Seroatlas · Human Serome Atlas

ERBB4

Receptor tyrosine-protein kinase erbB-4

Also known as: ALS19, ERBB4_HUMAN, HER4

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

Protein identityUniProt · HPA

UniProt accession
Q15303
Gene
ERBB4
Ensembl
ENSG00000178568
Chromosome
2
Canonical length
1308 aa
Protein class
Cancer-related genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Transporters
Quaternary structure
Homodimer

OverviewNCBI Gene

This gene is a member of the Tyr protein kinase family and the epidermal growth factor receptor subfamily. It encodes a single-pass type I membrane protein with multiple cysteine rich domains, a transmembrane domain, a tyrosine kinase domain, a phosphotidylinositol-3 kinase binding site and a PDZ domain binding motif. The protein binds to and is activated by neuregulins and other factors and induces a variety of cellular responses including mitogenesis and differentiation. Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment. Mutations in this gene have been associated with cancer. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1308 residues, UniProt reviewed canonical sequence.

>Q15303|ERBB4
     1  MKPATGLWVW VSLLVAAGTV QPSDSQSVCA GTENKLSSLS DLEQQYRALR KYYENCEVVM
    61  GNLEITSIEH NRDLSFLRSV REVTGYVLVA LNQFRYLPLE NLRIIRGTKL YEDRYALAIF
   121  LNYRKDGNFG LQELGLKNLT EILNGGVYVD QNKFLCYADT IHWQDIVRNP WPSNLTLVST
   181  NGSSGCGRCH KSCTGRCWGP TENHCQTLTR TVCAEQCDGR CYGPYVSDCC HRECAGGCSG
   241  PKDTDCFACM NFNDSGACVT QCPQTFVYNP TTFQLEHNFN AKYTYGAFCV KKCPHNFVVD
   301  SSSCVRACPS SKMEVEENGI KMCKPCTDIC PKACDGIGTG SLMSAQTVDS SNIDKFINCT
   361  KINGNLIFLV TGIHGDPYNA IEAIDPEKLN VFRTVREITG FLNIQSWPPN MTDFSVFSNL
   421  VTIGGRVLYS GLSLLILKQQ GITSLQFQSL KEISAGNIYI TDNSNLCYYH TINWTTLFST
   481  INQRIVIRDN RKAENCTAEG MVCNHLCSSD GCWGPGPDQC LSCRRFSRGR ICIESCNLYD
   541  GEFREFENGS ICVECDPQCE KMEDGLLTCH GPGPDNCTKC SHFKDGPNCV EKCPDGLQGA
   601  NSFIFKYADP DRECHPCHPN CTQGCNGPTS HDCIYYPWTG HSTLPQHART PLIAAGVIGG
   661  LFILVIVGLT FAVYVRRKSI KKKRALRRFL ETELVEPLTP SGTAPNQAQL RILKETELKR
   721  VKVLGSGAFG TVYKGIWVPE GETVKIPVAI KILNETTGPK ANVEFMDEAL IMASMDHPHL
   781  VRLLGVCLSP TIQLVTQLMP HGCLLEYVHE HKDNIGSQLL LNWCVQIAKG MMYLEERRLV
   841  HRDLAARNVL VKSPNHVKIT DFGLARLLEG DEKEYNADGG KMPIKWMALE CIHYRKFTHQ
   901  SDVWSYGVTI WELMTFGGKP YDGIPTREIP DLLEKGERLP QPPICTIDVY MVMVKCWMID
   961  ADSRPKFKEL AAEFSRMARD PQRYLVIQGD DRMKLPSPND SKFFQNLLDE EDLEDMMDAE
  1021  EYLVPQAFNI PPPIYTSRAR IDSNRSEIGH SPPPAYTPMS GNQFVYRDGG FAAEQGVSVP
  1081  YRAPTSTIPE APVAQGATAE IFDDSCCNGT LRKPVAPHVQ EDSSTQRYSA DPTVFAPERS
  1141  PRGELDEEGY MTPMRDKPKQ EYLNPVEENP FVSRRKNGDL QALDNPEYHN ASNGPPKAED
  1201  EYVNEPLYLN TFANTLGKAE YLKNNILSMP EKAKKAFDNP DYWNHSLPPR STLQHPDYLQ
  1261  EYSTKYFYKQ NGRIRPIVAE NPEYLSEFSL KPGTVLPPPP YRHRNTVV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ERBB4 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)
0.37
Highest tissue expression
11 nTPM

Expression across tissuesHPA

Tissue

  • fallopian tube: 11 nTPM
  • cerebral cortex: 7.7 nTPM
  • blood vessel: 7.6 nTPM
  • basal ganglia: 6.6 nTPM
  • amygdala: 6.5 nTPM
  • breast: 5.2 nTPM

Single-cell type

  • pituicytes/fscs: 10,590 nCPM
  • distal convoluted tubule cells: 6,348 nCPM
  • sertoli cells: 5,848 nCPM
  • loop of henle epithelial cells: 3,889 nCPM
  • astrocytes: 3,533 nCPM
  • renal connecting tubule cells: 3,168 nCPM

Immune cell

  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM
  • MAIT T-cell: 0 nTPM

Brain region

  • midbrain: 63 nTPM
  • basal ganglia: 54 nTPM
  • hypothalamus: 52 nTPM
  • cerebral cortex: 49 nTPM
  • amygdala: 47 nTPM
  • cerebellum: 46 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ERBB4.

Disease | AllUniProt

Conditions ERBB4 is implicated in, by any mechanism.

  • Amyotrophic lateral sclerosis 19 (ALS19) MIM:615515

Disease | GeneticClinVar

10 pathogenic / likely-pathogenic of 754 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

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)
0.27
gnomAD pLI
1
gnomAD missense Z
2.01
DepMap mean gene effect
-0.03
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% 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 ERBB4 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 ERBB4 as an antibody target. Whether an autoantibody or antibody against ERBB4 could matter depends on whether native ERBB4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ERBB4 is annotated at the cell surface, where native ERBB4 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 ERBB4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/ERBB4. 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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