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HERC5 HECT and RLD domain containing E3 ubiquitin protein ligase 5 [ Homo sapiens (human) ]

Gene ID: 51191, updated on 8-Aug-2021


Official Symbol
HERC5provided by HGNC
Official Full Name
HECT and RLD domain containing E3 ubiquitin protein ligase 5provided by HGNC
Primary source
See related
Ensembl:ENSG00000138646 MIM:608242
Gene type
protein coding
RefSeq status
Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
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]
Annotation information
Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
Broad expression in testis (RPKM 31.7), endometrium (RPKM 6.3) and 17 other tissues See more
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Genomic context

See HERC5 in Genome Data Viewer
Exon count:
Annotation release Status Assembly Chr Location
109.20210514 current GRCh38.p13 (GCF_000001405.39) 4 NC_000004.12 (88456604..88506170)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (89378270..89427314)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105377326 Neighboring gene HECT and RLD domain containing E3 ubiquitin protein ligase family member 6 Neighboring gene uncharacterized LOC102723458 Neighboring gene nuclear receptor coactivator 4 pseudogene 2 Neighboring gene PIGY upstream open reading frame Neighboring gene phosphatidylinositol glycan anchor biosynthesis class Y

Genomic regions, transcripts, and products


  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018


GeneRIFs: Gene References Into Functions

What's a GeneRIF?


Associated conditions

Description Tests
Genome-wide association study of lung function decline in adults with and without asthma.
GeneReviews: Not available

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Pr55(Gag) gag Interaction of HIV-1 Gag with HECT and RLD domain containing E3 ubiquitin protein ligase 5 (HERC5) is identified in a series of six affinity purification/mass spectrometry screens PubMed
gag HERC5-induced restriction of Gag particle production is distinct from ISG15-only restriction PubMed
gag HERC5 restricts HIV-1 Gag particle production by a mechanism dependent on its E3 ligase activity. This restriction correlates with the conjugation of ISG15 to Gag by HERC5 PubMed
gag HIV-1 Gag co-localizes with HERC5 in cells PubMed
Rev rev HERC5 relocalizes HIV-1 Rev from nucleus to nuclear membrane and cytoplasm to inhibit Rev/RRE function PubMed
Vpr vpr HIV-1 Vpr upregulates the gene expression of HERC5 in human monocyte-derived dendritic cells PubMed
capsid gag Both HERC5 and HERC5-C994A mutant inhibit HIV-1 particle production with decreased levels of HIV-1 CA in cells and virions PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem


Products Interactant Other Gene Complex Source Pubs Description

General gene information



Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ISG15 transferase activity IBA
Inferred from Biological aspect of Ancestor
more info
enables ISG15 transferase activity IDA
Inferred from Direct Assay
more info
enables RNA binding HDA PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
enables ubiquitin protein ligase activity IDA
Inferred from Direct Assay
more info
enables ubiquitin-protein transferase activity TAS
Traceable Author Statement
more info
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
located_in cytosol TAS
Traceable Author Statement
more info
located_in perinuclear region of cytoplasm IEA
Inferred from Electronic Annotation
more info

General protein information

Preferred Names
E3 ISG15--protein ligase HERC5
HECT domain and RCC1-like domain-containing protein 5
cyclin-E-binding protein 1
hect domain and RLD 5
probable E3 ubiquitin-protein ligase HERC5

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_016323.4NP_057407.2  E3 ISG15--protein ligase HERC5

    See identical proteins and their annotated locations for NP_057407.2

    Status: REVIEWED

    Source sequence(s)
    AC083829, AI336946, AK302142, AY337518, BC140716
    Consensus CDS
    ENSP00000264350.3, ENST00000264350.8
    Conserved Domains (4) summary
    HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
    HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
    RCC1; Regulator of chromosome condensation (RCC1) repeat
    RCC1_2; Regulator of chromosome condensation (RCC1) repeat

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly


  1. NC_000004.12 Reference GRCh38.p13 Primary Assembly

    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011532022.2XP_011530324.2  E3 ISG15--protein ligase HERC5 isoform X1

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