletadaPARLEYYENARKFRHSvraaaaaaaaaasgaaippliPPRRVITLYQCFSV 156
Cdd:cd13276     1 KAGWLEKQgefiKTWRRRWFVLK------QGKLFWFKEPDVTPYS---------------------KPRGVIDLSKCLTV 53

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 578838539  157 SQRADARYR-HLIALFTQDEYFAMVAENESEQESW 190
Cdd:cd13276    54 KSAEDATNKeNAFELSTPEETFYFIADNEKEKEEW 88
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 79-198 1.45e-04

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: 42.15  E-value: 1.45e-04
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539     79 VCKRGYLRKQKHG-----HRRYFVLKletadaPARLEYYENARKFRHSVraaaaaaaaaasgaaipplipPRRVITLYQC 153
Cdd:smart00233    1 VIKEGWLYKKSGGgkkswKKRYFVLF------NSTLLYYKSKKDKKSYK---------------------PKGSIDLSGC 53

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*....
gi 578838539    154 fSVSQRAD---ARYRHLIALFTQDEY-FAMVAENESEQESWYLLLSRLI 198
Cdd:smart00233   54 -TVREAPDpdsSKKPHCFEIKTSDRKtLLLQAESEEEREKWVEALRKAI 101
PTB cd00934
Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are ...
 242-324 6.73e-04

Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to bind peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.


Pssm-ID: 269911  Cd Length: 120  Bit Score: 40.96  E-value: 6.73e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838539  242 RGLGHRKELSGVFRLCLTDEEVVFVRLNTEVASVVVQLLSIRRCGH---SEQYFFLEVGRSTVIGPGELWMQVDDCVVAQ 318
Cdd:cd00934    31 AALKSSKRKPGPVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRdpdNPNVFAFIAGEEGGSGFRCHVFQCEDEEEAE 110


                  ....*.
gi 578838539  319 NMHELF 324
Cdd:cd00934   111 EILQAI 116
 
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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