ErbB3 Antibody – Mouse Monoclonal

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]

Function: Binds and is activated by neuregulins and NTAK. Ref.11

Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.16

Subunit structure: Monomer and homodimer. Heterodimer with each of the other ERBB receptors

Potential. Interacts with CSPG5, PA2G4, GRB7 and MUC1. Ref.8 Ref.9 Ref.10 Ref.11 Ref.15 Ref.16 Ref.17

Subcellular location: Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted.

Tissue specificity: Epithelial tissues and brain.

Developmental stage: Overexpressed in a subset of human mammary tumors.

Domain: The cytoplasmic part of the receptor may interact with the SH2 or SH3 domains of many signal-transducing proteins.

Post-translational modification: Ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase

By similarity. Subject to autophosphorylation.

Involvement in disease: Lethal congenital contracture syndrome 2 (LCCS2) [MIM:607598]: 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12

Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.Contains 1 protein kinase domain.