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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

GO - Biological processi

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
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

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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