insulin receptor substrate 4 (IRS-4, 160 kD phosphotyrosine protein, PY160, IRS4)

Function: - acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R & FGFR1, & a complex network of intracellular signaling molecules containing SH2 domains - involved in the IGF1R mitogenic signaling pathway - promotes the AKT1 signaling pathway & 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 & to a lesser extent in response to IL4 & GH on mitogenesis. - plays a role in growth, reproduction & glucose homeostasis - may act as negative regulators of the IGFI signaling pathway by suppressing the function of IRS1 & IRS2 - interacts with SOCS6 in response to stimulatiom with either insulin or IGF1 (putative) - interacts with CRK & CRKL - interaction with CRK is stronger than with CRKL - interacts with CRK via the phosphorylated YXXM motifs - interacts with GRB2 & PIK3R1 - interacts with PLC-gamma, SHC1, PTK6, PPP4C & NISCH - phosphorylated on Tyr in response to both insulin & IGF1 signaling - phosphorylated on Tyr-921 in response to FGF2 signaling - phosphorylation of Tyr-921 is required for GRB2, phospholipase C-gamma & phosphatidylinositol 3-kinase interaction Structure: - contains 1 IRS-type PTB domain - contains 1 PH domain Compartment: cell membrane, cytoplasmic side Expression: - expressed in myoblasts - expressed in liver & hepatocellular carcinoma - down-regulated by PPP4C (phosphatase-dependent)

General

membrane protein phosphoprotein

Properties

SIZE: entity length = 1257 aa MW = 134 kD COMPARTMENT: cytoplasm MOTIF: alanine-rich region {18-28} MOTIF: alanine residue (SEVERAL) PH domain {78-199} MOTIF: alanine-rich region {124-137} MOTIF: alanine residue (SEVERAL) alanine-rich region {218-226} MOTIF: alanine residue (SEVERAL) phosphotyrosine interaction domain NAME: phosphotyrosine interaction domain SITE: 231-335 YXXM motif 1 {487-490} proline-rich region SITE: 628-639 MOTIF: proline residue (SEVERAL) binding site SITE: 678-800 FOR-BINDING-OF: crk proto-oncogene MOTIF: YXXM motif 2 {700-703} YXXM motif 3 {717-720} YXXM motif 4 {743-746} YXXM motif 5 {779-782} YXXM motif 6 {828-831} binding site SITE: 895-897 FOR-BINDING-OF: growth factor receptor-bound protein-2 (grb2) YXXM motif 7 {921-924} MOTIF: Tyr phosphorylation site {Y921} alanine-rich region {1094-1212} MOTIF: alanine residue (SEVERAL)

Database Correlations

OMIM 603510 UniProt O14654 PFAM correlations

References

UniProt :accession O14654