Seroatlas · Human Serome Atlas

HERC5

E3 ISG15--protein ligase HERC5

Also known as: CEB1, HERC5_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
Q9UII4
Gene
HERC5
Ensembl
ENSG00000138646
Chromosome
4
Canonical length
1024 aa
Protein class
Predicted membrane proteins

OverviewNCBI Gene

This gene is a member of the HERC family of ubiquitin ligases and encodes a protein with a HECT domain and five RCC1 repeats. Pro-inflammatory cytokines upregulate expression of this gene in endothelial cells. The protein localizes to the cytoplasm and perinuclear region and functions as an interferon-induced E3 protein ligase that mediates ISGylation of protein targets. The protein also acts as a modulator of the antiviral immune response. The gene lies in a cluster of HERC family genes on chromosome 4. [provided by RefSeq, Aug 2021]

Canonical amino-acid sequenceUniProt

1024 residues, UniProt reviewed canonical sequence.

>Q9UII4|HERC5
     1  MERRSRRKSR RNGRSTAGKA AATQPAKSPG AQLWLFPSAA GLHRALLRRV EVTRQLCCSP
    61  GRLAVLERGG AGVQVHQLLA GSGGARTPKC IKLGKNMKIH SVDQGAEHML ILSSDGKPFE
   121  YDNYSMKHLR FESILQEKKI IQITCGDYHS LALSKGGELF AWGQNLHGQL GVGRKFPSTT
   181  TPQIVEHLAG VPLAQISAGE AHSMALSMSG NIYSWGKNEC GQLGLGHTES KDDPSLIEGL
   241  DNQKVEFVAC GGSHSALLTQ DGLLFTFGAG KHGQLGHNST QNELRPCLVA ELVGYRVTQI
   301  ACGRWHTLAY VSDLGKVFSF GSGKDGQLGN GGTRDQLMPL PVKVSSSEEL KLESHTSEKE
   361  LIMIAGGNQS ILLWIKKENS YVNLKRTIPT LNEGTVKRWI ADVETKRWQS TKREIQEIFS
   421  SPACLTGSFL RKRRTTEMMP VYLDLNKARN IFKELTQKDW ITNMITTCLK DNLLKRLPFH
   481  SPPQEALEIF FLLPECPMMH ISNNWESLVV PFAKVVCKMS DQSSLVLEEY WATLQESTFS
   541  KLVQMFKTAV ICQLDYWDES AEENGNVQAL LEMLKKLHRV NQVKCQLPES IFQVDELLHR
   601  LNFFVEVCRR YLWKMTVDAS ENVQCCVIFS HFPFIFNNLS KIKLLHTDTL LKIESKKHKA
   661  YLRSAAIEEE RESEFALRPT FDLTVRRNHL IEDVLNQLSQ FENEDLRKEL WVSFSGEIGY
   721  DLGGVKKEFF YCLFAEMIQP EYGMFMYPEG ASCMWFPVKP KFEKKRYFFF GVLCGLSLFN
   781  CNVANLPFPL ALFKKLLDQM PSLEDLKELS PDLGKNLQTL LDDEGDNFEE VFYIHFNVHW
   841  DRNDTNLIPN GSSITVNQTN KRDYVSKYIN YIFNDSVKAV YEEFRRGFYK MCDEDIIKLF
   901  HPEELKDVIV GNTDYDWKTF EKNARYEPGY NSSHPTIVMF WKAFHKLTLE EKKKFLVFLT
   961  GTDRLQMKDL NNMKITFCCP ESWNERDPIR ALTCFSVLFL PKYSTMETVE EALQEAINNN
  1021  RGFG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HERC5 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)
0.25
Highest tissue expression
54 nTPM

Expression across tissuesHPA

Tissue

  • testis: 54 nTPM
  • bone marrow: 18 nTPM
  • ovary: 16 nTPM
  • endometrium: 14 nTPM
  • thymus: 13 nTPM
  • smooth muscle: 13 nTPM

Single-cell type

  • differentiating spermatogonia: 513 nCPM
  • early primary spermatocytes: 470 nCPM
  • oocytes: 166 nCPM
  • undifferentiated spermatogonia: 138 nCPM
  • late primary spermatocytes: 75 nCPM
  • early spermatids: 74 nCPM

Immune cell

  • T-reg: 28 nTPM
  • neutrophil: 25 nTPM
  • basophil: 15 nTPM
  • eosinophil: 12 nTPM
  • memory CD4 T-cell: 8.7 nTPM
  • MAIT T-cell: 8.6 nTPM

Brain region

  • spinal cord: 13 nTPM
  • choroid plexus: 11 nTPM
  • medulla oblongata: 11 nTPM
  • white matter: 10 nTPM
  • pons: 9.7 nTPM
  • midbrain: 9.4 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)
0.71
gnomAD pLI
0
gnomAD missense Z
0.84
DepMap mean gene effect
0.03
DepMap dependency class
none

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 HERC5 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 HERC5 as an antibody target. Whether an autoantibody or antibody against HERC5 could matter depends on whether native HERC5 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

HERC5 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 HERC5 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/HERC5. 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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