Seroatlas · Human Serome Atlas

ERBB2

Receptor tyrosine-protein kinase erbB-2

Also known as: c-ERB-2, c-ERB2, CD340, ERBB2_HUMAN, HER-2, HER2, MLN-19, NEU, NGL, p185(erbB2)

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P04626
Gene
ERBB2
Ensembl
ENSG00000141736
Chromosome
17
Canonical length
1255 aa
Protein class
Cancer-related genes, CD markers, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Transporters
Subcellular location
Nucleoplasm,Plasma membrane,Cytosol
Quaternary structure
Homodimer

OverviewNCBI Gene

This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1255 residues, UniProt reviewed canonical sequence.

>P04626|ERBB2
     1  MELAALCRWG LLLALLPPGA ASTQVCTGTD MKLRLPASPE THLDMLRHLY QGCQVVQGNL
    61  ELTYLPTNAS LSFLQDIQEV QGYVLIAHNQ VRQVPLQRLR IVRGTQLFED NYALAVLDNG
   121  DPLNNTTPVT GASPGGLREL QLRSLTEILK GGVLIQRNPQ LCYQDTILWK DIFHKNNQLA
   181  LTLIDTNRSR ACHPCSPMCK GSRCWGESSE DCQSLTRTVC AGGCARCKGP LPTDCCHEQC
   241  AAGCTGPKHS DCLACLHFNH SGICELHCPA LVTYNTDTFE SMPNPEGRYT FGASCVTACP
   301  YNYLSTDVGS CTLVCPLHNQ EVTAEDGTQR CEKCSKPCAR VCYGLGMEHL REVRAVTSAN
   361  IQEFAGCKKI FGSLAFLPES FDGDPASNTA PLQPEQLQVF ETLEEITGYL YISAWPDSLP
   421  DLSVFQNLQV IRGRILHNGA YSLTLQGLGI SWLGLRSLRE LGSGLALIHH NTHLCFVHTV
   481  PWDQLFRNPH QALLHTANRP EDECVGEGLA CHQLCARGHC WGPGPTQCVN CSQFLRGQEC
   541  VEECRVLQGL PREYVNARHC LPCHPECQPQ NGSVTCFGPE ADQCVACAHY KDPPFCVARC
   601  PSGVKPDLSY MPIWKFPDEE GACQPCPINC THSCVDLDDK GCPAEQRASP LTSIISAVVG
   661  ILLVVVLGVV FGILIKRRQQ KIRKYTMRRL LQETELVEPL TPSGAMPNQA QMRILKETEL
   721  RKVKVLGSGA FGTVYKGIWI PDGENVKIPV AIKVLRENTS PKANKEILDE AYVMAGVGSP
   781  YVSRLLGICL TSTVQLVTQL MPYGCLLDHV RENRGRLGSQ DLLNWCMQIA KGMSYLEDVR
   841  LVHRDLAARN VLVKSPNHVK ITDFGLARLL DIDETEYHAD GGKVPIKWMA LESILRRRFT
   901  HQSDVWSYGV TVWELMTFGA KPYDGIPARE IPDLLEKGER LPQPPICTID VYMIMVKCWM
   961  IDSECRPRFR ELVSEFSRMA RDPQRFVVIQ NEDLGPASPL DSTFYRSLLE DDDMGDLVDA
  1021  EEYLVPQQGF FCPDPAPGAG GMVHHRHRSS STRSGGGDLT LGLEPSEEEA PRSPLAPSEG
  1081  AGSDVFDGDL GMGAAKGLQS LPTHDPSPLQ RYSEDPTVPL PSETDGYVAP LTCSPQPEYV
  1141  NQPDVRPQPP SPREGPLPAA RPAGATLERP KTLSPGKNGV VKDVFAFGGA VENPEYLTPQ
  1201  GGAAPQPHPP PAFSPAFDNL YYWDQDPPER GAPPSTFKGT PTAENPEYLG LDVPV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ERBB2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
1
Mean surface accessibility (rSASA)
0.35
Highest tissue expression
98 nTPM

Expression across tissuesHPA

Tissue

  • esophagus: 98 nTPM
  • skin: 87 nTPM
  • kidney: 84 nTPM
  • parathyroid gland: 77 nTPM
  • salivary gland: 66 nTPM
  • colon: 64 nTPM

Single-cell type

  • esophageal apical cells: 241 nCPM
  • prostatic club cells: 179 nCPM
  • renal collecting duct principal cells: 140 nCPM
  • extravillous trophoblasts: 135 nCPM
  • prostatic hillock cells: 130 nCPM
  • renal connecting tubule cells: 128 nCPM

Immune cell

  • gdT-cell: 5 nTPM
  • total PBMC: 1.7 nTPM
  • memory CD8 T-cell: 1.4 nTPM
  • naive CD8 T-cell: 1.4 nTPM
  • neutrophil: 1.2 nTPM
  • basophil: 1 nTPM

Brain region

  • choroid plexus: 39 nTPM
  • midbrain: 38 nTPM
  • medulla oblongata: 38 nTPM
  • basal ganglia: 32 nTPM
  • spinal cord: 29 nTPM
  • white matter: 24 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ERBB2.

Disease | AllUniProt

Conditions ERBB2 is implicated in, by any mechanism.

Disease | GeneticClinVar

25 pathogenic / likely-pathogenic of 828 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Disease | ImmuneIEDB

Conditions an epitope on ERBB2 was assayed in.

Disease | AutoantibodyPubMed

Conditions in which antibodies against ERBB2 are reported. Each links to that disease's full target list.

ReferencesPubMed · IEDB

Publications for ERBB2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

14 publications

Show 9 more

Reference: B cellIEDB

5 publications

Reference: T cellIEDB

48 publications

Show 20 more of 48 total

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.4
gnomAD pLI
0.01
gnomAD missense Z
3.25
DepMap mean gene effect
-0.33
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of ERBB2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ERBB2 as an antibody target. Whether an autoantibody or antibody against ERBB2 could matter depends on whether native ERBB2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ERBB2 is annotated at the cell surface, where native ERBB2 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label ERBB2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/ERBB2. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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