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

Summary

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 MIM:190151; AllianceGenome:HGNC:3431
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; FERLK; LCCS2; VSCN1; 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]
Expression: Broad expression in small intestine (RPKM 41.0), duodenum (RPKM 39.7) and 17 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q13.2

Exon count:: 30

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (56080108..56103505)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (56047558..56071109)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (56473892..56497289)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

SON is an essential RNA splicing factor promoting ErbB2 and ErbB3 expression in breast cancer.
Title: SON is an essential RNA splicing factor promoting ErbB2 and ErbB3 expression in breast cancer.
HER3 V104 mutations regulate cell signaling, growth, and drug sensitivity in cancer.
Title: HER3 V104 mutations regulate cell signaling, growth, and drug sensitivity in cancer.
Targeting HER2/HER3 co-mutations in metastatic breast cancer: Case reports of exceptional responders to trastuzumab and pertuzumab therapy.
Title: Targeting HER2/HER3 co-mutations in metastatic breast cancer: Case reports of exceptional responders to trastuzumab and pertuzumab therapy.
ERBB3 deficiency causes a multisystemic syndrome in human patient and zebrafish.
Title: ERBB3 deficiency causes a multisystemic syndrome in human patient and zebrafish.
Deciphering the Role of ERBB3 Isoforms in Renal Cell Carcinoma: A Comprehensive Genomic and Transcriptomic Analysis.
Title: Deciphering the Role of ERBB3 Isoforms in Renal Cell Carcinoma: A Comprehensive Genomic and Transcriptomic Analysis.
CD44s and CD44v8-10 isoforms confer acquired resistance to osimertinib by activating the ErbB3/STAT3 signaling pathway.
Title: CD44s and CD44v8-10 isoforms confer acquired resistance to osimertinib by activating the ErbB3/STAT3 signaling pathway.
Role of human epidermal growth factor receptor 3 in treatment resistance of anaplastic lymphoma kinase translocated non-small cell lung cancer.
Title: Role of human epidermal growth factor receptor 3 in treatment resistance of anaplastic lymphoma kinase translocated non-small cell lung cancer.
Androgen receptor transcriptional activity is required for heregulin-1beta-mediated nuclear localization of the HER3/ErbB3 receptor tyrosine kinase.
Title: Androgen receptor transcriptional activity is required for heregulin-1β-mediated nuclear localization of the HER3/ErbB3 receptor tyrosine kinase.
Pathogenic HER3 dimerization domain mutations create a structural bias towards un-conventional EGFR-HER3 signalling axis in breast cancer.
Title: Pathogenic HER3 dimerization domain mutations create a structural bias towards un-conventional EGFR-HER3 signalling axis in breast cancer.
Downregulation of circ_PLXND1 inhibits tumorigenesis of non-small cell lung carcinoma via miR-1287-5p/ERBB3 axis.
Title: Downregulation of circ_PLXND1 inhibits tumorigenesis of non-small cell lung carcinoma via miR-1287-5p/ERBB3 axis.

Submit: New GeneRIF Correction See all GeneRIFs (415)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Erythroleukemia, familial, susceptibility to MedGen: C5552985 OMIM: 133180 GeneReviews: Not available	Compare labs
Lethal congenital contracture syndrome 2 MedGen: C1843478 OMIM: 607598 GeneReviews: Not available	Compare labs
Visceral neuropathy, familial, 1, autosomal recessive MedGen: C1855733 OMIM: 243180 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A novel susceptibility locus for type 1 diabetes on Chr12q13 identified by a genome-wide association study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Association analyses identify three susceptibility Loci for vitiligo in the Chinese Han population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-35265 (e-PCR)
- UniSTS:48143

WI-16415 (e-PCR)
- UniSTS:75

G15952 (e-PCR)
- UniSTS:6750

G64347 (e-PCR)
- UniSTS:163940

RK1196_1197 (e-PCR)
- UniSTS:49271

D12S1388E (e-PCR)
- UniSTS:153779

STS-M34309 (e-PCR)
- UniSTS:6591

D12S1604 (e-PCR), detects polymorphism
- UniSTS:38862

ERBB3_1423 (e-PCR)
- UniSTS:277216

ERBB3_v469 (e-PCR)
- UniSTS:277216

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ErbB-3 class receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables growth factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables growth factor binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables neuregulin binding	IBA Inferred from Biological aspect of Ancestor more info
enables neuregulin binding	IDA Inferred from Direct Assay more info	PubMed
enables neuregulin receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine kinase activator activity	IDA Inferred from Direct Assay more info	PubMed
NOT enables protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane signaling receptor activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in ERBB2-ERBB3 signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in Schwann cell development	IEA Inferred from Electronic Annotation more info
involved_in Schwann cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in cell surface receptor protein tyrosine kinase signaling pathway	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cranial nerve development	ISS Inferred from Sequence or Structural Similarity more info
involved_in endocardial cushion development	IEA Inferred from Electronic Annotation more info
involved_in extrinsic apoptotic signaling pathway in absence of ligand	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heart development	ISS Inferred from Sequence or Structural Similarity more info
involved_in motor neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info
involved_in myelination	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of cell adhesion	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of motor neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neuron apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in neurogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peripheral nervous system development	ISS Inferred from Sequence or Structural Similarity more info
involved_in phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of calcineurin-NFAT signaling cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cardiac muscle tissue development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell population proliferation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in wound healing	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of ERBB3:ERBB2 complex	IDA Inferred from Direct Assay more info	PubMed
located_in apical plasma membrane	IEA Inferred from Electronic Annotation more info
is_active_in basal plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in lateral plasma membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of receptor complex	IDA Inferred from Direct Assay more info	PubMed
part_of receptor complex	ISS Inferred from Sequence or Structural Similarity more info	PubMed

General protein information

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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

EC 2.7.10.1

NP_001973.2

EC 2.7.10.1

XP_047284456.1

EC 2.7.10.1

XP_047284457.1

EC 2.7.10.1

XP_054227383.1

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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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

NG_011529.1 RefSeqGene

Range

4918..28400

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_996

mRNA and Protein(s)

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

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

ENSP00000415753.2, ENST00000411731.6

Conserved Domains (1) summary

pfam01030
Location:56 → 140

Recep_L_domain; Receptor L domain
NM_001982.4 → NP_001973.2 receptor tyrosine-protein kinase erbB-3 isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AA524528, BC082992, BU674508, DC347955

Consensus CDS

CCDS31833.1

UniProtKB/Swiss-Prot

A8K6L6, B4DIK7, B4DV32, E9PDT8, P21860, Q9BUD7

Related

ENSP00000267101.4, ENST00000267101.8

Conserved Domains (8) summary

cd05111
Location:701 → 979

PTK_HER3; Pseudokinase domain of the Protein Tyrosine Kinase, HER3

cd12095
Location:638 → 676

TM_ErbB3; Transmembrane domain of ErbB3, a Protein Tyrosine Kinase

smart00261
Location:548 → 592

FU; Furin-like repeats

cd00064
Location:226 → 266

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:183 → 329

Furin-like; Furin-like cysteine rich region

pfam01030
Location:353 → 474

Recep_L_domain; Receptor L domain

pfam07714
Location:709 → 965

Pkinase_Tyr; Protein tyrosine kinase

pfam14843
Location:499 → 630

GF_recep_IV; Growth factor receptor domain IV