Seroatlas · Human Serome Atlas

ERBB3

Receptor tyrosine-protein kinase erbB-3

Also known as: ERBB3_HUMAN, HER3, LCCS2

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

Protein identityUniProt · HPA

UniProt accession: P21860
Gene: ERBB3
Ensembl: ENSG00000065361
Chromosome: 12
Canonical length: 1342 aa
Protein class: Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins, Transporters
Subcellular location: Plasma membrane,Actin filaments
Secretome location: Secreted - unknown location
Quaternary structure: Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1342 residues, UniProt reviewed canonical sequence.

>P21860|ERBB3
     1  MRANDALQVL GLLFSLARGS EVGNSQAVCP GTLNGLSVTG DAENQYQTLY KLYERCEVVM
    61  GNLEIVLTGH NADLSFLQWI REVTGYVLVA MNEFSTLPLP NLRVVRGTQV YDGKFAIFVM
   121  LNYNTNSSHA LRQLRLTQLT EILSGGVYIE KNDKLCHMDT IDWRDIVRDR DAEIVVKDNG
   181  RSCPPCHEVC KGRCWGPGSE DCQTLTKTIC APQCNGHCFG PNPNQCCHDE CAGGCSGPQD
   241  TDCFACRHFN DSGACVPRCP QPLVYNKLTF QLEPNPHTKY QYGGVCVASC PHNFVVDQTS
   301  CVRACPPDKM EVDKNGLKMC EPCGGLCPKA CEGTGSGSRF QTVDSSNIDG FVNCTKILGN
   361  LDFLITGLNG DPWHKIPALD PEKLNVFRTV REITGYLNIQ SWPPHMHNFS VFSNLTTIGG
   421  RSLYNRGFSL LIMKNLNVTS LGFRSLKEIS AGRIYISANR QLCYHHSLNW TKVLRGPTEE
   481  RLDIKHNRPR RDCVAEGKVC DPLCSSGGCW GPGPGQCLSC RNYSRGGVCV THCNFLNGEP
   541  REFAHEAECF SCHPECQPME GTATCNGSGS DTCAQCAHFR DGPHCVSSCP HGVLGAKGPI
   601  YKYPDVQNEC RPCHENCTQG CKGPELQDCL GQTLVLIGKT HLTMALTVIA GLVVIFMMLG
   661  GTFLYWRGRR IQNKRAMRRY LERGESIEPL DPSEKANKVL ARIFKETELR KLKVLGSGVF
   721  GTVHKGVWIP EGESIKIPVC IKVIEDKSGR QSFQAVTDHM LAIGSLDHAH IVRLLGLCPG
   781  SSLQLVTQYL PLGSLLDHVR QHRGALGPQL LLNWGVQIAK GMYYLEEHGM VHRNLAARNV
   841  LLKSPSQVQV ADFGVADLLP PDDKQLLYSE AKTPIKWMAL ESIHFGKYTH QSDVWSYGVT
   901  VWELMTFGAE PYAGLRLAEV PDLLEKGERL AQPQICTIDV YMVMVKCWMI DENIRPTFKE
   961  LANEFTRMAR DPPRYLVIKR ESGPGIAPGP EPHGLTNKKL EEVELEPELD LDLDLEAEED
  1021  NLATTTLGSA LSLPVGTLNR PRGSQSLLSP SSGYMPMNQG NLGESCQESA VSGSSERCPR
  1081  PVSLHPMPRG CLASESSEGH VTGSEAELQE KVSMCRSRSR SRSPRPRGDS AYHSQRHSLL
  1141  TPVTPLSPPG LEEEDVNGYV MPDTHLKGTP SSREGTLSSV GLSSVLGTEE EDEDEEYEYM
  1201  NRRRRHSPPH PPRPSSLEEL GYEYMDVGSD LSASLGSTQS CPLHPVPIMP TAGTTPDEDY
  1261  EYMNRQRDGG GPGGDYAAMG ACPASEQGYE EMRAFQGPGH QAPHVHYARL KTLRSLEATD
  1321  SAFDNPDYWH SRLFPKANAQ RT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ERBB3 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): 0.4
Highest tissue expression: 83 nTPM

Expression across tissuesHPA

Tissue

liver: 83 nTPM
esophagus: 69 nTPM
salivary gland: 66 nTPM
small intestine: 65 nTPM
duodenum: 65 nTPM
skin: 64 nTPM

Single-cell type

oligodendrocytes: 307 nCPM
esophageal apical cells: 276 nCPM
enterocytes: 112 nCPM
esophageal suprabasal cells: 95 nCPM
schwann cells: 90 nCPM
prostatic club cells: 85 nCPM

Immune cell

basophil: 1 nTPM
neutrophil: 0.5 nTPM
naive CD8 T-cell: 0.2 nTPM
NK-cell: 0.2 nTPM
eosinophil: 0.1 nTPM
gdT-cell: 0.1 nTPM

Brain region

white matter: 103 nTPM
basal ganglia: 66 nTPM
cerebral cortex: 56 nTPM
medulla oblongata: 53 nTPM
thalamus: 52 nTPM
midbrain: 51 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ERBB3.

Disease | AllUniProt

Conditions ERBB3 is implicated in, by any mechanism.

Lethal congenital contracture syndrome 2 (LCCS2) MIM:607598
Erythroleukemia, familial (FERLK) MIM:133180
Visceral neuropathy, familial, 1, autosomal recessive (VSCN1) MIM:243180

Disease | GeneticClinVar

22 pathogenic / likely-pathogenic of 246 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Visceral neuropathy, familial, 1, autosomal recessive
Lethal congenital contracture syndrome 2
Malignant tumor of urinary bladder
ERBB3-related disorder
Erythroleukemia, familial, susceptibility to

Disease | ImmuneIEDB

Conditions an epitope on ERBB3 was assayed in.

head and neck squamous cell carcinoma T cell

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): 0.69
gnomAD pLI: 0
gnomAD missense Z: 1.39
DepMap mean gene effect: -0.28
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% 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 ERBB3 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 ERBB3 as an antibody target. Whether an autoantibody or antibody against ERBB3 could matter depends on whether native ERBB3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ERBB3 is annotated at the cell surface, where native ERBB3 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 ERBB3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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