Phospho-ERBB3 (Tyr1289)

This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

Full Name

Erb-B2 Receptor Tyrosine Kinase 3

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).

Biological Process

Cranial nerve development Source: BHF-UCL
Extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
Heart development Source: BHF-UCL
Negative regulation of cell adhesion Source: BHF-UCL
Negative regulation of neuron apoptotic process Source: BHF-UCL
Negative regulation of secretion Source: BHF-UCL
Negative regulation of signal transduction Source: BHF-UCL
Nervous system development Source: GO_Central
Neuron apoptotic process Source: BHF-UCL
Peripheral nervous system development Source: BHF-UCL
Phosphatidylinositol 3-kinase signaling Source: BHF-UCL
Positive regulation of cell population proliferation Source: GO_Central
Positive regulation of kinase activity Source: GO_Central
Positive regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
Positive regulation of protein tyrosine kinase activity Source: BHF-UCL
Regulation of cell population proliferation Source: BHF-UCL
Schwann cell differentiation Source: BHF-UCL
Signal transduction Source: UniProtKB
Transmembrane receptor protein tyrosine kinase signaling pathway Source: BHF-UCL
Wound healing Source: BHF-UCL

Cellular Location

Isoform 1: Cell membrane
Isoform 2: Secreted

Involvement in disease

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.
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.

Topology

Extracellular: 20-643
Helical: 644-664
Cytoplasmic: 665-1342

PTM

Autophosphorylated (PubMed:20351256). Ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778).