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ERBB3 erb-b2 receptor tyrosine kinase 3 [ Homo sapiens (human) ]

Gene ID: 2065, updated on 2-Aug-2015
Official Symbol
ERBB3provided by HGNC
Official Full Name
erb-b2 receptor tyrosine kinase 3provided by HGNC
Primary source
HGNC:HGNC:3431
See related
Ensembl:ENSG00000065361; HPRD:01820; MIM:190151; Vega:OTTHUMG00000170140
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HER3; LCCS2; ErbB-3; c-erbB3; erbB3-S; MDA-BF-1; c-erbB-3; p180-ErbB3; p45-sErbB3; p85-sErbB3
Summary
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]
Orthologs
See ERBB3 in Epigenomics, MapViewer
Location:
12q13
Exon count:
28
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 12 NC_000012.12 (56080025..56103507)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (56473809..56497291)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene IKAROS family zinc finger 4 (Eos) Neighboring gene uncharacterized LOC105369780 Neighboring gene ribosomal protein S26 Neighboring gene uncharacterized LOC105369782 Neighboring gene proliferation-associated 2G4, 38kDa Neighboring gene ribosomal protein L41

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Lethal congenital contracture syndrome 2
MedGen: C1843478 OMIM: 607598 GeneReviews: Not available
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NHGRI GWAS Catalog

Description
A novel susceptibility locus for type 1 diabetes on Chr12q13 identified by a genome-wide association study.
NHGRI GWA Catalog
Association analyses identify three susceptibility Loci for vitiligo in the Chinese Han population.
NHGRI GWA Catalog
Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.
NHGRI GWA Catalog
Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.
NHGRI GWA Catalog
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.
NHGRI GWA Catalog
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
NHGRI GWA Catalog
Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci.
NHGRI GWA Catalog
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
NHGRI GWA Catalog
Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes.
NHGRI GWA Catalog
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    Signaling by PDGF, organism-specific biosystemPlatelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary end...
  • Signaling by SCF-KIT, organism-specific biosystem (from REACTOME)
    Signaling by SCF-KIT, organism-specific biosystemStem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival...
  • Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R), organism-specific biosystem (from REACTOME)
    Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R), organism-specific biosystemBinding of IGF1 (IGF-I) or IGF2 (IGF-II) to the extracellular alpha peptides of the type 1 insulin-like growth factor receptor (IGF1R) triggers the activation of two major signaling pathways: the SOS...
  • Signaling by VEGF, organism-specific biosystem (from REACTOME)
    Signaling by VEGF, organism-specific biosystemIn normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angioge...
  • Signaling by the B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
    Signaling by the B Cell Receptor (BCR), organism-specific biosystemMature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, F...
  • Signalling by NGF, organism-specific biosystem (from REACTOME)
    Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
  • Signalling to ERKs, organism-specific biosystem (from REACTOME)
    Signalling to ERKs, organism-specific biosystemNeurotrophins utilize multiple pathways to activate ERKs (ERK1 and ERK2), a subgroup of the large MAP kinase (MAPK) family, from the plasma membrane. The major signalling pathways to ERKs are via RAS...
  • Signalling to RAS, organism-specific biosystem (from REACTOME)
    Signalling to RAS, organism-specific biosystemSignalling through Shc adaptor proteins appears to be identical for both NGF and EGF. It leads to a fast, but transient, MAPK/ERK activation, which is insufficient to explain the prolonged activation...
  • Signalling to p38 via RIT and RIN, organism-specific biosystem (from REACTOME)
    Signalling to p38 via RIT and RIN, organism-specific biosystemRIT and RIN are two small guanine nucleotide binding proteins that share more than 50% sequence identity with RAS, including highly conserved core effector domains. Unlike RAS, the C termini of RIT a...
  • VEGFA-VEGFR2 Pathway, organism-specific biosystem (from REACTOME)
    VEGFA-VEGFR2 Pathway, organism-specific biosystemAngiogenesis is the formation of new blood vessels from preexisting vasculature. One of the most important proangiogenic factors is vascular endothelial growth factor (VEGF). VEGF exerts its biologic...
  • VEGFR2 mediated cell proliferation, organism-specific biosystem (from REACTOME)
    VEGFR2 mediated cell proliferation, organism-specific biosystemVEGFR2 stimulates ERK not via GRB2-SOS-RAS, but via pY1175-dependent phosphorylation of PLC gamma and subsequent activation of PKCs. PKC plays an important mediatory role in the proliferative Ras/Raf...
  • a6b1 and a6b4 Integrin signaling, organism-specific biosystem (from Pathway Interaction Database)
    a6b1 and a6b4 Integrin signaling, organism-specific biosystem
    a6b1 and a6b4 Integrin signaling
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • MGC88033

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
growth factor binding IPI
Inferred from Physical Interaction
more info
PubMed 
growth factor binding ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein heterodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
protein heterodimerization activity IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity NAS
Non-traceable Author Statement
more info
PubMed 
protein tyrosine kinase activator activity IDA
Inferred from Direct Assay
more info
PubMed 
NOT protein tyrosine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
transmembrane signaling receptor activity ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
Process Evidence Code Pubs
Fc-epsilon receptor signaling pathway TAS
Traceable Author Statement
more info
 
Schwann cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
cranial nerve development ISS
Inferred from Sequence or Structural Similarity
more info
 
endocardial cushion development IEA
Inferred from Electronic Annotation
more info
 
epidermal growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
extrinsic apoptotic signaling pathway in absence of ligand IMP
Inferred from Mutant Phenotype
more info
PubMed 
fibroblast growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
heart development ISS
Inferred from Sequence or Structural Similarity
more info
 
innate immune response TAS
Traceable Author Statement
more info
 
negative regulation of cell adhesion IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of neuron apoptotic process ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of secretion IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of signal transduction IDA
Inferred from Direct Assay
more info
PubMed 
neuron apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
neurotrophin TRK receptor signaling pathway TAS
Traceable Author Statement
more info
 
peripheral nervous system development ISS
Inferred from Sequence or Structural Similarity
more info
 
phosphatidylinositol 3-kinase signaling IDA
Inferred from Direct Assay
more info
PubMed 
phosphatidylinositol-mediated signaling TAS
Traceable Author Statement
more info
 
positive regulation of calcineurin-NFAT signaling cascade IEA
Inferred from Electronic Annotation
more info
 
positive regulation of phosphatidylinositol 3-kinase signaling TAS
Traceable Author Statement
more info
PubMed 
positive regulation of protein tyrosine kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein phosphorylation IEA
Inferred from Electronic Annotation
more info
 
regulation of cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
signal transduction IDA
Inferred from Direct Assay
more info
PubMed 
transmembrane receptor protein tyrosine kinase signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
wound healing NAS
Non-traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
apical plasma membrane IEA
Inferred from Electronic Annotation
more info
 
basolateral plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
integral component of plasma membrane TAS
Traceable Author Statement
more info
PubMed 
intracellular IDA
Inferred from Direct Assay
more info
PubMed 
intracellular TAS
Traceable Author Statement
more info
 
lateral plasma membrane IEA
Inferred from Electronic Annotation
more info
 
plasma membrane TAS
Traceable Author Statement
more info
PubMed 
receptor complex IDA
Inferred from Direct Assay
more info
PubMed 
receptor complex ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
Preferred Names
receptor tyrosine-protein kinase erbB-3
Names
human epidermal growth factor receptor 3
proto-oncogene-like protein c-ErbB-3
tyrosine kinase-type cell surface receptor HER3
v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3
NP_001005915.1
NP_001973.2

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011529.1 RefSeqGene

    Range
    4918..28400
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001005915.1NP_001005915.1  receptor tyrosine-protein kinase erbB-3 isoform s precursor

    See identical proteins and their annotated locations for NP_001005915.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (s) lacks many 3' exons found in variant 1 and contains an alternate 3' exon of its own, that causes a frameshift. The resulting isoform (s) is shorter lacking the intermembrane region present in isoform 1, and is secreted outside the cell.
    Source sequence(s)
    AC034102, M34309, S61953
    Consensus CDS
    CCDS44918.1
    UniProtKB/Swiss-Prot
    P21860
    Related
    ENSP00000415753, OTTHUMP00000243040, ENST00000411731, OTTHUMT00000407621
    Conserved Domains (1) summary
    pfam01030
    Location:56140
    Recep_L_domain; Receptor L domain
  2. NM_001982.3NP_001973.2  receptor tyrosine-protein kinase erbB-3 isoform 1 precursor

    See identical proteins and their annotated locations for NP_001973.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AA524528, BC082992, BU674508, DC344156, DC347955
    Consensus CDS
    CCDS31833.1
    UniProtKB/Swiss-Prot
    P21860
    Related
    ENSP00000267101, OTTHUMP00000243039, ENST00000267101, OTTHUMT00000407619
    Conserved Domains (8) summary
    cd05111
    Location:701979
    PTK_HER3; Pseudokinase domain of the Protein Tyrosine Kinase, HER3
    cd12095
    Location:638676
    TM_ErbB3; Transmembrane domain of ErbB3, a Protein Tyrosine Kinase
    smart00261
    Location:180215
    FU; Furin-like repeats
    cd00064
    Location:226266
    FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.
    pfam00757
    Location:179332
    Furin-like; Furin-like cysteine rich region
    pfam01030
    Location:56167
    Recep_L_domain; Receptor L domain
    pfam07714
    Location:709965
    Pkinase_Tyr; Protein tyrosine kinase
    pfam14843
    Location:499630
    GF_recep_IV; Growth factor receptor domain IV

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p2 Primary Assembly

    Range
    56080025..56103507
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018923.2 Alternate CHM1_1.1

    Range
    56441254..56464656
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)