ID:HERC2_HUMAN DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase HERC2; EC=6.3.2.-; AltName: Full=HECT domain and RCC1-like domain-containing protein 2; 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. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: 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. SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton, 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. DOMAIN: The ZZ-type zinc finger mediates binding to SUMO1, and at lowe level SUMO2. PTM: Phosphorylation at Thr-4827 is required for interaction with RNF8. PTM: Sumoylated with SUMO1 by PIAS4 in response to double-strand breaks (DSBs), promoting the interaction with RNF8. POLYMORPHISM: 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. 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. SIMILARITY: Contains 1 cytochrome b5 heme-binding domain. SIMILARITY: Contains 1 DOC domain. SIMILARITY: Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain. SIMILARITY: Contains 1 MIB/HERC2 domain. SIMILARITY: Contains 19 RCC1 repeats. SIMILARITY: Contains 6 WD repeats. SIMILARITY: Contains 1 ZZ-type zinc finger.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O95714
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006281 DNA repair GO:0006303 double-strand break repair via nonhomologous end joining GO:0006886 intracellular protein transport GO:0006974 cellular response to DNA damage stimulus GO:0007283 spermatogenesis GO:0016567 protein ubiquitination GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
AF071172 - Homo sapiens HERC2 (HERC2) mRNA, complete cds. BC172911 - Synthetic construct Homo sapiens clone IMAGE:9094487 hect domain and RLD 2 (HERC2) gene, partial cds. BC148318 - Homo sapiens hect domain and RLD 2, mRNA (cDNA clone IMAGE:40121629), partial cds. AK122977 - Homo sapiens cDNA FLJ16724 fis, clone UTERU3004938, highly similar to Homo sapiens HERC2 (HERC2) mRNA. JD090071 - Sequence 71095 from Patent EP1572962. JD379231 - Sequence 360255 from Patent EP1572962. AL834183 - Homo sapiens mRNA; cDNA DKFZp547P028 (from clone DKFZp547P028). JD339384 - Sequence 320408 from Patent EP1572962. JD362222 - Sequence 343246 from Patent EP1572962. JD340320 - Sequence 321344 from Patent EP1572962. JD471493 - Sequence 452517 from Patent EP1572962. JD408170 - Sequence 389194 from Patent EP1572962. JD211350 - Sequence 192374 from Patent EP1572962. JD532155 - Sequence 513179 from Patent EP1572962. JD214216 - Sequence 195240 from Patent EP1572962. AK125229 - Homo sapiens cDNA FLJ43239 fis, clone HCHON2008112. DQ570449 - Homo sapiens piRNA piR-30561, complete sequence. JD036014 - Sequence 17038 from Patent EP1572962. JD020125 - Sequence 1149 from Patent EP1572962. JD454370 - Sequence 435394 from Patent EP1572962. JD434589 - Sequence 415613 from Patent EP1572962. JD288380 - Sequence 269404 from Patent EP1572962. JD253033 - Sequence 234057 from Patent EP1572962. JD265220 - Sequence 246244 from Patent EP1572962. JD527839 - Sequence 508863 from Patent EP1572962. JD546184 - Sequence 527208 from Patent EP1572962. JD081445 - Sequence 62469 from Patent EP1572962. BC172191 - Synthetic construct Homo sapiens clone IMAGE:9094352 hect domain and RLD 2 (HERC2) gene, partial cds. JD040201 - Sequence 21225 from Patent EP1572962. JD379299 - Sequence 360323 from Patent EP1572962. JD377863 - Sequence 358887 from Patent EP1572962. JD447635 - Sequence 428659 from Patent EP1572962. JD331985 - Sequence 313009 from Patent EP1572962. DQ593342 - Homo sapiens piRNA piR-33454, complete sequence. JD274150 - Sequence 255174 from Patent EP1572962. JD200805 - Sequence 181829 from Patent EP1572962. JD348603 - Sequence 329627 from Patent EP1572962. JD147786 - Sequence 128810 from Patent EP1572962. JD507662 - Sequence 488686 from Patent EP1572962. JD551484 - Sequence 532508 from Patent EP1572962. JD241783 - Sequence 222807 from Patent EP1572962. JD506365 - Sequence 487389 from Patent EP1572962. JD561702 - Sequence 542726 from Patent EP1572962. JD332076 - Sequence 313100 from Patent EP1572962. JD152576 - Sequence 133600 from Patent EP1572962. JD288164 - Sequence 269188 from Patent EP1572962. JD054143 - Sequence 35167 from Patent EP1572962. JD054142 - Sequence 35166 from Patent EP1572962. JD181710 - Sequence 162734 from Patent EP1572962. BC045544 - Homo sapiens hect domain and RLD 2, mRNA (cDNA clone IMAGE:5262032). BC142951 - Homo sapiens cDNA clone IMAGE:8860337, containing frame-shift errors. DQ584039 - Homo sapiens piRNA piR-51151, complete sequence. BC015486 - Homo sapiens, clone IMAGE:3886999, mRNA. JD523267 - Sequence 504291 from Patent EP1572962. JD539869 - Sequence 520893 from Patent EP1572962. JD441614 - Sequence 422638 from Patent EP1572962. JD420809 - Sequence 401833 from Patent EP1572962. JD400455 - Sequence 381479 from Patent EP1572962. JD193636 - Sequence 174660 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein O95714 (Reactome details) participates in the following event(s):
R-HSA-4551724 PIAS4 SUMOylates HERC2 with SUMO1 R-HSA-5682586 HERC2 and PIAS4 are recruited to DNA DSBs R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex R-HSA-983147 Release of E3 from polyubiquitinated substrate R-HSA-5682598 ATM phosphorylates HERC2 R-HSA-5682607 PIAS4 SUMOylates HERC2 with SUMO1 at DNA DSBs R-HSA-5684071 RNF4 ubiquitinates MDC1 R-HSA-5693599 Association of Ku heterodimer with ends of DNA double-strand break R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2 R-HSA-5682629 HERC2 facilitates UBE2N:UBE2V2 binding to RNF8 R-HSA-5682863 RNF168 binds DNA DSBs R-HSA-5683077 RNF8 and RNF168 ubiquitinate KDM4A,B R-HSA-5682858 RNF8 and RNF168 ubiquitinate H2AFX R-HSA-5693566 TP53BP1 associates with H4K20Me2 at DNA DSBs R-HSA-5683384 UIMC1 and FAM175A bind DNA DSBs R-HSA-5683405 PPP5C dephosphorylates TP53BP1 R-HSA-5683425 ATM phosphorylates TP53BP1 at DNA DSBs R-HSA-5693551 Phosphorylation of BRCA1-A complex at multiple sites by ATM R-HSA-5683385 Formation of BRCA1-A complex at DNA DSBs R-HSA-5683735 CHEK2 is recruited to DNA DSBs R-HSA-5683801 CHEK2 phosphorylates BRCA1 R-HSA-69891 Phosphorylation and activation of CHEK2 by ATM R-HSA-5684052 PIAS4 SUMOylates MDC1 R-HSA-5686685 RIF1 and PAX1IP bind TP53BP1 at DNA DSBs R-HSA-5686900 TP53BP1 recruits DCLRE1C to ATM R-HSA-5686704 Activated ATM phosphorylates DCLRE1C R-HSA-3108214 SUMOylation of DNA damage response and repair proteins R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation R-HSA-3108232 SUMO E3 ligases SUMOylate target proteins R-HSA-5693606 DNA Double Strand Break Response R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-5693571 Nonhomologous End-Joining (NHEJ) R-HSA-983169 Class I MHC mediated antigen processing & presentation R-HSA-2990846 SUMOylation R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-1280218 Adaptive Immune System R-HSA-597592 Post-translational protein modification R-HSA-73894 DNA Repair R-HSA-5693538 Homology Directed Repair R-HSA-168256 Immune System R-HSA-392499 Metabolism of proteins R-HSA-69473 G2/M DNA damage checkpoint R-HSA-69481 G2/M Checkpoints R-HSA-69620 Cell Cycle Checkpoints R-HSA-1640170 Cell Cycle
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
