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Aliases for HERC2 Gene

Aliases for HERC2 Gene

  • HECT And RLD Domain Containing E3 Ubiquitin Protein Ligase 2 2 3
  • Hect Domain And RLD 2 2 3
  • MRT38 3 6
  • SHEP1 3 6
  • Hect Domain And RCC1-Like Domain-Containing Protein 2 3
  • HECT Domain And RCC1-Like Domain-Containing Protein 2 4
  • Probable E3 Ubiquitin-Protein Ligase HERC2 3
  • E3 Ubiquitin-Protein Ligase HERC2 3
  • EC 6.3.2.- 4
  • D15F37S1 3
  • EC 6.3.2 63
  • Jdf2 3
  • P528 3

External Ids for HERC2 Gene

Summaries for HERC2 Gene

Entrez Gene Summary for HERC2 Gene

  • This gene belongs to the HERC gene family that encodes a group of unusually large proteins, which contain multiple structural domains. All members have at least 1 copy of an N-terminal region showing homology to the cell cycle regulator RCC1 and a C-terminal HECT (homologous to E6-AP C terminus) domain found in a number of E3 ubiquitin protein ligases. Genetic variations in this gene are associated with skin/hair/eye pigmentation variability. Multiple pseudogenes of this gene are located on chromosomes 15 and 16. [provided by RefSeq, Mar 2012]

GeneCards Summary for HERC2 Gene

HERC2 (HECT And RLD Domain Containing E3 Ubiquitin Protein Ligase 2) is a Protein Coding gene. Diseases associated with HERC2 include mental retardation, autosomal recessive 38 and developmental delay with autism spectrum disorder and gait instability. Among its related pathways are Class I MHC mediated antigen processing and presentation and Class I MHC mediated antigen processing and presentation. GO annotations related to this gene include ubiquitin-protein transferase activity and heme binding. An important paralog of this gene is HACE1.

UniProtKB/Swiss-Prot for HERC2 Gene

  • E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. Recruited to sites of DNA damage in response to ionizing radiation (IR) and facilitates the assembly of UBE2N and RNF8 promoting DNA damage-induced formation of Lys-63-linked ubiquitin chains. Acts as a mediator of binding specificity between UBE2N and RNF8. Involved in the maintenance of RNF168 levels. E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of XPA which influences the circadian oscillation of DNA excision repair activity.

Gene Wiki entry for HERC2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HERC2 Gene

Genomics for HERC2 Gene

Genomic Location for HERC2 Gene

Start:
28,111,037 bp from pter
End:
28,322,167 bp from pter
Size:
211,131 bases
Orientation:
Minus strand

Genomic View for HERC2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for HERC2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HERC2 Gene

Regulatory Elements for HERC2 Gene

Proteins for HERC2 Gene

  • Protein details for HERC2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95714-HERC2_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase HERC2
    Protein Accession:
    O95714
    Secondary Accessions:
    • Q86SV7
    • Q86SV8
    • Q86SV9
    • Q86YY3
    • Q86YY4
    • Q86YY5
    • Q86YY6
    • Q86YY7
    • Q86YY8
    • Q86YY9
    • Q86YZ0
    • Q86YZ1

    Protein attributes for HERC2 Gene

    Size:
    4834 amino acids
    Molecular mass:
    527228 Da
    Quaternary structure:
    • Interacts (when phosphorylated at Thr-4827 and sumoylated) with RNF8 (via FHA domain); this interaction increases after ionizing radiation (IR) treatment. Interacts with XPA. Interacts with NEURL4. Via its interaction with NEURL4, may indirectly interact with CCP110 and CEP97.
    Miscellaneous:
    • A regulatory element withinin an intron of the HERC2 gene inhibits OCA2 promoter. There are several single nucleotide polymorphisms within the OCA2 gene and within the HERC2 gene that have a statistical association with human eye color

    Three dimensional structures from OCA and Proteopedia for HERC2 Gene

neXtProt entry for HERC2 Gene

Proteomics data for HERC2 Gene at MOPED

Selected DME Specific Peptides for HERC2 Gene

Post-translational modifications for HERC2 Gene

  • Phosphorylation at Thr-4827 is required for interaction with RNF8.
  • Sumoylated with SUMO1 by PIAS4 in response to double-strand breaks (DSBs), promoting the interaction with RNF8.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys20, Lys95, Lys105, Lys990, Lys2657, Lys3690, Lys3780, and Lys3839

Other Protein References for HERC2 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for HERC2 Gene

Suggested Antigen Peptide Sequences for HERC2 Gene

Graphical View of Domain Structure for InterPro Entry

O95714

UniProtKB/Swiss-Prot:

HERC2_HUMAN
Domain:
  • The ZZ-type zinc finger mediates binding to SUMO1, and at lowe level SUMO2.:
    • O95714
  • The RCC1 repeats are grouped into three seven-bladed beta-propeller regions.:
    • O95714
  • Contains 1 cytochrome b5 heme-binding domain.:
    • O95714
  • Contains 1 DOC domain.:
    • O95714
  • Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.:
    • O95714
  • Contains 1 MIB/HERC2 domain.:
    • O95714
Similarity:
  • Contains 21 RCC1 repeats.:
    • O95714
  • Contains 1 ZZ-type zinc finger.:
    • O95714
genes like me logo Genes that share domains with HERC2: view

No data available for Gene Families for HERC2 Gene

Function for HERC2 Gene

Molecular function for HERC2 Gene

GENATLAS Biochemistry: HECT domain and RLD2,ancestral gene of a superfamily of low-copy repeat sequences in the PWCR/ANCR breakpoint cluster region
UniProtKB/Swiss-Prot Function: E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. Recruited to sites of DNA damage in response to ionizing radiation (IR) and facilitates the assembly of UBE2N and RNF8 promoting DNA damage-induced formation of Lys-63-linked ubiquitin chains. Acts as a mediator of binding specificity between UBE2N and RNF8. Involved in the maintenance of RNF168 levels. E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of XPA which influences the circadian oscillation of DNA excision repair activity.

Enzyme Numbers (IUBMB) for HERC2 Gene

Gene Ontology (GO) - Molecular Function for HERC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity IDA 20304803
GO:0005085 guanyl-nucleotide exchange factor activity NAS 9949213
GO:0005515 protein binding IPI 20023648
GO:0008270 zinc ion binding IEA --
GO:0016874 ligase activity IEA --
genes like me logo Genes that share ontologies with HERC2: view
genes like me logo Genes that share phenotypes with HERC2: view

miRNA for HERC2 Gene

No data available for Animal Models , Transcription Factor Targeting and HOMER Transcription for HERC2 Gene

Localization for HERC2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HERC2 Gene

Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole. Nucleus. Note=Recruited to sites of DNA damage in response to ionizing radiation (IR) via its interaction with RNF8. May loose association with centrosomes during mitosis.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for HERC2 Gene COMPARTMENTS Subcellular localization image for HERC2 gene
Compartment Confidence
cytoskeleton 5
nucleus 5
cytosol 3
mitochondrion 2

Gene Ontology (GO) - Cellular Components for HERC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 20304803
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IDA 20304803
GO:0005743 mitochondrial inner membrane IEA --
GO:0005814 centriole IEA --
genes like me logo Genes that share ontologies with HERC2: view

Pathways for HERC2 Gene

genes like me logo Genes that share pathways with HERC2: view

UniProtKB/Swiss-Prot O95714-HERC2_HUMAN

  • Pathway: Protein modification; protein ubiquitination

Gene Ontology (GO) - Biological Process for HERC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006281 DNA repair IDA 20023648
GO:0006886 intracellular protein transport NAS 9949213
GO:0006974 cellular response to DNA damage stimulus IDA 22508508
GO:0007283 spermatogenesis IEA --
GO:0016567 protein ubiquitination IDA 20304803
genes like me logo Genes that share ontologies with HERC2: view

Compounds for HERC2 Gene

(5) HMDB Compounds for HERC2 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine monophosphate
  • 5'-AMP
61-19-8
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
Heme
  • (protoporphyrinato)iron
14875-96-8
Phosphoric acid
  • acide phosphorique (FRENCH)
7664-38-2
Pyrophosphate
  • (4-)Diphosphoric acid ion
14000-31-8
genes like me logo Genes that share compounds with HERC2: view

Transcripts for HERC2 Gene

Alternative Splicing Database (ASD) splice patterns (SP) for HERC2 Gene

ExUns: 1a · 1b ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7
SP1: -
SP2:

Relevant External Links for HERC2 Gene

GeneLoc Exon Structure for
HERC2
ECgene alternative splicing isoforms for
HERC2

Expression for HERC2 Gene

mRNA expression in normal human tissues for HERC2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for HERC2 Gene

SOURCE GeneReport for Unigene cluster for HERC2 Gene Hs.434890

genes like me logo Genes that share expressions with HERC2: view

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for HERC2 Gene

Orthologs for HERC2 Gene

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

Orthologs for HERC2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia HERC2 36
  • 100 (a)
OneToOne
LOC453257 35
  • 97.6 (n)
  • 97.53 (a)
cow
(Bos Taurus)
Mammalia HERC2 35
  • 88.86 (n)
  • 95.88 (a)
HERC2 36
  • 96 (a)
OneToOne
dog
(Canis familiaris)
Mammalia HERC2 35
  • 89.73 (n)
  • 96.67 (a)
HERC2 36
  • 97 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Herc2 35
  • 87.33 (n)
  • 95.61 (a)
Herc2 16
Herc2 36
  • 96 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia HERC2 36
  • 90 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia HERC2 36
  • 92 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Herc2 35
  • 87.31 (n)
  • 95.74 (a)
chicken
(Gallus gallus)
Aves HERC2 35
  • 78.92 (n)
  • 91.54 (a)
HERC2 36
  • 91 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia HERC2 36
  • 91 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia herc2 35
  • 75.21 (n)
  • 87.21 (a)
zebrafish
(Danio rerio)
Actinopterygii herc2 35
  • 74.41 (n)
  • 85.32 (a)
herc2 36
  • 83 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP011823 35
  • 32 (n)
  • 17.07 (a)
fruit fly
(Drosophila melanogaster)
Insecta HERC2 35
  • 52.46 (n)
  • 48.33 (a)
HERC2 36
  • 44 (a)
OneToMany
HERC2 37
  • 68 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SAF1 38
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.11556 35
Species with no ortholog for HERC2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • 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)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • 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)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for HERC2 Gene

ENSEMBL:
Gene Tree for HERC2 (if available)
TreeFam:
Gene Tree for HERC2 (if available)

Paralogs for HERC2 Gene

Paralogs for HERC2 Gene

genes like me logo Genes that share paralogs with HERC2: view

Variants for HERC2 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for HERC2 Gene

O95714-HERC2_HUMAN
Genetic variants in HERC2 define the skin/hair/eye pigmentation variation locus 1 (SHEP1) [MIM:227220]; also known as skin/hair/eye pigmentation type 1, blue/nonblue eyes or skin/hair/eye pigmentation type 1, blue/brown eyes or skin/hair/eye pigmentation type 1, blond/brown hair or eye color, brown/blue or eye color, blue/nonblue or eye color type 3 (EYCL3) or brown eye color type 2 (BEY2) or hair color type 3 (HCL3). Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair

Sequence variations from dbSNP and Humsavar for HERC2 Gene

SNP ID Clin Chr 15 pos Sequence Context AA Info Type MAF
rs415423 -- 28,205,502(+) TAGGA(C/T)TGGGG intron-variant
rs916976 -- 28,268,367(-) TCCAA(C/T)TGCCC intron-variant
rs916977 -- 28,268,218(-) CTTCT(A/G)TCTAC intron-variant
rs1129038 -- 28,111,713(-) AGAGC(A/G)CTCGC utr-variant-3-prime
rs1133496 -- 28,144,734(-) ATCAG(C/T)GATGG reference, synonymous-codon

Structural Variations from Database of Genomic Variants (DGV) for HERC2 Gene

Variant ID Type Subtype PubMed ID
nsv428299 CNV Loss 18775914
dgv2287n71 CNV Loss 21882294
nsv903737 CNV Gain 21882294
essv14482 CNV CNV 17122850
dgv712e1 CNV Complex 17122850
dgv713e1 CNV Complex 17122850
esv2674813 CNV Deletion 23128226
esv2475219 CNV Insertion 19546169
nsv903738 CNV Gain 21882294
nsv469883 CNV Gain 16826518
esv28855 CNV Gain 19812545
nsv9205 CNV Gain+Loss 18304495
esv2749504 CNV Deletion 23290073
esv2749505 CNV Deletion 23290073
nsv903739 CNV Gain 21882294
nsv9206 CNV Loss 18304495
nsv9207 CNV Gain 18304495
nsv9208 CNV Gain+Loss 18304495
esv22824 CNV Gain+Loss 19812545
nsv433431 CNV Gain 18776910
nsv903743 CNV Gain 21882294

Relevant External Links for HERC2 Gene

HapMap Linkage Disequilibrium report
HERC2
Human Gene Mutation Database (HGMD)
HERC2

Disorders for HERC2 Gene

(2) OMIM Diseases for HERC2 Gene (605837)

UniProtKB/Swiss-Prot

HERC2_HUMAN
  • Mental retardation, autosomal recessive 38 (MRT38) [MIM:615516]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT38 is characterized by global developmental delay affecting motor, speech, adaptive, and social development. Patients manifest autistic features, aggression, self-injury, impulsivity, and distractibility. {ECO:0000269 PubMed:23065719}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(1) University of Copenhagen DISEASES for HERC2 Gene

Relevant External Links for HERC2

Genetic Association Database (GAD)
HERC2
Human Genome Epidemiology (HuGE) Navigator
HERC2
genes like me logo Genes that share disorders with HERC2: view

Publications for HERC2 Gene

  1. The ancestral gene for transcribed, low-copy repeats in the Prader- Willi/Angelman region encodes a large protein implicated in protein trafficking, which is deficient in mice with neuromuscular and spermiogenic abnormalities. (PMID: 9949213) Ji Y. … Nicholls R.D. (Hum. Mol. Genet. 1999) 2 3 4
  2. Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene. (PMID: 18252221) Kayser M. … van Duijn C.M. (Am. J. Hum. Genet. 2008) 3 4 48
  3. A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. (PMID: 18252222) Sturm R.A. … Montgomery G.W. (Am. J. Hum. Genet. 2008) 3 4
  4. Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis. (PMID: 18438405) Franke A. … Schreiber S. (Nat. Genet. 2008) 3 48
  5. A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation. (PMID: 18483556) Han J. … Hunter D.J. (PLoS Genet. 2008) 3 48

Products for HERC2 Gene

Sources for HERC2 Gene

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