P35568 · IRS1_HUMAN
- ProteinInsulin receptor substrate 1
- GeneIRS1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1242 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameInsulin receptor substrate 1
- Short namesIRS-1
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP35568
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Type 2 diabetes mellitus (T2D)
- Note
- DescriptionA multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
- See alsoMIM:125853
Natural variants in T2D
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_005301 | 723 | missing | in T2D; dbSNP:rs1259467443 | |
VAR_005302 | 1043 | S>Y | in T2D | |
VAR_005303 | 1095 | C>Y | in T2D |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_014853 | 158 | in dbSNP:rs1801108 | |||
Sequence: P → R | ||||||
Natural variant | VAR_014854 | 209 | in dbSNP:rs1801118 | |||
Sequence: M → T | ||||||
Mutagenesis | 307 | Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-312; A-527; A-636 and A-639. | ||||
Sequence: S → A | ||||||
Mutagenesis | 312 | Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-527; A-636 and A-639. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_005299 | 512 | in dbSNP:rs1801276 | |||
Sequence: A → P | ||||||
Mutagenesis | 527 | Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-312; A-636 and A-639. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_025320 | 608 | may contribute to insulin resistance by impairing metabolic signaling through PI3K-dependent pathways; dbSNP:rs104893642 | |||
Sequence: T → R | ||||||
Mutagenesis | 612 | Induces IRS1 degradation. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 632 | Does not affect IRS1 stability. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 636 | Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-312; A-527 and A-639. | ||||
Sequence: S → A | ||||||
Mutagenesis | 639 | Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-312; A-527 and A-636. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_005301 | 723 | in T2D; dbSNP:rs1259467443 | |||
Sequence: Missing | ||||||
Mutagenesis | 794 | Loss of phosphorylation by SIK2. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_014855 | 809 | in dbSNP:rs1801120 | |||
Sequence: S → F | ||||||
Natural variant | VAR_014856 | 892 | in dbSNP:rs1801277 | |||
Sequence: S → G | ||||||
Natural variant | VAR_005300 | 971 | in dbSNP:rs1801278 | |||
Sequence: G → R | ||||||
Natural variant | VAR_005302 | 1043 | in T2D | |||
Sequence: S → Y | ||||||
Natural variant | VAR_005303 | 1095 | in T2D | |||
Sequence: C → Y | ||||||
Natural variant | VAR_021837 | 1137 | in dbSNP:rs3731594 | |||
Sequence: D → N |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,581 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000084236 | 1-1242 | UniProt | Insulin receptor substrate 1 | |||
Sequence: MASPPESDGFSDVRKVGYLRKPKSMHKRFFVLRAASEAGGPARLEYYENEKKWRHKSSAPKRSIPLESCFNINKRADSKNKHLVALYTRDEHFAIAADSEAEQDSWYQALLQLHNRAKGHHDGAAALGAGGGGGSCSGSSGLGEAGEDLSYGDVPPGPAFKEVWQVILKPKGLGQTKNLIGIYRLCLTSKTISFVKLNSEAAAVVLQLMNIRRCGHSENFFFIEVGRSAVTGPGEFWMQVDDSVVAQNMHETILEAMRAMSDEFRPRSKSQSSSNCSNPISVPLRRHHLNNPPPSQVGLTRRSRTESITATSPASMVGGKPGSFRVRASSDGEGTMSRPASVDGSPVSPSTNRTHAHRHRGSARLHPPLNHSRSIPMPASRCSPSATSPVSLSSSSTSGHGSTSDCLFPRRSSASVSGSPSDGGFISSDEYGSSPCDFRSSFRSVTPDSLGHTPPARGEEELSNYICMGGKGPSTLTAPNGHYILSRGGNGHRCTPGTGLGTSPALAGDEAASAADLDNRFRKRTHSAGTSPTITHQKTPSQSSVASIEEYTEMMPAYPPGGGSGGRLPGHRHSAFVPTRSYPEEGLEMHPLERRGGHHRPDSSTLHTDDGYMPMSPGVAPVPSGRKGSGDYMPMSPKSVSAPQQIINPIRRHPQRVDPNGYMMMSPSGGCSPDIGGGPSSSSSSSNAVPSGTSYGKLWTNGVGGHHSHVLPHPKPPVESSGGKLLPCTGDYMNMSPVGDSNTSSPSDCYYGPEDPQHKPVLSYYSLPRSFKHTQRPGEPEEGARHQHLRLSTSSGRLLYAATADDSSSSTSSDSLGGGYCGARLEPSLPHPHHQVLQPHLPRKVDTAAQTNSRLARPTRLSLGDPKASTLPRAREQQQQQQPLLHPPEPKSPGEYVNIEFGSDQSGYLSGPVAFHSSPSVRCPSQLQPAPREEETGTEEYMKMDLGPGRRAAWQESTGVEMGRLGPAPPGAASICRPTRAVPSSRGDYMTMQMSCPRQSYVDTSPAAPVSYADMRTGIAAEEVSLPRATMAAASSSSAASASPTGPQGAAELAAHSSLLGGPQGPGGMSAFTRVNLSPNRNQSAKVIRADPQGCRRRHSSETFSSTPSATRVGNTVPFGAGAAVGGGGGSSSSSEDVKRHSSASFENVWLRPGELGGAPKEPAKLCGAAGGLENGLNYIDLDLVKDFKQCPQECTPEPQPPPPPPPHQPLGSGESSSTRRSSEDLSAYASISFQKQPEDRQ | |||||||
Modified residue | 3 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 3 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 36 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 99 | UniProt | Phosphoserine; by CK2 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 268 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 270 | UniProt | Phosphoserine; by RPS6KB1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 270 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 272 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 273 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 274 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 305 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 307 | UniProt | Phosphoserine; by RPS6KB1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 307 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 309 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 311 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 312 | UniProt | Phosphoserine; by IKKB, MAPK8 and RPS6KB1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 312 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 323 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 323 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 330 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 330 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 341 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 345 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 345 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 348 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 348 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 351 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 374 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 383 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 413 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 419 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 444 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 446 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 446 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 449 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 453 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 453 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 463 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 465 | UniProt | Phosphotyrosine; by INSR | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 465 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 502 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 503 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 527 | UniProt | Phosphoserine; by RPS6KB1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 527 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 530 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 531 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 551 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 608 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 612 | UniProt | Phosphotyrosine; by INSR | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 612 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 616 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 616 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 629 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 629 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 632 | UniProt | Phosphotyrosine; by INSR | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 632 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 636 | UniProt | Phosphoserine; by RPS6KB1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 636 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 662 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 662 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 766 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 794 | UniProt | Phosphoserine; by AMPK and SIK2 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 862 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 892 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 892 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 896 | UniProt | Phosphotyrosine; by INSR | ||||
Sequence: Y | |||||||
Modified residue | 941 | UniProt | Phosphotyrosine; by INSR | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 941 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 989 | UniProt | Phosphotyrosine; by INSR | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 989 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 1005 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1078 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1100 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1100 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1101 | UniProt | Phosphoserine; by RPS6KB1 and PKC/PRKCQ | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1101 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1103 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 1105 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1107 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 1142 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1143 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1145 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1179 | UniProt | Phosphotyrosine; by INSR | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 1196 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 1222 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1223 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1229 | UniProt | Phosphotyrosine; by INSR | ||||
Sequence: Y |
Post-translational modification
Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-312 phosphorylation inhibits insulin action through disruption of IRS1 interaction with the insulin receptor (By similarity).
Phosphorylation of Tyr-896 is required for GRB2-binding (By similarity).
Phosphorylated by ALK. Phosphorylated at Ser-270, Ser-307, Ser-636 and Ser-1101 by RPS6KB1; phosphorylation induces accelerated degradation of IRS1 (PubMed:18952604).
Phosphorylated on tyrosine residues in response to insulin (PubMed:23401856).
In skeletal muscles, dephosphorylated on Tyr-612 by TNS2 under anabolic conditions; dephosphorylation results in the proteasomal degradation of IRS1 (PubMed:23401856).
Phosphorylation of Tyr-896 is required for GRB2-binding (By similarity).
Phosphorylated by ALK. Phosphorylated at Ser-270, Ser-307, Ser-636 and Ser-1101 by RPS6KB1; phosphorylation induces accelerated degradation of IRS1 (PubMed:18952604).
Phosphorylated on tyrosine residues in response to insulin (PubMed:23401856).
In skeletal muscles, dephosphorylated on Tyr-612 by TNS2 under anabolic conditions; dephosphorylation results in the proteasomal degradation of IRS1 (PubMed:23401856).
Ubiquitinated by the Cul7-RING(FBXW8) complex in a mTOR-dependent manner, leading to its degradation: the Cul7-RING(FBXW8) complex recognizes and binds IRS1 previously phosphorylated by S6 kinase (RPS6KB1 or RPS6KB2).
S-nitrosylation at by BLVRB inhibits its activity.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Interacts with UBTF and PIK3CA (By similarity).
Interacts (via phosphorylated YXXM motifs) with PIK3R1 (By similarity).
Interacts with ROCK1 and FER (By similarity).
Interacts (via PH domain) with PHIP (By similarity).
Interacts with GRB2 (By similarity).
Interacts with SOCS7 (PubMed:16127460).
Interacts (via IRS-type PTB domain) with IGF1R and INSR (via the tyrosine-phosphorylated NPXY motif) (PubMed:7537849, PubMed:7541045, PubMed:7559478).
Interacts with ALK (PubMed:15226403, PubMed:16878150).
Interacts with EIF2AK2/PKR (By similarity).
Interacts with GKAP1 (By similarity).
Interacts with DGKZ in the absence of insulin; insulin stimulation decreases this interaction (By similarity).
Found in a ternary complex with DGKZ and PIP5K1A in the absence of insulin stimulation (By similarity).
Interacts with SQSTM1; the interaction is disrupted by the presence of tensin TNS2 (PubMed:25101860).
Interacts (via phosphorylated YXXM motifs) with PIK3R1 (By similarity).
Interacts with ROCK1 and FER (By similarity).
Interacts (via PH domain) with PHIP (By similarity).
Interacts with GRB2 (By similarity).
Interacts with SOCS7 (PubMed:16127460).
Interacts (via IRS-type PTB domain) with IGF1R and INSR (via the tyrosine-phosphorylated NPXY motif) (PubMed:7537849, PubMed:7541045, PubMed:7559478).
Interacts with ALK (PubMed:15226403, PubMed:16878150).
Interacts with EIF2AK2/PKR (By similarity).
Interacts with GKAP1 (By similarity).
Interacts with DGKZ in the absence of insulin; insulin stimulation decreases this interaction (By similarity).
Found in a ternary complex with DGKZ and PIP5K1A in the absence of insulin stimulation (By similarity).
Interacts with SQSTM1; the interaction is disrupted by the presence of tensin TNS2 (PubMed:25101860).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P35568 | BCAR3 O75815 | 3 | EBI-517592, EBI-702336 | |
BINARY | P35568 | ERBB2 P04626 | 2 | EBI-517592, EBI-641062 | |
BINARY | P35568 | INSR P06213 | 3 | EBI-517592, EBI-475899 | |
XENO | P35568 | NS P03495 | 2 | EBI-517592, EBI-2548993 | |
XENO | P35568 | P03070 | 2 | EBI-517592, EBI-617698 | |
BINARY | P35568 | PABPC1 P11940 | 2 | EBI-517592, EBI-81531 | |
BINARY | P35568 | PIK3CA P42336 | 41 | EBI-517592, EBI-2116585 | |
BINARY | P35568 | PIK3R1 P27986 | 12 | EBI-517592, EBI-79464 | |
BINARY | P35568 | PIK3R1 P27986-2 | 3 | EBI-517592, EBI-9090282 | |
BINARY | P35568 | PIK3R3 Q92569 | 4 | EBI-517592, EBI-79893 | |
BINARY | P35568 | PTPN11 Q06124 | 3 | EBI-517592, EBI-297779 | |
BINARY | P35568 | SFN P31947 | 2 | EBI-517592, EBI-476295 | |
BINARY | P35568 | YWHAE P62258 | 2 | EBI-517592, EBI-356498 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 3-137 | Mediates interaction with PHIP | ||||
Sequence: SPPESDGFSDVRKVGYLRKPKSMHKRFFVLRAASEAGGPARLEYYENEKKWRHKSSAPKRSIPLESCFNINKRADSKNKHLVALYTRDEHFAIAADSEAEQDSWYQALLQLHNRAKGHHDGAAALGAGGGGGSCS | ||||||
Domain | 12-115 | PH | ||||
Sequence: DVRKVGYLRKPKSMHKRFFVLRAASEAGGPARLEYYENEKKWRHKSSAPKRSIPLESCFNINKRADSKNKHLVALYTRDEHFAIAADSEAEQDSWYQALLQLHN | ||||||
Domain | 160-264 | IRS-type PTB | ||||
Sequence: FKEVWQVILKPKGLGQTKNLIGIYRLCLTSKTISFVKLNSEAAAVVLQLMNIRRCGHSENFFFIEVGRSAVTGPGEFWMQVDDSVVAQNMHETILEAMRAMSDEF | ||||||
Region | 262-430 | Disordered | ||||
Sequence: DEFRPRSKSQSSSNCSNPISVPLRRHHLNNPPPSQVGLTRRSRTESITATSPASMVGGKPGSFRVRASSDGEGTMSRPASVDGSPVSPSTNRTHAHRHRGSARLHPPLNHSRSIPMPASRCSPSATSPVSLSSSSTSGHGSTSDCLFPRRSSASVSGSPSDGGFISSDE | ||||||
Compositional bias | 266-281 | Polar residues | ||||
Sequence: PRSKSQSSSNCSNPIS | ||||||
Compositional bias | 293-316 | Polar residues | ||||
Sequence: PPSQVGLTRRSRTESITATSPASM | ||||||
Compositional bias | 376-430 | Polar residues | ||||
Sequence: PMPASRCSPSATSPVSLSSSSTSGHGSTSDCLFPRRSSASVSGSPSDGGFISSDE | ||||||
Motif | 465-468 | YXXM motif 1 | ||||
Sequence: YICM | ||||||
Motif | 551-554 | YXXM motif 2 | ||||
Sequence: YTEM | ||||||
Compositional bias | 592-606 | Basic and acidic residues | ||||
Sequence: LERRGGHHRPDSSTL | ||||||
Region | 592-616 | Disordered | ||||
Sequence: LERRGGHHRPDSSTLHTDDGYMPMS | ||||||
Motif | 612-615 | YXXM motif 3 | ||||
Sequence: YMPM | ||||||
Motif | 632-635 | YXXM motif 4 | ||||
Sequence: YMPM | ||||||
Motif | 662-665 | YXXM motif 5 | ||||
Sequence: YMMM | ||||||
Region | 668-693 | Disordered | ||||
Sequence: SGGCSPDIGGGPSSSSSSSNAVPSGT | ||||||
Compositional bias | 675-693 | Polar residues | ||||
Sequence: IGGGPSSSSSSSNAVPSGT | ||||||
Motif | 732-735 | YXXM motif 6 | ||||
Sequence: YMNM | ||||||
Region | 771-900 | Disordered | ||||
Sequence: FKHTQRPGEPEEGARHQHLRLSTSSGRLLYAATADDSSSSTSSDSLGGGYCGARLEPSLPHPHHQVLQPHLPRKVDTAAQTNSRLARPTRLSLGDPKASTLPRAREQQQQQQPLLHPPEPKSPGEYVNIE | ||||||
Compositional bias | 774-788 | Basic and acidic residues | ||||
Sequence: TQRPGEPEEGARHQH | ||||||
Compositional bias | 789-817 | Polar residues | ||||
Sequence: LRLSTSSGRLLYAATADDSSSSTSSDSLG | ||||||
Region | 896-898 | GRB2-binding | ||||
Sequence: YVN | ||||||
Region | 918-937 | Disordered | ||||
Sequence: SPSVRCPSQLQPAPREEETG | ||||||
Motif | 941-944 | YXXM motif 7 | ||||
Sequence: YMKM | ||||||
Motif | 989-992 | YXXM motif 8 | ||||
Sequence: YMTM | ||||||
Motif | 1012-1015 | YXXM motif 9 | ||||
Sequence: YADM | ||||||
Region | 1057-1146 | Disordered | ||||
Sequence: SSLLGGPQGPGGMSAFTRVNLSPNRNQSAKVIRADPQGCRRRHSSETFSSTPSATRVGNTVPFGAGAAVGGGGGSSSSSEDVKRHSSASF | ||||||
Compositional bias | 1071-1087 | Polar residues | ||||
Sequence: AFTRVNLSPNRNQSAKV | ||||||
Compositional bias | 1099-1114 | Polar residues | ||||
Sequence: HSSETFSSTPSATRVG | ||||||
Region | 1190-1242 | Disordered | ||||
Sequence: QCPQECTPEPQPPPPPPPHQPLGSGESSSTRRSSEDLSAYASISFQKQPEDRQ | ||||||
Compositional bias | 1195-1211 | Pro residues | ||||
Sequence: CTPEPQPPPPPPPHQPL | ||||||
Compositional bias | 1212-1236 | Polar residues | ||||
Sequence: GSGESSSTRRSSEDLSAYASISFQK |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,242
- Mass (Da)131,591
- Last updated1994-06-01 v1
- Checksum3C0EFD9E32B3E64A
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 134 | in Ref. 2; AAB21608 | ||||
Sequence: G → GG | ||||||
Compositional bias | 266-281 | Polar residues | ||||
Sequence: PRSKSQSSSNCSNPIS | ||||||
Compositional bias | 293-316 | Polar residues | ||||
Sequence: PPSQVGLTRRSRTESITATSPASM | ||||||
Sequence conflict | 362 | in Ref. 2; AAB21608 | ||||
Sequence: S → R | ||||||
Compositional bias | 376-430 | Polar residues | ||||
Sequence: PMPASRCSPSATSPVSLSSSSTSGHGSTSDCLFPRRSSASVSGSPSDGGFISSDE | ||||||
Sequence conflict | 384 | in Ref. 2; AAB21608 | ||||
Sequence: P → R | ||||||
Compositional bias | 592-606 | Basic and acidic residues | ||||
Sequence: LERRGGHHRPDSSTL | ||||||
Compositional bias | 675-693 | Polar residues | ||||
Sequence: IGGGPSSSSSSSNAVPSGT | ||||||
Compositional bias | 774-788 | Basic and acidic residues | ||||
Sequence: TQRPGEPEEGARHQH | ||||||
Compositional bias | 789-817 | Polar residues | ||||
Sequence: LRLSTSSGRLLYAATADDSSSSTSSDSLG | ||||||
Compositional bias | 1071-1087 | Polar residues | ||||
Sequence: AFTRVNLSPNRNQSAKV | ||||||
Compositional bias | 1099-1114 | Polar residues | ||||
Sequence: HSSETFSSTPSATRVG | ||||||
Compositional bias | 1195-1211 | Pro residues | ||||
Sequence: CTPEPQPPPPPPPHQPL | ||||||
Compositional bias | 1212-1236 | Polar residues | ||||
Sequence: GSGESSSTRRSSEDLSAYASISFQK |
Polymorphism
The Arg-971 polymorphism impairs the ability of insulin to stimulate glucose transport, glucose transporter translocation, and glycogen synthesis by affecting the PI3K/AKT1/GSK3 signaling pathway. The polymorphism at Arg-971 may contribute to the in vivo insulin resistance observed in carriers of this variant. Arg-971 could contribute to the risk for atherosclerotic cardiovascular diseases associated with non-insulin-dependent diabetes mellitus (NIDDM) by producing a cluster of insulin resistance-related metabolic abnormalities. In insulin-stimulated human endothelial cells from carriers of the Arg-971 polymorphism, genetic impairment of the IRS1/PI3K/PDPK1/AKT1 insulin signaling cascade results in impaired insulin-stimulated nitric oxide (NO) release and suggested that this may be a mechanism through which the Arg-971 polymorphism contributes to the genetic predisposition to develop endothelial dysfunction and cardiovascular disease. The Arg-971 polymorphism not only reduces phosphorylation of the substrate but allows IRS1 to act as an inhibitor of PI3K, producing global insulin resistance.
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
S85963 EMBL· GenBank· DDBJ | AAB21608.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
S62539 EMBL· GenBank· DDBJ | AAB27175.1 EMBL· GenBank· DDBJ | mRNA | ||
BC053895 EMBL· GenBank· DDBJ | AAH53895.1 EMBL· GenBank· DDBJ | mRNA |