Human Gene ERBB3 (ENST00000411731.6) from GENCODE V44
Description: Homo sapiens erb-b2 receptor tyrosine kinase 3 (ERBB3), transcript variant s, mRNA. (from RefSeq NM_001005915) RefSeq Summary (NM_001005915): 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]. Gencode Transcript: ENST00000411731.6 Gencode Gene: ENSG00000065361.17 Transcript (Including UTRs) Position: hg38 chr12:56,080,137-56,085,623 Size: 5,487 Total Exon Count: 3 Strand: + Coding Region Position: hg38 chr12:56,080,301-56,085,312 Size: 5,012 Coding Exon Count: 3
ID:ERBB3_HUMAN DESCRIPTION: RecName: Full=Receptor tyrosine-protein kinase erbB-3; EC=2.7.10.1; 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.
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
Reactome (by CSHL, EBI, and GO)
Protein P21860 (Reactome details) participates in the following event(s):
R-HSA-1247497 ERBB3 binds neuregulins R-HSA-1358801 ERBB3 binds RNF41 ubiquitin ligase R-HSA-1977958 ERBB4 forms heterodimers with ERBB3 R-HSA-1358790 RNF41 ubiquitinates ERBB3 R-HSA-1963589 ERBB2 forms heterodimers with ligand-activated ERBB receptors: EGFR, ERBB3 and ERBB4 R-HSA-1963582 Trans-autophosphorylation of ERBB2 heterodimers R-HSA-1963586 SRC family kinases phosphorylate ERBB2 R-HSA-1963581 Trans-autophosphorylation of p-Y877-ERBB2 heterodimers R-NUL-1248753 Shc1 binds phosphorylated ERBB2:ERBB3 heterodimers R-HSA-1250189 Binding of PI3K to ERBB2:P-ERBB3 heterodimer R-HSA-1306953 GRB7 binds phosphorylated heterodimer of ERBB2 and ERBB3 R-HSA-1358798 RNF41 binds neuregulin-activated ERBB3 R-HSA-1963563 MATK (CSK homologous kinase) binds phosphorylated ERBB2 R-HSA-1963578 SHC1 binds phosphorylated ERBB2 heterodimers R-HSA-6785636 Phosphorylated ERBB2 heterodimers bind MEMO1 R-HSA-8847995 Activated ERBB2 binds PTK6 (BRK) R-HSA-8863804 PTPN12 dephosphorylates ERBB2 on tyrosine Y1248 R-HSA-8848005 ERBB2 promotes PTK6 autophosphorylation R-HSA-1358792 RNF41 ubiquitinates activated ERBB3 R-HSA-1250195 SHC1 phosphorylation by ERBB2 heterodimers R-HSA-1250486 Recruitment of GRB2:SOS1 to p-SHC1 in complex with phosphorylated ERBB2 heterodimers R-HSA-6785648 MEMO1 binds RHOA:GTP:DIAPH1 R-HSA-1250462 PIP2 to PIP3 conversion by PI3K bound to phosphorylated heterodimer of ERBB2 and ERBB3 R-HSA-1250463 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-SHC1:Phosphorylated ERBB2 heterodimers R-HSA-2400009 PI3K inhibitors block PI3K catalytic activity R-HSA-2316434 PI3K phosphorylates PIP2 to PIP3 R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange R-HSA-1227986 Signaling by ERBB2 R-HSA-1358803 Downregulation of ERBB2:ERBB3 signaling R-HSA-1236394 Signaling by ERBB4 R-HSA-9006934 Signaling by Receptor Tyrosine Kinases R-HSA-8863795 Downregulation of ERBB2 signaling R-HSA-162582 Signal Transduction R-HSA-1963642 PI3K events in ERBB2 signaling R-HSA-1306955 GRB7 events in ERBB2 signaling R-HSA-1250196 SHC1 events in ERBB2 signaling R-HSA-6785631 ERBB2 Regulates Cell Motility R-HSA-8847993 ERBB2 Activates PTK6 Signaling R-HSA-8848021 Signaling by PTK6 R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer R-HSA-1257604 PIP3 activates AKT signaling R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-5673001 RAF/MAP kinase cascade R-HSA-2219528 PI3K/AKT Signaling in Cancer R-HSA-9006925 Intracellular signaling by second messengers R-HSA-199418 Negative regulation of the PI3K/AKT network R-HSA-5684996 MAPK1/MAPK3 signaling R-HSA-5663202 Diseases of signal transduction R-HSA-5683057 MAPK family signaling cascades R-HSA-1643685 Disease