IRS4 (insulin receptor substrate 4)

Gene

• Entrez ID: 8471
• Gene name: Insulin receptor substrate 4
• Gene symbol: IRS4
• Synonyms: CHNG9, IRS-4, PY160
• Chromosome: X
• Chromosome location: Xq22.3
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1603336347	AGCAC>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT037488	hsa-miR-744-5p	CLASH	23622248
MIRT038245	hsa-miR-330-5p	CLASH	23622248
MIRT039541	hsa-miR-652-3p	CLASH	23622248
MIRT040218	hsa-miR-615-3p	CLASH	23622248
MIRT040876	hsa-miR-18a-3p	CLASH	23622248
MIRT041502	hsa-miR-193b-3p	CLASH	23622248
MIRT042143	hsa-miR-484	CLASH	23622248
MIRT043291	hsa-miR-331-3p	CLASH	23622248
MIRT045789	hsa-miR-191-5p	CLASH	23622248
MIRT046069	hsa-miR-125b-5p	CLASH	23622248
MIRT046599	hsa-miR-222-3p	CLASH	23622248
MIRT050656	hsa-miR-18a-5p	CLASH	23622248
MIRT051115	hsa-miR-16-5p	CLASH	23622248
MIRT051562	hsa-let-7e-5p	CLASH	23622248
MIRT052242	hsa-let-7b-5p	CLASH	23622248
MIRT612863	hsa-miR-505-3p	HITS-CLIP	23824327
MIRT612863	hsa-miR-505-3p	HITS-CLIP	28735896
MIRT612864	hsa-miR-3591-3p	HITS-CLIP	23824327
MIRT612864	hsa-miR-3591-3p	HITS-CLIP	28735896
MIRT612865	hsa-miR-21-3p	HITS-CLIP	23824327
MIRT612865	hsa-miR-21-3p	HITS-CLIP	28735896

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005158	Function	Insulin receptor binding	IBA	21873635
GO:0005515	Function	Protein binding	IPI	11316748, 16273093, 25036637
GO:0005829	Component	Cytosol	IBA	21873635
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005886	Component	Plasma membrane	TAS
GO:0007165	Process	Signal transduction	TAS	9261155
GO:0008286	Process	Insulin receptor signaling pathway	IBA	21873635
GO:0043548	Function	Phosphatidylinositol 3-kinase binding	IBA	21873635

Other IDs

• MIM: 300904
• HGNC: 6128
• e!Ensembl: ENSG00000133124

Protein

• UniProt ID: O14654
• Protein name: Insulin receptor substrate 4 (IRS-4) (160 kDa phosphotyrosine protein) (py160) (Phosphoprotein of 160 kDa) (pp160)
• Protein function: Acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signaling molecules containing SH2 domains. Involved in the IGF1R mitogenic signaling pathway. Promotes the AKT1 signaling pathway and BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis. Interaction with GRB2 enhances insulin-stimulated mitogen-activated protein kinase activity. May be involved in nonreceptor tyrosine kinase signaling in myoblasts. Plays a pivotal role in the proliferation/differentiation of hepatoblastoma cell through EPHB2 activation upon IGF1 stimulation. May play a role in the signal transduction in response to insulin and to a lesser extent in response to IL4 and GH on mitogenesis. Plays a role in growth, reproduction and glucose homeostasis. May act as negative regulators of the IGF1 signaling pathway by suppressing the function of IRS1 and IRS2.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02174	IRS	231 → 333	PTB domain (IRS-1 type)	Domain

• Sequence:

  MASCSFTRDQATRRLRGAAAAAAAALAAVVTTPLLSSGTPTALIGTGSSCPGAMWLSTAT
  GSRSDSESEEEDLPVGEEVCKRGYLRKQKHGHRRYFVLKLETADAPARLEYYENARKFRH
  SVRAAAAAAAAAASGAAIPPLIPPRRVITLYQCFSVSQRADARYRHLIALFTQDEYFAMV
  AENESEQESWYLLLSRLILESKRRRCGTLGAQPDGEPAALAAAAAAEPPFYKDVWQVIVK
  PRGLGHRKELSGVFRLCLTDEEVVFVRLNTEVASVVVQLLSIRRCGHSEQYFFLEVGRST
  VIGPGELWMQVDDCVVAQNMHELFLEKMRALCADEYRARCRSYSISIGAHLLTLLSARRH
  LGLVPLEPGGWLRRSRFEQFCHLRAIGDGEDEMLFTRRFVTPSEPVAHSRRGRLHLPRGR
  RSRRAVSVPASFFRRLAPSPARPRHPAEAPNNGARLSSEVSGSGSGNFGEEGNPQGKEDQ
  EGSGGDYMPMNNWGSGNGRGSGGGQGSNGQGSSSHSSGGNQCSGEGQGSRGGQGSNGQGS
  GGNQCSRDGQGTAGGHGSGGGQRPGGGHGSGGGQGPGDGHGSGGGKNSGGGKGSGSGKGS
  DGDGERGKSLKKRSYFGKLTQSKQQQMPPPPPPPPPPPPAGGTGGKGKSGGRFRLYFCVD
  RGATKECKEAKEVKDAEIPEGAARGPHRARAFDEDEDDPYVPMRPGVATPLVSSSDYMPM
  APQNVSASKKRHSRSPFEDSRGYMMMFPRVSPPPAPSPPKAPDTNKEDDSKDNDSESDYM
  FMAPGAGAIPKNPRNPQGGSSSKSWSSYFSLPNPFRSSPLGQNDNSEYVPMLPGKFLGRG
  LDKEVSYNWDPKDAASKPSGEGSFSKPGDGGSPSKPSDHEPPKNKAKRPNRLSFITKGYK
  IKPKPQKPTHEQREADSSSDYVNMDFTKRESNTPAPSTQGLPDSWGIIAEPRQSAFSNYV
  NVEFGVPFPNPANDLSDLLRAIPRANPLSLDSARWPLPPLPLSATGSNAIEEEGDYIEVI
  FNSAMTPAMALADSAIRYDAETGRIYVVDPFSECCMDISLSPSRCSEPPPVARLLQEEEQ
  ERRRPQSRSQSFFAAARAAVSAFPTDSLERDLSPSSAPAVASAAEPTLALSQVVAAASAL
  AAAPGIGAAAAAAGFDSASARWFQPVANAADAEAVRGAQDVAGGSNPGAHNPSANLARGD
  NQAGGAAAAAAAPEPPPRSRRVPRPPEREDSDNDDDTHVRMDFARRDNQFDSPKRGR

• Sequence length: 1257