Seroatlas · Human Serome Atlas

IRS1

Insulin receptor substrate 1

Also known as: HIRS-1, IRS1_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P35568
Gene
IRS1
Ensembl
ENSG00000169047
Chromosome
2
Canonical length
1242 aa
Protein class
Disease related genes, Plasma proteins, Predicted intracellular proteins
Subcellular location
Nucleoplasm,Vesicles,Plasma membrane,Cytosol

OverviewNCBI Gene

This gene encodes a protein which is phosphorylated by insulin receptor tyrosine kinase. Mutations in this gene are associated with type II diabetes and susceptibility to insulin resistance. [provided by RefSeq, Nov 2009]

Canonical amino-acid sequenceUniProt

1242 residues, UniProt reviewed canonical sequence.

>P35568|IRS1
     1  MASPPESDGF SDVRKVGYLR KPKSMHKRFF VLRAASEAGG PARLEYYENE KKWRHKSSAP
    61  KRSIPLESCF NINKRADSKN KHLVALYTRD EHFAIAADSE AEQDSWYQAL LQLHNRAKGH
   121  HDGAAALGAG GGGGSCSGSS GLGEAGEDLS YGDVPPGPAF KEVWQVILKP KGLGQTKNLI
   181  GIYRLCLTSK TISFVKLNSE AAAVVLQLMN IRRCGHSENF FFIEVGRSAV TGPGEFWMQV
   241  DDSVVAQNMH ETILEAMRAM SDEFRPRSKS QSSSNCSNPI SVPLRRHHLN NPPPSQVGLT
   301  RRSRTESITA TSPASMVGGK PGSFRVRASS DGEGTMSRPA SVDGSPVSPS TNRTHAHRHR
   361  GSARLHPPLN HSRSIPMPAS RCSPSATSPV SLSSSSTSGH GSTSDCLFPR RSSASVSGSP
   421  SDGGFISSDE YGSSPCDFRS SFRSVTPDSL GHTPPARGEE ELSNYICMGG KGPSTLTAPN
   481  GHYILSRGGN GHRCTPGTGL GTSPALAGDE AASAADLDNR FRKRTHSAGT SPTITHQKTP
   541  SQSSVASIEE YTEMMPAYPP GGGSGGRLPG HRHSAFVPTR SYPEEGLEMH PLERRGGHHR
   601  PDSSTLHTDD GYMPMSPGVA PVPSGRKGSG DYMPMSPKSV SAPQQIINPI RRHPQRVDPN
   661  GYMMMSPSGG CSPDIGGGPS SSSSSSNAVP SGTSYGKLWT NGVGGHHSHV LPHPKPPVES
   721  SGGKLLPCTG DYMNMSPVGD SNTSSPSDCY YGPEDPQHKP VLSYYSLPRS FKHTQRPGEP
   781  EEGARHQHLR LSTSSGRLLY AATADDSSSS TSSDSLGGGY CGARLEPSLP HPHHQVLQPH
   841  LPRKVDTAAQ TNSRLARPTR LSLGDPKAST LPRAREQQQQ QQPLLHPPEP KSPGEYVNIE
   901  FGSDQSGYLS GPVAFHSSPS VRCPSQLQPA PREEETGTEE YMKMDLGPGR RAAWQESTGV
   961  EMGRLGPAPP GAASICRPTR AVPSSRGDYM TMQMSCPRQS YVDTSPAAPV SYADMRTGIA
  1021  AEEVSLPRAT MAAASSSSAA SASPTGPQGA AELAAHSSLL GGPQGPGGMS AFTRVNLSPN
  1081  RNQSAKVIRA DPQGCRRRHS SETFSSTPSA TRVGNTVPFG AGAAVGGGGG SSSSSEDVKR
  1141  HSSASFENVW LRPGELGGAP KEPAKLCGAA GGLENGLNYI DLDLVKDFKQ CPQECTPEPQ
  1201  PPPPPPPHQP LGSGESSSTR RSSEDLSAYA SISFQKQPED RQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IRS1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Intracellular
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.64
Highest tissue expression
26 nTPM

Expression across tissuesHPA

Tissue

  • skeletal muscle: 26 nTPM
  • ovary: 20 nTPM
  • thyroid gland: 19 nTPM
  • endometrium: 16 nTPM
  • fallopian tube: 14 nTPM
  • cervix: 13 nTPM

Single-cell type

  • adipocytes: 166 nCPM
  • renal collecting duct intercalated cells: 138 nCPM
  • adrenal cortex cells: 122 nCPM
  • breast lactating cells: 120 nCPM
  • platelets: 99 nCPM
  • hepatocytes: 97 nCPM

Immune cell

  • memory B-cell: 0.1 nTPM
  • naive B-cell: 0.1 nTPM
  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM

Brain region

  • cerebellum: 18 nTPM
  • cerebral cortex: 14 nTPM
  • spinal cord: 12 nTPM
  • medulla oblongata: 11 nTPM
  • basal ganglia: 11 nTPM
  • choroid plexus: 11 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IRS1.

Disease | AllUniProt

Conditions IRS1 is implicated in, by any mechanism.

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 206 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.5
gnomAD pLI
0.02
gnomAD missense Z
0.07
DepMap mean gene effect
-0.12
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of IRS1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads IRS1 as an antibody target. Whether an autoantibody or antibody against IRS1 could matter depends on whether native IRS1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

IRS1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label IRS1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/IRS1. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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