O95714 (HERC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	4834 AA.
Sequence status	Complete.
Protein existence	Evidence 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.11 Ref.12 Ref.16
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.11 Ref.12 Ref.16 Ref.17
Subcellular location	Cytoplasm. Cytoplasm › cytoskeleton › centrosome › centriole. Nucleus. Note: Recruited to sites of DNA damage in response to ionizing radiation (IR) via its interaction with RNF8. May loose association with centrosomes during mitosis. Ref.11 Ref.12 Ref.17
Domain	The ZZ-type zinc finger mediates binding to SUMO1, and at lowe level SUMO2. Ref.16
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.16
Polymorphism	Genetic variants in HERC2 define the skin/hair/eye pigmentation variation locus 1 (SHEP1) [MIM:227220]; also known as skin/hair/eye pigmentation type 1, blue/nonblue eyes or skin/hair/eye pigmentation type 1, blue/brown eyes or skin/hair/eye pigmentation type 1, blond/brown hair or eye color, brown/blue or eye color, blue/nonblue or eye color type 3 (EYCL3) or brown eye color type 2 (BEY2) or hair color type 3 (HCL3). Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair.
Miscellaneous	A regulatory element withinin an intron of the HERC2 gene inhibits OCA2 promoter. There are several single nucleotide polymorphisms within the OCA2 gene and within the HERC2 gene that have a statistical association with human eye color.
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 19 RCC1 repeats. Contains 6 WD repeats. Contains 1 ZZ-type zinc finger.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway
Cellular component	Cytoplasm Cytoskeleton Nucleus
Domain	Coiled coil Repeat WD repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Inferred from direct assay Ref.11. Source: UniProtKB intracellular protein transport Non-traceable author statement Ref.1. Source: UniProtKB protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from Biological aspect of Ancestor. Source: RefGenome spermatogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	centriole Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from direct assay Ref.12. Source: UniProtKB mitochondrial inner membrane Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay Ref.12. Source: UniProtKB
Molecular_function	SUMO binding Inferred from direct assay Ref.16. 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 activity Inferred from direct assay Ref.12. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 4834

4834

E3 ubiquitin-protein ligase HERC2

PRO_0000229739

Regions

Repeat

2 – 46

45

WD 1

Repeat

286 – 327

42

WD 2

Repeat

490 – 529

40

WD 3

Repeat

513 – 568

56

RCC1 1

Repeat

569 – 620

52

RCC1 2

Repeat

623 – 674

52

RCC1 3

Repeat

675 – 726

52

RCC1 4

Repeat

704 – 743

40

WD 4

Repeat

728 – 778

51

RCC1 5

Domain

1207 – 1283

77

Cytochrome b5 heme-binding

Domain

1859 – 1932

74

MIB/HERC2

Domain

2759 – 2936

178

DOC

Repeat

2958 – 3009

52

RCC1 6

Repeat

3010 – 3064

55

RCC1 7

Repeat

3065 – 3116

52

RCC1 8

Repeat

3118 – 3168

51

RCC1 9

Repeat

3171 – 3222

52

RCC1 10

Repeat

3224 – 3274

51

RCC1 11

Repeat

3275 – 3326

52

RCC1 12

Repeat

3926 – 3967

42

WD 5

Repeat

3951 – 4002

52

RCC1 13

Repeat

4004 – 4056

53

RCC1 14

Repeat

4058 – 4108

51

RCC1 15

Repeat

4110 – 4162

53

RCC1 16

Repeat

4164 – 4214

51

RCC1 17

Repeat

4216 – 4266

51

RCC1 18

Repeat

4241 – 4283

43

WD 6

Repeat

4268 – 4318

51

RCC1 19

Domain

4457 – 4794

338

HECT

Zinc finger

2702 – 2749

48

ZZ-type

Coiled coil

948 – 980

33

Potential

Sites

Active site

4762

1

Glycyl thioester intermediate By similarity

Amino acid modifications

Modified residue

647

1

Phosphothreonine Ref.15

Modified residue

1944

1

Phosphothreonine Ref.15

Modified residue

2454

1

Phosphoserine Ref.4 Ref.9 Ref.13

Modified residue

2928

1

Phosphoserine Ref.4 Ref.8 Ref.13 Ref.15

Modified residue

4810

1

Phosphoserine Ref.8

Modified residue

4811

1

Phosphoserine Ref.8

Modified residue

4814

1

Phosphoserine Ref.8

Modified residue

4827

1

Phosphothreonine Ref.11

Experimental info

Mutagenesis

2708

1

C → S: Abolishes binding to SUMO; when associated with S-2711. Ref.16

Mutagenesis

2711

1

C → S: Abolishes binding to SUMO; when associated with S-2708. Ref.16

Mutagenesis

4827

1

T → A: Prevents HERC2 C-terminal fragment binding to endogenous RNF8. Ref.11

Sequence conflict

1053

1

L → W in AAD08657. Ref.1

Sequence conflict

1150

1

G → D in AAD08657. Ref.1

Sequence conflict

1354

1

S → R in AAD08657. Ref.1

Sequence conflict

1566

1

T → M in AAD08657. Ref.1

Sequence conflict

1753

1

K → T in AAD08657. Ref.1

Sequence conflict

2444

1

R → H in AAD08657. Ref.1

Sequence conflict

2881

1

C → Y in AAD08657. Ref.1

Sequence conflict

3070

1

S → W in AAO27475. Ref.3

Sequence conflict

3346

1

P → R in AAO27476. Ref.3

Sequence conflict

3583 – 3584

2

VA → MP in AAO27480. Ref.3

Sequence conflict

3597

1

D → N in AAO27480. Ref.3

Sequence conflict

3808

1

F → S in AAO27481. Ref.3

Secondary structure

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4834

Helix Strand Turn

Details...

Helix

1212 – 1221

10

Beta strand

1225 – 1228

4

Beta strand

1231 – 1234

4

Helix

1235 – 1242

8

Helix

1250 – 1252

3

Helix

1257 – 1266

10

Helix

1270 – 1273

4

Helix

1274 – 1277

4

Beta strand

1278 – 1282

5

Helix

1285 – 1288

4

Beta strand

3954 – 3959

6

Beta strand

3971 – 3978

8

Helix

3980 – 3984

5

Beta strand

3987 – 3993

7

Beta strand

3996 – 4001

6

Beta strand

4006 – 4010

5

Helix

4013 – 4015

3

Beta strand

4018 – 4022

5

Beta strand

4025 – 4030

6

Helix

4032 – 4034

3

Beta strand

4039 – 4043

5

Beta strand

4049 – 4055

7

Beta strand

4060 – 4064

5

Helix

4067 – 4069

3

Beta strand

4073 – 4075

3

Beta strand

4079 – 4084

6

Helix

4086 – 4088

3

Beta strand

4093 – 4098

6

Beta strand

4100 – 4107

8

Beta strand

4112 – 4116

5

Helix

4119 – 4121

3

Beta strand

4125 – 4127

3

Beta strand

4131 – 4136

6

Helix

4138 – 4140

3

Beta strand

4145 – 4150

6

Beta strand

4156 – 4161

6

Turn

4162 – 4164

3

Beta strand

4165 – 4170

6

Helix

4173 – 4175

3

Beta strand

4178 – 4181

4

Beta strand

4185 – 4190

6

Helix

4192 – 4194

3

Beta strand

4199 – 4205

7

Beta strand

4208 – 4213

6

Beta strand

4218 – 4222

5

Helix

4225 – 4227

3

Beta strand

4231 – 4233

3

Beta strand

4237 – 4242

6

Helix

4244 – 4246

3

Beta strand

4251 – 4256

6

Beta strand

4258 – 4265

8

Beta strand

4270 – 4274

5

Beta strand

4283 – 4285

3

Beta strand

4289 – 4294

6

Helix

4296 – 4298

3

Beta strand

4305 – 4309

5

Beta strand

4312 – 4316

5

Sequences

	Sequence		Length	Mass (Da)
	O95714 [UniParc]. Last modified October 5, 2010. Version 2. Checksum: A323DC1DA6B221D0	FASTA	4,834	527,228
	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

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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. , 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"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].
[15]	"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, MASS SPECTROMETRY.
[16]	"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.
[17]	"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.
+	Additional computationally mapped references.

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 , 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.

IPI

IPI00005826.

RefSeq

NP_004658.3. NM_004667.5.

UniGene

Hs.434890.
Hs.610412.
Hs.741019.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KEO	NMR	-	A	1203-1296	[»]
3KCI	X-ray	1.80	A	3950-4321	[»]

ProteinModelPortal

O95714.

SMR

O95714. Positions 1205-1296, 1867-1929, 3953-4318.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-37632N.

IntAct

O95714. 11 interactions.

MINT

MINT-8415335.

PTM databases

PhosphoSite

O95714.

Proteomic databases

PaxDb

O95714.

PRIDE

O95714.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000261609; ENSP00000261609; ENSG00000128731.
ENST00000576092; ENSP00000458767; ENSG00000263162.

GeneID

8924.

KEGG

hsa:8924.

UCSC

uc001zbj.3. human.

Organism-specific databases

CTD

8924.

GeneCards

GC15M028356.

H-InvDB

HIX0012044.
HIX0017540.
HIX0038121.
HIX0038320.
HIX0038830.
HIX0173226.
HIX0173299.
HIX0194348.

HGNC

HGNC:4868. HERC2.

HPA

CAB017188.

MIM

227220. phenotype.
605837. gene.

neXtProt

NX_O95714.

PharmGKB

PA29243.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5021.

HOVERGEN

HBG081598.

InParanoid

O95714.

KO

K10595.

OMA

QLAFTRD.

OrthoDB

EOG41C6V9.

PhylomeDB

O95714.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

O95714.

Bgee

O95714.

Genevestigator

O95714.

GermOnline

ENSG00000128731. Homo sapiens.

Family and domain databases

Gene3D

2.130.10.30. 3 hits.
2.30.30.30. 1 hit.
2.60.120.260. 1 hit.
3.10.120.10. 1 hit.

InterPro

IPR004939. 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]

Pfam

PF03256. APC10. 1 hit.
PF11515. Cul7. 1 hit.
PF00173. Cyt-b5. 1 hit.
PF00632. HECT. 1 hit.
PF06701. MIB_HERC2. 1 hit.
PF00415. RCC1. 17 hits.
PF00569. ZZ. 1 hit.
[Graphical view]

PRINTS

PR00633. RCCNDNSATION.

SMART

SM00119. HECTc. 1 hit.
SM00706. TECPR. 5 hits.
SM00291. ZnF_ZZ. 1 hit.
[Graphical view]

SUPFAM

SSF55856. Cyt_B5. 1 hit.
SSF49785. Gal_bind_like. 1 hit.
SSF56204. HECT. 1 hit.
SSF50985. RCC1/BLIP-II. 3 hits.

PROSITE

PS00191. CYTOCHROME_B5_1. False negative.
PS50255. CYTOCHROME_B5_2. 1 hit.
PS51284. DOC. 1 hit.
PS50237. HECT. 1 hit.
PS51416. MIB_HERC2. 1 hit.
PS00625. RCC1_1. False negative.
PS00626. RCC1_2. 1 hit.
PS50012. RCC1_3. 18 hits.
PS00678. WD_REPEATS_1. False negative.
PS50082. WD_REPEATS_2. False negative.
PS50294. WD_REPEATS_REGION. False negative.
PS01357. ZF_ZZ_1. 1 hit.
PS50135. ZF_ZZ_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O95714.

GenomeRNAi

8924.

NextBio

33552.

SOURCE

Search...

Entry information

Entry name

HERC2_HUMAN

Accession

Primary (citable) accession number: O95714
Secondary accession number(s): Q86SV7 , 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:	May 29, 2013
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.