Human Gene ERBB3 (uc001sjh.3) Description and Page Index
Description: Homo sapiens v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) (ERBB3), transcript variant 1, mRNA. RefSeq Summary (NM_001982): 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]. Transcript (Including UTRs) Position: hg19 chr12:56,473,809-56,497,291 Size: 23,483 Total Exon Count: 28 Strand: + Coding Region Position: hg19 chr12:56,474,085-56,495,839 Size: 21,755 Coding Exon Count: 28
ID:ERBB3_HUMAN DESCRIPTION: RecName: Full=Receptor tyrosine-protein kinase erbB-3; EC=188.8.131.52; AltName: Full=Proto-oncogene-like protein c-ErbB-3; AltName: Full=Tyrosine kinase-type cell surface receptor HER3; Flags: Precursor; FUNCTION: Binds and is activated by neuregulins and NTAK. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. SUBUNIT: Monomer and homodimer. Heterodimer with each of the other ERBB receptors (Potential). Interacts with CSPG5, PA2G4, GRB7 and MUC1. INTERACTION: P00533:EGFR; NbExp=6; IntAct=EBI-720706, EBI-297353; P04626:ERBB2; NbExp=15; IntAct=EBI-720706, EBI-641062; Q15303:ERBB4; NbExp=4; IntAct=EBI-720706, EBI-80371; Q02297-7:NRG1; NbExp=3; IntAct=EBI-720706, EBI-2460927; P27986:PIK3R1; NbExp=23; IntAct=EBI-720706, EBI-79464; SUBCELLULAR LOCATION: Isoform 1: Cell membrane; Single-pass type I membrane protein. SUBCELLULAR LOCATION: 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. PTM: Ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (By similarity). Subject to autophosphorylation. DISEASE: Defects in ERBB3 are the cause of lethal congenital contracture syndrome type 2 (LCCS2) [MIM:607598]; also called Israeli Bedouin multiple contracture syndrome type A. LCCS2 is an autosomal recessive neurogenic form of a neonatally lethal arthrogryposis that is associated with atrophy of the anterior horn of the spinal cord. The LCCS2 syndrome is characterized by multiple joint contractures, anterior horn atrophy in the spinal cord, and a unique feature of a markedly distended urinary bladder. The phenotype suggests a spinal cord neuropathic etiology. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily. SIMILARITY: Contains 1 protein kinase domain.
Genetic Association Studies of Complex Diseases and Disorders
Autoimmune Diseases|Lupus Erythematosus, Systemic|Systemic lupus erythematosus Budarf ML et al. 2011, A targeted association study in systemic lupus erythematosus identifies multiple susceptibility alleles., Genes and immunity 12(1) : 51-8 2011.
Diabetes Mellitus, Type 1 John A Todd et al. Nature genetics 2007, Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes., Nature genetics.
Diabetes Mellitus, Type 1 Jason D Cooper et al. Nature genetics 2008, Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci., Nature genetics.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P21860
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BioCarta from NCI Cancer Genome Anatomy Project h_ErbB3Pathway - Neuroregulin receptor degredation protein-1 Controls ErbB3 receptor recycling h_her2Pathway - Role of ERBB2 in Signal Transduction and Oncology