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Conserved domains on  [gi|58331138|ref|NP_034702|]
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insulin receptor substrate 4 [Mus musculus]

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 ...
 232-335 9.91e-58

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: 194.01  E-value: 9.91e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138  232 YKDVWQVVVKPRGLGHRKELSGVFRLCLTDEEVVFVRLNTEV--ASVVVQLLSIRRCGHSEQYFFLEVGRSTVIGPGELW 309
Cdd:cd01204    1 FEHVWQVTVKKKGLGQSKNLTGIYRLCLTSKTLSLVKLNSEKnpPSVEIQLMNIRRCGHSENFFFIEVGRSAVTGPGELW 80

                         90       100
                 ....*....|....*....|....*.
gi 58331138  310 MQVDDSVVAQNMHELFLEKMRALCAD 335
Cdd:cd01204   81 MQVDDSVVAQNMHETILEAMKALSEE 106
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 78-203 7.33e-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: 151.67  E-value: 7.33e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138   78 DEVCKRGYLRKQKHGHRRYFVLKLETADAPARLEYYRNARKFRHSVraaaaaaeaaasgaavpaliPPRRVIILYQCFSV 157
Cdd:cd01257    1 TDVRKSGYLKKLKTMRKRYFVLRAESHGGPARLEYYENEKKFRRNA--------------------EPKRVIPLSSCFNI 60

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 58331138  158 SQRADARYRHLIALFTQDEYFAMVAENESEQESWYLLLSRLILESK 203
Cdd:cd01257   61 NKRADAKHKHLIALYTKDECFGLVAESEEEQDEWYQALLELQRPAR 106
 
Name Accession Description Interval E-value
PTB_IRS cd01204
Insulin receptor substrate phosphotyrosine-binding domain (PTBi); Insulin receptor substrate ...
 232-335 9.91e-58

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: 194.01  E-value: 9.91e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138  232 YKDVWQVVVKPRGLGHRKELSGVFRLCLTDEEVVFVRLNTEV--ASVVVQLLSIRRCGHSEQYFFLEVGRSTVIGPGELW 309
Cdd:cd01204    1 FEHVWQVTVKKKGLGQSKNLTGIYRLCLTSKTLSLVKLNSEKnpPSVEIQLMNIRRCGHSENFFFIEVGRSAVTGPGELW 80

                         90       100
                 ....*....|....*....|....*.
gi 58331138  310 MQVDDSVVAQNMHELFLEKMRALCAD 335
Cdd:cd01204   81 MQVDDSVVAQNMHETILEAMKALSEE 106
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 78-203 7.33e-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: 151.67  E-value: 7.33e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138   78 DEVCKRGYLRKQKHGHRRYFVLKLETADAPARLEYYRNARKFRHSVraaaaaaeaaasgaavpaliPPRRVIILYQCFSV 157
Cdd:cd01257    1 TDVRKSGYLKKLKTMRKRYFVLRAESHGGPARLEYYENEKKFRRNA--------------------EPKRVIPLSSCFNI 60

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 58331138  158 SQRADARYRHLIALFTQDEYFAMVAENESEQESWYLLLSRLILESK 203
Cdd:cd01257   61 NKRADAKHKHLIALYTKDECFGLVAESEEEQDEWYQALLELQRPAR 106
IRS pfam02174
PTB domain (IRS-1 type);
233-334 1.03e-39

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 142.39  E-value: 1.03e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138    233 KDVWQVVVKPRGLGHRKELSGVFRLCLTDEEVVFVRLNTEVASVVVQLLSIRRCGHSEQYFFLEVGRSTVIGPGELWMQV 312
Cdd:pfam02174    1 VEVFPVTVRRTGASERCGLSGSYRLCLTAEALTLDKLNTRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQT 80

                           90       100
                   ....*....|....*....|..
gi 58331138    313 DDsvvAQNMHELFLEKMRALCA 334
Cdd:pfam02174   81 DD---AEEIFETVLAAMKAQKE 99
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
233-334 1.13e-38

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 139.47  E-value: 1.13e-38
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138     233 KDVWQVVVKPRGLGHRKeLSGVFRLCLTDEEVVFVR-LNTEVASVVVQLLSIRRCGHSEQYFFLEVGRSTVIGPGELWMQ 311
Cdd:smart00310    1 KQFWVTIRKTEGLERCP-LSGSYRLRLTSEELVLWRgLNPRVELVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFTFQ 79

                            90       100
                    ....*....|....*....|...
gi 58331138     312 vddSVVAQNMHELFLEKMRALCA 334
Cdd:smart00310   80 ---TVVAQEIFQLVLEAMQAQKN 99
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 80-199 1.76e-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: 41.77  E-value: 1.76e-04
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138      80 VCKRGYLRKQKHG-----HRRYFVLKletadaPARLEYYRNARKFRHSVraaaaaaeaaasgaavpalipPRRVIILYQC 154
Cdd:smart00233    1 VIKEGWLYKKSGGgkkswKKRYFVLF------NSTLLYYKSKKDKKSYK---------------------PKGSIDLSGC 53

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*....
gi 58331138     155 fSVSQRAD---ARYRHLIALFTQDEY-FAMVAENESEQESWYLLLSRLI 199
Cdd:smart00233   54 -TVREAPDpdsSKKPHCFEIKTSDRKtLLLQAESEEEREKWVEALRKAI 101
 
Name Accession Description Interval E-value
PTB_IRS cd01204
Insulin receptor substrate phosphotyrosine-binding domain (PTBi); Insulin receptor substrate ...
 232-335 9.91e-58

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: 194.01  E-value: 9.91e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138  232 YKDVWQVVVKPRGLGHRKELSGVFRLCLTDEEVVFVRLNTEV--ASVVVQLLSIRRCGHSEQYFFLEVGRSTVIGPGELW 309
Cdd:cd01204    1 FEHVWQVTVKKKGLGQSKNLTGIYRLCLTSKTLSLVKLNSEKnpPSVEIQLMNIRRCGHSENFFFIEVGRSAVTGPGELW 80

                         90       100
                 ....*....|....*....|....*.
gi 58331138  310 MQVDDSVVAQNMHELFLEKMRALCAD 335
Cdd:cd01204   81 MQVDDSVVAQNMHETILEAMKALSEE 106
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 78-203 7.33e-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: 151.67  E-value: 7.33e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138   78 DEVCKRGYLRKQKHGHRRYFVLKLETADAPARLEYYRNARKFRHSVraaaaaaeaaasgaavpaliPPRRVIILYQCFSV 157
Cdd:cd01257    1 TDVRKSGYLKKLKTMRKRYFVLRAESHGGPARLEYYENEKKFRRNA--------------------EPKRVIPLSSCFNI 60

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 58331138  158 SQRADARYRHLIALFTQDEYFAMVAENESEQESWYLLLSRLILESK 203
Cdd:cd01257   61 NKRADAKHKHLIALYTKDECFGLVAESEEEQDEWYQALLELQRPAR 106
IRS pfam02174
PTB domain (IRS-1 type);
233-334 1.03e-39

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 142.39  E-value: 1.03e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138    233 KDVWQVVVKPRGLGHRKELSGVFRLCLTDEEVVFVRLNTEVASVVVQLLSIRRCGHSEQYFFLEVGRSTVIGPGELWMQV 312
Cdd:pfam02174    1 VEVFPVTVRRTGASERCGLSGSYRLCLTAEALTLDKLNTRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQT 80

                           90       100
                   ....*....|....*....|..
gi 58331138    313 DDsvvAQNMHELFLEKMRALCA 334
Cdd:pfam02174   81 DD---AEEIFETVLAAMKAQKE 99
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
233-334 1.13e-38

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 139.47  E-value: 1.13e-38
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138     233 KDVWQVVVKPRGLGHRKeLSGVFRLCLTDEEVVFVR-LNTEVASVVVQLLSIRRCGHSEQYFFLEVGRSTVIGPGELWMQ 311
Cdd:smart00310    1 KQFWVTIRKTEGLERCP-LSGSYRLRLTSEELVLWRgLNPRVELVVWPLLSLRRYGRDKVFFFFEAGRRCVSGPGEFTFQ 79

                            90       100
                    ....*....|....*....|...
gi 58331138     312 vddSVVAQNMHELFLEKMRALCA 334
Cdd:smart00310   80 ---TVVAQEIFQLVLEAMQAQKN 99
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 78-191 5.81e-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: 46.08  E-value: 5.81e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138   78 DEVCKRGYL----RKQKHGHRRYFVLKletadaPARLEYYRNARKFRhsvraaaaaaeaaasgaavpalipPRRVIILYQ 153
Cdd:cd13298    4 DRVLKSGYLlkrsRKTKNWKKRWVVLR------PCQLSYYKDEKEYK------------------------LRRVINLSE 53

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 58331138  154 CFSVSQRADARYRHLIALFTQDEYFAMVAENESEQESW 191
Cdd:cd13298   54 LLAVAPLKDKKRKNVFGIYTPSKNLHFRATSEKDANEW 91
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
 84-191 8.50e-06

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: 45.87  E-value: 8.50e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138   84 GYLRKQKHGH--------RRYFVLKL-ETADAPARLEYYRNarkfRHSVRaaaaaaeaaasgaavpalipPRRVIILYQC 154
Cdd:cd13324    5 GWLTKSPPEKkiwraawrRRWFVLRSgRLSGGQDVLEYYTD----DHCKK--------------------LKGIIDLDQC 60

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 58331138  155 FSVSQ-----RADARYRHLIALFTQDEYFAMVAENESEQESW 191
Cdd:cd13324   61 EQVDAgltfeKKKFKNQFIFDIRTPKRTYYLVAETEEEMNKW 102
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
 82-191 6.57e-05

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: 43.07  E-value: 6.57e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138   82 KRGYLRKQ----KHGHRRYFVLKletadaPARLEYYRNARKFRHSvraaaaaaeaaasgaavpaliPPRRVIILYQCFSV 157
Cdd:cd13276    1 KAGWLEKQgefiKTWRRRWFVLK------QGKLFWFKEPDVTPYS---------------------KPRGVIDLSKCLTV 53

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 58331138  158 SQRADARYR-HLIALFTQDEYFAMVAENESEQESW 191
Cdd:cd13276   54 KSAEDATNKeNAFELSTPEETFYFIADNEKEKEEW 88
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 80-199 1.76e-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: 41.77  E-value: 1.76e-04
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138      80 VCKRGYLRKQKHG-----HRRYFVLKletadaPARLEYYRNARKFRHSVraaaaaaeaaasgaavpalipPRRVIILYQC 154
Cdd:smart00233    1 VIKEGWLYKKSGGgkkswKKRYFVLF------NSTLLYYKSKKDKKSYK---------------------PKGSIDLSGC 53

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*....
gi 58331138     155 fSVSQRAD---ARYRHLIALFTQDEY-FAMVAENESEQESWYLLLSRLI 199
Cdd:smart00233   54 -TVREAPDpdsSKKPHCFEIKTSDRKtLLLQAESEEEREKWVEALRKAI 101
PTB cd00934
Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are ...
 243-325 7.89e-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: 40.57  E-value: 7.89e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58331138  243 RGLGHRKELSGVFRLCLTDEEVVFVRLNTEVASVVVQLLSIRRCGH---SEQYFFLEVGRSTVIGPGELWMQVDDSVVAQ 319
Cdd:cd00934   31 AALKSSKRKPGPVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRdpdNPNVFAFIAGEEGGSGFRCHVFQCEDEEEAE 110


                 ....*.
gi 58331138  320 NMHELF 325
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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