HERC5 Gene (Protein Coding)

HECT And RLD Domain Containing E3 Ubiquitin Protein Ligase 5

GC04P088457
GIFtS:
40
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 ge... See more...

Aliases for HERC5 Gene

Aliases for HERC5 Gene

  • HECT And RLD Domain Containing E3 Ubiquitin Protein Ligase 5 2 3 5
  • CEB1 2 3 4
  • HECT Domain And RCC1-Like Domain-Containing Protein 5 3 4
  • E3 ISG15--Protein Ligase HERC5 3 4
  • Cyclin-E-Binding Protein 1 3 4
  • Hect Domain And RLD 5 2 3
  • CEBP1 3 4
  • Probable E3 Ubiquitin-Protein Ligase HERC5 3
  • EC 2.3.2.- 4
  • EC 6.3.2 51
  • HERC5 5

External Ids for HERC5 Gene

Previous GeneCards Identifiers for HERC5 Gene

  • GC04P089837
  • GC04P089735
  • GC04P089597
  • GC04P089378
  • GC04P085130

Summaries for HERC5 Gene

Entrez Gene Summary for HERC5 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 gene lies in a cluster of HERC family genes on chromosome 4. [provided by RefSeq, Jul 2008]

GeneCards Summary for HERC5 Gene

HERC5 (HECT And RLD Domain Containing E3 Ubiquitin Protein Ligase 5) is a Protein Coding gene. Diseases associated with HERC5 include Influenza. Among its related pathways are RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways and Innate Immune System. Gene Ontology (GO) annotations related to this gene include ubiquitin-protein transferase activity. An important paralog of this gene is HERC6.

UniProtKB/Swiss-Prot Summary for HERC5 Gene

  • Major E3 ligase for ISG15 conjugation. Acts as a positive regulator of innate antiviral response in cells induced by interferon. Functions as part of the ISGylation machinery that recognizes target proteins in a broad and relatively non-specific manner. Catalyzes ISGylation of IRF3 which results in sustained activation, it attenuates IRF3-PIN1 interaction, which antagonizes IRF3 ubiquitination and degradation, and boosts the antiviral response. Catalyzes ISGylation of influenza A viral NS1 which attenuates virulence; ISGylated NS1 fails to form homodimers and thus to interact with its RNA targets. Catalyzes ISGylation of papillomavirus type 16 L1 protein which results in dominant-negative effect on virus infectivity. Physically associated with polyribosomes, broadly modifies newly synthesized proteins in a cotranslational manner. In an interferon-stimulated cell, newly translated viral proteins are primary targets of ISG15.

Gene Wiki entry for HERC5 Gene

Additional gene information for HERC5 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HERC5 Gene

Genomics for HERC5 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for HERC5 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH04J088455 Promoter/Enhancer 2.2 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 252.6 +0.7 666 3.9 ZBTB10 FEZF1 NR2C1 IKZF1 ZNF217 CTCF ZEB1 ZIC2 HOMEZ ZNF610 HERC5 HSALNG0035759 lnc-PYURF-3 HERC6 ENSG00000270720 LOC102723458 PIGY PYURF
GH04J088381 Enhancer 0.8 FANTOM5 ENCODE 13.2 -74.4 -74361 2.3 SP1 ZNF316 ELF1 IKZF1 ATF2 POLR2A MAFK IKZF2 ZNF687 MTA2 HERC6 HERC5 HSALNG0035755 piR-43325-067
GH04J088212 Enhancer 0.7 Ensembl ENCODE 4.9 -244.3 -244303 1 CTCF RAD51 REST TRIM22 SMC3 RAD21 DMAP1 RB1 MEIS2 ARID2 HERC5 RF00619-030 RNU6ATAC31P ENSG00000251285 lnc-PPM1K-2 ABCG2 PKD2
GH04J088791 Enhancer 1.2 FANTOM5 Ensembl ENCODE dbSUPER 1.8 +336.4 336396 3.2 BCL11A CTCF BATF IKZF1 RAD21 NR2F1 SP7 ZNF217 ATF7 HLF FAM13A-AS1 NAP1L5 FAM13A HERC6 HERC5 lnc-NAP1L5-3 piR-31937-158 TIGD2
GH04J088482 Enhancer 0.2 Ensembl 12 +25.8 25797 0.8 HERC5 HERC6 PPM1K PPM1K-DT RNU6-818P lnc-PYURF-1 RF01061-130 PIGY PYURF
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HERC5 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HERC5

Top Transcription factor binding sites by QIAGEN in the HERC5 gene promoter:
  • CUTL1
  • FOXD3
  • FOXO3
  • FOXO3a
  • FOXO3b
  • Gfi-1
  • HNF-3beta
  • NF-kappaB
  • NF-kappaB1

Genomic Locations for HERC5 Gene

Latest Assembly
chr4:88,456,604-88,506,170
(GRCh38/hg38)
Size:
49,567 bases
Orientation:
Plus strand

Previous Assembly
chr4:89,378,270-89,427,314
(GRCh37/hg19 by Entrez Gene)
Size:
49,045 bases
Orientation:
Plus strand

chr4:89,378,268-89,427,314
(GRCh37/hg19 by Ensembl)
Size:
49,047 bases
Orientation:
Plus strand

Genomic View for HERC5 Gene

Genes around HERC5 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HERC5 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HERC5 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for HERC5 Gene

Proteins for HERC5 Gene

Products:

  1. Antibodies for research
  2. Protein products for research
  3. Assay products for research

  • Protein details for HERC5 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UII4-HERC5_HUMAN
    Recommended name:
    E3 ISG15--protein ligase HERC5
    Protein Accession:
    Q9UII4
    Secondary Accessions:
    • B2RTQ1
    • Q69G20

    Protein attributes for HERC5 Gene

    Size:
    1024 amino acids
    Molecular mass:
    116852 Da
    Quaternary structure:
    • Binds to CCNA1, CCNB1, CCND1 and CCNE1. Interacts with UBE2L6. Interacts with IRF3, this interaction is marginal in resting cells but enhanced upon viral infection. Interacts with influenza A virus NS1.

neXtProt entry for HERC5 Gene

Protein Expression for HERC5 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Selected DME Specific Peptides for HERC5 Gene

Q9UII4:
  • GQLGHNST
  • YHSLALSK

Post-translational modifications for HERC5 Gene

Other Protein References for HERC5 Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for HERC5 Gene

Gene Families for HERC5 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted membrane proteins

Protein Domains for HERC5 Gene

InterPro:
Blocks:
  • HECT domain (Ubiquitin-protein ligase)
  • Regulator of chromosome condensation, RCC1
ProtoNet:

Suggested Antigen Peptide Sequences for HERC5 Gene

GenScript: Design optimal peptide antigens:
  • HECT domain and RCC1-like domain-containing protein 5 (HERC5_HUMAN)
genes like me logo Genes that share domains with HERC5: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for HERC5 Gene

Function for HERC5 Gene

Products:

  1. Animal Models for research
  2. CRISPR products for research
  3. miRNA products for research
  4. Inhibitory RNAs for research
  5. Clone products for research
  6. Cell Lines for research

Molecular function for HERC5 Gene

UniProtKB/Swiss-Prot Function:
Major E3 ligase for ISG15 conjugation. Acts as a positive regulator of innate antiviral response in cells induced by interferon. Functions as part of the ISGylation machinery that recognizes target proteins in a broad and relatively non-specific manner. Catalyzes ISGylation of IRF3 which results in sustained activation, it attenuates IRF3-PIN1 interaction, which antagonizes IRF3 ubiquitination and degradation, and boosts the antiviral response. Catalyzes ISGylation of influenza A viral NS1 which attenuates virulence; ISGylated NS1 fails to form homodimers and thus to interact with its RNA targets. Catalyzes ISGylation of papillomavirus type 16 L1 protein which results in dominant-negative effect on virus infectivity. Physically associated with polyribosomes, broadly modifies newly synthesized proteins in a cotranslational manner. In an interferon-stimulated cell, newly translated viral proteins are primary targets of ISG15.
UniProtKB/Swiss-Prot Induction:
By IFNB1/IFN-beta. In endothelial cells, by TNF, IL1B/interleukin-1B and by bacterial lipopolysaccharides (LPS), hardly induced in other cells of the vascular wall such as primary smooth muscle cells and fibroblasts. By viral infection.

Enzyme Numbers (IUBMB) for HERC5 Gene

Phenotypes From GWAS Catalog for HERC5 Gene

Gene Ontology (GO) - Molecular Function for HERC5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003723 RNA binding HDA 22658674
GO:0004842 ubiquitin-protein transferase activity IEA,TAS --
GO:0005515 protein binding IPI 20133869
GO:0016740 transferase activity IEA --
GO:0042296 ISG15 transferase activity IDA 20308324
genes like me logo Genes that share ontologies with HERC5: view
genes like me logo Genes that share phenotypes with HERC5: view

Animal Models for research

miRNA for HERC5 Gene

miRTarBase miRNAs that target HERC5

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HERC5

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for HERC5 Gene

Localization for HERC5 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HERC5 Gene

Cytoplasm, perinuclear region. Note=Associated with the polyribosomes, probably via the 60S subunit.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HERC5 gene
Compartment Confidence
cytosol 5
nucleus 4
extracellular 2
plasma membrane 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for HERC5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 10581175
GO:0005829 cytosol TAS --
GO:0048471 perinuclear region of cytoplasm IEA --
genes like me logo Genes that share ontologies with HERC5: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for HERC5 Gene

Pathways & Interactions for HERC5 Gene

genes like me logo Genes that share pathways with HERC5: view

Gene Ontology (GO) - Biological Process for HERC5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000079 regulation of cyclin-dependent protein serine/threonine kinase activity TAS 10581175
GO:0000209 protein polyubiquitination TAS --
GO:0002376 immune system process IEA --
GO:0016567 protein ubiquitination IEA,IDA 15331633
GO:0018215 protein phosphopantetheinylation IEA --
genes like me logo Genes that share ontologies with HERC5: view

No data available for SIGNOR curated interactions for HERC5 Gene

Drugs & Compounds for HERC5 Gene

Products:

  1. Drug products for research
No Compound Related Data Available

Transcripts for HERC5 Gene

Products:

  1. CRISPR products for research
  2. miRNA products for research
  3. Inhibitory RNAs for research
  4. Clone products for research

mRNA/cDNA for HERC5 Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HERC5

Alternative Splicing Database (ASD) splice patterns (SP) for HERC5 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^ 24a ·
SP1: - - -
SP2:
SP3: - -
SP4: -
SP5:

ExUns: 24b ^ 25 ^ 26
SP1:
SP2:
SP3:
SP4:
SP5:

Relevant External Links for HERC5 Gene

GeneLoc Exon Structure for
HERC5

Expression for HERC5 Gene

Products:

  1. Primer products for research
  2. Gene Expression Assays for research

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HERC5 Gene

mRNA expression in normal human tissues for HERC5 Gene
mRNA expression by BioGPS for HERC5 GenemRNA expression by GTEx for HERC5 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HERC5 Gene

This gene is overexpressed in Testis (x7.8).

Protein differential expression in normal tissues from HIPED for HERC5 Gene

This gene is overexpressed in Fetal ovary (28.0), Ovary (20.2), and Testis (18.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for HERC5 Gene



Protein tissue co-expression partners for HERC5 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HERC5

SOURCE GeneReport for Unigene cluster for HERC5 Gene:

Hs.26663

mRNA Expression by UniProt/SwissProt for HERC5 Gene:

Q9UII4-HERC5_HUMAN
Tissue specificity: Expressed in testis and to a lesser degree in brain, ovary and placenta. Found in most tissues at low levels.

Evidence on tissue expression from TISSUES for HERC5 Gene

  • Nervous system(4.4)
  • Blood(2)
genes like me logo Genes that share expression patterns with HERC5: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for HERC5 Gene

Orthologs for HERC5 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for HERC5 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia HERC5 30 31
  • 96.21 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia HERC5 30 31
  • 84.79 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia HERC5 30 31
  • 80.8 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia HERC5 31
  • 32 (a)
 OneToOne
Zebrafish
(Danio rerio)
 Actinopterygii HERC5 (4 of 4) 31
  • 32 (a)
 OneToMany
HERC5 (3 of 4) 31
  • 32 (a)
 OneToMany
HERC5 (1 of 4) 31
  • 31 (a)
 OneToMany
HERC5 (2 of 4) 31
  • 30 (a)
 OneToMany
Fruit Fly
(Drosophila melanogaster)
 Insecta CG6678 31
  • 19 (a)
 OneToMany
Worm
(Caenorhabditis elegans)
 Secernentea K11D2.1 31
  • 21 (a)
 OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes ATS1 33
Sea Squirt
(Ciona savignyi)
 Ascidiacea -- 31
  • 25 (a)
 OneToMany
Species where no ortholog for HERC5 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Mouse (Mus musculus)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)

Evolution for HERC5 Gene

ENSEMBL:
Gene Tree for HERC5 (if available)
TreeFam:
Gene Tree for HERC5 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HERC5: view image

Paralogs for HERC5 Gene

Paralogs for HERC5 Gene

(6) SIMAP similar genes for HERC5 Gene using alignment to 2 proteins:

  • HERC5_HUMAN
  • E9PBL0_HUMAN
genes like me logo Genes that share paralogs with HERC5: view

Variants for HERC5 Gene

Products:

  1. SNP Genotyping and Copy Number Assays for research

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HERC5 Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
rs17014143 Benign: not provided. - 88,463,975(+) G/Ap.Ala301Thr
NM_016323.4(HERC5):c.901G>A (p.Ala301Thr) 		MISSENSE
rs78393149 Benign: not provided 88,469,243(+) G/A
NM_016323.4(HERC5):c.1221G>A (p.Arg407=) 		SYNONYMOUS
rs78613619 Benign: not provided 88,463,979(+) G/C
NM_016323.4(HERC5):c.905G>C (p.Cys302Ser) 		MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for HERC5 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for HERC5 Gene

Variant ID Type Subtype PubMed ID
nsv1112857 CNV deletion 24896259

Variation tolerance for HERC5 Gene

Residual Variation Intolerance Score: 20.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.31; 62.96% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HERC5 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
HERC5

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HERC5 Gene

Disorders for HERC5 Gene

MalaCards: The human disease database

(1) MalaCards diseases for HERC5 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
influenza
  • flu
- elite association - COSMIC cancer census association via MalaCards
Search HERC5 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HERC5

Genetic Association Database
(GAD)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with HERC5: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HERC5 Gene

Publications for HERC5 Gene

  1. HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates type I IFN-induced ISGylation of protein targets. (PMID: 16815975) Wong JJ … Chin KC (Proceedings of the National Academy of Sciences of the United States of America 2006) 3 4 23
  2. HERC5, a HECT E3 ubiquitin ligase tightly regulated in LPS activated endothelial cells. (PMID: 15331633) Kroismayr R … Lipp J (Journal of cell science 2004) 3 4 23
  3. A novel human gene encoding HECT domain and RCC1-like repeats interacts with cyclins and is potentially regulated by the tumor suppressor proteins. (PMID: 10581175) Mitsui K … Ohtsubo M (Biochemical and biophysical research communications 1999) 2 3 4
  4. Genome-wide association study of lung function decline in adults with and without asthma. (PMID: 22424883) Imboden M … Probst-Hensch NM (The Journal of allergy and clinical immunology 2012) 3 41
  5. Positive regulation of interferon regulatory factor 3 activation by Herc5 via ISG15 modification. (PMID: 20308324) Shi HX … Wang C (Molecular and cellular biology 2010) 3 4

ExternalLinks

View latest publications for HERC5 gene in Mastermind

Products for HERC5 Gene

Sources for HERC5 Gene