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Conserved domains on  [gi|300680969|sp|B4HWI2|]
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RecName: Full=Insulin receptor substrate 1; AltName: Full=Protein chico

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 ...
 122-235 1.39e-55

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: 187.46  E-value: 1.39e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300680969 122 YDQVWQVVIQKKGISEKVGITGTYHCCLTSKSLTFVCIGPEKTPngedrvASIEILLTTIRRCGHASpqCIFYVELGRQS 201
Cdd:cd01204    1 FEHVWQVTVKKKGLGQSKNLTGIYRLCLTSKTLSLVKLNSEKNP------PSVEIQLMNIRRCGHSE--NFFFIEVGRSA 72

                         90       100       110
                 ....*....|....*....|....*....|....
gi 300680969 202 VLGSGDLWMETDNAAVATNMHNMILSAMSAKTES 235
Cdd:cd01204   73 VTGPGELWMQVDDSVVAQNMHETILEAMKALSEE 106
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 25-112 1.80e-39

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: 141.66  E-value: 1.80e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300680969  25 FFVLYEETSTSSARLEYYDTEKKFLQRAEPKRVIYLKNCFNINRRLDTKHRFVIVLSSRDGGFGIVLENENDLRKWLDKL 104
Cdd:cd01257   19 YFVLRAESHGGPARLEYYENEKKFRRNAEPKRVIPLSSCFNINKRADAKHKHLIALYTKDECFGLVAESEEEQDEWYQAL 98


                 ....*...
gi 300680969 105 LVLQRNIA 112
Cdd:cd01257   99 LELQRPAR 106
 
Name Accession Description Interval E-value
PTB_IRS cd01204
Insulin receptor substrate phosphotyrosine-binding domain (PTBi); Insulin receptor substrate ...
 122-235 1.39e-55

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: 187.46  E-value: 1.39e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300680969 122 YDQVWQVVIQKKGISEKVGITGTYHCCLTSKSLTFVCIGPEKTPngedrvASIEILLTTIRRCGHASpqCIFYVELGRQS 201
Cdd:cd01204    1 FEHVWQVTVKKKGLGQSKNLTGIYRLCLTSKTLSLVKLNSEKNP------PSVEIQLMNIRRCGHSE--NFFFIEVGRSA 72

                         90       100       110
                 ....*....|....*....|....*....|....
gi 300680969 202 VLGSGDLWMETDNAAVATNMHNMILSAMSAKTES 235
Cdd:cd01204   73 VTGPGELWMQVDDSVVAQNMHETILEAMKALSEE 106
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 25-112 1.80e-39

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: 141.66  E-value: 1.80e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300680969  25 FFVLYEETSTSSARLEYYDTEKKFLQRAEPKRVIYLKNCFNINRRLDTKHRFVIVLSSRDGGFGIVLENENDLRKWLDKL 104
Cdd:cd01257   19 YFVLRAESHGGPARLEYYENEKKFRRNAEPKRVIPLSSCFNINKRADAKHKHLIALYTKDECFGLVAESEEEQDEWYQAL 98


                 ....*...
gi 300680969 105 LVLQRNIA 112
Cdd:cd01257   99 LELQRPAR 106
IRS pfam02174
PTB domain (IRS-1 type);
123-234 1.60e-32

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 121.59  E-value: 1.60e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300680969  123 DQVWQVVIQKKGISEKVGITGTYHCCLTSKSLTFVcigpektpNGEDRVASIEILLTTIRRCGHAspQCIFYVELGRQSV 202
Cdd:pfam02174   1 VEVFPVTVRRTGASERCGLSGSYRLCLTAEALTLD--------KLNTRVPLVSWPLTSLRRYGRD--KNFFSFEAGRRCV 70

                          90       100       110
                  ....*....|....*....|....*....|..
gi 300680969  203 LGSGDLWMETDNaavATNMHNMILSAMSAKTE 234
Cdd:pfam02174  71 TGEGEFWFQTDD---AEEIFETVLAAMKAQKE 99
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
124-231 4.27e-15

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 71.67  E-value: 4.27e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300680969   124 QVWQVVIQKKGiSEKVGITGTYHCCLTSKSLTFVCIGpektpngEDRVASIEILLTTIRRCGHASpqCIFYVELGRQSVL 203
Cdd:smart00310   2 QFWVTIRKTEG-LERCPLSGSYRLRLTSEELVLWRGL-------NPRVELVVWPLLSLRRYGRDK--VFFFFEAGRRCVS 71

                           90       100
                   ....*....|....*....|....*...
gi 300680969   204 GSGDLWMETdnaAVATNMHNMILSAMSA 231
Cdd:smart00310  72 GPGEFTFQT---VVAQEIFQLVLEAMQA 96
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 25-104 3.40e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 41.01  E-value: 3.40e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300680969   25 FFVLYEEtstssaRLEYYDtEKKFLQRAEPKRVIYLKNC----FNINRRLDTKHRFVIVLSSRDGGFGIVL--ENENDLR 98
Cdd:pfam00169  22 YFVLFDG------SLLYYK-DDKSGKSKEPKGSISLSGCevveVVASDSPKRKFCFELRTGERTGKRTYLLqaESEEERK 94


                  ....*.
gi 300680969   99 KWLDKL 104
Cdd:pfam00169  95 DWIKAI 100
 
Name Accession Description Interval E-value
PTB_IRS cd01204
Insulin receptor substrate phosphotyrosine-binding domain (PTBi); Insulin receptor substrate ...
 122-235 1.39e-55

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: 187.46  E-value: 1.39e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300680969 122 YDQVWQVVIQKKGISEKVGITGTYHCCLTSKSLTFVCIGPEKTPngedrvASIEILLTTIRRCGHASpqCIFYVELGRQS 201
Cdd:cd01204    1 FEHVWQVTVKKKGLGQSKNLTGIYRLCLTSKTLSLVKLNSEKNP------PSVEIQLMNIRRCGHSE--NFFFIEVGRSA 72

                         90       100       110
                 ....*....|....*....|....*....|....
gi 300680969 202 VLGSGDLWMETDNAAVATNMHNMILSAMSAKTES 235
Cdd:cd01204   73 VTGPGELWMQVDDSVVAQNMHETILEAMKALSEE 106
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 25-112 1.80e-39

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: 141.66  E-value: 1.80e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300680969  25 FFVLYEETSTSSARLEYYDTEKKFLQRAEPKRVIYLKNCFNINRRLDTKHRFVIVLSSRDGGFGIVLENENDLRKWLDKL 104
Cdd:cd01257   19 YFVLRAESHGGPARLEYYENEKKFRRNAEPKRVIPLSSCFNINKRADAKHKHLIALYTKDECFGLVAESEEEQDEWYQAL 98


                 ....*...
gi 300680969 105 LVLQRNIA 112
Cdd:cd01257   99 LELQRPAR 106
IRS pfam02174
PTB domain (IRS-1 type);
123-234 1.60e-32

PTB domain (IRS-1 type);


Pssm-ID: 460473  Cd Length: 99  Bit Score: 121.59  E-value: 1.60e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300680969  123 DQVWQVVIQKKGISEKVGITGTYHCCLTSKSLTFVcigpektpNGEDRVASIEILLTTIRRCGHAspQCIFYVELGRQSV 202
Cdd:pfam02174   1 VEVFPVTVRRTGASERCGLSGSYRLCLTAEALTLD--------KLNTRVPLVSWPLTSLRRYGRD--KNFFSFEAGRRCV 70

                          90       100       110
                  ....*....|....*....|....*....|..
gi 300680969  203 LGSGDLWMETDNaavATNMHNMILSAMSAKTE 234
Cdd:pfam02174  71 TGEGEFWFQTDD---AEEIFETVLAAMKAQKE 99
PTBI smart00310
Phosphotyrosine-binding domain (IRS1-like);
124-231 4.27e-15

Phosphotyrosine-binding domain (IRS1-like);


Pssm-ID: 197644  Cd Length: 99  Bit Score: 71.67  E-value: 4.27e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300680969   124 QVWQVVIQKKGiSEKVGITGTYHCCLTSKSLTFVCIGpektpngEDRVASIEILLTTIRRCGHASpqCIFYVELGRQSVL 203
Cdd:smart00310   2 QFWVTIRKTEG-LERCPLSGSYRLRLTSEELVLWRGL-------NPRVELVVWPLLSLRRYGRDK--VFFFFEAGRRCVS 71

                           90       100
                   ....*....|....*....|....*...
gi 300680969   204 GSGDLWMETdnaAVATNMHNMILSAMSA 231
Cdd:smart00310  72 GPGEFTFQT---VVAQEIFQLVLEAMQA 96
PH_PLEKHD1 cd13281
Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH ...
 25-104 1.98e-04

Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH domain; Human PLEKHD1 (also called UPF0639, pleckstrin homology domain containing, family D (with M protein repeats) member 1) is a single transcript and contains a single PH domain. PLEKHD1 is conserved in human, chimpanzee, , dog, cow, mouse, chicken, zebrafish, and Caenorhabditis elegans. 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: 270099  Cd Length: 139  Bit Score: 42.31  E-value: 1.98e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300680969  25 FFVLYEetstsSARLEYYDTEKKFLQRAE-----PKRVIYLKNCFnINRRLDTKHRFVIVLSSRDGGFGIVL--ENENDL 97
Cdd:cd13281   34 FFIIKE-----GFLLYYSESEKKDFEKTRhfnihPKGVIPLGGCS-IEAVEDPGKPYAISISHSDFKGNIILaaDSEFEQ 107


                 ....*..
gi 300680969  98 RKWLDKL 104
Cdd:cd13281  108 EKWLDML 114
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 25-104 3.40e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 41.01  E-value: 3.40e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300680969   25 FFVLYEEtstssaRLEYYDtEKKFLQRAEPKRVIYLKNC----FNINRRLDTKHRFVIVLSSRDGGFGIVL--ENENDLR 98
Cdd:pfam00169  22 YFVLFDG------SLLYYK-DDKSGKSKEPKGSISLSGCevveVVASDSPKRKFCFELRTGERTGKRTYLLqaESEEERK 94


                  ....*.
gi 300680969   99 KWLDKL 104
Cdd:pfam00169  95 DWIKAI 100
 
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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