Seroatlas · Human Serome Atlas

HERC4

Probable E3 ubiquitin-protein ligase HERC4

Also known as: DKFZP564G092, HERC4_HUMAN, KIAA1593

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

Protein identityUniProt · HPA

UniProt accession
Q5GLZ8
Gene
HERC4
Ensembl
ENSG00000148634
Chromosome
10
Canonical length
1057 aa
Protein class
Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins
Subcellular location
Nucleoli fibrillar center,Cytosol

OverviewNCBI Gene

HERC4 belongs to the HERC family of ubiquitin ligases, all of which contain a HECT domain and at least 1 RCC1 (MIM 179710)-like domain (RLD). The 350-amino acid HECT domain is predicted to catalyze the formation of a thioester with ubiquitin before transferring it to a substrate, and the RLD is predicted to act as a guanine nucleotide exchange factor for small G proteins (Hochrainer et al., 2005 [PubMed 15676274]).[supplied by OMIM, Mar 2008]

Canonical amino-acid sequenceUniProt

1057 residues, UniProt reviewed canonical sequence.

>Q5GLZ8|HERC4
     1  MLCWGNASFG QLGLGGIDEE IVLEPRKSDF FINKRVRDVG CGLRHTVFVL DDGTVYTCGC
    61  NDLGQLGHEK SRKKPEQVVA LDAQNIVAVS CGEAHTLALN DKGQVYAWGL DSDGQLGLVG
   121  SEECIRVPRN IKSLSDIQIV QVACGYYHSL ALSKASEVFC WGQNKYGQLG LGTDCKKQTS
   181  PQLLKSLLGI PFMQVAAGGA HSFVLTLSGA IFGWGRNKFG QLGLNDENDR YVPNLLKSLR
   241  SQKIVYICCG EDHTAALTKE GGVFTFGAGG YGQLGHNSTS HEINPRKVFE LMGSIVTEIA
   301  CGRQHTSAFV PSSGRIYSFG LGGNGQLGTG STSNRKSPFT VKGNWYPYNG QCLPDIDSEE
   361  YFCVKRIFSG GDQSFSHYSS PQNCGPPDDF RCPNPTKQIW TVNEALIQKW LSYPSGRFPV
   421  EIANEIDGTF SSSGCLNGSF LAVSNDDHYR TGTRFSGVDM NAARLLFHKL IQPDHPQISQ
   481  QVAASLEKNL IPKLTSSLPD VEALRFYLTL PECPLMSDSN NFTTIAIPFG TALVNLEKAP
   541  LKVLENWWSV LEPPLFLKIV ELFKEVVVHL LKLYKIGIPP SERRIFNSFL HTALKVLEIL
   601  HRVNEKMGQI IQYDKFYIHE VQELIDIRND YINWVQQQAY GMDVNHGLTE LADIPVTICT
   661  YPFVFDAQAK TTLLQTDAVL QMQMAIDQAH RQNVSSLFLP VIESVNPCLI LVVRRENIVG
   721  DAMEVLRKTK NIDYKKPLKV IFVGEDAVDA GGVRKEFFLL IMRELLDPKY GMFRYYEDSR
   781  LIWFSDKTFE DSDLFHLIGV ICGLAIYNCT IVDLHFPLAL YKKLLKKKPS LDDLKELMPD
   841  VGRSMQQLLD YPEDDIEETF CLNFTITVEN FGATEVKELV LNGADTAVNK QNRQEFVDAY
   901  VDYIFNKSVA SLFDAFHAGF HKVCGGKVLL LFQPNELQAM VIGNTNYDWK ELEKNTEYKG
   961  EYWAEHPTIK IFWEVFHELP LEKKKQFLLF LTGSDRIPIL GMKSLKLVIQ STGGGEEYLP
  1021  VSHTCFNLLD LPKYTEKETL RSKLIQAIDH NEGFSLI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HERC4 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
Intracellular
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.23
Highest tissue expression
20 nTPM

Expression across tissuesHPA

Tissue

  • lymph node: 20 nTPM
  • adrenal gland: 20 nTPM
  • tonsil: 18 nTPM
  • liver: 17 nTPM
  • spleen: 17 nTPM
  • placenta: 16 nTPM

Single-cell type

  • neutrophils: 728 nCPM
  • neutrophil progenitors: 432 nCPM
  • podocytes: 429 nCPM
  • fibro-adipogenic progenitors: 401 nCPM
  • sertoli cells: 398 nCPM
  • adrenal cortex cells: 392 nCPM

Immune cell

  • basophil: 11 nTPM
  • neutrophil: 6.8 nTPM
  • eosinophil: 6.7 nTPM
  • myeloid DC: 5.7 nTPM
  • T-reg: 5.6 nTPM
  • NK-cell: 5.2 nTPM

Brain region

  • white matter: 48 nTPM
  • hypothalamus: 42 nTPM
  • hippocampal formation: 38 nTPM
  • medulla oblongata: 37 nTPM
  • midbrain: 37 nTPM
  • cerebral cortex: 36 nTPM

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)
0.25
gnomAD pLI
1
gnomAD missense Z
4.31
DepMap mean gene effect
0
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

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads HERC4 as an antibody target. Whether an autoantibody or antibody against HERC4 could matter depends on whether native HERC4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

HERC4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label HERC4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/HERC4. 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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