135:
113:
124:
276:) for proteasomal degradation. FBXL5 regulates the stability of the iron regulatory protein (IR2), which in turn controls the stability of proteins overlooking cellular iron homeostasis. Depletion of HERC2 results in decreased cellular iron levels. Iron is an essential nutrient in cells, but high levels can be cytotoxic, so maintaining cellular levels is important.
105:
It has an N-terminal bilobed HECT domain, conferring E3 ligase functionality, as well as 3 RLD domains with seven-bladed β-propeller folds. In addition to these HERC family hallmarks, it has several other motifs; a cytochrome-b5-like domain, several potential phosphorylation sites, and a ZZ-type zinc
2239:
Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de
Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ (March 2000).
171:
is linked to darker pigmentation and dominant over the lighter pigment recessive allele. The rs12913832 SNP, located in intron 86 of the HERC2 gene contains a silencing sequence that can inhibit the expression of OCA2 and, if both recessive alleles are present, can homozygously cause blue eyes. This
304:
phenotype attributed to HERC2 in mice, AS is associated with seizures, developmental delay, intellectual disability and jerky movements. While a variety of disturbances to this locus can cause AS, all known mechanisms affect the functioning and expression of the E6AP E3 ligase, which also sits at
2403:
Sulem P, Gudbjartsson DF, Stacey SN, Helgason A, Rafnar T, Magnusson KP, Manolescu A, Karason A, Palsson A, Thorleifsson G, Jakobsdottir M, Steinberg S, Pálsson S, Jonasson F, Sigurgeirsson B, Thorisdottir K, Ragnarsson R, Benediktsdottir KR, Aben KK, Kiemeney LA, Olafsson JH, Gulcher J, Kong A,
739:
Kayser M, Liu F, Janssens AC, Rivadeneira F, Lao O, van Duijn K, Vermeulen M, Arp P, Jhamai MM, van Ijcken WF, den Dunnen JT, Heath S, Zelenika D, Despriet DD, Klaver CC, Vingerling JR, de Jong PT, Hofman A, Aulchenko YS, Uitterlinden AG, Oostra BA, van Duijn CM (February 2008).
2293:
Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW (June 2004). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation".
930:
Eiberg H, Troelsen J, Nielsen M, Mikkelsen A, Mengel-From J, Kjaer KW, Hansen L (March 2008). "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".
237:, a RING finger ubiquitin ligase to the E2 ubiquitin-conjugating enzyme UBC13. This association is required for RNF8 mediated Lys-63 poly-ubiquitination signalling, which both recruits and retains repair factors at the site of DNA damage to commence
316:
and features resembling AS. In addition, a homozygous deletion of both OCA2 and HERC2 genes was recently reported as presenting with severe developmental abnormalities. These phenotypes are suggestive of a role for HERC2 in normal neurodevelopment.
608:"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"
1414:
Bekker-Jensen S, Rendtlew
Danielsen J, Fugger K, Gromova I, Nerstedt A, Lukas C, Bartek J, Lukas J, Mailand N (January 2010). "HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes".
101:
HERC2 encodes a 4834-amino acid protein with a theoretical size of 528 kDa. While a full structure has not yet been elucidated, potentially due to its large size, partial structures of its domains have been captured.
511:
Hochrainer K, Mayer H, Baranyi U, Binder B, Lipp J, Kroismayr R (February 2005). "The human HERC family of ubiquitin ligases: novel members, genomic organization, expression profiling, and evolutionary aspects".
1987:
Yoo NJ, Park SW, Lee SH (December 2011). "Frameshift mutations of ubiquitination-related genes HERC2, HERC3, TRIP12, UBE2Q1 and UBE4B in gastric and colorectal carcinomas with microsatellite instability".
23:, implicated in DNA repair regulation, pigmentation and neurological disorders. It is encoded by a gene of the same name belonging to the HERC family, which typically encodes large protein products with
305:
this locus. HER2 is an allosteric activator of E6AP, and lies at the most commonly deleted region in AS. Its deletion could result in the inactivation of E6AP and consequently the development of AS.
2064:
Imai Y, Kobayashi Y, Inoshita T, Meng H, Arano T, Uemura K, Asano T, Yoshimi K, Zhang CL, Matsumoto G, Ohtsuka T, Kageyama R, Kiyonari H, Shioi G, Nukina N, Hattori N, Takahashi R (September 2015).
1930:
Ferguson R, Vogelsang M, Ucisik-Akkaya E, Rai K, Pilarski R, Martinez CN, Rendleman J, Kazlow E, Nagdimov K, Osman I, Klein RJ, Davidorf FH, Cebulla CM, Abdel-Rahman MH, Kirchhoff T (August 2016).
1143:
Donnelly MP, Paschou P, Grigorenko E, Gurwitz D, Barta C, Lu RB, Zhukova OV, Kim JJ, Siniscalco M, New M, Li H, Kajuna SL, Manolopoulos VG, Speed WC, Pakstis AJ, Kidd JR, Kidd KK (May 2012).
320:
Certain alleles of HERC2 has recently been implicated in increasing the risk of iris cancer. Due its role in pigment determination, three HERC2 SNPs have been highlighted as associated with
1782:
Harlalka GV, Baple EL, Cross H, KĂĽhnle S, Cubillos-Rojas M, Matentzoglu K, Patton MA, Wagner K, Coblentz R, Ford DL, Mackay DJ, Chioza BA, Scheffner M, Rosa JL, Crosby AH (February 2013).
288:, which is necessary for its transcriptional activity. Silencing of HERC2 reportedly inhibits the expression of genes regulated by p53 and also results in increased cellular growth.
211:
and essential for DNA damage repair pathways. Regulating DNA repair pathways is necessary, as unchecked they can target and excise undamaged DNA, potentially leading to mutation.
159:
variability in humans. In particular, the rs916977 and rs12913832 SNPs have been reported as good predictors of this trait, and the latter is also significantly associated with
58:
are known to cause hypo-pigmentation and pink eye phenotypes, as well reduced growth, jerky gait, male sterility, female semi-sterility, and maternal behaviour defects in mice.
2157:"Molecular characterization of radiation- and chemically induced mutations associated with neuromuscular tremors, runting, juvenile lethality, and sperm defects in jdf2 mice"
1832:
Puffenberger EG, Jinks RN, Wang H, Xin B, Fiorentini C, Sherman EA, Degrazio D, Shaw C, Sougnez C, Cibulskis K, Gabriel S, Kelley RI, Morton DH, Strauss KA (December 2012).
2122:"Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro"
82:. This region on chromosome 15 is susceptible to breaks during chromosomal rearrangement and there are at least 12 partial duplicates of HERC2 between 15q11–15q13.
1062:
647:
Brilliant MH (1992). "The mouse pink-eyed dilution locus: a model for aspects of Prader-Willi syndrome, Angelman syndrome, and a form of hypomelanosis of Ito".
2331:
Fu GK, Wang JT, Yang J, Au-Young J, Stuve LL (July 2004). "Circular rapid amplification of cDNA ends for high-throughput extension cloning of partial genes".
547:
Lehman AL, Nakatsu Y, Ching A, Bronson RT, Oakey RJ, Keiper-Hrynko N, Finger JN, Durham-Pierre D, Horton DB, Newton JM, Lyon MF, Brilliant MH (August 1998).
109:
Expression of HERC2 is ubiquitous, though particularly high in the brain and testes. Cellular localisation is predominantly to the nucleus and cytoplasm.
252:
repair protein for proteolysis. XPA is involved in recognising DNA damage and provides a scaffold for other repair factors to bind at the damage site.
312:
families, a homozygous proline to leucine missense mutation within the first RLD domain has been implicated in a neurodevelopmental disorder with
264:
architecture in conjunction with NEURL4 other ubiquitinated binding partners. Its absence is associated with aberrant centrosome morphology.
887:
Branicki W, Brudnik U, Wojas-Pelc A (March 2009). "Interactions between HERC2, OCA2 and MC1R may influence human pigmentation phenotype".
106:
finger motif. This is likely involved in protein binding, and has recently been identified as a SUMOylation target following DNA damage.
272:
HERC2 has recently been associated with regulating iron metabolism through ubiquitinating the F-box and leucine-rich repeat protein 5 (
222:. Under normal conditions HERC2 associates with USP20 and ubiquitinates it for degradation. Under replication stress, for example a
1881:
Morice-Picard F, Benard G, Rezvani HR, Lasseaux E, Simon D, Moutton S, Rooryck C, Lacombe D, Baumann C, Arveiler B (January 2016).
392:
387:
362:
89:
have been identified and they are strongly associated with human iris colour variability, functioning to repress expression of
1093:"A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color"
2404:
Thorsteinsdottir U, Stefansson K (December 2007). "Genetic determinants of hair, eye and skin pigmentation in
Europeans".
176:
is present in almost all people with blue eyes and is hypothesised as being the founder mutation of blue eyes in humans.
54:
in mice: the runty, jerky, sterile (rjs) phenotype and the juvenile development and fertility-2 (Jdf2) phenotype. Mutant
230:, stabilising it to then bind and activate Chk1. This allows for DNA replication to be paused and the error corrected.
1679:"The E3 ubiquitin protein ligase HERC2 modulates the activity of tumor protein p53 by regulating its oligomerization"
1070:
838:
Danielsen JR, Povlsen LK, Villumsen BH, Streicher W, Nilsson J, Wikström M, Bekker-Jensen S, Mailand N (April 2012).
1569:"Interaction proteomics identify NEURL4 and the HECT E3 ligase HERC2 as novel modulators of centrosome architecture"
606:
Ji Y, Walkowicz MJ, Buiting K, Johnson DK, Tarvin RE, Rinchik EM, Horsthemke B, Stubbs L, Nicholls RD (March 1999).
2155:
Walkowicz M, Ji Y, Ren X, Horsthemke B, Russell LB, Johnson D, Rinchik EM, Nicholls RD, Stubbs L (September 1999).
2120:
Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (April 1997).
2066:"The Parkinson's Disease-Associated Protein Kinase LRRK2 Modulates Notch Signaling through the Endosomal Pathway"
1834:"A homozygous missense mutation in HERC2 associated with global developmental delay and autism spectrum disorder"
1507:"Circadian control of XPA and excision repair of cisplatin-DNA damage by cryptochrome and HERC2 ubiquitin ligase"
183:; particularly in the north and east, where it nears fixation. The variant is also found at high frequencies in
1783:
1192:
218:-directed DNA damage/cell cycle checkpoint response by regulating the stability of the deubiquitination enzyme
86:
742:"Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene"
134:
1091:
Sturm RA, Duffy DL, Zhao ZZ, Leite FP, Stark MS, Hayward NK, Martin NG, Montgomery GW (February 2008).
245:
1883:"Complete loss of function of the ubiquitin ligase HERC2 causes a severe neurodevelopmental phenotype"
840:"DNA damage-inducible SUMOylation of HERC2 promotes RNF8 binding via a novel SUMO-binding Zinc finger"
549:"A very large protein with diverse functional motifs is deficient in rjs (runty, jerky, sterile) mice"
2198:"Structure of the highly conserved HERC2 gene and of multiple partially duplicated paralogs in human"
692:"Structure of the highly conserved HERC2 gene and of multiple partially duplicated paralogs in human"
1731:
KĂĽhnle S, Kogel U, Glockzin S, Marquardt A, Ciechanover A, Matentzoglu K, Scheffner M (June 2011).
332:
238:
1216:"DNA repair excision nuclease attacks undamaged DNA. A potential source of spontaneous mutations"
789:
Lemak A, Gutmanas A, Chitayat S, Karra M, Farès C, Sunnerhagen M, Arrowsmith CH (January 2011).
331:
In accordance to its role in facilitating p53 oligomerization, HERC2 may be causally related to
1368:"HERC2 Interacts with Claspin and regulates DNA origin firing and replication fork progression"
335:
and Li-Fraumeni-like syndromes, which occur in the absence of sufficient p53 oligomerization.
1677:
Cubillos-Rojas M, Amair-Pinedo F, Peiró-Jordán R, Bartrons R, Ventura F, Rosa JL (May 2014).
1463:"Coordinated regulation of XPA stability by ATR and HERC2 during nucleotide excision repair"
2253:
1943:
1518:
560:
1733:"Physical and functional interaction of the HECT ubiquitin-protein ligases E6AP and HERC2"
1044:
8:
79:
2257:
1947:
1522:
564:
480:
455:
2429:
2391:
2319:
2184:
2092:
2065:
1964:
1931:
1907:
1882:
1863:
1814:
1759:
1732:
1705:
1678:
1649:
1622:
1595:
1568:
1541:
1506:
1440:
1340:
1315:
1314:
Yuan J, Luo K, Deng M, Li Y, Yin P, Gao B, Fang Y, Wu P, Liu T, Lou Z (December 2014).
1286:
1261:
1169:
1144:
1117:
1092:
1006:
956:
912:
864:
839:
815:
790:
766:
741:
672:
493:
2222:
2197:
2023:
Wu W, Sato K, Koike A, Nishikawa H, Koizumi H, Venkitaraman AR, Ohta T (August 2010).
1623:"HERC2 targets the iron regulator FBXL5 for degradation and modulates iron metabolism"
716:
691:
2421:
2383:
2348:
2311:
2281:
2276:
2241:
2227:
2176:
2143:
2097:
2046:
2005:
1969:
1912:
1855:
1818:
1806:
1764:
1710:
1654:
1600:
1546:
1484:
1432:
1389:
1366:
Izawa N, Wu W, Sato K, Nishikawa H, Kato A, Boku N, Itoh F, Ohta T (September 2011).
1345:
1291:
1237:
1174:
1122:
998:
994:
948:
904:
900:
869:
820:
771:
721:
664:
629:
588:
583:
548:
529:
485:
419:
325:
297:
112:
2433:
2360:
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006).
2323:
1867:
676:
2451:
2413:
2395:
2373:
2362:"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks"
2340:
2303:
2271:
2261:
2217:
2209:
2188:
2168:
2133:
2087:
2077:
2036:
1997:
1959:
1951:
1902:
1894:
1845:
1798:
1754:
1744:
1700:
1690:
1644:
1634:
1590:
1580:
1536:
1526:
1474:
1444:
1424:
1379:
1335:
1327:
1281:
1273:
1227:
1164:
1156:
1112:
1104:
990:
960:
940:
916:
896:
859:
851:
810:
802:
791:"A novel strategy for NMR resonance assignment and protein structure determination"
761:
753:
711:
703:
656:
619:
578:
568:
521:
497:
475:
467:
208:
20:
2041:
2024:
1802:
1384:
1367:
1010:
2082:
2001:
309:
123:
2344:
2242:"Shotgun sequencing of the human transcriptome with ORF expressed sequence tags"
525:
2378:
2361:
2246:
Proceedings of the
National Academy of Sciences of the United States of America
1511:
Proceedings of the
National Academy of Sciences of the United States of America
1108:
757:
553:
Proceedings of the
National Academy of Sciences of the United States of America
456:"Functional and pathological relevance of HERC family proteins: a decade later"
321:
223:
35:
2196:
Ji Y, Rebert NA, Joslin JM, Higgins MJ, Schultz RA, Nicholls RD (March 2000).
1676:
1160:
944:
806:
690:
Ji Y, Rebert NA, Joslin JM, Higgins MJ, Schultz RA, Nicholls RD (March 2000).
471:
284:
HERC2 helps to regulate p53 signalling by facilitating the oligomerization of
2445:
2138:
2121:
1749:
1695:
1639:
1585:
1531:
1413:
573:
2425:
2387:
2352:
2315:
2285:
2266:
2231:
2180:
2101:
2050:
2009:
1973:
1916:
1859:
1810:
1768:
1714:
1658:
1604:
1567:
Al-Hakim AK, Bashkurov M, Gingras AC, Durocher D, Pelletier L (June 2012).
1550:
1488:
1436:
1393:
1349:
1295:
1241:
1232:
1215:
1178:
1126:
1002:
975:
952:
908:
873:
824:
775:
725:
533:
489:
184:
2172:
2147:
1898:
1784:"Mutation of HERC2 causes developmental delay with Angelman-like features"
1331:
855:
668:
633:
624:
607:
592:
300:(AS), specifically when a region of this locus is deleted. Similar to the
1479:
1462:
1277:
1262:"HERC2/USP20 coordinates CHK1 activation by modulating CLASPIN stability"
233:
At the site of doubles stranded breaks, HERC2 facilitates the binding of
50:
gene locus, was first identified in 1990 as the gene responsible for two
27:
2213:
1932:"Genetic markers of pigmentation are novel risk loci for uveal melanoma"
707:
2417:
2238:
1850:
1833:
660:
453:
429:
261:
164:
160:
127:
The cytochrome-b5-like domain of HERC2, captured with NMR spectroscopy
24:
1955:
138:
The first RLD domain of HERC2, captured at 2.6 Ă… by X-ray diffraction
116:
The third RLD domain of HERC2, captured at 1.8 Ă… by X-ray diffraction
1025:
424:
188:
156:
139:
128:
117:
51:
2156:
1428:
2307:
454:
Sánchez-Tena S, Cubillos-Rojas M, Schneider T, Rosa JL (May 2016).
226:
mismatch error, USP20 disassociates from HERC2 and deubiquitinates
196:
173:
75:
1880:
1316:"HERC2-USP20 axis regulates DNA damage checkpoint through Claspin"
837:
1929:
1620:
192:
1566:
1142:
2402:
313:
180:
168:
55:
1621:
Moroishi T, Yamauchi T, Nishiyama M, Nakayama KI (June 2014).
1505:
Kang TH, Lindsey-Boltz LA, Reardon JT, Sancar A (March 2010).
1504:
929:
407:
397:
382:
377:
367:
352:
273:
227:
219:
215:
1730:
738:
510:
2119:
357:
347:
234:
90:
71:
31:
2025:"HERC2 is an E3 ligase that targets BRCA1 for degradation"
788:
2063:
1145:"A global view of the OCA2-HERC2 region and pigmentation"
886:
605:
546:
402:
372:
324:. HERC2 frameshift mutations have also been described in
285:
249:
2292:
2154:
1831:
1781:
1069:. University of Copenhagen. 2008-01-30. Archived from
2359:
2195:
689:
296:
The 15q11-q13 locus of HERC2 is also associated with
2022:
1365:
1017:
1213:
1090:
2330:
1461:Lee TH, Park JM, Leem SH, Kang TH (January 2014).
1193:"Allele Frequency For Polymorphic Site: rs916977"
1063:"Blue-eyed humans have a single, common ancestor"
2443:
74:and its transcription is under the control of a
1460:
343:HERC2 is known to interact with the following:
260:HERC2 has been implicated in regulating stable
1313:
1260:Zhu M, Zhao H, Liao J, Xu X (December 2014).
1259:
1214:Branum ME, Reardon JT, Sancar A (July 2001).
1084:
976:"Genetics of human iris colour and patterns"
973:
923:
155:SNPs of HERC2 are strongly associated with
1986:
2377:
2275:
2265:
2221:
2137:
2091:
2081:
2040:
1963:
1906:
1849:
1758:
1748:
1704:
1694:
1648:
1638:
1594:
1584:
1540:
1530:
1478:
1383:
1339:
1285:
1231:
1168:
1116:
863:
814:
765:
715:
646:
623:
582:
572:
479:
1042:
1026:"Here's what made those brown eyes blue"
1023:
291:
133:
122:
111:
70:gene is located at 15q13, encoded by 93
2444:
1616:
1614:
1138:
1136:
1045:"One Common Ancestor Behind Blue Eyes"
255:
202:
1726:
1724:
1672:
1670:
1668:
1562:
1560:
1500:
1498:
1456:
1454:
1409:
1407:
1405:
1403:
1361:
1359:
1309:
1307:
1305:
1255:
1253:
1251:
244:HERC2 is also involved in regulating
46:HERC2, previously referred to as the
983:Pigment Cell & Melanoma Research
974:Sturm RA, Larsson M (October 2009).
460:Cellular and Molecular Life Sciences
449:
447:
445:
96:
1737:The Journal of Biological Chemistry
1683:The Journal of Biological Chemistry
1627:The Journal of Biological Chemistry
1611:
1573:Molecular & Cellular Proteomics
1220:The Journal of Biological Chemistry
1133:
214:It is involved in coordinating the
179:The rs916977 SNP is most common in
145:
13:
2112:
1887:European Journal of Human Genetics
1721:
1665:
1557:
1495:
1451:
1400:
1356:
1302:
1248:
1097:American Journal of Human Genetics
746:American Journal of Human Genetics
279:
267:
14:
2463:
442:
995:10.1111/j.1755-148X.2009.00606.x
901:10.1111/j.1469-1809.2009.00504.x
2057:
2016:
1980:
1923:
1874:
1825:
1775:
1207:
1185:
967:
880:
338:
239:homologous recombination repair
150:
831:
782:
732:
683:
640:
599:
540:
504:
1:
2042:10.1158/0008-5472.CAN-10-1304
1803:10.1136/jmedgenet-2012-101367
1385:10.1158/0008-5472.CAN-11-0385
435:
61:
2083:10.1371/journal.pgen.1005503
2002:10.1097/pat.0b013e32834c7e78
207:HERC2 is a component of the
7:
2345:10.1016/j.ygeno.2004.01.011
1791:Journal of Medical Genetics
844:The Journal of Cell Biology
795:Journal of Biomolecular NMR
526:10.1016/j.ygeno.2004.10.006
413:
21:E3 ubiquitin protein ligase
10:
2468:
2379:10.1016/j.cell.2006.09.026
1109:10.1016/j.ajhg.2007.11.005
758:10.1016/j.ajhg.2007.10.003
246:nucleotide excision repair
41:
1161:10.1007/s00439-011-1110-x
945:10.1007/s00439-007-0460-x
807:10.1007/s10858-010-9458-0
472:10.1007/s00018-016-2139-8
1423:(1): 80–6, sup pp 1–12.
889:Annals of Human Genetics
612:Human Molecular Genetics
1750:10.1074/jbc.M110.205211
1696:10.1074/jbc.M113.527978
1640:10.1074/jbc.M113.541490
1586:10.1074/mcp.M111.014233
1532:10.1073/pnas.0915085107
1043:Bryner J (2008-01-31).
1024:Bryner J (2008-01-31).
574:10.1073/pnas.95.16.9436
2267:10.1073/pnas.97.7.3491
2139:10.1093/dnares/4.2.141
1320:Nucleic Acids Research
1266:Nucleic Acids Research
1233:10.1074/jbc.M101032200
248:by ubiquitinating the
167:colour. The ancestral
142:
131:
120:
2173:10.1007/s003359901106
1899:10.1038/ejhg.2016.139
856:10.1083/jcb.201106152
292:Clinical significance
137:
126:
115:
2296:Nature Biotechnology
1480:10.1038/onc.2012.539
333:Li-Fraumeni syndrome
2258:2000PNAS...97.3491D
2214:10.1101/gr.10.3.319
1948:2016NatSR...631191F
1523:2010PNAS..107.4890K
1417:Nature Cell Biology
1332:10.1093/nar/gku1034
708:10.1101/gr.10.3.319
625:10.1093/hmg/8.3.533
565:1998PNAS...95.9436L
430:DNA repair pathways
256:Centrosome assembly
203:DNA repair pathways
2418:10.1038/ng.2007.13
1936:Scientific Reports
1851:10.1002/humu.22237
1579:(6): M111.014233.
1278:10.1093/nar/gku978
661:10.1007/bf00355717
326:colorectal cancers
143:
132:
121:
85:At least 15 HERC2
1956:10.1038/srep31191
420:Angelman Syndrome
298:Angelman syndrome
97:Protein structure
2459:
2437:
2399:
2381:
2356:
2327:
2289:
2279:
2269:
2235:
2225:
2192:
2161:Mammalian Genome
2151:
2141:
2106:
2105:
2095:
2085:
2061:
2055:
2054:
2044:
2020:
2014:
2013:
1984:
1978:
1977:
1967:
1927:
1921:
1920:
1910:
1878:
1872:
1871:
1853:
1829:
1823:
1822:
1788:
1779:
1773:
1772:
1762:
1752:
1728:
1719:
1718:
1708:
1698:
1689:(21): 14782–95.
1674:
1663:
1662:
1652:
1642:
1633:(23): 16430–41.
1618:
1609:
1608:
1598:
1588:
1564:
1555:
1554:
1544:
1534:
1502:
1493:
1492:
1482:
1458:
1449:
1448:
1411:
1398:
1397:
1387:
1363:
1354:
1353:
1343:
1326:(21): 13110–21.
1311:
1300:
1299:
1289:
1272:(21): 13074–81.
1257:
1246:
1245:
1235:
1211:
1205:
1204:
1202:
1200:
1189:
1183:
1182:
1172:
1140:
1131:
1130:
1120:
1088:
1082:
1081:
1079:
1078:
1059:
1057:
1056:
1051:. Imaginova Corp
1040:
1038:
1037:
1021:
1015:
1014:
980:
971:
965:
964:
927:
921:
920:
884:
878:
877:
867:
835:
829:
828:
818:
786:
780:
779:
769:
736:
730:
729:
719:
687:
681:
680:
649:Mammalian Genome
644:
638:
637:
627:
603:
597:
596:
586:
576:
544:
538:
537:
508:
502:
501:
483:
451:
209:replication fork
146:Protein function
30:and one or more
2467:
2466:
2462:
2461:
2460:
2458:
2457:
2456:
2442:
2441:
2440:
2412:(12): 1443–52.
2406:Nature Genetics
2202:Genome Research
2115:
2113:Further reading
2110:
2109:
2076:(9): e1005503.
2062:
2058:
2035:(15): 6384–92.
2029:Cancer Research
2021:
2017:
1985:
1981:
1928:
1924:
1879:
1875:
1844:(12): 1639–46.
1830:
1826:
1786:
1780:
1776:
1743:(22): 19410–6.
1729:
1722:
1675:
1666:
1619:
1612:
1565:
1558:
1503:
1496:
1459:
1452:
1429:10.1038/ncb2008
1412:
1401:
1372:Cancer Research
1364:
1357:
1312:
1303:
1258:
1249:
1226:(27): 25421–6.
1212:
1208:
1198:
1196:
1191:
1190:
1186:
1141:
1134:
1089:
1085:
1076:
1074:
1061:
1054:
1052:
1035:
1033:
1022:
1018:
978:
972:
968:
928:
924:
885:
881:
836:
832:
787:
783:
737:
733:
696:Genome Research
688:
684:
645:
641:
604:
600:
559:(16): 9436–41.
545:
541:
509:
505:
466:(10): 1955–68.
452:
443:
438:
416:
341:
310:Old Order Amish
294:
282:
280:Other functions
270:
268:Iron metabolism
258:
205:
153:
148:
99:
64:
44:
12:
11:
5:
2465:
2455:
2454:
2439:
2438:
2400:
2357:
2328:
2308:10.1038/nbt971
2290:
2236:
2193:
2152:
2116:
2114:
2111:
2108:
2107:
2056:
2015:
1979:
1922:
1873:
1838:Human Mutation
1824:
1774:
1720:
1664:
1610:
1556:
1517:(11): 4890–5.
1494:
1450:
1399:
1378:(17): 5621–5.
1355:
1301:
1247:
1206:
1184:
1149:Human Genetics
1132:
1083:
1016:
966:
933:Human Genetics
922:
879:
830:
781:
731:
682:
639:
598:
539:
503:
440:
439:
437:
434:
433:
432:
427:
422:
415:
412:
411:
410:
405:
400:
395:
390:
385:
380:
375:
370:
365:
360:
355:
350:
340:
337:
322:uveal melanoma
293:
290:
281:
278:
269:
266:
257:
254:
224:DNA polymerase
204:
201:
152:
149:
147:
144:
98:
95:
63:
60:
43:
40:
9:
6:
4:
3:
2:
2464:
2453:
2450:
2449:
2447:
2435:
2431:
2427:
2423:
2419:
2415:
2411:
2407:
2401:
2397:
2393:
2389:
2385:
2380:
2375:
2372:(3): 635–48.
2371:
2367:
2363:
2358:
2354:
2350:
2346:
2342:
2339:(1): 205–10.
2338:
2334:
2329:
2325:
2321:
2317:
2313:
2309:
2305:
2302:(6): 707–16.
2301:
2297:
2291:
2287:
2283:
2278:
2273:
2268:
2263:
2259:
2255:
2252:(7): 3491–6.
2251:
2247:
2243:
2237:
2233:
2229:
2224:
2219:
2215:
2211:
2208:(3): 319–29.
2207:
2203:
2199:
2194:
2190:
2186:
2182:
2178:
2174:
2170:
2166:
2162:
2158:
2153:
2149:
2145:
2140:
2135:
2132:(2): 141–50.
2131:
2127:
2123:
2118:
2117:
2103:
2099:
2094:
2089:
2084:
2079:
2075:
2071:
2070:PLOS Genetics
2067:
2060:
2052:
2048:
2043:
2038:
2034:
2030:
2026:
2019:
2011:
2007:
2003:
1999:
1995:
1991:
1983:
1975:
1971:
1966:
1961:
1957:
1953:
1949:
1945:
1941:
1937:
1933:
1926:
1918:
1914:
1909:
1904:
1900:
1896:
1892:
1888:
1884:
1877:
1869:
1865:
1861:
1857:
1852:
1847:
1843:
1839:
1835:
1828:
1820:
1816:
1812:
1808:
1804:
1800:
1796:
1792:
1785:
1778:
1770:
1766:
1761:
1756:
1751:
1746:
1742:
1738:
1734:
1727:
1725:
1716:
1712:
1707:
1702:
1697:
1692:
1688:
1684:
1680:
1673:
1671:
1669:
1660:
1656:
1651:
1646:
1641:
1636:
1632:
1628:
1624:
1617:
1615:
1606:
1602:
1597:
1592:
1587:
1582:
1578:
1574:
1570:
1563:
1561:
1552:
1548:
1543:
1538:
1533:
1528:
1524:
1520:
1516:
1512:
1508:
1501:
1499:
1490:
1486:
1481:
1476:
1472:
1468:
1464:
1457:
1455:
1446:
1442:
1438:
1434:
1430:
1426:
1422:
1418:
1410:
1408:
1406:
1404:
1395:
1391:
1386:
1381:
1377:
1373:
1369:
1362:
1360:
1351:
1347:
1342:
1337:
1333:
1329:
1325:
1321:
1317:
1310:
1308:
1306:
1297:
1293:
1288:
1283:
1279:
1275:
1271:
1267:
1263:
1256:
1254:
1252:
1243:
1239:
1234:
1229:
1225:
1221:
1217:
1210:
1194:
1188:
1180:
1176:
1171:
1166:
1162:
1158:
1155:(5): 683–96.
1154:
1150:
1146:
1139:
1137:
1128:
1124:
1119:
1114:
1110:
1106:
1103:(2): 424–31.
1102:
1098:
1094:
1087:
1073:on 2008-11-08
1072:
1068:
1064:
1050:
1046:
1031:
1027:
1020:
1012:
1008:
1004:
1000:
996:
992:
989:(5): 544–62.
988:
984:
977:
970:
962:
958:
954:
950:
946:
942:
939:(2): 177–87.
938:
934:
926:
918:
914:
910:
906:
902:
898:
895:(2): 160–70.
894:
890:
883:
875:
871:
866:
861:
857:
853:
850:(2): 179–87.
849:
845:
841:
834:
826:
822:
817:
812:
808:
804:
800:
796:
792:
785:
777:
773:
768:
763:
759:
755:
752:(2): 411–23.
751:
747:
743:
735:
727:
723:
718:
713:
709:
705:
702:(3): 319–29.
701:
697:
693:
686:
678:
674:
670:
666:
662:
658:
655:(4): 187–91.
654:
650:
643:
635:
631:
626:
621:
618:(3): 533–42.
617:
613:
609:
602:
594:
590:
585:
580:
575:
570:
566:
562:
558:
554:
550:
543:
535:
531:
527:
523:
520:(2): 153–64.
519:
515:
507:
499:
495:
491:
487:
482:
477:
473:
469:
465:
461:
457:
450:
448:
446:
441:
431:
428:
426:
423:
421:
418:
417:
409:
406:
404:
401:
399:
396:
394:
391:
389:
386:
384:
381:
379:
376:
374:
371:
369:
366:
364:
361:
359:
356:
354:
351:
349:
346:
345:
344:
336:
334:
329:
327:
323:
318:
315:
311:
306:
303:
299:
289:
287:
277:
275:
265:
263:
253:
251:
247:
242:
240:
236:
231:
229:
225:
221:
217:
212:
210:
200:
198:
194:
190:
186:
182:
177:
175:
170:
166:
162:
158:
141:
136:
130:
125:
119:
114:
110:
107:
103:
94:
92:
88:
83:
81:
77:
73:
69:
59:
57:
53:
49:
39:
37:
33:
29:
26:
22:
18:
2409:
2405:
2369:
2365:
2336:
2332:
2299:
2295:
2249:
2245:
2205:
2201:
2167:(9): 870–8.
2164:
2160:
2129:
2126:DNA Research
2125:
2073:
2069:
2059:
2032:
2028:
2018:
1996:(7): 753–5.
1993:
1989:
1982:
1942:(1): 31191.
1939:
1935:
1925:
1893:(1): 52–58.
1890:
1886:
1876:
1841:
1837:
1827:
1797:(2): 65–73.
1794:
1790:
1777:
1740:
1736:
1686:
1682:
1630:
1626:
1576:
1572:
1514:
1510:
1473:(1): 19–25.
1470:
1466:
1420:
1416:
1375:
1371:
1323:
1319:
1269:
1265:
1223:
1219:
1209:
1197:. Retrieved
1187:
1152:
1148:
1100:
1096:
1086:
1075:. Retrieved
1071:the original
1066:
1053:. Retrieved
1048:
1034:. Retrieved
1029:
1019:
986:
982:
969:
936:
932:
925:
892:
888:
882:
847:
843:
833:
801:(1): 27–38.
798:
794:
784:
749:
745:
734:
699:
695:
685:
652:
648:
642:
615:
611:
601:
556:
552:
542:
517:
513:
506:
463:
459:
342:
339:Interactions
330:
319:
307:
301:
295:
283:
271:
259:
243:
232:
213:
206:
185:North Africa
178:
154:
151:Pigmentation
108:
104:
100:
93:'s product.
84:
67:
65:
47:
45:
34:-like (RLD)
28:HECT domains
16:
15:
1049:LiveScience
1030:Health News
157:iris colour
19:is a giant
1077:2008-11-06
1055:2008-11-06
1036:2008-11-06
1032:. NBC News
436:References
262:centrosome
62:Gene locus
52:phenotypes
25:C-terminal
1990:Pathology
1819:206997462
425:Eye color
189:Near East
66:The full
2446:Category
2434:19313549
2426:17952075
2388:17081983
2353:15203218
2333:Genomics
2324:27764390
2316:15146197
2286:10737800
2232:10720573
2181:10441737
2102:26355680
2051:20631078
2010:22124266
1974:27499155
1917:27759030
1868:10372349
1860:23065719
1811:23243086
1769:21493713
1715:24722987
1659:24778179
1605:22261722
1551:20304803
1489:23178497
1467:Oncogene
1437:20023648
1394:21775519
1350:25355518
1296:25326330
1242:11353769
1195:. ALFRED
1179:22065085
1127:18252222
1003:19619260
953:18172690
909:19208107
874:22508508
825:21161328
776:18252221
726:10720573
677:32406842
534:15676274
514:Genomics
490:26801221
481:11108380
414:See also
197:Americas
195:and the
174:genotype
80:promoter
2452:Ligases
2396:7827573
2254:Bibcode
2189:5542559
2148:9205841
2093:4565672
1965:4976361
1944:Bibcode
1908:5159772
1760:3103319
1706:4031533
1650:4047410
1596:3433907
1542:2841896
1519:Bibcode
1445:9996031
1341:4245938
1287:4245974
1199:22 June
1170:3325407
1118:2427173
961:9886658
917:5233533
865:3328386
816:3715383
767:2427174
669:1611213
634:9949213
593:9689098
561:Bibcode
498:7457614
378:Claspin
228:claspin
193:Oceania
56:alleles
42:History
36:domains
2432:
2424:
2394:
2386:
2351:
2322:
2314:
2284:
2274:
2230:
2223:311424
2220:
2187:
2179:
2146:
2100:
2090:
2049:
2008:
1972:
1962:
1915:
1905:
1866:
1858:
1817:
1809:
1767:
1757:
1713:
1703:
1657:
1647:
1603:
1593:
1549:
1539:
1487:
1443:
1435:
1392:
1348:
1338:
1294:
1284:
1240:
1177:
1167:
1125:
1115:
1011:893259
1009:
1001:
959:
951:
915:
907:
872:
862:
823:
813:
774:
764:
724:
717:311424
714:
675:
667:
632:
591:
581:
532:
496:
488:
478:
393:RNF168
388:NEURL4
314:autism
187:, the
181:Europe
169:allele
140:(4L1M)
129:(2KEO)
118:(3KCI)
2430:S2CID
2392:S2CID
2320:S2CID
2277:16267
2185:S2CID
1864:S2CID
1815:S2CID
1787:(PDF)
1441:S2CID
1007:S2CID
979:(PDF)
957:S2CID
913:S2CID
673:S2CID
584:21356
494:S2CID
408:LRRK2
398:BRCA1
368:USP20
363:UBC13
353:FBXL5
274:FBXL5
220:USP20
78:rich
72:exons
68:HERC2
17:HERC2
2422:PMID
2384:PMID
2366:Cell
2349:PMID
2312:PMID
2282:PMID
2228:PMID
2177:PMID
2144:PMID
2098:PMID
2047:PMID
2006:PMID
1970:PMID
1913:PMID
1856:PMID
1807:PMID
1765:PMID
1711:PMID
1655:PMID
1601:PMID
1547:PMID
1485:PMID
1433:PMID
1390:PMID
1346:PMID
1292:PMID
1238:PMID
1201:2016
1175:PMID
1123:PMID
1067:News
999:PMID
949:PMID
905:PMID
870:PMID
821:PMID
772:PMID
722:PMID
665:PMID
630:PMID
589:PMID
530:PMID
486:PMID
383:E6AP
358:OCA2
348:RNF8
235:RNF8
216:Chk1
165:hair
163:and
161:skin
91:OCA2
87:SNPs
32:RCC1
2414:doi
2374:doi
2370:127
2341:doi
2304:doi
2272:PMC
2262:doi
2218:PMC
2210:doi
2169:doi
2134:doi
2088:PMC
2078:doi
2037:doi
1998:doi
1960:PMC
1952:doi
1903:PMC
1895:doi
1846:doi
1799:doi
1755:PMC
1745:doi
1741:286
1701:PMC
1691:doi
1687:289
1645:PMC
1635:doi
1631:289
1591:PMC
1581:doi
1537:PMC
1527:doi
1515:107
1475:doi
1425:doi
1380:doi
1336:PMC
1328:doi
1282:PMC
1274:doi
1228:doi
1224:276
1165:PMC
1157:doi
1153:131
1113:PMC
1105:doi
991:doi
941:doi
937:123
897:doi
860:PMC
852:doi
848:197
811:PMC
803:doi
762:PMC
754:doi
712:PMC
704:doi
657:doi
620:doi
579:PMC
569:doi
522:doi
476:PMC
468:doi
403:p53
373:XPA
308:In
302:rjs
286:p53
250:XPA
76:CpG
48:rjs
2448::
2428:.
2420:.
2410:39
2408:.
2390:.
2382:.
2368:.
2364:.
2347:.
2337:84
2335:.
2318:.
2310:.
2300:22
2298:.
2280:.
2270:.
2260:.
2250:97
2248:.
2244:.
2226:.
2216:.
2206:10
2204:.
2200:.
2183:.
2175:.
2165:10
2163:.
2159:.
2142:.
2128:.
2124:.
2096:.
2086:.
2074:11
2072:.
2068:.
2045:.
2033:70
2031:.
2027:.
2004:.
1994:43
1992:.
1968:.
1958:.
1950:.
1938:.
1934:.
1911:.
1901:.
1891:25
1889:.
1885:.
1862:.
1854:.
1842:33
1840:.
1836:.
1813:.
1805:.
1795:50
1793:.
1789:.
1763:.
1753:.
1739:.
1735:.
1723:^
1709:.
1699:.
1685:.
1681:.
1667:^
1653:.
1643:.
1629:.
1625:.
1613:^
1599:.
1589:.
1577:11
1575:.
1571:.
1559:^
1545:.
1535:.
1525:.
1513:.
1509:.
1497:^
1483:.
1471:33
1469:.
1465:.
1453:^
1439:.
1431:.
1421:12
1419:.
1402:^
1388:.
1376:71
1374:.
1370:.
1358:^
1344:.
1334:.
1324:42
1322:.
1318:.
1304:^
1290:.
1280:.
1270:42
1268:.
1264:.
1250:^
1236:.
1222:.
1218:.
1173:.
1163:.
1151:.
1147:.
1135:^
1121:.
1111:.
1101:82
1099:.
1095:.
1065:.
1060:;
1047:.
1041:;
1028:.
1005:.
997:.
987:22
985:.
981:.
955:.
947:.
935:.
911:.
903:.
893:73
891:.
868:.
858:.
846:.
842:.
819:.
809:.
799:49
797:.
793:.
770:.
760:.
750:82
748:.
744:.
720:.
710:.
700:10
698:.
694:.
671:.
663:.
651:.
628:.
614:.
610:.
587:.
577:.
567:.
557:95
555:.
551:.
528:.
518:85
516:.
492:.
484:.
474:.
464:73
462:.
458:.
444:^
328:.
241:.
199:.
191:,
38:.
2436:.
2416::
2398:.
2376::
2355:.
2343::
2326:.
2306::
2288:.
2264::
2256::
2234:.
2212::
2191:.
2171::
2150:.
2136::
2130:4
2104:.
2080::
2053:.
2039::
2012:.
2000::
1976:.
1954::
1946::
1940:6
1919:.
1897::
1870:.
1848::
1821:.
1801::
1771:.
1747::
1717:.
1693::
1661:.
1637::
1607:.
1583::
1553:.
1529::
1521::
1491:.
1477::
1447:.
1427::
1396:.
1382::
1352:.
1330::
1298:.
1276::
1244:.
1230::
1203:.
1181:.
1159::
1129:.
1107::
1080:.
1058:.
1039:.
1013:.
993::
963:.
943::
919:.
899::
876:.
854::
827:.
805::
778:.
756::
728:.
706::
679:.
659::
653:3
636:.
622::
616:8
595:.
571::
563::
536:.
524::
500:.
470::
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
