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UniProtKB - O95714 (HERC2_HUMAN)

Protein

E3 ubiquitin-protein ligase HERC2

Gene

HERC2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 + N6-ubiquitinyl-[acceptor protein]-L-lysine.1 Publication

Pathwayi: protein ubiquitination

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 keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei4762Glycyl thioester intermediatePROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri2702 – 2749ZZ-typePROSITE-ProRule annotationAdd BLAST48

GO - Molecular functioni

  • guanyl-nucleotide exchange factor activity Source: UniProtKB
  • SUMO binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: InterPro
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionTransferase
Biological processDNA damage, DNA repair, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-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
SIGNORiO95714
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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000128731.15
HGNCiHGNC:4868 HERC2
MIMi605837 gene
neXtProtiNX_O95714

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & 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.
See also OMIM:615516
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069282594P → 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 keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2708C → S: Abolishes binding to SUMO; when associated with S-2711. 1 Publication1
Mutagenesisi2711C → S: Abolishes binding to SUMO; when associated with S-2708. 1 Publication1
Mutagenesisi4827T → A: Prevents HERC2 C-terminal fragment binding to endogenous RNF8. 1 Publication1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi8924
GeneReviewsiHERC2
MalaCardsiHERC2
MIMi227220 phenotype
615516 phenotype
OpenTargetsiENSG00000128731
Orphaneti329195 Developmental delay with autism spectrum disorder and gait instability
PharmGKBiPA29243

Polymorphism and mutation databases

BioMutaiHERC2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002297391 – 4834E3 ubiquitin-protein ligase HERC2Add BLAST4834

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei272PhosphothreonineCombined sources1
Modified residuei647PhosphothreonineCombined sources1
Modified residuei1577PhosphoserineBy similarity1
Modified residuei1942PhosphoserineBy similarity1
Modified residuei1944PhosphothreonineCombined sources1
Modified residuei2454PhosphoserineCombined sources1
Modified residuei2928PhosphoserineCombined sources1
Modified residuei4810PhosphoserineCombined sources1
Modified residuei4811PhosphoserineCombined sources1
Modified residuei4814PhosphoserineCombined sources1
Modified residuei4827Phosphothreonine1 Publication1

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 conjugation

Proteomic databases

EPDiO95714
MaxQBiO95714
PaxDbiO95714
PeptideAtlasiO95714
PRIDEiO95714
ProteomicsDBi51008

PTM databases

GlyConnecti1191
iPTMnetiO95714
PhosphoSitePlusiO95714

Expressioni

Gene expression databases

BgeeiENSG00000128731 Expressed in 221 organ(s), highest expression level in endothelial cell
ExpressionAtlasiO95714 baseline and differential
GenevisibleiO95714 HS

Organism-specific databases

HPAiCAB017188
HPA048389

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 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi114438, 258 interactors
CORUMiO95714
DIPiDIP-37632N
IntActiO95714, 93 interactors
MINTiO95714
STRINGi9606.ENSP00000261609

Structurei

Secondary structure

14834
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO95714
SMRiO95714
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95714

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati415 – 461RCC1 1-1PROSITE-ProRule annotation1 PublicationAdd BLAST47
Repeati462 – 512RCC1 1-2PROSITE-ProRule annotation1 PublicationAdd BLAST51
Repeati513 – 568RCC1 1-3PROSITE-ProRule annotation1 PublicationAdd BLAST56
Repeati569 – 620RCC1 1-4PROSITE-ProRule annotation1 PublicationAdd BLAST52
Repeati623 – 674RCC1 1-5PROSITE-ProRule annotation1 PublicationAdd BLAST52
Repeati675 – 726RCC1 1-6PROSITE-ProRule annotation1 PublicationAdd BLAST52
Repeati728 – 778RCC1 1-7PROSITE-ProRule annotation1 PublicationAdd BLAST51
Domaini1207 – 1283Cytochrome b5 heme-bindingPROSITE-ProRule annotationAdd BLAST77
Domaini1859 – 1932MIB/HERC2PROSITE-ProRule annotationAdd BLAST74
Domaini2759 – 2936DOCPROSITE-ProRule annotationAdd BLAST178
Repeati2958 – 3009RCC1 2-1PROSITE-ProRule annotation1 PublicationAdd BLAST52
Repeati3010 – 3064RCC1 2-2PROSITE-ProRule annotation1 PublicationAdd BLAST55
Repeati3065 – 3116RCC1 2-3PROSITE-ProRule annotation1 PublicationAdd BLAST52
Repeati3118 – 3168RCC1 2-4PROSITE-ProRule annotation1 PublicationAdd BLAST51
Repeati3171 – 3222RCC1 2-5PROSITE-ProRule annotation1 PublicationAdd BLAST52
Repeati3224 – 3274RCC1 2-6PROSITE-ProRule annotation1 PublicationAdd BLAST51
Repeati3275 – 3326RCC1 2-7PROSITE-ProRule annotation1 PublicationAdd BLAST52
Repeati3951 – 4002RCC1 3-1PROSITE-ProRule annotation1 PublicationAdd BLAST52
Repeati4004 – 4056RCC1 3-2PROSITE-ProRule annotation1 PublicationAdd BLAST53
Repeati4058 – 4108RCC1 3-3PROSITE-ProRule annotation1 PublicationAdd BLAST51
Repeati4110 – 4162RCC1 3-4PROSITE-ProRule annotation1 PublicationAdd BLAST53
Repeati4164 – 4214RCC1 3-5PROSITE-ProRule annotation1 PublicationAdd BLAST51
Repeati4216 – 4266RCC1 3-6PROSITE-ProRule annotation1 PublicationAdd BLAST51
Repeati4268 – 4318RCC1 3-7PROSITE-ProRule annotation1 PublicationAdd BLAST51
Domaini4457 – 4794HECTPROSITE-ProRule annotationAdd BLAST338

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili948 – 980Sequence analysisAdd BLAST33

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 keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri2702 – 2749ZZ-typePROSITE-ProRule annotationAdd BLAST48

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1426 Eukaryota
COG5021 LUCA
COG5184 LUCA
GeneTreeiENSGT00910000144004
HOVERGENiHBG081598
InParanoidiO95714
KOiK10595
OMAiIMEMGFT
OrthoDBiEOG091G000E
PhylomeDBiO95714
TreeFamiTF320636

Family and domain databases

CDDicd08664 APC10-HERC2, 1 hit
cd00078 HECTc, 1 hit
Gene3Di2.130.10.30, 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
InterProiView 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
PfamiView 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
PRINTSiPR00633 RCCNDNSATION
SMARTiView 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
SUPFAMiSSF159034 SSF159034, 1 hit
SSF49785 SSF49785, 1 hit
SSF50985 SSF50985, 3 hits
SSF55856 SSF55856, 1 hit
SSF56204 SSF56204, 1 hit
PROSITEiView 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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 6 potential isoforms that are computationally mapped.Show allAlign All

O95714-1 [UniParc]FASTAAdd to basket
« Hide
        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
Length:4,834
Mass (Da):527,228
Last modified:October 5, 2010 - v2
Checksum:iA323DC1DA6B221D0
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0J9YVP0A0A0J9YVP0_HUMAN
E3 ubiquitin-protein ligase HERC2
HERC2
2,081Annotation score:
A0A0G2JPS8A0A0G2JPS8_HUMAN
E3 ubiquitin-protein ligase HERC2
HERC2
523Annotation score:
A0A0J9YXQ8A0A0J9YXQ8_HUMAN
E3 ubiquitin-protein ligase HERC2
HERC2
959Annotation score:
H3BUQ1H3BUQ1_HUMAN
E3 ubiquitin-protein ligase HERC2
HERC2
200Annotation score:
H3BRG9H3BRG9_HUMAN
E3 ubiquitin-protein ligase HERC2
HERC2
80Annotation score:
A0A0G2JLM1A0A0G2JLM1_HUMAN
E3 ubiquitin-protein ligase HERC2
HERC2
24Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1053L → W in AAD08657 (PubMed:9949213).Curated1
Sequence conflicti1150G → D in AAD08657 (PubMed:9949213).Curated1
Sequence conflicti1354S → R in AAD08657 (PubMed:9949213).Curated1
Sequence conflicti1566T → M in AAD08657 (PubMed:9949213).Curated1
Sequence conflicti1753K → T in AAD08657 (PubMed:9949213).Curated1
Sequence conflicti2444R → H in AAD08657 (PubMed:9949213).Curated1
Sequence conflicti2881C → Y in AAD08657 (PubMed:9949213).Curated1
Sequence conflicti3070S → W in AAO27475 (PubMed:10720573).Curated1
Sequence conflicti3346P → R in AAO27476 (PubMed:10720573).Curated1
Sequence conflicti3583 – 3584VA → MP in AAO27480 (PubMed:10720573).Curated2
Sequence conflicti3597D → N in AAO27480 (PubMed:10720573).Curated1
Sequence conflicti3808F → S in AAO27481 (PubMed:10720573).Curated1

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 keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069282594P → 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
CCDSiCCDS10021.1
RefSeqiNP_004658.3, NM_004667.5
UniGeneiHs.434890
Hs.610412
Hs.741019

Genome annotation databases

EnsembliENST00000261609; ENSP00000261609; ENSG00000128731
GeneIDi8924
KEGGihsa:8924
UCSCiuc001zbj.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
CCDSiCCDS10021.1
RefSeqiNP_004658.3, NM_004667.5
UniGeneiHs.434890
Hs.610412
Hs.741019

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KEONMR-A1203-1296[»]
3KCIX-ray1.80A3951-4321[»]
4L1MX-ray2.60A/B/C417-790[»]
ProteinModelPortaliO95714
SMRiO95714
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114438, 258 interactors
CORUMiO95714
DIPiDIP-37632N
IntActiO95714, 93 interactors
MINTiO95714
STRINGi9606.ENSP00000261609

PTM databases

GlyConnecti1191
iPTMnetiO95714
PhosphoSitePlusiO95714

Polymorphism and mutation databases

BioMutaiHERC2

Proteomic databases

EPDiO95714
MaxQBiO95714
PaxDbiO95714
PeptideAtlasiO95714
PRIDEiO95714
ProteomicsDBi51008

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261609; ENSP00000261609; ENSG00000128731
GeneIDi8924
KEGGihsa:8924
UCSCiuc001zbj.5 human

Organism-specific databases

CTDi8924
DisGeNETi8924
EuPathDBiHostDB:ENSG00000128731.15
GeneCardsiHERC2
GeneReviewsiHERC2
H-InvDBiHIX0012044
HIX0017540
HIX0038121
HIX0038320
HIX0038830
HIX0173226
HIX0173299
HIX0194348
HGNCiHGNC:4868 HERC2
HPAiCAB017188
HPA048389
MalaCardsiHERC2
MIMi227220 phenotype
605837 gene
615516 phenotype
neXtProtiNX_O95714
OpenTargetsiENSG00000128731
Orphaneti329195 Developmental delay with autism spectrum disorder and gait instability
PharmGKBiPA29243
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1426 Eukaryota
COG5021 LUCA
COG5184 LUCA
GeneTreeiENSGT00910000144004
HOVERGENiHBG081598
InParanoidiO95714
KOiK10595
OMAiIMEMGFT
OrthoDBiEOG091G000E
PhylomeDBiO95714
TreeFamiTF320636

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-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
SIGNORiO95714

Miscellaneous databases

ChiTaRSiHERC2 human
EvolutionaryTraceiO95714
GeneWikiiHERC2
GenomeRNAii8924
PROiPR:O95714
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000128731 Expressed in 221 organ(s), highest expression level in endothelial cell
ExpressionAtlasiO95714 baseline and differential
GenevisibleiO95714 HS

Family and domain databases

CDDicd08664 APC10-HERC2, 1 hit
cd00078 HECTc, 1 hit
Gene3Di2.130.10.30, 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
InterProiView 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
PfamiView 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
PRINTSiPR00633 RCCNDNSATION
SMARTiView 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
SUPFAMiSSF159034 SSF159034, 1 hit
SSF49785 SSF49785, 1 hit
SSF50985 SSF50985, 3 hits
SSF55856 SSF55856, 1 hit
SSF56204 SSF56204, 1 hit
PROSITEiView 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
ProtoNetiSearch...

Entry informationi

Entry nameiHERC2_HUMAN
AccessioniPrimary (citable) accession number: O95714
Secondary accession number(s): Q86SV7
, Q86SV8, Q86SV9, Q86YY3, Q86YY4, Q86YY5, Q86YY6, Q86YY7, Q86YY8, Q86YY9, Q86YZ0, Q86YZ1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: October 5, 2010
Last modified: November 7, 2018
This is version 167 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
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