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O95714 (HERC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase HERC2

EC=6.3.2.-
Alternative name(s):
HECT domain and RCC1-like domain-containing protein 2
Gene names
Name:HERC2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length4834 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.12 Ref.13 Ref.17

Pathway

Protein modification; protein ubiquitination.

Subunit 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. Ref.12 Ref.13 Ref.17 Ref.18

Subcellular location

Cytoplasm. Cytoplasmcytoskeletonmicrotubule organizing centercentrosomecentriole. 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. Ref.12 Ref.13 Ref.18

Domain

The ZZ-type zinc finger mediates binding to SUMO1, and at lowe level SUMO2. Ref.17

The RCC1 repeats are grouped into three seven-bladed beta-propeller regions. Ref.17

Post-translational modification

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. Ref.17

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.

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20

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.

Sequence similarities

Contains 1 cytochrome b5 heme-binding domain.

Contains 1 DOC domain.

Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.

Contains 1 MIB/HERC2 domain.

Contains 21 RCC1 repeats.

Contains 1 ZZ-type zinc finger.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
Ubl conjugation pathway
   Cellular componentCytoplasm
Cytoskeleton
Nucleus
   DiseaseDisease mutation
Mental retardation
   DomainCoiled coil
Repeat
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Inferred from direct assay Ref.12. Source: UniProtKB

cellular response to DNA damage stimulus

Inferred from direct assay Ref.17. Source: UniProtKB

intracellular protein transport

Non-traceable author statement Ref.1. Source: UniProtKB

protein ubiquitination

Inferred from direct assay Ref.13. Source: UniProtKB

protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of GTPase activity

Non-traceable author statement Ref.1. Source: GOC

spermatogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcentriole

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay Ref.13. Source: UniProtKB

mitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay Ref.13. Source: UniProtKB

   Molecular_functionSUMO binding

Inferred from direct assay Ref.17. Source: UniProtKB

guanyl-nucleotide exchange factor activity

Non-traceable author statement Ref.1. Source: UniProtKB

heme binding

Inferred from electronic annotation. Source: InterPro

ubiquitin protein ligase binding

Inferred from physical interaction Ref.17. Source: UniProtKB

ubiquitin-protein ligase activity

Inferred from direct assay Ref.13. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 48344834E3 ubiquitin-protein ligase HERC2
PRO_0000229739

Regions

Repeat415 – 46147RCC1 1-1
Repeat462 – 51251RCC1 1-2
Repeat513 – 56856RCC1 1-3
Repeat569 – 62052RCC1 1-4
Repeat623 – 67452RCC1 1-5
Repeat675 – 72652RCC1 1-6
Repeat728 – 77851RCC1 1-7
Domain1207 – 128377Cytochrome b5 heme-binding
Domain1859 – 193274MIB/HERC2
Domain2759 – 2936178DOC
Repeat2958 – 300952RCC1 2-1
Repeat3010 – 306455RCC1 2-2
Repeat3065 – 311652RCC1 2-3
Repeat3118 – 316851RCC1 2-4
Repeat3171 – 322252RCC1 2-5
Repeat3224 – 327451RCC1 2-6
Repeat3275 – 332652RCC1 2-7
Repeat3951 – 400252RCC1 3-1
Repeat4004 – 405653RCC1 3-2
Repeat4058 – 410851RCC1 3-3
Repeat4110 – 416253RCC1 3-4
Repeat4164 – 421451RCC1 3-5
Repeat4216 – 426651RCC1 3-6
Repeat4268 – 431851RCC1 3-7
Domain4457 – 4794338HECT
Zinc finger2702 – 274948ZZ-type
Coiled coil948 – 98033 Potential

Sites

Active site47621Glycyl thioester intermediate By similarity

Amino acid modifications

Modified residue6471Phosphothreonine Ref.16
Modified residue15771Phosphoserine By similarity
Modified residue19441Phosphothreonine Ref.16
Modified residue24541Phosphoserine Ref.4 Ref.10 Ref.14
Modified residue29281Phosphoserine Ref.4 Ref.8 Ref.14 Ref.16
Modified residue48101Phosphoserine Ref.8
Modified residue48111Phosphoserine Ref.8
Modified residue48141Phosphoserine Ref.8
Modified residue48271Phosphothreonine Ref.12

Natural variations

Natural variant5941P → L in MRT38; less stable than wild-type; diffuse cytosolic localization with the formation of abnormal aggregates. Ref.20
VAR_069282

Experimental info

Mutagenesis27081C → S: Abolishes binding to SUMO; when associated with S-2711. Ref.17
Mutagenesis27111C → S: Abolishes binding to SUMO; when associated with S-2708. Ref.17
Mutagenesis48271T → A: Prevents HERC2 C-terminal fragment binding to endogenous RNF8. Ref.12
Sequence conflict10531L → W in AAD08657. Ref.1
Sequence conflict11501G → D in AAD08657. Ref.1
Sequence conflict13541S → R in AAD08657. Ref.1
Sequence conflict15661T → M in AAD08657. Ref.1
Sequence conflict17531K → T in AAD08657. Ref.1
Sequence conflict24441R → H in AAD08657. Ref.1
Sequence conflict28811C → Y in AAD08657. Ref.1
Sequence conflict30701S → W in AAO27475. Ref.3
Sequence conflict33461P → R in AAO27476. Ref.3
Sequence conflict3583 – 35842VA → MP in AAO27480. Ref.3
Sequence conflict35971D → N in AAO27480. Ref.3
Sequence conflict38081F → S in AAO27481. Ref.3

Secondary structure

............................................................................................................................................................................................... 4834
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O95714 [UniParc].

Last modified October 5, 2010. Version 2.
Checksum: A323DC1DA6B221D0

FASTA4,834527,228
        10         20         30         40         50         60 
MPSESFCLAA QARLDSKWLK TDIQLAFTRD GLCGLWNEMV KDGEIVYTGT ESTQNGELPP 

        70         80         90        100        110        120 
RKDDSVEPSG TKKEDLNDKE KKDEEETPAP IYRAKSILDS WVWGKQPDVN ELKECLSVLV 

       130        140        150        160        170        180 
KEQQALAVQS ATTTLSALRL KQRLVILERY FIALNRTVFQ ENVKVKWKSS GISLPPVDKK 

       190        200        210        220        230        240 
SSRPAGKGVE GLARVGSRAA LSFAFAFLRR AWRSGEDADL CSELLQESLD ALRALPEASL 

       250        260        270        280        290        300 
FDESTVSSVW LEVVERATRF LRSVVTGDVH GTPATKGPGS IPLQDQHLAL AILLELAVQR 

       310        320        330        340        350        360 
GTLSQMLSAI LLLLQLWDSG AQETDNERSA QGTSAPLLPL LQRFQSIICR KDAPHSEGDM 

       370        380        390        400        410        420 
HLLSGPLSPN ESFLRYLTLP QDNELAIDLR QTAVVVMAHL DRLATPCMPP LCSSPTSHKG 

       430        440        450        460        470        480 
SLQEVIGWGL IGWKYYANVI GPIQCEGLAN LGVTQIACAE KRFLILSRNG RVYTQAYNSD 

       490        500        510        520        530        540 
TLAPQLVQGL ASRNIVKIAA HSDGHHYLAL AATGEVYSWG CGDGGRLGHG DTVPLEEPKV 

       550        560        570        580        590        600 
ISAFSGKQAG KHVVHIACGS TYSAAITAEG ELYTWGRGNY GRLGHGSSED EAIPMLVAGL 

       610        620        630        640        650        660 
KGLKVIDVAC GSGDAQTLAV TENGQVWSWG DGDYGKLGRG GSDGCKTPKL IEKLQDLDVV 

       670        680        690        700        710        720 
KVRCGSQFSI ALTKDGQVYS WGKGDNQRLG HGTEEHVRYP KLLEGLQGKK VIDVAAGSTH 

       730        740        750        760        770        780 
CLALTEDSEV HSWGSNDQCQ HFDTLRVTKP EPAALPGLDT KHIVGIACGP AQSFAWSSCS 

       790        800        810        820        830        840 
EWSIGLRVPF VVDICSMTFE QLDLLLRQVS EGMDGSADWP PPQEKECVAV ATLNLLRLQL 

       850        860        870        880        890        900 
HAAISHQVDP EFLGLGLGSI LLNSLKQTVV TLASSAGVLS TVQSAAQAVL QSGWSVLLPT 

       910        920        930        940        950        960 
AEERARALSA LLPCAVSGNE VNISPGRRFM IDLLVGSLMA DGGLESALHA AITAEIQDIE 

       970        980        990       1000       1010       1020 
AKKEAQKEKE IDEQEANAST FHRSRTPLDK DLINTGICES SGKQCLPLVQ LIQQLLRNIA 

      1030       1040       1050       1060       1070       1080 
SQTVARLKDV ARRISSCLDF EQHSRERSAS LDLLLRFQRL LISKLYPGES IGQTSDISSP 

      1090       1100       1110       1120       1130       1140 
ELMGVGSLLK KYTALLCTHI GDILPVAASI ASTSWRHFAE VAYIVEGDFT GVLLPELVVS 

      1150       1160       1170       1180       1190       1200 
IVLLLSKNAG LMQEAGAVPL LGGLLEHLDR FNHLAPGKER DDHEELAWPG IMESFFTGQN 

      1210       1220       1230       1240       1250       1260 
CRNNEEVTLI RKADLENHNK DGGFWTVIDG KVYDIKDFQT QSLTGNSILA QFAGEDPVVA 

      1270       1280       1290       1300       1310       1320 
LEAALQFEDT RESMHAFCVG QYLEPDQEIV TIPDLGSLSS PLIDTERNLG LLLGLHASYL 

      1330       1340       1350       1360       1370       1380 
AMSTPLSPVE IECAKWLQSS IFSGGLQTSQ IHYSYNEEKD EDHCSSPGGT PASKSRLCSH 

      1390       1400       1410       1420       1430       1440 
RRALGDHSQA FLQAIADNNI QDHNVKDFLC QIERYCRQCH LTTPIMFPPE HPVEEVGRLL 

      1450       1460       1470       1480       1490       1500 
LCCLLKHEDL GHVALSLVHA GALGIEQVKH RTLPKSVVDV CRVVYQAKCS LIKTHQEQGR 

      1510       1520       1530       1540       1550       1560 
SYKEVCAPVI ERLRFLFNEL RPAVCNDLSI MSKFKLLSSL PRWRRIAQKI IRERRKKRVP 

      1570       1580       1590       1600       1610       1620 
KKPESTDDEE KIGNEESDLE EACILPHSPI NVDKRPIAIK SPKDKWQPLL STVTGVHKYK 

      1630       1640       1650       1660       1670       1680 
WLKQNVQGLY PQSPLLSTIA EFALKEEPVD VEKMRKCLLK QLERAEVRLE GIDTILKLAS 

      1690       1700       1710       1720       1730       1740 
KNFLLPSVQY AMFCGWQRLI PEGIDIGEPL TDCLKDVDLI PPFNRMLLEV TFGKLYAWAV 

      1750       1760       1770       1780       1790       1800 
QNIRNVLMDA SAKFKELGIQ PVPLQTITNE NPSGPSLGTI PQARFLLVML SMLTLQHGAN 

      1810       1820       1830       1840       1850       1860 
NLDLLLNSGM LALTQTALRL IGPSCDNVEE DMNASAQGAS ATVLEETRKE TAPVQLPVSG 

      1870       1880       1890       1900       1910       1920 
PELAAMMKIG TRVMRGVDWK WGDQDGPPPG LGRVIGELGE DGWIRVQWDT GSTNSYRMGK 

      1930       1940       1950       1960       1970       1980 
EGKYDLKLAE LPAAAQPSAE DSDTEDDSEA EQTERNIHPT AMMFTSTINL LQTLCLSAGV 

      1990       2000       2010       2020       2030       2040 
HAEIMQSEAT KTLCGLLRML VESGTTDKTS SPNRLVYREQ HRSWCTLGFV RSIALTPQVC 

      2050       2060       2070       2080       2090       2100 
GALSSPQWIT LLMKVVEGHA PFTATSLQRQ ILAVHLLQAV LPSWDKTERA RDMKCLVEKL 

      2110       2120       2130       2140       2150       2160 
FDFLGSLLTT CSSDVPLLRE STLRRRRVRP QASLTATHSS TLAEEVVALL RTLHSLTQWN 

      2170       2180       2190       2200       2210       2220 
GLINKYINSQ LRSITHSFVG RPSEGAQLED YFPDSENPEV GGLMAVLAVI GGIDGRLRLG 

      2230       2240       2250       2260       2270       2280 
GQVMHDEFGE GTVTRITPKG KITVQFSDMR TCRVCPLNQL KPLPAVAFNV NNLPFTEPML 

      2290       2300       2310       2320       2330       2340 
SVWAQLVNLA GSKLEKHKIK KSTKQAFAGQ VDLDLLRCQQ LKLYILKAGR ALLSHQDKLR 

      2350       2360       2370       2380       2390       2400 
QILSQPAVQE TGTVHTDDGA VVSPDLGDMS PEGPQPPMIL LQQLLASATQ PSPVKAIFDK 

      2410       2420       2430       2440       2450       2460 
QELEAAALAV CQCLAVESTH PSSPGFEDCS SSEATTPVAV QHIRPARVKR RKQSPVPALP 

      2470       2480       2490       2500       2510       2520 
IVVQLMEMGF SRRNIEFALK SLTGASGNAS SLPGVEALVG WLLDHSDIQV TELSDADTVS 

      2530       2540       2550       2560       2570       2580 
DEYSDEEVVE DVDDAAYSMS TGAVVTESQT YKKRADFLSN DDYAVYVREN IQVGMMVRCC 

      2590       2600       2610       2620       2630       2640 
RAYEEVCEGD VGKVIKLDRD GLHDLNVQCD WQQKGGTYWV RYIHVELIGY PPPSSSSHIK 

      2650       2660       2670       2680       2690       2700 
IGDKVRVKAS VTTPKYKWGS VTHQSVGVVK AFSANGKDII VDFPQQSHWT GLLSEMELVP 

      2710       2720       2730       2740       2750       2760 
SIHPGVTCDG CQMFPINGSR FKCRNCDDFD FCETCFKTKK HNTRHTFGRI NEPGQSAVFC 

      2770       2780       2790       2800       2810       2820 
GRSGKQLKRC HSSQPGMLLD SWSRMVKSLN VSSSVNQASR LIDGSEPCWQ SSGSQGKHWI 

      2830       2840       2850       2860       2870       2880 
RLEIFPDVLV HRLKMIVDPA DSSYMPSLVV VSGGNSLNNL IELKTININP SDTTVPLLND 

      2890       2900       2910       2920       2930       2940 
CTEYHRYIEI AIKQCRSSGI DCKIHGLILL GRIRAEEEDL AAVPFLASDN EEEEDEKGNS 

      2950       2960       2970       2980       2990       3000 
GSLIRKKAAG LESAATIRTK VFVWGLNDKD QLGGLKGSKI KVPSFSETLS ALNVVQVAGG 

      3010       3020       3030       3040       3050       3060 
SKSLFAVTVE GKVYACGEAT NGRLGLGISS GTVPIPRQIT ALSSYVVKKV AVHSGGRHAT 

      3070       3080       3090       3100       3110       3120 
ALTVDGKVFS WGEGDDGKLG HFSRMNCDKP RLIEALKTKR IRDIACGSSH SAALTSSGEL 

      3130       3140       3150       3160       3170       3180 
YTWGLGEYGR LGHGDNTTQL KPKMVKVLLG HRVIQVACGS RDAQTLALTD EGLVFSWGDG 

      3190       3200       3210       3220       3230       3240 
DFGKLGRGGS EGCNIPQNIE RLNGQGVCQI ECGAQFSLAL TKSGVVWTWG KGDYFRLGHG 

      3250       3260       3270       3280       3290       3300 
SDVHVRKPQV VEGLRGKKIV HVAVGALHCL AVTDSGQVYA WGDNDHGQQG NGTTTVNRKP 

      3310       3320       3330       3340       3350       3360 
TLVQGLEGQK ITRVACGSSH SVAWTTVDVA TPSVHEPVLF QTARDPLGAS YLGVPSDADS 

      3370       3380       3390       3400       3410       3420 
SAASNKISGA SNSKPNRPSL AKILLSLDGN LAKQQALSHI LTALQIMYAR DAVVGALMPA 

      3430       3440       3450       3460       3470       3480 
AMIAPVECPS FSSAAPSDAS AMASPMNGEE CMLAVDIEDR LSPNPWQEKR EIVSSEDAVT 

      3490       3500       3510       3520       3530       3540 
PSAVTPSAPS ASARPFIPVT DDLGAASIIA ETMTKTKEDV ESQNKAAGPE PQALDEFTSL 

      3550       3560       3570       3580       3590       3600 
LIADDTRVVV DLLKLSVCSR AGDRGRDVLS AVLSGMGTAY PQVADMLLEL CVTELEDVAT 

      3610       3620       3630       3640       3650       3660 
DSQSGRLSSQ PVVVESSHPY TDDTSTSGTV KIPGAEGLRV EFDRQCSTER RHDPLTVMDG 

      3670       3680       3690       3700       3710       3720 
VNRIVSVRSG REWSDWSSEL RIPGDELKWK FISDGSVNGW GWRFTVYPIM PAAGPKELLS 

      3730       3740       3750       3760       3770       3780 
DRCVLSCPSM DLVTCLLDFR LNLASNRSIV PRLAASLAAC AQLSALAASH RMWALQRLRK 

      3790       3800       3810       3820       3830       3840 
LLTTEFGQSI NINRLLGEND GETRALSFTG SALAALVKGL PEALQRQFEY EDPIVRGGKQ 

      3850       3860       3870       3880       3890       3900 
LLHSPFFKVL VALACDLELD TLPCCAETHK WAWFRRYCMA SRVAVALDKR TPLPRLFLDE 

      3910       3920       3930       3940       3950       3960 
VAKKIRELMA DSENMDVLHE SHDIFKREQD EQLVQWMNRR PDDWTLSAGG SGTIYGWGHN 

      3970       3980       3990       4000       4010       4020 
HRGQLGGIEG AKVKVPTPCE ALATLRPVQL IGGEQTLFAV TADGKLYATG YGAGGRLGIG 

      4030       4040       4050       4060       4070       4080 
GTESVSTPTL LESIQHVFIK KVAVNSGGKH CLALSSEGEV YSWGEAEDGK LGHGNRSPCD 

      4090       4100       4110       4120       4130       4140 
RPRVIESLRG IEVVDVAAGG AHSACVTAAG DLYTWGKGRY GRLGHSDSED QLKPKLVEAL 

      4150       4160       4170       4180       4190       4200 
QGHRVVDIAC GSGDAQTLCL TDDDTVWSWG DGDYGKLGRG GSDGCKVPMK IDSLTGLGVV 

      4210       4220       4230       4240       4250       4260 
KVECGSQFSV ALTKSGAVYT WGKGDYHRLG HGSDDHVRRP RQVQGLQGKK VIAIATGSLH 

      4270       4280       4290       4300       4310       4320 
CVCCTEDGEV YTWGDNDEGQ LGDGTTNAIQ RPRLVAALQG KKVNRVACGS AHTLAWSTSK 

      4330       4340       4350       4360       4370       4380 
PASAGKLPAQ VPMEYNHLQE IPIIALRNRL LLLHHLSELF CPCIPMFDLE GSLDETGLGP 

      4390       4400       4410       4420       4430       4440 
SVGFDTLRGI LISQGKEAAF RKVVQATMVR DRQHGPVVEL NRIQVKRSRS KGGLAGPDGT 

      4450       4460       4470       4480       4490       4500 
KSVFGQMCAK MSSFGPDSLL LPHRVWKVKF VGESVDDCGG GYSESIAEIC EELQNGLTPL 

      4510       4520       4530       4540       4550       4560 
LIVTPNGRDE SGANRDCYLL SPAARAPVHS SMFRFLGVLL GIAIRTGSPL SLNLAEPVWK 

      4570       4580       4590       4600       4610       4620 
QLAGMSLTIA DLSEVDKDFI PGLMYIRDNE ATSEEFEAMS LPFTVPSASG QDIQLSSKHT 

      4630       4640       4650       4660       4670       4680 
HITLDNRAEY VRLAINYRLH EFDEQVAAVR EGMARVVPVP LLSLFTGYEL ETMVCGSPDI 

      4690       4700       4710       4720       4730       4740 
PLHLLKSVAT YKGIEPSASL IQWFWEVMES FSNTERSLFL RFVWGRTRLP RTIADFRGRD 

      4750       4760       4770       4780       4790       4800 
FVIQVLDKYN PPDHFLPESY TCFFLLKLPR YSCKQVLEEK LKYAIHFCKS IDTDDYARIA 

      4810       4820       4830 
LTGEPAADDS SDDSDNEDVD SFASDSTQDY LTGH 

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References

« Hide 'large scale' references
[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."
Ji Y., Walkowicz M.J., Buiting K., Johnson D.K., Tarvin R.E., Rinchik E.M., Horsthemke B., Stubbs L., Nicholls R.D.
Hum. Mol. Genet. 8:533-542(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Structure of the highly conserved HERC2 gene and of multiple partially duplicated paralogs in human."
Ji Y., Rebert N.A., Joslin J.M., Higgins M.J., Schultz R.A., Nicholls R.D.
Genome Res. 10:319-329(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 2818-2895; 2909-2957; 2963-3290; 3317-3363; 3389-3430; 3458-3495; 3512-3527; 3533-3633; 3635-3821; 3826-4084; 4097-4505 AND 4529-4834, GENE STRUCTURE.
[4]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2454 AND SER-2928, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[5]"Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene."
Kayser M., Liu F., Janssens A.C.J.W., Rivadeneira F., Lao O., van Duijn K., Vermeulen M., Arp P., Jhamai M.M., van Ijcken W.F.J., den Dunnen J.T., Heath S., Zelenika D., Despriet D.D.G., Klaver C.C.W., Vingerling J.R., de Jong P.T.V.M., Hofman A. expand/collapse author list , Aulchenko Y.S., Uitterlinden A.G., Oostra B.A., van Duijn C.M.
Am. J. Hum. Genet. 82:411-423(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SHEP1.
[6]"A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color."
Sturm R.A., Duffy D.L., Zhao Z.Z., Leite F.P.M., Stark M.S., Hayward N.K., Martin N.G., Montgomery G.W.
Am. J. Hum. Genet. 82:424-431(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SHEP1.
[7]"Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression."
Eiberg H., Troelsen J., Nielsen M., Mikkelsen A., Mengel-From J., Kjaer K.W., Hansen L.
Hum. Genet. 123:177-187(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SHEP1, REGULATION OF OCA2.
[8]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2928; SER-4810; SER-4811 AND SER-4814, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2454, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[11]"Human eye colour and HERC2, OCA2 and MATP."
Mengel-From J., Borsting C., Sanchez J.J., Eiberg H., Morling N.
Forensic Sci. Int. Genet. 4:323-328(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: MISCELLANEOUS.
[12]"HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes."
Bekker-Jensen S., Rendtlew Danielsen J., Fugger K., Gromova I., Nerstedt A., Lukas C., Bartek J., Lukas J., Mailand N.
Nat. Cell Biol. 12:80-86(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RNF8, PHOSPHORYLATION AT THR-4827, MUTAGENESIS OF THR-4827, SUBCELLULAR LOCATION.
[13]"Circadian control of XPA and excision repair of cisplatin-DNA damage by cryptochrome and HERC2 ubiquitin ligase."
Kang T.H., Lindsey-Boltz L.A., Reardon J.T., Sancar A.
Proc. Natl. Acad. Sci. U.S.A. 107:4890-4895(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, UBIQUITIN LIGASE ACTIVITY, INTERACTION WITH XPA, SUBCELLULAR LOCATION.
[14]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2454 AND SER-2928, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-647; THR-1944 AND SER-2928, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"DNA damage-inducible SUMOylation of HERC2 promotes RNF8 binding via a novel SUMO-binding Zinc finger."
Danielsen J.R., Povlsen L.K., Villumsen B.H., Streicher W., Nilsson J., Wikstrom M., Bekker-Jensen S., Mailand N.
J. Cell Biol. 197:179-187(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION, FUNCTION, SUMO-BINDING, DOMAIN, INTERACTION WITH RNF8, MUTAGENESIS OF CYS-2708 AND CYS-2711.
[18]"Interaction proteomics identify NEURL4 and the HECT E3 ligase HERC2 as novel modulators of centrosome architecture."
Al-Hakim A.K., Bashkurov M., Gingras A.C., Durocher D., Pelletier L.
Mol. Cell. Proteomics 11:M111.014233.01-M111.014233.14(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CCP110; CEP97 AND NEURL4, SUBCELLULAR LOCATION.
[19]"Structure of the first RCC1-like domain of HERC2."
Tempel W., Khan M.B., Dong A., Hu J., Li Y., Bountra C., Arrowsmith C.H., Edwards A.M., Tong Y.
Submitted (JUN-2013) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 417-790, RCC1 REPEATS.
[20]"A homozygous missense mutation in HERC2 associated with global developmental delay and autism spectrum disorder."
Puffenberger E.G., Jinks R.N., Wang H., Xin B., Fiorentini C., Sherman E.A., Degrazio D., Shaw C., Sougnez C., Cibulskis K., Gabriel S., Kelley R.I., Morton D.H., Strauss K.A.
Hum. Mutat. 33:1639-1646(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MRT38 LEU-594, CHARACTERIZATION OF VARIANT MRT38 LEU-594.
+Additional computationally mapped references.

Web resources

Hect domain and RLD 2 (HERC2)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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 expand/collapse EMBL AC list , 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.
RefSeqNP_004658.3. NM_004667.5.
UniGeneHs.434890.
Hs.610412.
Hs.741019.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KEONMR-A1203-1296[»]
3KCIX-ray1.80A3950-4321[»]
4L1MX-ray2.60A/B/C417-790[»]
ProteinModelPortalO95714.
SMRO95714. Positions 422-779, 1205-1296, 1867-1929, 3953-4318.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114438. 44 interactions.
DIPDIP-37632N.
IntActO95714. 14 interactions.
MINTMINT-8415335.

PTM databases

PhosphoSiteO95714.

Proteomic databases

PaxDbO95714.
PRIDEO95714.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261609; ENSP00000261609; ENSG00000128731.
ENST00000576092; ENSP00000458767; ENSG00000263162.
GeneID8924.
KEGGhsa:8924.
UCSCuc001zbj.4. human.

Organism-specific databases

CTD8924.
GeneCardsGC15M028356.
H-InvDBHIX0012044.
HIX0017540.
HIX0038121.
HIX0038320.
HIX0038830.
HIX0173226.
HIX0173299.
HIX0194348.
HGNCHGNC:4868. HERC2.
HPACAB017188.
HPA048389.
MIM227220. phenotype.
605837. gene.
615516. phenotype.
neXtProtNX_O95714.
Orphanet329195. Developmental delay with autism spectrum disorder and gait instability.
PharmGKBPA29243.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5021.
HOVERGENHBG081598.
InParanoidO95714.
KOK10595.
OMAGHGTDVH.
PhylomeDBO95714.
TreeFamTF320636.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressO95714.
BgeeO95714.
GenevestigatorO95714.

Family and domain databases

Gene3D2.130.10.30. 3 hits.
2.30.30.30. 1 hit.
2.60.120.260. 1 hit.
3.10.120.10. 1 hit.
InterProIPR004939. APC_su10/DOC_dom.
IPR006624. Beta-propeller_rpt_TECPR.
IPR021097. CPH_domain.
IPR001199. Cyt_B5-like_heme/steroid-bd.
IPR008979. Galactose-bd-like.
IPR000569. HECT.
IPR010606. Mib_Herc2.
IPR009091. RCC1/BLIP-II.
IPR000408. Reg_chr_condens.
IPR014722. Rib_L2_dom2.
IPR000433. Znf_ZZ.
[Graphical view]
PfamPF03256. APC10. 1 hit.
PF11515. Cul7. 1 hit.
PF00173. Cyt-b5. 1 hit.
PF00632. HECT. 1 hit.
PF06701. MIB_HERC2. 1 hit.
PF00415. RCC1. 18 hits.
PF00569. ZZ. 1 hit.
[Graphical view]
PRINTSPR00633. RCCNDNSATION.
SMARTSM00119. HECTc. 1 hit.
SM00706. TECPR. 5 hits.
SM00291. ZnF_ZZ. 1 hit.
[Graphical view]
SUPFAMSSF49785. SSF49785. 1 hit.
SSF50985. SSF50985. 3 hits.
SSF55856. SSF55856. 1 hit.
SSF56204. SSF56204. 1 hit.
PROSITEPS50255. 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.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO95714.
GeneWikiHERC2.
GenomeRNAi8924.
NextBio33552.
PROO95714.
SOURCESearch...

Entry information

Entry nameHERC2_HUMAN
AccessionPrimary (citable) accession number: O95714
Secondary accession number(s): Q86SV7 expand/collapse secondary AC list , Q86SV8, Q86SV9, Q86YY3, Q86YY4, Q86YY5, Q86YY6, Q86YY7, Q86YY8, Q86YY9, Q86YZ0, Q86YZ1
Entry history
Integrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: October 5, 2010
Last modified: April 16, 2014
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM