UniProtKB - O95714 (HERC2_HUMAN)
Protein
E3 ubiquitin-protein ligase HERC2
Gene
HERC2
Organism
Homo sapiens (Human)
Status
Functioni
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. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333).4 Publications
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.
Catalytic activityi
- S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.1 Publication EC:2.3.2.26
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 4762 | Glycyl thioester intermediatePROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 2702 – 2749 | ZZ-typePROSITE-ProRule annotationAdd BLAST | 48 |
GO - Molecular functioni
- guanyl-nucleotide exchange factor activity Source: UniProtKB
- SUMO binding Source: UniProtKB
- ubiquitin protein ligase activity Source: UniProtKB
- ubiquitin protein ligase binding Source: UniProtKB
- zinc ion binding Source: InterPro
GO - Biological processi
- cellular response to DNA damage stimulus Source: UniProtKB
- double-strand break repair via nonhomologous end joining Source: Reactome
- intracellular protein transport Source: UniProtKB
- proteasome-mediated ubiquitin-dependent protein catabolic process Source: Ensembl
- protein ubiquitination Source: UniProtKB
- spermatogenesis Source: Ensembl
Keywordsi
Molecular function | Transferase |
Biological process | DNA damage, DNA repair, Ubl conjugation pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | O95714 |
Reactomei | 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-5693571, Nonhomologous End-Joining (NHEJ) R-HSA-5693607, Processing of DNA double-strand break ends R-HSA-69473, G2/M DNA damage checkpoint R-HSA-983168, Antigen processing: Ubiquitination & Proteasome degradation |
SIGNORi | O95714 |
UniPathwayi | UPA00143 |
Names & Taxonomyi
Protein namesi | Recommended name: E3 ubiquitin-protein ligase HERC2 (EC:2.3.2.261 Publication)Alternative name(s): HECT domain and RCC1-like domain-containing protein 2 HECT-type E3 ubiquitin transferase HERC2 |
Gene namesi | Name:HERC2Imported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000128731.15 |
HGNCi | HGNC:4868, HERC2 |
MIMi | 605837, gene |
neXtProti | NX_O95714 |
Subcellular locationi
Cytoskeleton
- centriole Source: UniProtKB-SubCell
Cytosol
- cytosol Source: HPA
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: HPA
Other locations
Keywords - Cellular componenti
Cytoplasm, Cytoskeleton, NucleusPathology & Biotechi
Involvement in diseasei
Mental retardation, autosomal recessive 38 (MRT38)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_069282 | 594 | P → L in MRT38; less stable than wild-type; diffuse cytosolic localization with the formation of abnormal aggregates. 1 PublicationCorresponds to variant dbSNP:rs397518474EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 2708 | C → S: Abolishes binding to SUMO; when associated with S-2711. 1 Publication | 1 | |
Mutagenesisi | 2711 | C → S: Abolishes binding to SUMO; when associated with S-2708. 1 Publication | 1 | |
Mutagenesisi | 4827 | T → A: Prevents HERC2 C-terminal fragment binding to endogenous RNF8. 1 Publication | 1 |
Keywords - Diseasei
Disease mutation, Mental retardationOrganism-specific databases
DisGeNETi | 8924 |
GeneReviewsi | HERC2 |
MalaCardsi | HERC2 |
MIMi | 227220, phenotype 615516, phenotype |
OpenTargetsi | ENSG00000128731 |
Orphaneti | 329195, Developmental delay with autism spectrum disorder and gait instability |
PharmGKBi | PA29243 |
Miscellaneous databases
Pharosi | O95714, Tbio |
Polymorphism and mutation databases
BioMutai | HERC2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000229739 | 1 – 4834 | E3 ubiquitin-protein ligase HERC2Add BLAST | 4834 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 272 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 647 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 1577 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1942 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1944 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 2454 | PhosphoserineCombined sources | 1 | |
Modified residuei | 2928 | PhosphoserineCombined sources | 1 | |
Modified residuei | 4810 | PhosphoserineCombined sources | 1 | |
Modified residuei | 4811 | PhosphoserineCombined sources | 1 | |
Modified residuei | 4814 | PhosphoserineCombined sources | 1 | |
Modified residuei | 4827 | Phosphothreonine1 Publication | 1 |
Post-translational modificationi
Phosphorylation at Thr-4827 is required for interaction with RNF8.1 Publication
Sumoylated with SUMO1 by PIAS4 in response to double-strand breaks (DSBs), promoting the interaction with RNF8.1 Publication
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | O95714 |
jPOSTi | O95714 |
MassIVEi | O95714 |
MaxQBi | O95714 |
PaxDbi | O95714 |
PeptideAtlasi | O95714 |
PRIDEi | O95714 |
ProteomicsDBi | 51008 |
PTM databases
GlyConnecti | 1191, 2 N-Linked glycans (2 sites) |
GlyGeni | O95714, 2 sites, 1 N-linked glycan (1 site) |
iPTMneti | O95714 |
PhosphoSitePlusi | O95714 |
Expressioni
Gene expression databases
Bgeei | ENSG00000128731, Expressed in endothelial cell and 231 other tissues |
ExpressionAtlasi | O95714, baseline and differential |
Genevisiblei | O95714, HS |
Organism-specific databases
HPAi | ENSG00000128731, Low tissue specificity |
Interactioni
Subunit structurei
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.
4 PublicationsBinary interactionsi
Hide detailsO95714
With | #Exp. | IntAct |
---|---|---|
UBE3A - isoform I [Q05086-2] | 5 | EBI-1058922,EBI-10175863 |
XPA [P23025] | 4 | EBI-1058922,EBI-295222 |
GO - Molecular functioni
- guanyl-nucleotide exchange factor activity Source: UniProtKB
- SUMO binding Source: UniProtKB
- ubiquitin protein ligase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 114438, 389 interactors |
CORUMi | O95714 |
DIPi | DIP-37632N |
IntActi | O95714, 124 interactors |
MINTi | O95714 |
STRINGi | 9606.ENSP00000261609 |
Miscellaneous databases
RNActi | O95714, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | O95714 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O95714 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 415 – 461 | RCC1 1-1PROSITE-ProRule annotation1 PublicationAdd BLAST | 47 | |
Repeati | 462 – 512 | RCC1 1-2PROSITE-ProRule annotation1 PublicationAdd BLAST | 51 | |
Repeati | 513 – 568 | RCC1 1-3PROSITE-ProRule annotation1 PublicationAdd BLAST | 56 | |
Repeati | 569 – 620 | RCC1 1-4PROSITE-ProRule annotation1 PublicationAdd BLAST | 52 | |
Repeati | 623 – 674 | RCC1 1-5PROSITE-ProRule annotation1 PublicationAdd BLAST | 52 | |
Repeati | 675 – 726 | RCC1 1-6PROSITE-ProRule annotation1 PublicationAdd BLAST | 52 | |
Repeati | 728 – 778 | RCC1 1-7PROSITE-ProRule annotation1 PublicationAdd BLAST | 51 | |
Domaini | 1207 – 1283 | Cytochrome b5 heme-bindingPROSITE-ProRule annotationAdd BLAST | 77 | |
Domaini | 1859 – 1932 | MIB/HERC2PROSITE-ProRule annotationAdd BLAST | 74 | |
Domaini | 2759 – 2936 | DOCPROSITE-ProRule annotationAdd BLAST | 178 | |
Repeati | 2958 – 3009 | RCC1 2-1PROSITE-ProRule annotation1 PublicationAdd BLAST | 52 | |
Repeati | 3010 – 3064 | RCC1 2-2PROSITE-ProRule annotation1 PublicationAdd BLAST | 55 | |
Repeati | 3065 – 3116 | RCC1 2-3PROSITE-ProRule annotation1 PublicationAdd BLAST | 52 | |
Repeati | 3118 – 3168 | RCC1 2-4PROSITE-ProRule annotation1 PublicationAdd BLAST | 51 | |
Repeati | 3171 – 3222 | RCC1 2-5PROSITE-ProRule annotation1 PublicationAdd BLAST | 52 | |
Repeati | 3224 – 3274 | RCC1 2-6PROSITE-ProRule annotation1 PublicationAdd BLAST | 51 | |
Repeati | 3275 – 3326 | RCC1 2-7PROSITE-ProRule annotation1 PublicationAdd BLAST | 52 | |
Repeati | 3951 – 4002 | RCC1 3-1PROSITE-ProRule annotation1 PublicationAdd BLAST | 52 | |
Repeati | 4004 – 4056 | RCC1 3-2PROSITE-ProRule annotation1 PublicationAdd BLAST | 53 | |
Repeati | 4058 – 4108 | RCC1 3-3PROSITE-ProRule annotation1 PublicationAdd BLAST | 51 | |
Repeati | 4110 – 4162 | RCC1 3-4PROSITE-ProRule annotation1 PublicationAdd BLAST | 53 | |
Repeati | 4164 – 4214 | RCC1 3-5PROSITE-ProRule annotation1 PublicationAdd BLAST | 51 | |
Repeati | 4216 – 4266 | RCC1 3-6PROSITE-ProRule annotation1 PublicationAdd BLAST | 51 | |
Repeati | 4268 – 4318 | RCC1 3-7PROSITE-ProRule annotation1 PublicationAdd BLAST | 51 | |
Domaini | 4457 – 4794 | HECTPROSITE-ProRule annotationAdd BLAST | 338 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 948 – 980 | Sequence analysisAdd BLAST | 33 |
Domaini
The ZZ-type zinc finger mediates binding to SUMO1, and at low level SUMO2.1 Publication
The RCC1 repeats are grouped into three seven-bladed beta-propeller regions.1 Publication
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 2702 – 2749 | ZZ-typePROSITE-ProRule annotationAdd BLAST | 48 |
Keywords - Domaini
Coiled coil, Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | KOG1426, Eukaryota |
GeneTreei | ENSGT00940000154975 |
HOGENOMi | CLU_000101_0_0_1 |
InParanoidi | O95714 |
OMAi | MQAFCVG |
OrthoDBi | 1062377at2759 |
PhylomeDBi | O95714 |
TreeFami | TF320636 |
Family and domain databases
CDDi | cd08664, APC10-HERC2, 1 hit cd00078, HECTc, 1 hit cd02344, ZZ_HERC2, 1 hit |
Gene3Di | 2.130.10.30, 3 hits 2.30.30.30, 1 hit 2.30.30.920, 1 hit 2.60.120.260, 1 hit 3.10.120.10, 1 hit 3.30.60.90, 1 hit |
InterProi | View protein in InterPro IPR004939, APC_su10/DOC_dom IPR006624, Beta-propeller_rpt_TECPR IPR021097, CPH_domain IPR001199, Cyt_B5-like_heme/steroid-bd IPR036400, Cyt_B5-like_heme/steroid_sf IPR008979, Galactose-bd-like_sf IPR000569, HECT_dom IPR035983, Hect_E3_ubiquitin_ligase IPR037976, HERC2_APC10 IPR010606, Mib_Herc2 IPR037252, Mib_Herc2_sf IPR009091, RCC1/BLIP-II IPR000408, Reg_chr_condens IPR014722, Rib_L2_dom2 IPR000433, Znf_ZZ IPR043145, Znf_ZZ_sf IPR041987, ZZ_HERC2 |
Pfami | View protein in Pfam PF03256, ANAPC10, 1 hit PF11515, Cul7, 1 hit PF00173, Cyt-b5, 1 hit PF00632, HECT, 1 hit PF06701, MIB_HERC2, 1 hit PF00415, RCC1, 16 hits PF00569, ZZ, 1 hit |
PRINTSi | PR00633, RCCNDNSATION |
SMARTi | View protein in SMART SM01337, APC10, 1 hit SM01117, Cyt-b5, 1 hit SM00119, HECTc, 1 hit SM00706, TECPR, 5 hits SM00291, ZnF_ZZ, 1 hit |
SUPFAMi | SSF159034, SSF159034, 1 hit SSF49785, SSF49785, 1 hit SSF50985, SSF50985, 3 hits SSF55856, SSF55856, 1 hit SSF56204, SSF56204, 1 hit |
PROSITEi | View protein in PROSITE PS50255, CYTOCHROME_B5_2, 1 hit PS51284, DOC, 1 hit PS50237, HECT, 1 hit PS51416, MIB_HERC2, 1 hit PS00626, RCC1_2, 1 hit PS50012, RCC1_3, 18 hits PS01357, ZF_ZZ_1, 1 hit PS50135, ZF_ZZ_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 7 potential isoforms that are computationally mapped.Show allAlign All
O95714-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MPSESFCLAA QARLDSKWLK TDIQLAFTRD GLCGLWNEMV KDGEIVYTGT
60 70 80 90 100
ESTQNGELPP RKDDSVEPSG TKKEDLNDKE KKDEEETPAP IYRAKSILDS
110 120 130 140 150
WVWGKQPDVN ELKECLSVLV KEQQALAVQS ATTTLSALRL KQRLVILERY
160 170 180 190 200
FIALNRTVFQ ENVKVKWKSS GISLPPVDKK SSRPAGKGVE GLARVGSRAA
210 220 230 240 250
LSFAFAFLRR AWRSGEDADL CSELLQESLD ALRALPEASL FDESTVSSVW
260 270 280 290 300
LEVVERATRF LRSVVTGDVH GTPATKGPGS IPLQDQHLAL AILLELAVQR
310 320 330 340 350
GTLSQMLSAI LLLLQLWDSG AQETDNERSA QGTSAPLLPL LQRFQSIICR
360 370 380 390 400
KDAPHSEGDM HLLSGPLSPN ESFLRYLTLP QDNELAIDLR QTAVVVMAHL
410 420 430 440 450
DRLATPCMPP LCSSPTSHKG SLQEVIGWGL IGWKYYANVI GPIQCEGLAN
460 470 480 490 500
LGVTQIACAE KRFLILSRNG RVYTQAYNSD TLAPQLVQGL ASRNIVKIAA
510 520 530 540 550
HSDGHHYLAL AATGEVYSWG CGDGGRLGHG DTVPLEEPKV ISAFSGKQAG
560 570 580 590 600
KHVVHIACGS TYSAAITAEG ELYTWGRGNY GRLGHGSSED EAIPMLVAGL
610 620 630 640 650
KGLKVIDVAC GSGDAQTLAV TENGQVWSWG DGDYGKLGRG GSDGCKTPKL
660 670 680 690 700
IEKLQDLDVV KVRCGSQFSI ALTKDGQVYS WGKGDNQRLG HGTEEHVRYP
710 720 730 740 750
KLLEGLQGKK VIDVAAGSTH CLALTEDSEV HSWGSNDQCQ HFDTLRVTKP
760 770 780 790 800
EPAALPGLDT KHIVGIACGP AQSFAWSSCS EWSIGLRVPF VVDICSMTFE
810 820 830 840 850
QLDLLLRQVS EGMDGSADWP PPQEKECVAV ATLNLLRLQL HAAISHQVDP
860 870 880 890 900
EFLGLGLGSI LLNSLKQTVV TLASSAGVLS TVQSAAQAVL QSGWSVLLPT
910 920 930 940 950
AEERARALSA LLPCAVSGNE VNISPGRRFM IDLLVGSLMA DGGLESALHA
960 970 980 990 1000
AITAEIQDIE AKKEAQKEKE IDEQEANAST FHRSRTPLDK DLINTGICES
1010 1020 1030 1040 1050
SGKQCLPLVQ LIQQLLRNIA SQTVARLKDV ARRISSCLDF EQHSRERSAS
1060 1070 1080 1090 1100
LDLLLRFQRL LISKLYPGES IGQTSDISSP ELMGVGSLLK KYTALLCTHI
1110 1120 1130 1140 1150
GDILPVAASI ASTSWRHFAE VAYIVEGDFT GVLLPELVVS IVLLLSKNAG
1160 1170 1180 1190 1200
LMQEAGAVPL LGGLLEHLDR FNHLAPGKER DDHEELAWPG IMESFFTGQN
1210 1220 1230 1240 1250
CRNNEEVTLI RKADLENHNK DGGFWTVIDG KVYDIKDFQT QSLTGNSILA
1260 1270 1280 1290 1300
QFAGEDPVVA LEAALQFEDT RESMHAFCVG QYLEPDQEIV TIPDLGSLSS
1310 1320 1330 1340 1350
PLIDTERNLG LLLGLHASYL AMSTPLSPVE IECAKWLQSS IFSGGLQTSQ
1360 1370 1380 1390 1400
IHYSYNEEKD EDHCSSPGGT PASKSRLCSH RRALGDHSQA FLQAIADNNI
1410 1420 1430 1440 1450
QDHNVKDFLC QIERYCRQCH LTTPIMFPPE HPVEEVGRLL LCCLLKHEDL
1460 1470 1480 1490 1500
GHVALSLVHA GALGIEQVKH RTLPKSVVDV CRVVYQAKCS LIKTHQEQGR
1510 1520 1530 1540 1550
SYKEVCAPVI ERLRFLFNEL RPAVCNDLSI MSKFKLLSSL PRWRRIAQKI
1560 1570 1580 1590 1600
IRERRKKRVP KKPESTDDEE KIGNEESDLE EACILPHSPI NVDKRPIAIK
1610 1620 1630 1640 1650
SPKDKWQPLL STVTGVHKYK WLKQNVQGLY PQSPLLSTIA EFALKEEPVD
1660 1670 1680 1690 1700
VEKMRKCLLK QLERAEVRLE GIDTILKLAS KNFLLPSVQY AMFCGWQRLI
1710 1720 1730 1740 1750
PEGIDIGEPL TDCLKDVDLI PPFNRMLLEV TFGKLYAWAV QNIRNVLMDA
1760 1770 1780 1790 1800
SAKFKELGIQ PVPLQTITNE NPSGPSLGTI PQARFLLVML SMLTLQHGAN
1810 1820 1830 1840 1850
NLDLLLNSGM LALTQTALRL IGPSCDNVEE DMNASAQGAS ATVLEETRKE
1860 1870 1880 1890 1900
TAPVQLPVSG PELAAMMKIG TRVMRGVDWK WGDQDGPPPG LGRVIGELGE
1910 1920 1930 1940 1950
DGWIRVQWDT GSTNSYRMGK EGKYDLKLAE LPAAAQPSAE DSDTEDDSEA
1960 1970 1980 1990 2000
EQTERNIHPT AMMFTSTINL LQTLCLSAGV HAEIMQSEAT KTLCGLLRML
2010 2020 2030 2040 2050
VESGTTDKTS SPNRLVYREQ HRSWCTLGFV RSIALTPQVC GALSSPQWIT
2060 2070 2080 2090 2100
LLMKVVEGHA PFTATSLQRQ ILAVHLLQAV LPSWDKTERA RDMKCLVEKL
2110 2120 2130 2140 2150
FDFLGSLLTT CSSDVPLLRE STLRRRRVRP QASLTATHSS TLAEEVVALL
2160 2170 2180 2190 2200
RTLHSLTQWN GLINKYINSQ LRSITHSFVG RPSEGAQLED YFPDSENPEV
2210 2220 2230 2240 2250
GGLMAVLAVI GGIDGRLRLG GQVMHDEFGE GTVTRITPKG KITVQFSDMR
2260 2270 2280 2290 2300
TCRVCPLNQL KPLPAVAFNV NNLPFTEPML SVWAQLVNLA GSKLEKHKIK
2310 2320 2330 2340 2350
KSTKQAFAGQ VDLDLLRCQQ LKLYILKAGR ALLSHQDKLR QILSQPAVQE
2360 2370 2380 2390 2400
TGTVHTDDGA VVSPDLGDMS PEGPQPPMIL LQQLLASATQ PSPVKAIFDK
2410 2420 2430 2440 2450
QELEAAALAV CQCLAVESTH PSSPGFEDCS SSEATTPVAV QHIRPARVKR
2460 2470 2480 2490 2500
RKQSPVPALP IVVQLMEMGF SRRNIEFALK SLTGASGNAS SLPGVEALVG
2510 2520 2530 2540 2550
WLLDHSDIQV TELSDADTVS DEYSDEEVVE DVDDAAYSMS TGAVVTESQT
2560 2570 2580 2590 2600
YKKRADFLSN DDYAVYVREN IQVGMMVRCC RAYEEVCEGD VGKVIKLDRD
2610 2620 2630 2640 2650
GLHDLNVQCD WQQKGGTYWV RYIHVELIGY PPPSSSSHIK IGDKVRVKAS
2660 2670 2680 2690 2700
VTTPKYKWGS VTHQSVGVVK AFSANGKDII VDFPQQSHWT GLLSEMELVP
2710 2720 2730 2740 2750
SIHPGVTCDG CQMFPINGSR FKCRNCDDFD FCETCFKTKK HNTRHTFGRI
2760 2770 2780 2790 2800
NEPGQSAVFC GRSGKQLKRC HSSQPGMLLD SWSRMVKSLN VSSSVNQASR
2810 2820 2830 2840 2850
LIDGSEPCWQ SSGSQGKHWI RLEIFPDVLV HRLKMIVDPA DSSYMPSLVV
2860 2870 2880 2890 2900
VSGGNSLNNL IELKTININP SDTTVPLLND CTEYHRYIEI AIKQCRSSGI
2910 2920 2930 2940 2950
DCKIHGLILL GRIRAEEEDL AAVPFLASDN EEEEDEKGNS GSLIRKKAAG
2960 2970 2980 2990 3000
LESAATIRTK VFVWGLNDKD QLGGLKGSKI KVPSFSETLS ALNVVQVAGG
3010 3020 3030 3040 3050
SKSLFAVTVE GKVYACGEAT NGRLGLGISS GTVPIPRQIT ALSSYVVKKV
3060 3070 3080 3090 3100
AVHSGGRHAT ALTVDGKVFS WGEGDDGKLG HFSRMNCDKP RLIEALKTKR
3110 3120 3130 3140 3150
IRDIACGSSH SAALTSSGEL YTWGLGEYGR LGHGDNTTQL KPKMVKVLLG
3160 3170 3180 3190 3200
HRVIQVACGS RDAQTLALTD EGLVFSWGDG DFGKLGRGGS EGCNIPQNIE
3210 3220 3230 3240 3250
RLNGQGVCQI ECGAQFSLAL TKSGVVWTWG KGDYFRLGHG SDVHVRKPQV
3260 3270 3280 3290 3300
VEGLRGKKIV HVAVGALHCL AVTDSGQVYA WGDNDHGQQG NGTTTVNRKP
3310 3320 3330 3340 3350
TLVQGLEGQK ITRVACGSSH SVAWTTVDVA TPSVHEPVLF QTARDPLGAS
3360 3370 3380 3390 3400
YLGVPSDADS SAASNKISGA SNSKPNRPSL AKILLSLDGN LAKQQALSHI
3410 3420 3430 3440 3450
LTALQIMYAR DAVVGALMPA AMIAPVECPS FSSAAPSDAS AMASPMNGEE
3460 3470 3480 3490 3500
CMLAVDIEDR LSPNPWQEKR EIVSSEDAVT PSAVTPSAPS ASARPFIPVT
3510 3520 3530 3540 3550
DDLGAASIIA ETMTKTKEDV ESQNKAAGPE PQALDEFTSL LIADDTRVVV
3560 3570 3580 3590 3600
DLLKLSVCSR AGDRGRDVLS AVLSGMGTAY PQVADMLLEL CVTELEDVAT
3610 3620 3630 3640 3650
DSQSGRLSSQ PVVVESSHPY TDDTSTSGTV KIPGAEGLRV EFDRQCSTER
3660 3670 3680 3690 3700
RHDPLTVMDG VNRIVSVRSG REWSDWSSEL RIPGDELKWK FISDGSVNGW
3710 3720 3730 3740 3750
GWRFTVYPIM PAAGPKELLS DRCVLSCPSM DLVTCLLDFR LNLASNRSIV
3760 3770 3780 3790 3800
PRLAASLAAC AQLSALAASH RMWALQRLRK LLTTEFGQSI NINRLLGEND
3810 3820 3830 3840 3850
GETRALSFTG SALAALVKGL PEALQRQFEY EDPIVRGGKQ LLHSPFFKVL
3860 3870 3880 3890 3900
VALACDLELD TLPCCAETHK WAWFRRYCMA SRVAVALDKR TPLPRLFLDE
3910 3920 3930 3940 3950
VAKKIRELMA DSENMDVLHE SHDIFKREQD EQLVQWMNRR PDDWTLSAGG
3960 3970 3980 3990 4000
SGTIYGWGHN HRGQLGGIEG AKVKVPTPCE ALATLRPVQL IGGEQTLFAV
4010 4020 4030 4040 4050
TADGKLYATG YGAGGRLGIG GTESVSTPTL LESIQHVFIK KVAVNSGGKH
4060 4070 4080 4090 4100
CLALSSEGEV YSWGEAEDGK LGHGNRSPCD RPRVIESLRG IEVVDVAAGG
4110 4120 4130 4140 4150
AHSACVTAAG DLYTWGKGRY GRLGHSDSED QLKPKLVEAL QGHRVVDIAC
4160 4170 4180 4190 4200
GSGDAQTLCL TDDDTVWSWG DGDYGKLGRG GSDGCKVPMK IDSLTGLGVV
4210 4220 4230 4240 4250
KVECGSQFSV ALTKSGAVYT WGKGDYHRLG HGSDDHVRRP RQVQGLQGKK
4260 4270 4280 4290 4300
VIAIATGSLH CVCCTEDGEV YTWGDNDEGQ LGDGTTNAIQ RPRLVAALQG
4310 4320 4330 4340 4350
KKVNRVACGS AHTLAWSTSK PASAGKLPAQ VPMEYNHLQE IPIIALRNRL
4360 4370 4380 4390 4400
LLLHHLSELF CPCIPMFDLE GSLDETGLGP SVGFDTLRGI LISQGKEAAF
4410 4420 4430 4440 4450
RKVVQATMVR DRQHGPVVEL NRIQVKRSRS KGGLAGPDGT KSVFGQMCAK
4460 4470 4480 4490 4500
MSSFGPDSLL LPHRVWKVKF VGESVDDCGG GYSESIAEIC EELQNGLTPL
4510 4520 4530 4540 4550
LIVTPNGRDE SGANRDCYLL SPAARAPVHS SMFRFLGVLL GIAIRTGSPL
4560 4570 4580 4590 4600
SLNLAEPVWK QLAGMSLTIA DLSEVDKDFI PGLMYIRDNE ATSEEFEAMS
4610 4620 4630 4640 4650
LPFTVPSASG QDIQLSSKHT HITLDNRAEY VRLAINYRLH EFDEQVAAVR
4660 4670 4680 4690 4700
EGMARVVPVP LLSLFTGYEL ETMVCGSPDI PLHLLKSVAT YKGIEPSASL
4710 4720 4730 4740 4750
IQWFWEVMES FSNTERSLFL RFVWGRTRLP RTIADFRGRD FVIQVLDKYN
4760 4770 4780 4790 4800
PPDHFLPESY TCFFLLKLPR YSCKQVLEEK LKYAIHFCKS IDTDDYARIA
4810 4820 4830
LTGEPAADDS SDDSDNEDVD SFASDSTQDY LTGH
Computationally mapped potential isoform sequencesi
There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0J9YVP0 | A0A0J9YVP0_HUMAN | E3 ubiquitin-protein ligase HERC2 | HERC2 | 2,081 | Annotation score: | ||
A0A3B3IRP6 | A0A3B3IRP6_HUMAN | E3 ubiquitin-protein ligase HERC2 | HERC2 | 1,454 | Annotation score: | ||
A0A0G2JPS8 | A0A0G2JPS8_HUMAN | E3 ubiquitin-protein ligase HERC2 | HERC2 | 523 | Annotation score: | ||
A0A0J9YXQ8 | A0A0J9YXQ8_HUMAN | E3 ubiquitin-protein ligase HERC2 | HERC2 | 959 | Annotation score: | ||
H3BUQ1 | H3BUQ1_HUMAN | E3 ubiquitin-protein ligase HERC2 | HERC2 | 200 | Annotation score: | ||
H3BRG9 | H3BRG9_HUMAN | E3 ubiquitin-protein ligase HERC2 | HERC2 | 80 | Annotation score: | ||
A0A0G2JLM1 | A0A0G2JLM1_HUMAN | E3 ubiquitin-protein ligase HERC2 | HERC2 | 24 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 1053 | L → W in AAD08657 (PubMed:9949213).Curated | 1 | |
Sequence conflicti | 1150 | G → D in AAD08657 (PubMed:9949213).Curated | 1 | |
Sequence conflicti | 1354 | S → R in AAD08657 (PubMed:9949213).Curated | 1 | |
Sequence conflicti | 1566 | T → M in AAD08657 (PubMed:9949213).Curated | 1 | |
Sequence conflicti | 1753 | K → T in AAD08657 (PubMed:9949213).Curated | 1 | |
Sequence conflicti | 2444 | R → H in AAD08657 (PubMed:9949213).Curated | 1 | |
Sequence conflicti | 2881 | C → Y in AAD08657 (PubMed:9949213).Curated | 1 | |
Sequence conflicti | 3070 | S → W in AAO27475 (PubMed:10720573).Curated | 1 | |
Sequence conflicti | 3346 | P → R in AAO27476 (PubMed:10720573).Curated | 1 | |
Sequence conflicti | 3583 – 3584 | VA → MP in AAO27480 (PubMed:10720573).Curated | 2 | |
Sequence conflicti | 3597 | D → N in AAO27480 (PubMed:10720573).Curated | 1 | |
Sequence conflicti | 3808 | F → S in AAO27481 (PubMed:10720573).Curated | 1 |
Polymorphismi
Genetic variants in HERC2 define the skin/hair/eye pigmentation variation locus 1 (SHEP1) [MIMi: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.
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_069282 | 594 | P → L in MRT38; less stable than wild-type; diffuse cytosolic localization with the formation of abnormal aggregates. 1 PublicationCorresponds to variant dbSNP:rs397518474EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF071172 mRNA Translation: AAD08657.1 AC091304 Genomic DNA No translation available. AC126332 Genomic DNA No translation available. AC135329 Genomic DNA No translation available. AF224243, AF224242 Genomic DNA Translation: AAO27473.1 AF224245, AF224244 Genomic DNA Translation: AAO27474.1 AF224249 , AF224246, AF224247, AF224248 Genomic DNA Translation: AAO27475.1 AF224251, AF224250 Genomic DNA Translation: AAO27476.1 AF224255, AF224254 Genomic DNA Translation: AAO27479.1 AF224252 Genomic DNA Translation: AAO27477.1 AF224253 Genomic DNA Translation: AAO27478.1 AF224257, AF224256 Genomic DNA Translation: AAO27480.1 AF225401, AF225400 Genomic DNA Translation: AAO27481.1 AF225404, AF225402, AF225403 Genomic DNA Translation: AAO27482.1 AF225407, AF225405, AF225406 Genomic DNA Translation: AAO27483.1 AF225409, AF225408 Genomic DNA Translation: AAO27484.1 |
CCDSi | CCDS10021.1 |
RefSeqi | NP_004658.3, NM_004667.5 |
Genome annotation databases
Ensembli | ENST00000261609; ENSP00000261609; ENSG00000128731 |
GeneIDi | 8924 |
KEGGi | hsa:8924 |
UCSCi | uc001zbj.5, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
Hect domain and RLD 2 (HERC2) Leiden Open Variation Database (LOVD) |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF071172 mRNA Translation: AAD08657.1 AC091304 Genomic DNA No translation available. AC126332 Genomic DNA No translation available. AC135329 Genomic DNA No translation available. AF224243, AF224242 Genomic DNA Translation: AAO27473.1 AF224245, AF224244 Genomic DNA Translation: AAO27474.1 AF224249 , AF224246, AF224247, AF224248 Genomic DNA Translation: AAO27475.1 AF224251, AF224250 Genomic DNA Translation: AAO27476.1 AF224255, AF224254 Genomic DNA Translation: AAO27479.1 AF224252 Genomic DNA Translation: AAO27477.1 AF224253 Genomic DNA Translation: AAO27478.1 AF224257, AF224256 Genomic DNA Translation: AAO27480.1 AF225401, AF225400 Genomic DNA Translation: AAO27481.1 AF225404, AF225402, AF225403 Genomic DNA Translation: AAO27482.1 AF225407, AF225405, AF225406 Genomic DNA Translation: AAO27483.1 AF225409, AF225408 Genomic DNA Translation: AAO27484.1 |
CCDSi | CCDS10021.1 |
RefSeqi | NP_004658.3, NM_004667.5 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2KEO | NMR | - | A | 1203-1296 | [»] | |
3KCI | X-ray | 1.80 | A | 3951-4321 | [»] | |
4L1M | X-ray | 2.60 | A/B/C | 417-790 | [»] | |
6WW3 | X-ray | 2.10 | A/B | 2702-2755 | [»] | |
6WW4 | X-ray | 2.25 | A/B | 2702-2751 | [»] | |
SMRi | O95714 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114438, 389 interactors |
CORUMi | O95714 |
DIPi | DIP-37632N |
IntActi | O95714, 124 interactors |
MINTi | O95714 |
STRINGi | 9606.ENSP00000261609 |
PTM databases
GlyConnecti | 1191, 2 N-Linked glycans (2 sites) |
GlyGeni | O95714, 2 sites, 1 N-linked glycan (1 site) |
iPTMneti | O95714 |
PhosphoSitePlusi | O95714 |
Polymorphism and mutation databases
BioMutai | HERC2 |
Proteomic databases
EPDi | O95714 |
jPOSTi | O95714 |
MassIVEi | O95714 |
MaxQBi | O95714 |
PaxDbi | O95714 |
PeptideAtlasi | O95714 |
PRIDEi | O95714 |
ProteomicsDBi | 51008 |
Protocols and materials databases
Antibodypediai | 22335, 51 antibodies |
Genome annotation databases
Ensembli | ENST00000261609; ENSP00000261609; ENSG00000128731 |
GeneIDi | 8924 |
KEGGi | hsa:8924 |
UCSCi | uc001zbj.5, human |
Organism-specific databases
CTDi | 8924 |
DisGeNETi | 8924 |
EuPathDBi | HostDB:ENSG00000128731.15 |
GeneCardsi | HERC2 |
GeneReviewsi | HERC2 |
HGNCi | HGNC:4868, HERC2 |
HPAi | ENSG00000128731, Low tissue specificity |
MalaCardsi | HERC2 |
MIMi | 227220, phenotype 605837, gene 615516, phenotype |
neXtProti | NX_O95714 |
OpenTargetsi | ENSG00000128731 |
Orphaneti | 329195, Developmental delay with autism spectrum disorder and gait instability |
PharmGKBi | PA29243 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1426, Eukaryota |
GeneTreei | ENSGT00940000154975 |
HOGENOMi | CLU_000101_0_0_1 |
InParanoidi | O95714 |
OMAi | MQAFCVG |
OrthoDBi | 1062377at2759 |
PhylomeDBi | O95714 |
TreeFami | TF320636 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
PathwayCommonsi | O95714 |
Reactomei | 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-5693571, Nonhomologous End-Joining (NHEJ) R-HSA-5693607, Processing of DNA double-strand break ends R-HSA-69473, G2/M DNA damage checkpoint R-HSA-983168, Antigen processing: Ubiquitination & Proteasome degradation |
SIGNORi | O95714 |
Miscellaneous databases
BioGRID-ORCSi | 8924, 32 hits in 850 CRISPR screens |
ChiTaRSi | HERC2, human |
EvolutionaryTracei | O95714 |
GeneWikii | HERC2 |
GenomeRNAii | 8924 |
Pharosi | O95714, Tbio |
PROi | PR:O95714 |
RNActi | O95714, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000128731, Expressed in endothelial cell and 231 other tissues |
ExpressionAtlasi | O95714, baseline and differential |
Genevisiblei | O95714, HS |
Family and domain databases
CDDi | cd08664, APC10-HERC2, 1 hit cd00078, HECTc, 1 hit cd02344, ZZ_HERC2, 1 hit |
Gene3Di | 2.130.10.30, 3 hits 2.30.30.30, 1 hit 2.30.30.920, 1 hit 2.60.120.260, 1 hit 3.10.120.10, 1 hit 3.30.60.90, 1 hit |
InterProi | View protein in InterPro IPR004939, APC_su10/DOC_dom IPR006624, Beta-propeller_rpt_TECPR IPR021097, CPH_domain IPR001199, Cyt_B5-like_heme/steroid-bd IPR036400, Cyt_B5-like_heme/steroid_sf IPR008979, Galactose-bd-like_sf IPR000569, HECT_dom IPR035983, Hect_E3_ubiquitin_ligase IPR037976, HERC2_APC10 IPR010606, Mib_Herc2 IPR037252, Mib_Herc2_sf IPR009091, RCC1/BLIP-II IPR000408, Reg_chr_condens IPR014722, Rib_L2_dom2 IPR000433, Znf_ZZ IPR043145, Znf_ZZ_sf IPR041987, ZZ_HERC2 |
Pfami | View protein in Pfam PF03256, ANAPC10, 1 hit PF11515, Cul7, 1 hit PF00173, Cyt-b5, 1 hit PF00632, HECT, 1 hit PF06701, MIB_HERC2, 1 hit PF00415, RCC1, 16 hits PF00569, ZZ, 1 hit |
PRINTSi | PR00633, RCCNDNSATION |
SMARTi | View protein in SMART SM01337, APC10, 1 hit SM01117, Cyt-b5, 1 hit SM00119, HECTc, 1 hit SM00706, TECPR, 5 hits SM00291, ZnF_ZZ, 1 hit |
SUPFAMi | SSF159034, SSF159034, 1 hit SSF49785, SSF49785, 1 hit SSF50985, SSF50985, 3 hits SSF55856, SSF55856, 1 hit SSF56204, SSF56204, 1 hit |
PROSITEi | View protein in PROSITE PS50255, CYTOCHROME_B5_2, 1 hit PS51284, DOC, 1 hit PS50237, HECT, 1 hit PS51416, MIB_HERC2, 1 hit PS00626, RCC1_2, 1 hit PS50012, RCC1_3, 18 hits PS01357, ZF_ZZ_1, 1 hit PS50135, ZF_ZZ_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HERC2_HUMAN | |
Accessioni | O95714Primary (citable) accession number: O95714 Secondary accession number(s): Q86SV7 Q86YZ1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 4, 2006 |
Last sequence update: | October 5, 2010 | |
Last modified: | December 2, 2020 | |
This is version 182 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - Human chromosome 15
Human chromosome 15: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations