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Entry version 209 (08 May 2019)
Sequence version 1 (01 Jun 1994)
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Protein

Insulin receptor substrate 1

Gene

IRS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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).By similarity1 Publication

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionTransducer

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-109704 PI3K Cascade
R-HSA-112399 IRS-mediated signalling
R-HSA-112412 SOS-mediated signalling
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1266695 Interleukin-7 signaling
R-HSA-198203 PI3K/AKT activation
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-2428928 IRS-related events triggered by IGF1R
R-HSA-2586552 Signaling by Leptin
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-74713 IRS activation
R-HSA-74749 Signal attenuation
R-HSA-9603381 Activated NTRK3 signals through PI3K
R-HSA-982772 Growth hormone receptor signaling

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
P35568

SIGNOR Signaling Network Open Resource

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SIGNORi
P35568

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Insulin receptor substrate 1
Short name:
IRS-1
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:IRS1
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 2

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:6125 IRS1

Online Mendelian Inheritance in Man (OMIM)

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MIMi
147545 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_P35568

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Diabetes mellitus, non-insulin-dependent (NIDDM)3 Publications
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionA multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own 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 also OMIM:125853
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_005301723Missing in NIDDM. 1 Publication1
Natural variantiVAR_0053021043S → Y in NIDDM. 1 Publication1
Natural variantiVAR_0053031095C → Y in NIDDM. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi307S → A: Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-312; A-527; A-636 and A-639. 1 Publication1
Mutagenesisi312S → A: Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-527; A-636 and A-639. 1 Publication1
Mutagenesisi527S → A: Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-312; A-636 and A-639. 1 Publication1
Mutagenesisi636S → A: Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-312; A-527 and A-639. 1 Publication1
Mutagenesisi639S → A: Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-312; A-527 and A-636. 1 Publication1
Mutagenesisi794S → A: Loss of phosphorylation by SIK2. 1 Publication1

Keywords - Diseasei

Diabetes mellitus, Disease mutation

Organism-specific databases

DisGeNET

More...
DisGeNETi
3667

MalaCards human disease database

More...
MalaCardsi
IRS1
MIMi125853 phenotype

Open Targets

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OpenTargetsi
ENSG00000169047

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA203

Chemistry databases

Drug and drug target database

More...
DrugBanki
DB08513 [4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
IRS1

Domain mapping of disease mutations (DMDM)

More...
DMDMi
547738

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000842361 – 1242Insulin receptor substrate 1Add BLAST1242

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei3PhosphoserineBy similarity1
Modified residuei99Phosphoserine; by CK2By similarity1
Modified residuei270Phosphoserine; by RPS6KB11 Publication1
Modified residuei307Phosphoserine; by RPS6KB12 Publications1
Modified residuei312Phosphoserine; by IKKB, MAPK8 and RPS6KB12 Publications1
Modified residuei323PhosphoserineCombined sources1
Modified residuei330PhosphoserineBy similarity1
Modified residuei345PhosphoserineBy similarity1
Modified residuei348PhosphoserineCombined sources1
Modified residuei419PhosphoserineBy similarity1
Modified residuei446PhosphothreonineBy similarity1
Modified residuei453PhosphothreonineCombined sources1
Modified residuei465Phosphotyrosine; by INSRBy similarity1
Modified residuei527Phosphoserine; by RPS6KB1Combined sources1 Publication1
Modified residuei612Phosphotyrosine; by INSRBy similarity1
Modified residuei629PhosphoserineCombined sources1
Modified residuei632Phosphotyrosine; by INSRBy similarity1
Modified residuei636Phosphoserine; by RPS6KB1Combined sources2 Publications1
Modified residuei662PhosphotyrosineCombined sources1
Modified residuei794Phosphoserine; by AMPK and SIK21 Publication1
Modified residuei892PhosphoserineBy similarity1
Modified residuei896Phosphotyrosine; by INSRBy similarity1
Modified residuei941Phosphotyrosine; by INSR1 Publication1
Modified residuei989Phosphotyrosine; by INSRBy similarity1
Modified residuei1100PhosphoserineBy similarity1
Modified residuei1101Phosphoserine; by RPS6KB1 and PKC/PRKCQ2 Publications1
Modified residuei1179Phosphotyrosine; by INSRBy similarity1
Modified residuei1229Phosphotyrosine; by INSRBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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. Phosphorylated on tyrosine residues in response to insulin (By similarity).By similarity4 Publications
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).1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P35568

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P35568

MaxQB - The MaxQuant DataBase

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MaxQBi
P35568

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P35568

PeptideAtlas

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PeptideAtlasi
P35568

PRoteomics IDEntifications database

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PRIDEi
P35568

ProteomicsDB human proteome resource

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ProteomicsDBi
55088

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P35568

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P35568

Miscellaneous databases

CutDB - Proteolytic event database

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PMAP-CutDBi
P35568

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000169047 Expressed in 237 organ(s), highest expression level in endometrium

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P35568 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P35568 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
CAB005261
HPA046433

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

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:7541045, PubMed:7559478, PubMed:7537849). 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).By similarity6 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
109874, 79 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
P35568

Database of interacting proteins

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DIPi
DIP-523N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
P35568

Protein interaction database and analysis system

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IntActi
P35568, 29 interactors

Molecular INTeraction database

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MINTi
P35568

STRING: functional protein association networks

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STRINGi
9606.ENSP00000304895

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

11242
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IRSNMR-A157-267[»]
1K3AX-ray2.10B891-902[»]
1QQGX-ray2.30A/B4-267[»]
2Z8CX-ray3.25B731-736[»]
5U1MX-ray1.80A161-265[»]
6BNTX-ray3.20B607-620[»]

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P35568

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P35568

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini12 – 115PHPROSITE-ProRule annotationAdd BLAST104
Domaini160 – 264IRS-type PTBPROSITE-ProRule annotationAdd BLAST105

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni3 – 137Mediates interaction with PHIPBy similarityAdd BLAST135
Regioni896 – 898GRB2-bindingBy similarity3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi465 – 468YXXM motif 14
Motifi551 – 554YXXM motif 24
Motifi612 – 615YXXM motif 34
Motifi632 – 635YXXM motif 44
Motifi662 – 665YXXM motif 54
Motifi732 – 735YXXM motif 64
Motifi941 – 944YXXM motif 74
Motifi989 – 992YXXM motif 84
Motifi1012 – 1015YXXM motif 94

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi128 – 134Poly-Gly7
Compositional biasi268 – 444Ser-richAdd BLAST177
Compositional biasi680 – 686Poly-Ser7
Compositional biasi807 – 815Poly-Ser9
Compositional biasi877 – 882Poly-Gln6
Compositional biasi1192 – 1210Pro-richAdd BLAST19

Keywords - Domaini

Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
ENOG410IXEK Eukaryota
ENOG410Z9EP LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000161579

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000113103

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P35568

KEGG Orthology (KO)

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KOi
K16172

Identification of Orthologs from Complete Genome Data

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OMAi
NGYMMMS

Database of Orthologous Groups

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OrthoDBi
298675at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
P35568

TreeFam database of animal gene trees

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TreeFami
TF325994

Family and domain databases

Conserved Domains Database

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CDDi
cd01204 PTB_IRS, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
2.30.29.30, 2 hits

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR039011 IRS
IPR002404 IRS_PTB
IPR011993 PH-like_dom_sf
IPR001849 PH_domain

The PANTHER Classification System

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PANTHERi
PTHR10614 PTHR10614, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF02174 IRS, 1 hit
PF00169 PH, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR00628 INSULINRSI

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00233 PH, 1 hit
SM00310 PTBI, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS51064 IRS_PTB, 1 hit
PS50003 PH_DOMAIN, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

P35568-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MASPPESDGF SDVRKVGYLR KPKSMHKRFF VLRAASEAGG PARLEYYENE
60 70 80 90 100
KKWRHKSSAP KRSIPLESCF NINKRADSKN KHLVALYTRD EHFAIAADSE
110 120 130 140 150
AEQDSWYQAL LQLHNRAKGH HDGAAALGAG GGGGSCSGSS GLGEAGEDLS
160 170 180 190 200
YGDVPPGPAF KEVWQVILKP KGLGQTKNLI GIYRLCLTSK TISFVKLNSE
210 220 230 240 250
AAAVVLQLMN IRRCGHSENF FFIEVGRSAV TGPGEFWMQV DDSVVAQNMH
260 270 280 290 300
ETILEAMRAM SDEFRPRSKS QSSSNCSNPI SVPLRRHHLN NPPPSQVGLT
310 320 330 340 350
RRSRTESITA TSPASMVGGK PGSFRVRASS DGEGTMSRPA SVDGSPVSPS
360 370 380 390 400
TNRTHAHRHR GSARLHPPLN HSRSIPMPAS RCSPSATSPV SLSSSSTSGH
410 420 430 440 450
GSTSDCLFPR RSSASVSGSP SDGGFISSDE YGSSPCDFRS SFRSVTPDSL
460 470 480 490 500
GHTPPARGEE ELSNYICMGG KGPSTLTAPN GHYILSRGGN GHRCTPGTGL
510 520 530 540 550
GTSPALAGDE AASAADLDNR FRKRTHSAGT SPTITHQKTP SQSSVASIEE
560 570 580 590 600
YTEMMPAYPP GGGSGGRLPG HRHSAFVPTR SYPEEGLEMH PLERRGGHHR
610 620 630 640 650
PDSSTLHTDD GYMPMSPGVA PVPSGRKGSG DYMPMSPKSV SAPQQIINPI
660 670 680 690 700
RRHPQRVDPN GYMMMSPSGG CSPDIGGGPS SSSSSSNAVP SGTSYGKLWT
710 720 730 740 750
NGVGGHHSHV LPHPKPPVES SGGKLLPCTG DYMNMSPVGD SNTSSPSDCY
760 770 780 790 800
YGPEDPQHKP VLSYYSLPRS FKHTQRPGEP EEGARHQHLR LSTSSGRLLY
810 820 830 840 850
AATADDSSSS TSSDSLGGGY CGARLEPSLP HPHHQVLQPH LPRKVDTAAQ
860 870 880 890 900
TNSRLARPTR LSLGDPKAST LPRAREQQQQ QQPLLHPPEP KSPGEYVNIE
910 920 930 940 950
FGSDQSGYLS GPVAFHSSPS VRCPSQLQPA PREEETGTEE YMKMDLGPGR
960 970 980 990 1000
RAAWQESTGV EMGRLGPAPP GAASICRPTR AVPSSRGDYM TMQMSCPRQS
1010 1020 1030 1040 1050
YVDTSPAAPV SYADMRTGIA AEEVSLPRAT MAAASSSSAA SASPTGPQGA
1060 1070 1080 1090 1100
AELAAHSSLL GGPQGPGGMS AFTRVNLSPN RNQSAKVIRA DPQGCRRRHS
1110 1120 1130 1140 1150
SETFSSTPSA TRVGNTVPFG AGAAVGGGGG SSSSSEDVKR HSSASFENVW
1160 1170 1180 1190 1200
LRPGELGGAP KEPAKLCGAA GGLENGLNYI DLDLVKDFKQ CPQECTPEPQ
1210 1220 1230 1240
PPPPPPPHQP LGSGESSSTR RSSEDLSAYA SISFQKQPED RQ
Length:1,242
Mass (Da):131,591
Last modified:June 1, 1994 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i3C0EFD9E32B3E64A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti134G → GG in AAB21608 (PubMed:1311924).Curated1
Sequence conflicti362S → R in AAB21608 (PubMed:1311924).Curated1
Sequence conflicti384P → R in AAB21608 (PubMed:1311924).Curated1

<p>This subsection of the ‘Sequence’ section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement_in_disease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

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.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_014853158P → R. Corresponds to variant dbSNP:rs1801108Ensembl.1
Natural variantiVAR_014854209M → T. Corresponds to variant dbSNP:rs1801118Ensembl.1
Natural variantiVAR_005299512A → P1 PublicationCorresponds to variant dbSNP:rs1801276EnsemblClinVar.1
Natural variantiVAR_025320608T → R May contribute to insulin resistance by impairing metabolic signaling through PI3K-dependent pathways. 1 PublicationCorresponds to variant dbSNP:rs104893642EnsemblClinVar.1
Natural variantiVAR_005301723Missing in NIDDM. 1 Publication1
Natural variantiVAR_014855809S → F. Corresponds to variant dbSNP:rs1801120Ensembl.1
Natural variantiVAR_014856892S → G. Corresponds to variant dbSNP:rs1801277Ensembl.1
Natural variantiVAR_005300971G → R5 PublicationsCorresponds to variant dbSNP:rs1801278EnsemblClinVar.1
Natural variantiVAR_0053021043S → Y in NIDDM. 1 Publication1
Natural variantiVAR_0053031095C → Y in NIDDM. 1 Publication1
Natural variantiVAR_0218371137D → N. Corresponds to variant dbSNP:rs3731594Ensembl.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
S85963 Genomic DNA Translation: AAB21608.1
S62539 mRNA Translation: AAB27175.1
BC053895 mRNA Translation: AAH53895.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS2463.1

Protein sequence database of the Protein Information Resource

More...
PIRi
I53160 JS0670

NCBI Reference Sequences

More...
RefSeqi
NP_005535.1, NM_005544.2

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000305123; ENSP00000304895; ENSG00000169047

Database of genes from NCBI RefSeq genomes

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GeneIDi
3667

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:3667

UCSC genome browser

More...
UCSCi
uc002voh.5 human

Keywords - Coding sequence diversityi

Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S85963 Genomic DNA Translation: AAB21608.1
S62539 mRNA Translation: AAB27175.1
BC053895 mRNA Translation: AAH53895.1
CCDSiCCDS2463.1
PIRiI53160 JS0670
RefSeqiNP_005535.1, NM_005544.2

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IRSNMR-A157-267[»]
1K3AX-ray2.10B891-902[»]
1QQGX-ray2.30A/B4-267[»]
2Z8CX-ray3.25B731-736[»]
5U1MX-ray1.80A161-265[»]
6BNTX-ray3.20B607-620[»]
SMRiP35568
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109874, 79 interactors
CORUMiP35568
DIPiDIP-523N
ELMiP35568
IntActiP35568, 29 interactors
MINTiP35568
STRINGi9606.ENSP00000304895

Chemistry databases

DrugBankiDB08513 [4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID

PTM databases

iPTMnetiP35568
PhosphoSitePlusiP35568

Polymorphism and mutation databases

BioMutaiIRS1
DMDMi547738

Proteomic databases

EPDiP35568
jPOSTiP35568
MaxQBiP35568
PaxDbiP35568
PeptideAtlasiP35568
PRIDEiP35568
ProteomicsDBi55088

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
3667
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000305123; ENSP00000304895; ENSG00000169047
GeneIDi3667
KEGGihsa:3667
UCSCiuc002voh.5 human

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
3667
DisGeNETi3667

GeneCards: human genes, protein and diseases

More...
GeneCardsi
IRS1
HGNCiHGNC:6125 IRS1
HPAiCAB005261
HPA046433
MalaCardsiIRS1
MIMi125853 phenotype
147545 gene
neXtProtiNX_P35568
OpenTargetsiENSG00000169047
PharmGKBiPA203

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiENOG410IXEK Eukaryota
ENOG410Z9EP LUCA
GeneTreeiENSGT00940000161579
HOGENOMiHOG000113103
InParanoidiP35568
KOiK16172
OMAiNGYMMMS
OrthoDBi298675at2759
PhylomeDBiP35568
TreeFamiTF325994

Enzyme and pathway databases

ReactomeiR-HSA-109704 PI3K Cascade
R-HSA-112399 IRS-mediated signalling
R-HSA-112412 SOS-mediated signalling
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1266695 Interleukin-7 signaling
R-HSA-198203 PI3K/AKT activation
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-2428928 IRS-related events triggered by IGF1R
R-HSA-2586552 Signaling by Leptin
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-74713 IRS activation
R-HSA-74749 Signal attenuation
R-HSA-9603381 Activated NTRK3 signals through PI3K
R-HSA-982772 Growth hormone receptor signaling
SignaLinkiP35568
SIGNORiP35568

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
IRS1 human
EvolutionaryTraceiP35568

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
IRS1

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
3667
PMAP-CutDBiP35568

Protein Ontology

More...
PROi
PR:P35568

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000169047 Expressed in 237 organ(s), highest expression level in endometrium
ExpressionAtlasiP35568 baseline and differential
GenevisibleiP35568 HS

Family and domain databases

CDDicd01204 PTB_IRS, 1 hit
Gene3Di2.30.29.30, 2 hits
InterProiView protein in InterPro
IPR039011 IRS
IPR002404 IRS_PTB
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
PANTHERiPTHR10614 PTHR10614, 1 hit
PfamiView protein in Pfam
PF02174 IRS, 1 hit
PF00169 PH, 1 hit
PRINTSiPR00628 INSULINRSI
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00310 PTBI, 1 hit
PROSITEiView protein in PROSITE
PS51064 IRS_PTB, 1 hit
PS50003 PH_DOMAIN, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiIRS1_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P35568
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: May 8, 2019
This is version 209 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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