Seroatlas · Human Serome Atlas

IRS4

Insulin receptor substrate 4

Also known as: IRS-4, IRS4_HUMAN, PY160

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

Protein identityUniProt · HPA

UniProt accession: O14654
Gene: IRS4
Ensembl: ENSG00000133124
Chromosome: X
Canonical length: 1257 aa
Protein class: Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins

OverviewNCBI Gene

IRS4 encodes the insulin receptor substrate 4, a cytoplasmic protein that contains many potential tyrosine and serine/threonine phosphorylation sites. Tyrosine-phosphorylated IRS4 protein has been shown to associate with cytoplasmic signalling molecules that contain SH2 domains. The IRS4 protein is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation.. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1257 residues, UniProt reviewed canonical sequence.

>O14654|IRS4
     1  MASCSFTRDQ ATRRLRGAAA AAAAALAAVV TTPLLSSGTP TALIGTGSSC PGAMWLSTAT
    61  GSRSDSESEE EDLPVGEEVC KRGYLRKQKH GHRRYFVLKL ETADAPARLE YYENARKFRH
   121  SVRAAAAAAA AAASGAAIPP LIPPRRVITL YQCFSVSQRA DARYRHLIAL FTQDEYFAMV
   181  AENESEQESW YLLLSRLILE SKRRRCGTLG AQPDGEPAAL AAAAAAEPPF YKDVWQVIVK
   241  PRGLGHRKEL SGVFRLCLTD EEVVFVRLNT EVASVVVQLL SIRRCGHSEQ YFFLEVGRST
   301  VIGPGELWMQ VDDCVVAQNM HELFLEKMRA LCADEYRARC RSYSISIGAH LLTLLSARRH
   361  LGLVPLEPGG WLRRSRFEQF CHLRAIGDGE DEMLFTRRFV TPSEPVAHSR RGRLHLPRGR
   421  RSRRAVSVPA SFFRRLAPSP ARPRHPAEAP NNGARLSSEV SGSGSGNFGE EGNPQGKEDQ
   481  EGSGGDYMPM NNWGSGNGRG SGGGQGSNGQ GSSSHSSGGN QCSGEGQGSR GGQGSNGQGS
   541  GGNQCSRDGQ GTAGGHGSGG GQRPGGGHGS GGGQGPGDGH GSGGGKNSGG GKGSGSGKGS
   601  DGDGERGKSL KKRSYFGKLT QSKQQQMPPP PPPPPPPPPA GGTGGKGKSG GRFRLYFCVD
   661  RGATKECKEA KEVKDAEIPE GAARGPHRAR AFDEDEDDPY VPMRPGVATP LVSSSDYMPM
   721  APQNVSASKK RHSRSPFEDS RGYMMMFPRV SPPPAPSPPK APDTNKEDDS KDNDSESDYM
   781  FMAPGAGAIP KNPRNPQGGS SSKSWSSYFS LPNPFRSSPL GQNDNSEYVP MLPGKFLGRG
   841  LDKEVSYNWD PKDAASKPSG EGSFSKPGDG GSPSKPSDHE PPKNKAKRPN RLSFITKGYK
   901  IKPKPQKPTH EQREADSSSD YVNMDFTKRE SNTPAPSTQG LPDSWGIIAE PRQSAFSNYV
   961  NVEFGVPFPN PANDLSDLLR AIPRANPLSL DSARWPLPPL PLSATGSNAI EEEGDYIEVI
  1021  FNSAMTPAMA LADSAIRYDA ETGRIYVVDP FSECCMDISL SPSRCSEPPP VARLLQEEEQ
  1081  ERRRPQSRSQ SFFAAARAAV SAFPTDSLER DLSPSSAPAV ASAAEPTLAL SQVVAAASAL
  1141  AAAPGIGAAA AAAGFDSASA RWFQPVANAA DAEAVRGAQD VAGGSNPGAH NPSANLARGD
  1201  NQAGGAAAAA AAPEPPPRSR RVPRPPERED SDNDDDTHVR MDFARRDNQF DSPKRGR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IRS4 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: Cell surface
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.62
Highest tissue expression: 24 nTPM

Expression across tissuesHPA

Tissue

pituitary gland: 24 nTPM
hypothalamus: 6 nTPM
ovary: 3.5 nTPM
thymus: 3.5 nTPM
choroid plexus: 3.3 nTPM
cervix: 2.4 nTPM

Single-cell type

somatotrophs: 409 nCPM
thyrotrophs: 152 nCPM
gonadotrophs: 112 nCPM
lactotrophs: 85 nCPM
medullary thymic epithelial cells: 29 nCPM
mucous neck cells: 21 nCPM

Immune cell

basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM
intermediate monocyte: 0 nTPM
MAIT T-cell: 0 nTPM

Brain region

hypothalamus: 32 nTPM
choroid plexus: 18 nTPM
basal ganglia: 8.9 nTPM
pons: 7.7 nTPM
midbrain: 6.3 nTPM
medulla oblongata: 4.8 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IRS4.

Disease | AllUniProt

Conditions IRS4 is implicated in, by any mechanism.

Hypothyroidism, congenital, non-goitrous, 9 (CHNG9) MIM:301035

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 168 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Hypothyroidism, congenital, nongoitrous, 9

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): 0.43
gnomAD pLI: 0.58
gnomAD missense Z: 0.09
DepMap mean gene effect: -0.13
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% 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 IRS4 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 IRS4 as an antibody target. Whether an autoantibody or antibody against IRS4 could matter depends on whether native IRS4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

IRS4 is annotated at the cell surface, where native IRS4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label IRS4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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