Recombinant Human Receptor tyrosine-protein kinase erbB-3 (ERBB3), partial (Active)

Function

Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778). May also be activated by CSPG5 (PubMed:15358134). Involved in the regulation of myeloid cell differentiation (PubMed:27416908)

Subcellular Location

Secreted

Disease Association

Lethal congenital contracture syndrome 2 (LCCS2) : A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy, and congenital non-progressive joint contractures (arthrogryposis). The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS2 patients manifest craniofacial/ocular findings, lack of hydrops, multiple pterygia, and fractures, as well as a normal duration of pregnancy and a unique feature of a markedly distended urinary bladder (neurogenic bladder defect). The phenotype suggests a spinal cord neuropathic etiology. [The disease is caused by variants affecting the gene represented in this entry] | Erythroleukemia, familial (FERLK) : An autosomal dominant myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood. Disease penetrance is incomplete. [Disease susceptibility may be associated with variants affecting the gene represented in this entry] | Visceral neuropathy, familial, 1, autosomal recessive (VSCN1) : An autosomal recessive disorder characterized by intestinal dysmotility due to aganglionosis (Hirschsprung disease), hypoganglionosis, and/or chronic intestinal pseudoobstruction. Additional variable features are progressive peripheral neuropathy, arthrogryposis, hypoplasia or aplasia of the olfactory bulb and of the external auditory canals, microtia or anotia, and facial dysmorphism. Some patients present structural cardiac anomalies and arthrogryposis with multiple pterygia. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Epithelial tissues and brain

Subunit

Monomer and homodimer. Heterodimer with each of the other ERBB receptors (Potential). Interacts with CSPG5 (PubMed:15358134). Interacts with GRB7 (PubMed:9516479). Interacts with MUC1 (PubMed:12939402). Interacts with MYOC (By similarity). Interacts with isoform 2 of PA2G4 (PubMed:11325528, PubMed:16832058). Found in a ternary complex with NRG1 and ITGAV:ITGB3 or ITGA6:ITGB4 (PubMed:20682778)

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• Plowman G.D. et al. Molecular cloning and expression of an additional epidermal growth factor receptor-related gene. — Proc. Natl. Acad. Sci. U.S.A. (1990)
• Katoh M. et al. c-erbB3 gene encodes secreted as well as transmembrane receptor tyrosine kinase. — Biochem. Biophys. Res. Commun. (1993)
• Kalnine N. et al. Cloning of human full-length CDSs in BD Creator(TM) system donor vector. (MAY-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Scherer S.E. et al. The finished DNA sequence of human chromosome 12. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Fiddes R.J. et al. Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals a novel target selectivity for erbB3. — J. Biol. Chem. (1998)