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

Summary

Official Symbol: HERC5provided by HGNC
Official Full Name: HECT and RLD domain containing E3 ubiquitin protein ligase 5provided by HGNC
Primary source: HGNC:HGNC:24368
See related: Ensembl:ENSG00000138646 MIM:608242; AllianceGenome:HGNC:24368
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CEB1; CEBP1
Summary: 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.
Expression: Broad expression in testis (RPKM 31.7), endometrium (RPKM 6.3) and 17 other tissues See more
Orthologs: all
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Genomic context

Location:: 4q22.1

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (88457119..88506163)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (91788779..91837819)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (89378270..89427314)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HERC5 downregulation in non-small cell lung cancer is associated with altered energy metabolism and metastasis.
Title: HERC5 downregulation in non-small cell lung cancer is associated with altered energy metabolism and metastasis.
Posttranslational ISGylation of NLRP3 by HERC enzymes facilitates inflammasome activation in models of inflammation.
Title: Posttranslational ISGylation of NLRP3 by HERC enzymes facilitates inflammasome activation in models of inflammation.
The E3 ligase HERC5 promotes antimycobacterial responses in macrophages by ISGylating the phosphatase PTEN.
Title: The E3 ligase HERC5 promotes antimycobacterial responses in macrophages by ISGylating the phosphatase PTEN.
HERC5/IFI16/p53 signaling mediates breast cancer cell proliferation and migration.
Title: HERC5/IFI16/p53 signaling mediates breast cancer cell proliferation and migration.
Downregulation of HERC5 E3 ligase attenuates the ubiquitination of CtBP1 to inhibit apoptosis in colorectal cancer cells.
Title: Downregulation of HERC5 E3 ligase attenuates the ubiquitination of CtBP1 to inhibit apoptosis in colorectal cancer cells.
HERC5 E3 ligase mediates ISGylation of hepatitis B virus X protein to promote viral replication.
Title: HERC5 E3 ligase mediates ISGylation of hepatitis B virus X protein to promote viral replication.
Weighted gene correlation network analysis identifies RSAD2, HERC5, and CCL8 as prognostic candidates for breast cancer.
Title: Weighted gene correlation network analysis identifies RSAD2, HERC5, and CCL8 as prognostic candidates for breast cancer.
Low HERC5 expression is associated with HIV infections.
Title: Evolution-Guided Structural and Functional Analyses of the HERC Family Reveal an Ancient Marine Origin and Determinants of Antiviral Activity.
A synonymous mutation at rs6857425 (T-C) was present in the same region among all study groups (T-C), irrespective of their HIV status.
Title: HECT Domain and RCC1-Like Domain-Containing Protein 5 (HERC-5) Gene Polymorphisms in HIV-1-Infected Individuals: A Study from India.
Results show that HERC5 mediates covalent ISG15 conjugation to parkin in mammalian cells and that ISG15 is conjugated to the Lys349 and Lys369 residues of parkin.
Title: Covalent ISG15 conjugation positively regulates the ubiquitin E3 ligase activity of parkin.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study of lung function decline in adults with and without asthma. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G33451 (e-PCR)
- UniSTS:29461

D4S442E (e-PCR)
- UniSTS:147491

SHGC-32389 (e-PCR)
- UniSTS:79292

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	PubMed
enables RNA binding	HDA more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin-protein transferase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in ISG15-protein conjugation	IBA Inferred from Biological aspect of Ancestor more info
involved_in ISG15-protein conjugation	IDA Inferred from Direct Assay more info	PubMed
involved_in PKR/eIFalpha signaling	TAS Traceable Author Statement more info
involved_in defense response to virus	IEA Inferred from Electronic Annotation more info
involved_in innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in protein polyubiquitination	IEA Inferred from Electronic Annotation more info
involved_in protein ubiquitination	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cyclin-dependent protein serine/threonine kinase activity	TAS Traceable Author Statement more info	PubMed
involved_in regulation of defense response to virus	IDA Inferred from Direct Assay more info	PubMed
involved_in ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
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

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Preferred Names: E3 ISG15--protein ligase HERC5

Names: 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)

NM_016323.4 → NP_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

CCDS3630.1

UniProtKB/Swiss-Prot

B2RTQ1, Q69G20, Q9UII4

Related

ENSP00000264350.3, ENST00000264350.8

Conserved Domains (4) summary

smart00119
Location:705 → 1023

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:681 → 1024

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 ...

pfam00415
Location:261 → 309

RCC1; Regulator of chromosome condensation (RCC1) repeat

pfam13540
Location:140 → 169

RCC1_2; Regulator of chromosome condensation (RCC1) repeat