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FLASH GENE

Symbol

ERBB2

contributors: mct - updated : 11-06-2011

HGNC name	v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)
HGNC id	3430

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	17q12      Physical location : 37.844.392 - 37.884.914
Synonym name	herstatin
	epidermal growth factor (EGF) receptor
	c-erb B2/neu protein
	tyrosine kinase-type cell surface receptor HER2
	metastatic lymph node gene 19 protein
	proto-oncogene c-ErbB-2
	CD340 antigen
	proto-oncogene Neu
Synonym symbol(s)	HER2, NGL, NEU, TKR1, HER-2, c-erb B2, ERBB-2, CD340
EC.number	2.7.10.1

DNA

TYPE	functioning gene
STRUCTURE	40.52 kb     30 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	see NF1 NF1

Physical map

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004448 27 - 4624 NP_004439 137.91 1255 - 1985 2999974 a 27 exons variant lacking exons 1, 2, 3 and 4 encoding for the longest product NM_001005862 30 splicing 4816 NP_001005862 134.72 1225 secreted fetal liver, kidney 1999 10485918 a 30 exon variant lacking exon 5 retaining intron 8 subdomain I, II

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic spleen       highly Endocrine pancreas       highly Reproductive male system prostate     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, fetal

Text	kidney, liver and in the developing nervous system

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an extracellular domain with four subdomains I-IV
	a single transmembrane (TM) protein with extensive homology to the epidermal growth factor receptor
	a cytoplasmic catalytic domain
	a Blocking ErbB2 Degradation or BED domain, that is the factor restricting the ligand-induced degradation of ERBB2
	specific N-glycan in domain III playing an essential role in regulating receptor dimerization and transforming activity
	a putative NLS with three clusters of basic amino acids (RRRHIVRKRTLRR (amino acids 645-657)) in the juxtamembrane region

conjugated

GlycoP , PhosphoP

mono polymer

homomer , heteromer , dimer

HOMOLOGY

interspecies	homolog to rattus Erbb2 (88.13 pc)
	homolog to murine Erbb2 (87.73 pc)
	homolog to zebrafish erbb2 (59.08 pc)

intraspecies

homolog to avian erythroblastic leukemia viral (v-erb-b) oncogene 2

Homologene

FAMILY	epidermal growth factor (EGF) receptor family
	class I tyrosine protein kinase family
	erythroblastosis oncogene B (ERBB)-like oncogene family

CATEGORY

enzyme , protooncogene , signaling , receptor membrane

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,nucleus,nucleolus
text	type I membrane protein
	detected in the nucleus

basic FUNCTION	acting as a coreceptor for multiple stroma-derived growth factors i.e EGF-like ligands and neuregulins, and as a coreceptor for GPCR signaling in the heart
	involved in androgen receptor transactivation of inducing prostate-specific antigen (PSA) through the MAP kinase pathway
	playing a critical role for normal cardiac function and prevention of dilated cardiomyopathy (together with ERBB4 and neuregulin)
	modulating epidemal growth factor signaling pathways resulting in growth arrest
	required for the distal morphogenesis of the mammary gland
	playing a pivotal role for integrating signaling networks involving multiple classes of extracellular signals
	requires ITGA5 for anoikis resistance via SRC regulation of receptor activity in human mammary epithelial cells
	ERBB2 regulation having important implications in cancer, and for developing therapeutic approaches that target novel aspects of this orphan receptor
	controls microtubule capture by recruiting MACF1 to the plasma membrane of migrating cells
	may be dependent on ERBB3 to drive growth and survival of breast cancer cells
	novel function of nuclear ERBB2 in enhancing rRNA gene transcription by RNA polymerase-I (RNA Pol I)
	nuclear ERBB2 functions as a regulator of rRNA synthesis and cellular translation, which may contribute to tumor development and progression

CELLULAR PROCESS	cell cycle, division

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

signal transduction

growth factors pathway

a component	heterodimerizing with other ERBBs, secreted by ligand-binding members of EGFR family
	heterodimer with ERBB3, ERBB4
	complexes with cofilin, ERBB2 and PLCG1

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP

protein	AP2 for regulation by oestrogen
	WITH GRB7 (to regulating cell proliferation)
	PRKCABP
	PLXNB1
	interaction with LNX1, an E3 ubiquitin ligase that can target interacting proteins for degradation through ubiquitination
	nuclear ERBB2 physically associates with beta-actin and RNA Pol I, coinciding with active RNA Pol I transcription sites in nucleoli

cell & other

REGULATION

activated by

NRGs isoforms

induced by

PIN1 (PIN1 amplifies EGF signaling in breast cancer cells through its interaction with MAP2K1 and then enhances ERBB2 expression)

inhibited by	its alternative isoform herstatin that disrupts ERBB2 dimers
	ETV4

Other

regulated by N-glycosylation that controls ErbB signaling by various mechanisms

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in primary gastric cancer and prostate carcinoma with metastasis and poor prognosis, pancreas, colon and ovary carcinoma, cholangiocarcinoma tumoral       gain of function in primary breast and uterus endometrial cancer and in low grade osteosarcoma with increased survival tumoral somatic mutation       in dilated cardiomyopathy tumoral     --over   in neuro/glioblastoma and in non-small cell lung cancer tumoral   amplification     in many types of cancer, including breast cancer tumoral somatic mutation       in the lung squamous cell carcinoma (kinase domain mutation ) tumoral     --over   in breast cancer cells with poor prognostic (with enhanced tumorigenicity, propensity to metastasize and resistance to endocrine therapy) tumoral   amplification     loss of beclin 1 and ERBB2 amplification (both on 17q21) in breast cancers tumoral     --over   patients breast cancer with higher CCNA2 and ERBB2 expressions had significantly shorter disease-free survival periods

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	overexpression in breast cancer cells are known to be poor prognostic markers and are strong predictors of benefit from treatment with ERBB2-targeting agents
Therapy target
	System Type Disorder Pubmed cancer reproductive breast selected RNA aptamer is a potential cancer imaging agent by targeting malignant cells of breast cancer overexpressing the ERBB2 receptor cancer reproductive breast blockade of ERBB2:TGFB crosstalk may significantly enhance the efficiency of conventional therapies in breast cancer patients with ERBB2 overexpression cancer reproductive breast anti-ERBB2 human compact antibody-RNase (Erb-hcAb-RNase) could be a promising candidate for the immunotherapy of ERBB2-positive tumours cancer reproductive breast therapeutic inhibitors of ERBB3 should be used in combination with HER2 inhibitors and PI3K pathway inhibitors in patients with ERBB2- and PI3K-dependent cancers

ANIMAL & CELL MODELS