UBP7_HUMAN
ID UBP7_HUMAN Reviewed; 1102 AA.
AC Q93009; A6NMY8; B7Z815; H0Y3G8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 04-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 7;
DE EC=3.4.19.12 {ECO:0000269|PubMed:11923872, ECO:0000269|PubMed:12507430, ECO:0000269|PubMed:14506283, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:16964248, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:21745816};
DE AltName: Full=Deubiquitinating enzyme 7;
DE AltName: Full=Herpesvirus-associated ubiquitin-specific protease {ECO:0000303|PubMed:9034339};
DE AltName: Full=Ubiquitin thioesterase 7;
DE AltName: Full=Ubiquitin-specific-processing protease 7;
GN Name=USP7 {ECO:0000303|PubMed:12093161, ECO:0000312|HGNC:HGNC:12630};
GN Synonyms=HAUSP {ECO:0000303|PubMed:9034339};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, CATALYTIC
RP ACTIVITY, SUBCELLULAR LOCATION, AND INTERACTION WITH HERPESVIRUS 1
RP TRANS-ACTING TRANSCRIPTIONAL PROTEIN ICP0/VMW110.
RC TISSUE=Mammary cancer;
RX PubMed=9034339; DOI=10.1093/emboj/16.3.566;
RA Everett R.D., Meredith M., Orr A., Cross A., Kathoria M., Parkinson J.;
RT "A novel ubiquitin-specific protease is dynamically associated with the PML
RT nuclear domain and binds to a herpesvirus regulatory protein.";
RL EMBO J. 16:566-577(1997).
RN [2]
RP ERRATUM OF PUBMED:9034339.
RX PubMed=9130697; DOI=10.1093/emboj/16.7.1519;
RA Everett R.D., Meredith M., Orr A., Cross A., Kathoria M., Parkinson J.;
RL EMBO J. 16:1519-1530(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 705-1102 (ISOFORM 1), SUBCELLULAR LOCATION,
RP AND INTERACTION WITH ATXN1.
RX PubMed=12093161; DOI=10.1006/mcne.2002.1103;
RA Hong S., Kim S.J., Ka S., Choi I., Kang S.;
RT "USP7, a ubiquitin-specific protease, interacts with ataxin-1, the SCA1
RT gene product.";
RL Mol. Cell. Neurosci. 20:298-306(2002).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH TP53, MUTAGENESIS OF
RP CYS-223, AND ACTIVE SITE.
RX PubMed=11923872; DOI=10.1038/nature737;
RA Li M., Chen D., Shiloh A., Luo J., Nikolaev A.Y., Qin J., Gu W.;
RT "Deubiquitination of p53 by HAUSP is an important pathway for p53
RT stabilization.";
RL Nature 416:648-653(2002).
RN [8]
RP FUNCTION (MICROBIAL INFECTION), SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES,
RP ACTIVITY REGULATION, INTERACTION WITH HERPESVIRUS 1 TRANS-ACTING
RP TRANSCRIPTIONAL PROTEIN ICP0/VMW110 AND EBV EBNA1 (MICROBIAL INFECTION),
RP AND REGION.
RX PubMed=14506283; DOI=10.1074/jbc.m307200200;
RA Holowaty M.N., Sheng Y., Nguyen T., Arrowsmith C., Frappier L.;
RT "Protein interaction domains of the ubiquitin-specific protease,
RT USP7/HAUSP.";
RL J. Biol. Chem. 278:47753-47761(2003).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH MDM2, MUTAGENESIS OF
RP CYS-223, AND ACTIVE SITE.
RX PubMed=15053880; DOI=10.1016/s1097-2765(04)00157-1;
RA Li M., Brooks C.L., Kon N., Gu W.;
RT "A dynamic role of HAUSP in the p53-Mdm2 pathway.";
RL Mol. Cell 13:879-886(2004).
RN [10]
RP FUNCTION (MICROBIAL INFECTION), UBIQUITINATION, AND INTERACTION WITH
RP HERPESVIRUS 1 TRANS-ACTING TRANSCRIPTIONAL PROTEIN ICP0/VMW110 (MICROBIAL
RP INFECTION).
RX PubMed=16160161; DOI=10.1128/jvi.79.19.12342-12354.2005;
RA Boutell C., Canning M., Orr A., Everett R.D.;
RT "Reciprocal activities between herpes simplex virus type 1 regulatory
RT protein ICP0, a ubiquitin E3 ligase, and ubiquitin-specific protease
RT USP7.";
RL J. Virol. 79:12342-12354(2005).
RN [11]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH DAXX AND MDM2, INTERACTION WITH
RP DAXX, AND SUBCELLULAR LOCATION.
RX PubMed=16845383; DOI=10.1038/ncb1442;
RA Tang J., Qu L.K., Zhang J., Wang W., Michaelson J.S., Degenhardt Y.Y.,
RA El-Deiry W.S., Yang X.;
RT "Critical role for Daxx in regulating Mdm2.";
RL Nat. Cell Biol. 8:855-862(2006).
RN [12]
RP FUNCTION, INTERACTION WITH FOXO4, MUTAGENESIS OF CYS-223, AND CATALYTIC
RP ACTIVITY.
RX PubMed=16964248; DOI=10.1038/ncb1469;
RA van der Horst A., de Vries-Smits A.M., Brenkman A.B., van Triest M.H.,
RA van den Broek N., Colland F., Maurice M.M., Burgering B.M.;
RT "FOXO4 transcriptional activity is regulated by monoubiquitination and
RT USP7/HAUSP.";
RL Nat. Cell Biol. 8:1064-1073(2006).
RN [13]
RP SUBUNIT, PHOSPHORYLATION AT SER-18 AND SER-963, UBIQUITINATION AT LYS-869,
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17651432; DOI=10.1111/j.1742-4658.2007.05952.x;
RA Fernandez-Montalvan A., Bouwmeester T., Joberty G., Mader R., Mahnke M.,
RA Pierrat B., Schlaeppi J.M., Worpenberg S., Gerhartz B.;
RT "Biochemical characterization of USP7 reveals post-translational
RT modification sites and structural requirements for substrate processing and
RT subcellular localization.";
RL FEBS J. 274:4256-4270(2007).
RN [14]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH DAXX; RASSF1 AND MDM2, AND
RP INTERACTION WITH DAXX AND MDM2.
RX PubMed=18566590; DOI=10.1038/emboj.2008.115;
RA Song M.S., Song S.J., Kim S.Y., Oh H.J., Lim D.S.;
RT "The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by
RT disrupting the MDM2-DAXX-HAUSP complex.";
RL EMBO J. 27:1863-1874(2008).
RN [15]
RP RETRACTION NOTICE OF PUBMED:18566590, AND CAUTION.
RX PubMed=18768758; DOI=10.1091/mbc.e08-01-0067;
RA Zweitzig D.R., Shcherbik N., Haines D.S.;
RT "AAA ATPase p97 and adaptor UBXD1 suppress MDM2 ubiquitination and
RT degradation and promote constitutive p53 turnover.";
RL Mol. Biol. Cell 19:5029-5029(2008).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH PTEN, MUTAGENESIS OF
RP CYS-223, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18716620; DOI=10.1038/nature07290;
RA Song M.S., Salmena L., Carracedo A., Egia A., Lo-Coco F.,
RA Teruya-Feldstein J., Pandolfi P.P.;
RT "The deubiquitinylation and localization of PTEN are regulated by a HAUSP-
RT PML network.";
RL Nature 455:813-817(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-963, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH HERPESVIRUS 1 TRANS-ACTING
RP TRANSCRIPTIONAL PROTEIN ICP0/VMW110 (MICROBIAL INFECTION), SUBCELLULAR
RP LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, AND ALTERNATIVE SPLICING
RP (ISOFORM 2).
RX PubMed=18590780; DOI=10.1016/j.virusres.2008.05.017;
RA Antrobus R., Boutell C.;
RT "Identification of a novel higher molecular weight isoform of USP7/HAUSP
RT that interacts with the Herpes simplex virus type-1 immediate early protein
RT ICP0.";
RL Virus Res. 137:64-71(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-869; LYS-1084 AND LYS-1096, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [21]
RP FUNCTION.
RX PubMed=20153724; DOI=10.1016/j.bbrc.2010.02.051;
RA Tang J., Qu L., Pang M., Yang X.;
RT "Daxx is reciprocally regulated by Mdm2 and Hausp.";
RL Biochem. Biophys. Res. Commun. 393:542-545(2010).
RN [22]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH THE PRC1-LIKE COMPLEX.
RX PubMed=20601937; DOI=10.1038/emboj.2010.129;
RA Maertens G.N., El Messaoudi-Aubert S., Elderkin S., Hiom K., Peters G.;
RT "Ubiquitin-specific proteases 7 and 11 modulate Polycomb regulation of the
RT INK4a tumour suppressor.";
RL EMBO J. 29:2553-2565(2010).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [25]
RP INTERACTION WITH TSPYL5.
RX PubMed=21170034; DOI=10.1038/ncb2142;
RA Epping M.T., Meijer L.A., Krijgsman O., Bos J.L., Pandolfi P.P.,
RA Bernards R.;
RT "TSPYL5 suppresses p53 levels and function by physical interaction with
RT USP7.";
RL Nat. Cell Biol. 13:102-108(2011).
RN [26]
RP FUNCTION, INTERACTION WITH REST, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP INDUCTION, AND MUTAGENESIS OF CYS-223.
RX PubMed=21258371; DOI=10.1038/ncb2153;
RA Huang Z., Wu Q., Guryanova O.A., Cheng L., Shou W., Rich J.N., Bao S.;
RT "Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural
RT progenitor cells.";
RL Nat. Cell Biol. 13:142-152(2011).
RN [27]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH DNMT1 AND UHRF1, MUTAGENESIS
RP OF CYS-223, AND ACTIVE SITE.
RX PubMed=21745816; DOI=10.1093/nar/gkr528;
RA Felle M., Joppien S., Nemeth A., Diermeier S., Thalhammer V., Dobner T.,
RA Kremmer E., Kappler R., Langst G.;
RT "The USP7/Dnmt1 complex stimulates the DNA methylation activity of Dnmt1
RT and regulates the stability of UHRF1.";
RL Nucleic Acids Res. 39:8355-8365(2011).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [29]
RP INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEINS UL35 AND UL35A (MICROBIAL
RP INFECTION).
RX PubMed=22072767; DOI=10.1128/jvi.05442-11;
RA Salsman J., Jagannathan M., Paladino P., Chan P.K., Dellaire G., Raught B.,
RA Frappier L.;
RT "Proteomic profiling of the human cytomegalovirus UL35 gene products
RT reveals a role for UL35 in the DNA repair response.";
RL J. Virol. 86:806-820(2012).
RN [30]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH UHRF1, MUTAGENESIS OF
RP CYS-223, AND ACTIVE SITE.
RX PubMed=22411829; DOI=10.1073/pnas.1116349109;
RA Ma H., Chen H., Guo X., Wang Z., Sowa M.E., Zheng L., Hu S., Zeng P.,
RA Guo R., Diao J., Lan F., Harper J.W., Shi Y.G., Xu Y., Shi Y.;
RT "M phase phosphorylation of the epigenetic regulator UHRF1 regulates its
RT physical association with the deubiquitylase USP7 and stability.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:4828-4833(2012).
RN [31]
RP FUNCTION, AND LINKAGE SPECIFICITY.
RX PubMed=22689415; DOI=10.1002/cbic.201200261;
RA Iphofer A., Kummer A., Nimtz M., Ritter A., Arnold T., Frank R.,
RA van den Heuvel J., Kessler B.M., Jansch L., Franke R.;
RT "Profiling ubiquitin linkage specificities of deubiquitinating enzymes with
RT branched ubiquitin isopeptide probes.";
RL ChemBioChem 13:1416-1420(2012).
RN [32]
RP INTERACTION WITH MEX3C.
RX PubMed=22863774; DOI=10.1038/emboj.2012.218;
RA Cano F., Bye H., Duncan L.M., Buchet-Poyau K., Billaud M., Wills M.R.,
RA Lehner P.J.;
RT "The RNA-binding E3 ubiquitin ligase MEX-3C links ubiquitination with MHC-I
RT mRNA degradation.";
RL EMBO J. 31:3596-3606(2012).
RN [33]
RP FUNCTION, AND INTERACTION WITH UVSSA.
RX PubMed=22466611; DOI=10.1038/ng.2230;
RA Schwertman P., Lagarou A., Dekkers D.H., Raams A., van der Hoek A.C.,
RA Laffeber C., Hoeijmakers J.H., Demmers J.A., Fousteri M., Vermeulen W.,
RA Marteijn J.A.;
RT "UV-sensitive syndrome protein UVSSA recruits USP7 to regulate
RT transcription-coupled repair.";
RL Nat. Genet. 44:598-602(2012).
RN [34]
RP FUNCTION, AND INTERACTION WITH UVSSA.
RX PubMed=22466612; DOI=10.1038/ng.2228;
RA Zhang X., Horibata K., Saijo M., Ishigami C., Ukai A., Kanno S.I.,
RA Tahara H., Neilan E.G., Honma M., Nohmi T., Yasui A., Tanaka K.;
RT "Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in
RT transcription-coupled DNA repair.";
RL Nat. Genet. 44:593-597(2012).
RN [35]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION,
RP INTERACTION WITH FOXP3, AND INDUCTION.
RX PubMed=23973222; DOI=10.1016/j.immuni.2013.05.018;
RA van Loosdregt J., Fleskens V., Fu J., Brenkman A.B., Bekker C.P.,
RA Pals C.E., Meerding J., Berkers C.R., Barbi J., Grone A., Sijts A.J.,
RA Maurice M.M., Kalkhoven E., Prakken B.J., Ovaa H., Pan F., Zaiss D.M.,
RA Coffer P.J.;
RT "Stabilization of the transcription factor Foxp3 by the deubiquitinase USP7
RT increases Treg-cell-suppressive capacity.";
RL Immunity 39:259-271(2013).
RN [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [37]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [38]
RP INTERACTION WITH RNF220.
RX PubMed=25266658; DOI=10.1128/mcb.00731-14;
RA Ma P., Yang X., Kong Q., Li C., Yang S., Li Y., Mao B.;
RT "The ubiquitin ligase RNF220 enhances canonical Wnt signaling through USP7-
RT mediated deubiquitination of beta-catenin.";
RL Mol. Cell. Biol. 34:4355-4366(2014).
RN [39]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH ABRAXAS2 AND TP53, AND
RP SUBCELLULAR LOCATION.
RX PubMed=25283148; DOI=10.1038/ncomms6059;
RA Zhang J., Cao M., Dong J., Li C., Xu W., Zhan Y., Wang X., Yu M., Ge C.,
RA Ge Z., Yang X.;
RT "ABRO1 suppresses tumourigenesis and regulates the DNA damage response by
RT stabilizing p53.";
RL Nat. Commun. 5:5059-5059(2014).
RN [40]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-869, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [41]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=25865756; DOI=10.1038/ncomms7752;
RA Cui H., Guo M., Xu D., Ding Z.C., Zhou G., Ding H.F., Zhang J., Tang Y.,
RA Yan C.;
RT "The stress-responsive gene ATF3 regulates the histone acetyltransferase
RT Tip60.";
RL Nat. Commun. 6:6752-6752(2015).
RN [42]
RP INTERACTION WITH ERCC6.
RX PubMed=26030138; DOI=10.1371/journal.pone.0128558;
RA Nicolai S., Filippi S., Caputo M., Cipak L., Gregan J., Ammerer G.,
RA Frontini M., Willems D., Prantera G., Balajee A.S., Proietti-De-Santis L.;
RT "Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group
RT B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin
RT Dynamics.";
RL PLoS ONE 10:E0128558-E0128558(2015).
RN [43]
RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN A COMPLEX WITH OGT AND
RP KMT2E, INTERACTION WITH OGT AND KMT2E, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF CYS-223.
RX PubMed=26678539; DOI=10.1371/journal.pone.0145023;
RA Ding X., Jiang W., Zhou P., Liu L., Wan X., Yuan X., Wang X., Chen M.,
RA Chen J., Yang J., Kong C., Li B., Peng C., Wong C.C., Hou F., Zhang Y.;
RT "Mixed lineage leukemia 5 (MLL5) protein stability is cooperatively
RT regulated by O-GlcNac transferase (OGT) and ubiquitin specific protease 7
RT (USP7).";
RL PLoS ONE 10:E0145023-E0145023(2015).
RN [44]
RP FUNCTION, INTERACTION WITH CRY2, AND MUTAGENESIS OF CYS-223.
RX PubMed=27123980; DOI=10.1371/journal.pone.0154263;
RA Hirano A., Nakagawa T., Yoshitane H., Oyama M., Kozuka-Hata H.,
RA Lanjakornsiripan D., Fukada Y.;
RT "USP7 and TDP-43: pleiotropic regulation of cryptochrome protein stability
RT paces the oscillation of the mammalian circadian clock.";
RL PLoS ONE 11:E0154263-E0154263(2016).
RN [45]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-223.
RX PubMed=28655758; DOI=10.1074/jbc.m117.780130;
RA Jiang L., Xiong J., Zhan J., Yuan F., Tang M., Zhang C., Cao Z., Chen Y.,
RA Lu X., Li Y., Wang H., Wang L., Wang J., Zhu W.G., Wang H.;
RT "Ubiquitin-specific peptidase 7 (USP7)-mediated deubiquitination of the
RT histone deacetylase SIRT7 regulates gluconeogenesis.";
RL J. Biol. Chem. 292:13296-13311(2017).
RN [46]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-869 AND LYS-882, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 208-560 IN COMPLEX WITH UBIQUITIN,
RP CATALYTIC ACTIVITY, ACTIVE SITE, MUTAGENESIS OF CYS-223; HIS-456 AND
RP HIS-464, AND INTERACTION WITH TP53.
RX PubMed=12507430; DOI=10.1016/s0092-8674(02)01199-6;
RA Hu M., Li P., Li M., Li W., Yao T., Wu J.-W., Gu W., Cohen R.E., Shi Y.;
RT "Crystal structure of a UBP-family deubiquitinating enzyme in isolation and
RT in complex with ubiquitin aldehyde.";
RL Cell 111:1041-1054(2002).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 54-205 IN COMPLEX WITH EBNA1, AND
RP INTERACTION WITH EBV EBNA1.
RX PubMed=15808506; DOI=10.1016/j.molcel.2005.02.029;
RA Saridakis V., Sheng Y., Sarkari F., Holowaty M.N., Shire K., Nguyen T.,
RA Zhang R.G., Liao J., Lee W., Edwards A.M., Arrowsmith C.H., Frappier L.;
RT "Structure of the p53 binding domain of HAUSP/USP7 bound to Epstein-Barr
RT nuclear antigen 1 implications for EBV-mediated immortalization.";
RL Mol. Cell 18:25-36(2005).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 43-560 IN COMPLEX WITH TP53 AND
RP MDM2, AND INTERACTION WITH TP53 AND MDM2.
RX PubMed=16402859; DOI=10.1371/journal.pbio.0040027;
RA Hu M., Gu L., Li M., Jeffrey P.D., Gu W., Shi Y.;
RT "Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7:
RT implications for the regulation of the p53-MDM2 pathway.";
RL PLoS Biol. 4:228-239(2006).
RN [50]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 54-205 IN COMPLEX WITH TP53 AND
RP MDM2, INTERACTION WITH TP53 AND MDM2, AND MUTAGENESIS OF ASP-164 AND
RP TRP-165.
RX PubMed=16474402; DOI=10.1038/nsmb1067;
RA Sheng Y., Saridakis V., Sarkari F., Duan S., Wu T., Arrowsmith C.H.,
RA Frappier L.;
RT "Molecular recognition of p53 and MDM2 by USP7/HAUSP.";
RL Nat. Struct. Mol. Biol. 13:285-291(2006).
RN [51]
RP FUNCTION, INTERACTION WITH OTUD4; ALKBH3 AND USP9X, MUTAGENESIS OF CYS-223,
RP AND ACTIVE SITE.
RX PubMed=25944111; DOI=10.15252/embj.201490497;
RA Zhao Y., Majid M.C., Soll J.M., Brickner J.R., Dango S., Mosammaparast N.;
RT "Noncanonical regulation of alkylation damage resistance by the OTUD4
RT deubiquitinase.";
RL EMBO J. 34:1687-1703(2015).
CC -!- FUNCTION: Hydrolase that deubiquitinates target proteins such as FOXO4,
CC KAT5, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX
CC (PubMed:11923872, PubMed:15053880, PubMed:16964248, PubMed:18716620,
CC PubMed:25283148, PubMed:25865756, PubMed:26678539, PubMed:28655758).
CC Together with DAXX, prevents MDM2 self-ubiquitination and enhances the
CC E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53
CC ubiquitination and proteasomal degradation (PubMed:15053880,
CC PubMed:16845383, PubMed:18566590, PubMed:20153724). Deubiquitinates
CC p53/TP53, preventing degradation of p53/TP53, and enhances p53/TP53-
CC dependent transcription regulation, cell growth repression and
CC apoptosis (PubMed:25283148). Deubiquitinates p53/TP53 and MDM2 and
CC strongly stabilizes p53/TP53 even in the presence of excess MDM2, and
CC also induces p53/TP53-dependent cell growth repression and apoptosis
CC (PubMed:11923872). Deubiquitination of FOXO4 in presence of hydrogen
CC peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced
CC transcriptional activity (PubMed:16964248). In association with DAXX,
CC is involved in the deubiquitination and translocation of PTEN from the
CC nucleus to the cytoplasm, both processes that are counteracted by PML
CC (PubMed:18716620). Deubiquitinates KMT2E/MLL5 preventing KMT2E/MLL5
CC proteasomal-mediated degradation (PubMed:26678539). Involved in cell
CC proliferation during early embryonic development. Involved in
CC transcription-coupled nucleotide excision repair (TC-NER) in response
CC to UV damage: recruited to DNA damage sites following interaction with
CC KIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV-
CC induced degradation of ERCC6 (PubMed:22466611, PubMed:22466612).
CC Involved in maintenance of DNA methylation via its interaction with
CC UHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1,
CC preventing their degradation and promoting DNA methylation by DNMT1
CC (PubMed:21745816, PubMed:22411829). Deubiquitinates alkylation repair
CC enzyme ALKBH3. OTUD4 recruits USP7 and USP9X to stabilize ALKBH3,
CC thereby promoting the repair of alkylated DNA lesions
CC (PubMed:25944111). Acts as a chromatin regulator via its association
CC with the Polycomb group (PcG) multiprotein PRC1-like complex; may act
CC by deubiquitinating components of the PRC1-like complex
CC (PubMed:20601937). Able to mediate deubiquitination of histone H2B; it
CC is however unsure whether this activity takes place in vivo
CC (PubMed:20601937). Exhibits a preference towards 'Lys-48'-linked
CC ubiquitin chains (PubMed:22689415). Increases regulatory T-cells (Treg)
CC suppressive capacity by deubiquitinating and stabilizing the
CC transcription factor FOXP3 which is crucial for Treg cell function
CC (PubMed:23973222). Plays a role in the maintenance of the circadian
CC clock periodicity via deubiquitination and stabilization of the CRY1
CC and CRY2 proteins (PubMed:27123980). Deubiquitinates REST, thereby
CC stabilizing REST and promoting the maintenance of neural progenitor
CC cells (PubMed:21258371). Deubiquitinates SIRT7, inhibiting SIRT7
CC histone deacetylase activity and regulating gluconeogenesis
CC (PubMed:28655758). {ECO:0000269|PubMed:11923872,
CC ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:16845383,
CC ECO:0000269|PubMed:16964248, ECO:0000269|PubMed:18566590,
CC ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:20153724,
CC ECO:0000269|PubMed:20601937, ECO:0000269|PubMed:21258371,
CC ECO:0000269|PubMed:21745816, ECO:0000269|PubMed:22411829,
CC ECO:0000269|PubMed:22466611, ECO:0000269|PubMed:22466612,
CC ECO:0000269|PubMed:22689415, ECO:0000269|PubMed:23973222,
CC ECO:0000269|PubMed:25283148, ECO:0000269|PubMed:25865756,
CC ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:26678539,
CC ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28655758}.
CC -!- FUNCTION: (Microbial infection) Contributes to the overall
CC stabilization and trans-activation capability of the herpesvirus 1
CC trans-acting transcriptional protein ICP0/VMW110 during HSV-1
CC infection. {ECO:0000269|PubMed:14506283, ECO:0000269|PubMed:16160161,
CC ECO:0000269|PubMed:18590780}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:11923872,
CC ECO:0000269|PubMed:12507430, ECO:0000269|PubMed:14506283,
CC ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:16964248,
CC ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:21745816,
CC ECO:0000269|PubMed:25865756, ECO:0000269|PubMed:26678539,
CC ECO:0000269|PubMed:28655758};
CC -!- ACTIVITY REGULATION: Inhibited by N-ethyl-maleimide (NEM) and divalent
CC cations. Tolerates high concentrations of NaCl but is inhibited at
CC concentrations of 195 mM and higher. {ECO:0000269|PubMed:14506283}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Active from pH 7.0 to 9.5. {ECO:0000269|PubMed:14506283};
CC -!- SUBUNIT: Monomer. Homodimer. Part of a complex with DAXX, MDM2, RASSF1
CC and USP7 (PubMed:18566590). Part of a complex with DAXX, MDM2 and USP7
CC (PubMed:16845383). Interacts with MDM2; the interaction is independent
CC of p53/TP53. Interacts with DAXX; the interaction is direct and
CC independent of MDM2 and p53/TP53 (PubMed:16845383). Component of a
CC complex composed of KMT2E/MLL5 (isoform 3), OGT (isoform 1) and USP7;
CC the complex stabilizes KMT2E/MLL5, preventing KMT2E/MLL5 ubiquitination
CC and proteosomal-mediated degradation (PubMed:26678539). Interacts (via
CC MATH domain) with KMT2E/MLL5 isoform 3 (PubMed:26678539). Interacts
CC with OGT isoform 1 (PubMed:26678539). Interacts with FOXO4; the
CC interaction is enhanced in presence of hydrogen peroxide and occurs
CC independently of p53/TP53 (PubMed:16964248). Interacts with p53/TP53;
CC the interaction is enhanced in response to DNA damage
CC (PubMed:25283148). Interacts with TSPYL5; this impairs interaction with
CC p53/TP53 (PubMed:21170034). Interacts with PTEN; the interaction is
CC direct (PubMed:18716620). Interacts with ATXN1 and the strength of
CC interaction is influenced by the length of the poly-Gln region in ATXN1
CC (PubMed:12093161). A weaker interaction seen with mutants having longer
CC poly-Gln regions (PubMed:12093161). Interacts with KIAA1530/UVSSA
CC (PubMed:22466611, PubMed:22466612). Interacts with ABRAXAS2; the
CC interaction is direct (PubMed:25283148). Identified in a complex with
CC TP53/p53 and ABRAXAS2 (PubMed:25283148). Interacts with MEX3C and
CC antagonizes its ability to degrade mRNA (PubMed:22863774). Interacts
CC with DNMT1 and UHRF1 (PubMed:21745816, PubMed:22411829). Interacts with
CC FOXP3 (PubMed:23973222). Interacts (via MATH domain) with RNF220.
CC Associated component of the Polycomb group (PcG) multiprotein PRC1-like
CC complex (PubMed:20601937). Interacts with EPOP (By similarity).
CC Interacts with OTUD4 and USP9X; the interaction is direct
CC (PubMed:25944111). Interacts with CRY2 (PubMed:27123980). Interacts
CC with REST (PubMed:21258371). Interacts with ERCC6 (PubMed:26030138).
CC {ECO:0000250|UniProtKB:Q6A4J8, ECO:0000269|PubMed:12093161,
CC ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:16964248,
CC ECO:0000269|PubMed:18566590, ECO:0000269|PubMed:18716620,
CC ECO:0000269|PubMed:20601937, ECO:0000269|PubMed:21170034,
CC ECO:0000269|PubMed:21258371, ECO:0000269|PubMed:21745816,
CC ECO:0000269|PubMed:22411829, ECO:0000269|PubMed:22466611,
CC ECO:0000269|PubMed:22466612, ECO:0000269|PubMed:22863774,
CC ECO:0000269|PubMed:25266658, ECO:0000269|PubMed:25283148,
CC ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:26030138,
CC ECO:0000269|PubMed:26678539, ECO:0000269|PubMed:27123980}.
CC -!- SUBUNIT: (Microbial infection) Isoform 1 and isoform 2 interact with
CC herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110
CC (PubMed:9034339, PubMed:14506283, PubMed:16160161, PubMed:18590780).
CC Binding to ICP0/VMW110 may modulate the substrate specificity or
CC activity of USP7 to stabilize viral proteins.
CC {ECO:0000269|PubMed:14506283, ECO:0000269|PubMed:16160161,
CC ECO:0000269|PubMed:18590780, ECO:0000269|PubMed:9034339}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus EBNA1.
CC EBNA1 shows a 10-fold higher affinity than p53/TP53 and can compete
CC with it for USP7 binding. {ECO:0000269|PubMed:14506283}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus
CC proteins UL35 and UL35A; these interactions inhibit the ability of USP7
CC to form nuclear bodies. {ECO:0000269|PubMed:22072767}.
CC -!- INTERACTION:
CC Q93009; P52594: AGFG1; NbExp=2; IntAct=EBI-302474, EBI-996560;
CC Q93009; Q49AR9: ANKS1A; NbExp=3; IntAct=EBI-302474, EBI-11954519;
CC Q93009; Q6W2J9: BCOR; NbExp=3; IntAct=EBI-302474, EBI-950027;
CC Q93009; P35226: BMI1; NbExp=8; IntAct=EBI-302474, EBI-2341576;
CC Q93009; Q9UPA5: BSN; NbExp=2; IntAct=EBI-302474, EBI-1642820;
CC Q93009; Q9HC52: CBX8; NbExp=7; IntAct=EBI-302474, EBI-712912;
CC Q93009; Q13620: CUL4B; NbExp=2; IntAct=EBI-302474, EBI-456067;
CC Q93009; O14529: CUX2; NbExp=2; IntAct=EBI-302474, EBI-20889964;
CC Q93009; Q9UER7: DAXX; NbExp=14; IntAct=EBI-302474, EBI-77321;
CC Q93009; Q96L91: EP400; NbExp=2; IntAct=EBI-302474, EBI-399163;
CC Q93009; P03372: ESR1; NbExp=3; IntAct=EBI-302474, EBI-78473;
CC Q93009; P78312: FAM193A; NbExp=2; IntAct=EBI-302474, EBI-2873877;
CC Q93009; Q86YZ3: HRNR; NbExp=2; IntAct=EBI-302474, EBI-1047017;
CC Q93009; Q9NXR8: ING3; NbExp=2; IntAct=EBI-302474, EBI-769503;
CC Q93009; P02545: LMNA; NbExp=4; IntAct=EBI-302474, EBI-351935;
CC Q93009; P43361: MAGEA8; NbExp=2; IntAct=EBI-302474, EBI-10182930;
CC Q93009; Q9HCI5: MAGEE1; NbExp=3; IntAct=EBI-302474, EBI-949966;
CC Q93009; Q9UJ55: MAGEL2; NbExp=2; IntAct=EBI-302474, EBI-5668174;
CC Q93009; P21145: MAL; NbExp=3; IntAct=EBI-302474, EBI-3932027;
CC Q93009; Q13233: MAP3K1; NbExp=2; IntAct=EBI-302474, EBI-49776;
CC Q93009; Q00987: MDM2; NbExp=35; IntAct=EBI-302474, EBI-389668;
CC Q93009; O15151: MDM4; NbExp=16; IntAct=EBI-302474, EBI-398437;
CC Q93009; Q5U5Q3: MEX3C; NbExp=3; IntAct=EBI-302474, EBI-2864451;
CC Q93009; Q8IWI9: MGA; NbExp=3; IntAct=EBI-302474, EBI-2815196;
CC Q93009; Q2M2H8: MGAM2; NbExp=2; IntAct=EBI-302474, EBI-20850333;
CC Q93009; P55197: MLLT10; NbExp=2; IntAct=EBI-302474, EBI-1104952;
CC Q93009; Q99836: MYD88; NbExp=3; IntAct=EBI-302474, EBI-447677;
CC Q93009; P46531: NOTCH1; NbExp=3; IntAct=EBI-302474, EBI-636374;
CC Q93009; P49790: NUP153; NbExp=2; IntAct=EBI-302474, EBI-286779;
CC Q93009; P52948: NUP98; NbExp=2; IntAct=EBI-302474, EBI-295727;
CC Q93009; P35227: PCGF2; NbExp=5; IntAct=EBI-302474, EBI-2129767;
CC Q93009; Q8NDX5: PHC3; NbExp=3; IntAct=EBI-302474, EBI-1223801;
CC Q93009; Q53GL0: PLEKHO1; NbExp=3; IntAct=EBI-302474, EBI-949945;
CC Q93009; Q96HA1: POM121; NbExp=2; IntAct=EBI-302474, EBI-739990;
CC Q93009; P60484-1: PTEN; NbExp=5; IntAct=EBI-302474, EBI-15722967;
CC Q93009; P06400: RB1; NbExp=8; IntAct=EBI-302474, EBI-491274;
CC Q93009; Q06587: RING1; NbExp=5; IntAct=EBI-302474, EBI-752313;
CC Q93009; Q99496: RNF2; NbExp=5; IntAct=EBI-302474, EBI-722416;
CC Q93009; O15047: SETD1A; NbExp=2; IntAct=EBI-302474, EBI-540779;
CC Q93009; P84022: SMAD3; NbExp=2; IntAct=EBI-302474, EBI-347161;
CC Q93009; P18583: SON; NbExp=2; IntAct=EBI-302474, EBI-1053513;
CC Q93009; P48431: SOX2; NbExp=3; IntAct=EBI-302474, EBI-6124081;
CC Q93009; Q8NB59: SYT14; NbExp=2; IntAct=EBI-302474, EBI-30843486;
CC Q93009; Q99426: TBCB; NbExp=2; IntAct=EBI-302474, EBI-764356;
CC Q93009; Q9NQB0: TCF7L2; NbExp=2; IntAct=EBI-302474, EBI-924724;
CC Q93009; P04637: TP53; NbExp=18; IntAct=EBI-302474, EBI-366083;
CC Q93009; Q14669: TRIP12; NbExp=3; IntAct=EBI-302474, EBI-308443;
CC Q93009; Q12816: TRO; NbExp=2; IntAct=EBI-302474, EBI-950001;
CC Q93009; Q6ZSZ6: TSHZ1; NbExp=2; IntAct=EBI-302474, EBI-11318342;
CC Q93009; Q86VY4: TSPYL5; NbExp=4; IntAct=EBI-302474, EBI-3436472;
CC Q93009; O75386: TULP3; NbExp=2; IntAct=EBI-302474, EBI-5357290;
CC Q93009; Q5T6F2: UBAP2; NbExp=2; IntAct=EBI-302474, EBI-2514383;
CC Q93009; Q5T4S7: UBR4; NbExp=2; IntAct=EBI-302474, EBI-1995940;
CC Q93009; Q9H4A3: WNK1; NbExp=2; IntAct=EBI-302474, EBI-457907;
CC Q93009; Q15007: WTAP; NbExp=2; IntAct=EBI-302474, EBI-751647;
CC Q93009; P49750: YLPM1; NbExp=2; IntAct=EBI-302474, EBI-712871;
CC Q93009; Q9ULU4: ZMYND8; NbExp=2; IntAct=EBI-302474, EBI-765834;
CC Q93009; O15014: ZNF609; NbExp=2; IntAct=EBI-302474, EBI-948874;
CC Q93009; P36508: ZNF76; NbExp=3; IntAct=EBI-302474, EBI-7254550;
CC Q93009; P03211: EBNA1; Xeno; NbExp=5; IntAct=EBI-302474, EBI-996522;
CC Q93009; Q77UV9: KIE-2; Xeno; NbExp=2; IntAct=EBI-302474, EBI-2608731;
CC Q93009; O35618: Mdm4; Xeno; NbExp=4; IntAct=EBI-302474, EBI-2603376;
CC Q93009; F5H9D8: vIRF-4; Xeno; NbExp=13; IntAct=EBI-302474, EBI-15951580;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21258371,
CC ECO:0000269|PubMed:23973222, ECO:0000269|PubMed:25283148,
CC ECO:0000269|PubMed:26678539}. Cytoplasm {ECO:0000269|PubMed:25283148}.
CC Nucleus, PML body {ECO:0000269|PubMed:9034339}. Chromosome
CC {ECO:0000269|PubMed:20601937}. Note=Present in a minority of ND10
CC nuclear bodies. Association with ICP0/VMW110 at early times of
CC infection leads to an increased proportion of USP7-containing ND10.
CC Colocalizes with ATXN1 in the nucleus. Colocalized with DAXX in
CC speckled structures. Colocalized with PML and PTEN in promyelocytic
CC leukemia protein (PML) nuclear bodies.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q93009-1; Sequence=Displayed;
CC Name=2; Synonyms=USP7 beta;
CC IsoId=Q93009-2; Sequence=Not described;
CC Name=3;
CC IsoId=Q93009-3; Sequence=VSP_054884;
CC -!- TISSUE SPECIFICITY: Expressed in neural progenitor cells (at protein
CC level) (PubMed:21258371). Widely expressed. Overexpressed in prostate
CC cancer. {ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:21258371}.
CC -!- INDUCTION: Up-regulated in regulatory T-cells (Treg). Down-regulated
CC during neural progenitor cell differentiation (PubMed:21258371).
CC {ECO:0000269|PubMed:21258371, ECO:0000269|PubMed:23973222}.
CC -!- DOMAIN: The C-terminus plays a role in its oligomerization.
CC {ECO:0000250}.
CC -!- PTM: Isoform 1: Phosphorylated. Isoform 1 is phosphorylated at
CC positions Ser-18 and Ser-963. Isoform 2: Not phosphorylated.
CC {ECO:0000269|PubMed:17651432}.
CC -!- PTM: Isoform 1: Polyneddylated. Isoform 2: Not Polyneddylated.
CC -!- PTM: Isoform 1 and isoform 2: Not sumoylated.
CC -!- PTM: Isoform 1 and isoform 2: Polyubiquitinated by herpesvirus 1 trans-
CC acting transcriptional protein ICP0/VMW110; leading to its subsequent
CC proteasomal degradation. Isoform 1: Ubiquitinated at Lys-869.
CC {ECO:0000269|PubMed:16160161, ECO:0000269|PubMed:17651432}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
CC -!- CAUTION: Was reported to interact with UBXN6 but the corresponding
CC article has been retracted (PubMed:18768758).
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/USP7ID42773ch16p13.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; Z72499; CAA96580.1; -; mRNA.
DR EMBL; AK302771; BAH13801.1; -; mRNA.
DR EMBL; AC022167; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471112; EAW85194.1; -; Genomic_DNA.
DR CCDS; CCDS32385.1; -. [Q93009-1]
DR CCDS; CCDS66941.1; -. [Q93009-3]
DR RefSeq; NP_001273386.1; NM_001286457.1. [Q93009-3]
DR RefSeq; NP_001308787.1; NM_001321858.1.
DR RefSeq; NP_003461.2; NM_003470.2. [Q93009-1]
DR PDB; 1NB8; X-ray; 2.30 A; A/B=208-560.
DR PDB; 1NBF; X-ray; 2.30 A; A/B/E=208-560.
DR PDB; 1YY6; X-ray; 1.70 A; A=54-204.
DR PDB; 1YZE; X-ray; 2.00 A; A/B/C=54-205.
DR PDB; 2F1W; X-ray; 1.65 A; A=53-206.
DR PDB; 2F1X; X-ray; 2.30 A; A/B=53-200.
DR PDB; 2F1Y; X-ray; 1.70 A; A=53-198.
DR PDB; 2F1Z; X-ray; 3.20 A; A/B=43-560.
DR PDB; 2FOJ; X-ray; 1.60 A; A=54-205.
DR PDB; 2FOO; X-ray; 2.20 A; A=54-205.
DR PDB; 2FOP; X-ray; 2.10 A; A=54-205.
DR PDB; 2KVR; NMR; -; A=537-664.
DR PDB; 2XXN; X-ray; 1.60 A; A=63-205.
DR PDB; 2YLM; X-ray; 2.70 A; A=560-1084.
DR PDB; 3MQR; X-ray; 1.80 A; A=54-205.
DR PDB; 3MQS; X-ray; 2.40 A; C=54-205.
DR PDB; 4JJQ; X-ray; 1.95 A; A=54-205.
DR PDB; 4KG9; X-ray; 1.70 A; A=54-205.
DR PDB; 4M5W; X-ray; 2.24 A; A=207-560.
DR PDB; 4M5X; X-ray; 2.19 A; A/B=207-560.
DR PDB; 4PYZ; X-ray; 2.84 A; A/B=537-793.
DR PDB; 4WPH; X-ray; 2.92 A; A/B=535-888.
DR PDB; 4WPI; X-ray; 3.40 A; A/B=535-888.
DR PDB; 4YOC; X-ray; 2.92 A; C=560-1102.
DR PDB; 4YSI; X-ray; 1.02 A; A=63-205.
DR PDB; 4Z96; X-ray; 2.85 A; A=560-1083.
DR PDB; 4Z97; X-ray; 3.00 A; A=560-1083.
DR PDB; 5C56; X-ray; 2.69 A; A=560-1102.
DR PDB; 5C6D; X-ray; 2.29 A; A/B=561-881.
DR PDB; 5FWI; X-ray; 3.40 A; C=207-882.
DR PDB; 5GG4; X-ray; 3.11 A; A/B/C/D=560-890.
DR PDB; 5J7T; X-ray; 3.20 A; A=211-881.
DR PDB; 5JTJ; X-ray; 3.32 A; A=209-554, A=1084-1102.
DR PDB; 5JTV; X-ray; 3.31 A; A/C/E/G=207-554, A/C/E/G=882-1102.
DR PDB; 5KYB; X-ray; 2.20 A; A/B=208-554.
DR PDB; 5KYC; X-ray; 1.43 A; B=208-554.
DR PDB; 5KYD; X-ray; 1.62 A; A=208-554.
DR PDB; 5KYE; X-ray; 1.97 A; A/B=208-554.
DR PDB; 5KYF; X-ray; 1.45 A; B=208-554.
DR PDB; 5N9R; X-ray; 2.23 A; A/B=207-560.
DR PDB; 5N9T; X-ray; 1.73 A; A/B=207-560.
DR PDB; 5NGE; X-ray; 2.35 A; A/B=208-560.
DR PDB; 5NGF; X-ray; 2.33 A; A/B=208-560.
DR PDB; 5UQV; X-ray; 2.84 A; A/B=208-554.
DR PDB; 5UQX; X-ray; 2.23 A; A/B=208-555.
DR PDB; 5VS6; X-ray; 2.27 A; A/B=208-560.
DR PDB; 5VSB; X-ray; 1.85 A; A/B=208-560.
DR PDB; 5VSK; X-ray; 3.33 A; A/B=208-560.
DR PDB; 5WHC; X-ray; 2.55 A; A/B=209-554.
DR PDB; 6F5H; X-ray; 2.16 A; A/B=207-560.
DR PDB; 6M1K; X-ray; 2.25 A; A/B=208-554.
DR PDB; 6P5L; X-ray; 3.30 A; A/B=535-890.
DR PDB; 6VN2; X-ray; 2.93 A; A/B=207-555.
DR PDB; 6VN3; X-ray; 2.73 A; A/B=207-555.
DR PDB; 6VN4; X-ray; 2.69 A; A/B=207-555.
DR PDB; 6VN5; X-ray; 2.90 A; A/B=207-555.
DR PDB; 6VN6; X-ray; 2.99 A; A/B=207-555.
DR PDB; 7CM2; X-ray; 2.25 A; A/B=208-560.
DR PDBsum; 1NB8; -.
DR PDBsum; 1NBF; -.
DR PDBsum; 1YY6; -.
DR PDBsum; 1YZE; -.
DR PDBsum; 2F1W; -.
DR PDBsum; 2F1X; -.
DR PDBsum; 2F1Y; -.
DR PDBsum; 2F1Z; -.
DR PDBsum; 2FOJ; -.
DR PDBsum; 2FOO; -.
DR PDBsum; 2FOP; -.
DR PDBsum; 2KVR; -.
DR PDBsum; 2XXN; -.
DR PDBsum; 2YLM; -.
DR PDBsum; 3MQR; -.
DR PDBsum; 3MQS; -.
DR PDBsum; 4JJQ; -.
DR PDBsum; 4KG9; -.
DR PDBsum; 4M5W; -.
DR PDBsum; 4M5X; -.
DR PDBsum; 4PYZ; -.
DR PDBsum; 4WPH; -.
DR PDBsum; 4WPI; -.
DR PDBsum; 4YOC; -.
DR PDBsum; 4YSI; -.
DR PDBsum; 4Z96; -.
DR PDBsum; 4Z97; -.
DR PDBsum; 5C56; -.
DR PDBsum; 5C6D; -.
DR PDBsum; 5FWI; -.
DR PDBsum; 5GG4; -.
DR PDBsum; 5J7T; -.
DR PDBsum; 5JTJ; -.
DR PDBsum; 5JTV; -.
DR PDBsum; 5KYB; -.
DR PDBsum; 5KYC; -.
DR PDBsum; 5KYD; -.
DR PDBsum; 5KYE; -.
DR PDBsum; 5KYF; -.
DR PDBsum; 5N9R; -.
DR PDBsum; 5N9T; -.
DR PDBsum; 5NGE; -.
DR PDBsum; 5NGF; -.
DR PDBsum; 5UQV; -.
DR PDBsum; 5UQX; -.
DR PDBsum; 5VS6; -.
DR PDBsum; 5VSB; -.
DR PDBsum; 5VSK; -.
DR PDBsum; 5WHC; -.
DR PDBsum; 6F5H; -.
DR PDBsum; 6M1K; -.
DR PDBsum; 6P5L; -.
DR PDBsum; 6VN2; -.
DR PDBsum; 6VN3; -.
DR PDBsum; 6VN4; -.
DR PDBsum; 6VN5; -.
DR PDBsum; 6VN6; -.
DR PDBsum; 7CM2; -.
DR AlphaFoldDB; Q93009; -.
DR BMRB; Q93009; -.
DR SMR; Q93009; -.
DR BioGRID; 113622; 545.
DR CORUM; Q93009; -.
DR DIP; DIP-29053N; -.
DR ELM; Q93009; -.
DR IntAct; Q93009; 495.
DR MINT; Q93009; -.
DR STRING; 9606.ENSP00000343535; -.
DR BindingDB; Q93009; -.
DR ChEMBL; CHEMBL2157850; -.
DR MEROPS; C19.016; -.
DR GlyGen; Q93009; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q93009; -.
DR MetOSite; Q93009; -.
DR PhosphoSitePlus; Q93009; -.
DR SwissPalm; Q93009; -.
DR BioMuta; USP7; -.
DR DMDM; 212276477; -.
DR EPD; Q93009; -.
DR jPOST; Q93009; -.
DR MassIVE; Q93009; -.
DR MaxQB; Q93009; -.
DR PaxDb; Q93009; -.
DR PeptideAtlas; Q93009; -.
DR PRIDE; Q93009; -.
DR ProteomicsDB; 6915; -.
DR ProteomicsDB; 75669; -. [Q93009-1]
DR ABCD; Q93009; 3 sequenced antibodies.
DR Antibodypedia; 2881; 759 antibodies from 43 providers.
DR DNASU; 7874; -.
DR Ensembl; ENST00000344836.9; ENSP00000343535.4; ENSG00000187555.16. [Q93009-1]
DR Ensembl; ENST00000381886.8; ENSP00000371310.4; ENSG00000187555.16. [Q93009-3]
DR GeneID; 7874; -.
DR KEGG; hsa:7874; -.
DR MANE-Select; ENST00000344836.9; ENSP00000343535.4; NM_003470.3; NP_003461.2.
DR UCSC; uc002czk.4; human. [Q93009-1]
DR CTD; 7874; -.
DR DisGeNET; 7874; -.
DR GeneCards; USP7; -.
DR HGNC; HGNC:12630; USP7.
DR HPA; ENSG00000187555; Low tissue specificity.
DR MalaCards; USP7; -.
DR MIM; 602519; gene.
DR neXtProt; NX_Q93009; -.
DR OpenTargets; ENSG00000187555; -.
DR Orphanet; 500055; 16p13.2 microdeletion syndrome.
DR PharmGKB; PA37255; -.
DR VEuPathDB; HostDB:ENSG00000187555; -.
DR eggNOG; KOG1863; Eukaryota.
DR GeneTree; ENSGT00940000156053; -.
DR InParanoid; Q93009; -.
DR OMA; KMKGTCL; -.
DR OrthoDB; 77113at2759; -.
DR PhylomeDB; Q93009; -.
DR TreeFam; TF105667; -.
DR PathwayCommons; Q93009; -.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-HSA-6781827; Transcription-Coupled Nucleotide Excision Repair (TC-NER).
DR Reactome; R-HSA-6782135; Dual incision in TC-NER.
DR Reactome; R-HSA-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-HSA-6804757; Regulation of TP53 Degradation.
DR Reactome; R-HSA-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR Reactome; R-HSA-8948747; Regulation of PTEN localization.
DR SABIO-RK; Q93009; -.
DR SignaLink; Q93009; -.
DR SIGNOR; Q93009; -.
DR BioGRID-ORCS; 7874; 544 hits in 1127 CRISPR screens.
DR ChiTaRS; USP7; human.
DR EvolutionaryTrace; Q93009; -.
DR GeneWiki; USP7; -.
DR GenomeRNAi; 7874; -.
DR Pharos; Q93009; Tchem.
DR PRO; PR:Q93009; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q93009; protein.
DR Bgee; ENSG00000187555; Expressed in Brodmann (1909) area 23 and 206 other tissues.
DR ExpressionAtlas; Q93009; baseline and differential.
DR Genevisible; Q93009; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0101005; F:deubiquitinase activity; IMP:UniProtKB.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0002039; F:p53 binding; IDA:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0035616; P:histone H2B conserved C-terminal lysine deubiquitination; ISS:UniProtKB.
DR GO; GO:0010216; P:maintenance of DNA methylation; IMP:UniProtKB.
DR GO; GO:0035520; P:monoubiquitinated protein deubiquitination; IDA:MGI.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:1901537; P:positive regulation of DNA demethylation; IDA:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; TAS:Reactome.
DR GO; GO:0042752; P:regulation of circadian rhythm; IDA:UniProtKB.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0006111; P:regulation of gluconeogenesis; IDA:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB.
DR GO; GO:1905279; P:regulation of retrograde transport, endosome to Golgi; IMP:UniProtKB.
DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
DR GO; GO:1904353; P:regulation of telomere capping; TAS:BHF-UCL.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR DisProt; DP00941; -.
DR Gene3D; 2.60.210.10; -; 1.
DR IDEAL; IID00176; -.
DR InterPro; IPR002083; MATH/TRAF_dom.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR008974; TRAF-like.
DR InterPro; IPR024729; USP7_ICP0-binding_dom.
DR InterPro; IPR029346; USP_C.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF00917; MATH; 1.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF14533; USP7_C2; 1.
DR Pfam; PF12436; USP7_ICP0_bdg; 1.
DR SMART; SM00061; MATH; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50144; MATH; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Biological rhythms;
KW Chromosome; Cytoplasm; Developmental protein; Direct protein sequencing;
KW DNA damage; DNA repair; Host-virus interaction; Hydrolase; Isopeptide bond;
KW Nucleus; Phosphoprotein; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..1102
FT /note="Ubiquitin carboxyl-terminal hydrolase 7"
FT /id="PRO_0000080626"
FT DOMAIN 68..195
FT /note="MATH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00129"
FT DOMAIN 214..521
FT /note="USP"
FT REGION 1..208
FT /note="Interaction with TSPYL5"
FT /evidence="ECO:0000269|PubMed:21170034"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 53..208
FT /note="Interaction with p53/TP53, MDM2 and EBNA1"
FT /evidence="ECO:0000269|PubMed:14506283"
FT REGION 70..205
FT /note="Necessary for nuclear localization"
FT REGION 622..801
FT /note="Interaction with ICP0/VMW110"
FT /evidence="ECO:0000269|PubMed:16160161"
FT COMPBIAS 1..16
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 223
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:12507430,
FT ECO:0000269|PubMed:25944111, ECO:0000305|PubMed:11923872,
FT ECO:0000305|PubMed:15053880, ECO:0000305|PubMed:16964248,
FT ECO:0000305|PubMed:18716620, ECO:0000305|PubMed:21745816,
FT ECO:0000305|PubMed:22411829"
FT ACT_SITE 464
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:12507430"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17651432,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 49
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6A4J8"
FT MOD_RES 869
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 963
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17651432,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 1084
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 1096
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CROSSLNK 869
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25114211,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 869
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:17651432"
FT CROSSLNK 882
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..25
FT /note="MNHQQQQQQQKAGEQQLSEPEDMEM -> MAGNHRLGL (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054884"
FT MUTAGEN 164
FT /note="D->A: Decreased binding to p53/TP53 and MDM2."
FT /evidence="ECO:0000269|PubMed:16474402"
FT MUTAGEN 165
FT /note="W->A: Loss of binding to p53/TP53 and MDM2."
FT /evidence="ECO:0000269|PubMed:16474402"
FT MUTAGEN 223
FT /note="C->A: Complete loss of activity. Localized in the
FT nucleus and does not inhibit FOXO4-dependent
FT transcriptional activity. Loss of ability to deubiquitinate
FT CRY2."
FT /evidence="ECO:0000269|PubMed:11923872,
FT ECO:0000269|PubMed:12507430, ECO:0000269|PubMed:15053880,
FT ECO:0000269|PubMed:16964248, ECO:0000269|PubMed:18716620,
FT ECO:0000269|PubMed:21745816, ECO:0000269|PubMed:22411829,
FT ECO:0000269|PubMed:27123980"
FT MUTAGEN 223
FT /note="C->S: Catalytically inactive mutant. No effect on
FT p53/TP53 and PTEN binding but is defective in
FT deubiquitinating p53/TP53 and PTEN. Partial loss of
FT KMT2E/mml5 deubiquitination. Decreases deubiquitinase
FT activity toward 'Lys-48'-polyubiquitinated ALKBH3. Reduced
FT deubiquitination of REST."
FT /evidence="ECO:0000269|PubMed:11923872,
FT ECO:0000269|PubMed:12507430, ECO:0000269|PubMed:15053880,
FT ECO:0000269|PubMed:16964248, ECO:0000269|PubMed:18716620,
FT ECO:0000269|PubMed:21258371, ECO:0000269|PubMed:21745816,
FT ECO:0000269|PubMed:22411829, ECO:0000269|PubMed:25944111,
FT ECO:0000269|PubMed:26678539, ECO:0000269|PubMed:28655758"
FT MUTAGEN 456
FT /note="H->A: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:12507430"
FT MUTAGEN 464
FT /note="H->A: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:12507430"
FT CONFLICT 201
FT /note="H -> I (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 205
FT /note="W -> P (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="S -> Q (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1045
FT /note="M -> T (in Ref. 1; CAA96580)"
FT /evidence="ECO:0000305"
FT CONFLICT 1066
FT /note="Q -> T (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 67..77
FT /evidence="ECO:0007829|PDB:4YSI"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:4YSI"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:4YSI"
FT STRAND 95..105
FT /evidence="ECO:0007829|PDB:4YSI"
FT STRAND 106..110
FT /evidence="ECO:0007829|PDB:2F1X"
FT STRAND 113..122
FT /evidence="ECO:0007829|PDB:4YSI"
FT STRAND 131..140
FT /evidence="ECO:0007829|PDB:4YSI"
FT HELIX 146..148
FT /evidence="ECO:0007829|PDB:4YSI"
FT STRAND 150..159
FT /evidence="ECO:0007829|PDB:4YSI"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:2F1Z"
FT STRAND 164..172
FT /evidence="ECO:0007829|PDB:4YSI"
FT HELIX 173..176
FT /evidence="ECO:0007829|PDB:4YSI"
FT TURN 179..181
FT /evidence="ECO:0007829|PDB:4YSI"
FT STRAND 182..185
FT /evidence="ECO:0007829|PDB:2XXN"
FT STRAND 188..197
FT /evidence="ECO:0007829|PDB:4YSI"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:4YSI"
FT TURN 208..211
FT /evidence="ECO:0007829|PDB:5N9T"
FT TURN 221..224
FT /evidence="ECO:0007829|PDB:1NB8"
FT HELIX 225..233
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 236..243
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:6VN3"
FT TURN 252..254
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 256..269
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 277..283
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 288..293
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 296..311
FT /evidence="ECO:0007829|PDB:5KYC"
FT TURN 315..318
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 319..324
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 326..338
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 340..348
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 350..353
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 360..367
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 371..373
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 375..377
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 382..384
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 385..387
FT /evidence="ECO:0007829|PDB:5J7T"
FT STRAND 389..396
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 400..407
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 409..411
FT /evidence="ECO:0007829|PDB:5KYC"
FT TURN 413..415
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 429..432
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 434..436
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 437..439
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 442..444
FT /evidence="ECO:0007829|PDB:6F5H"
FT STRAND 447..457
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 459..461
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 463..469
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 473..475
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 478..481
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 484..487
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 490..493
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 495..497
FT /evidence="ECO:0007829|PDB:5KYC"
FT TURN 502..506
FT /evidence="ECO:0007829|PDB:5KYD"
FT HELIX 507..510
FT /evidence="ECO:0007829|PDB:5KYC"
FT STRAND 511..520
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 521..523
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 524..527
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 533..535
FT /evidence="ECO:0007829|PDB:5KYC"
FT HELIX 538..547
FT /evidence="ECO:0007829|PDB:5KYC"
FT TURN 551..555
FT /evidence="ECO:0007829|PDB:6P5L"
FT HELIX 556..560
FT /evidence="ECO:0007829|PDB:6P5L"
FT HELIX 561..563
FT /evidence="ECO:0007829|PDB:5C56"
FT STRAND 564..570
FT /evidence="ECO:0007829|PDB:5C6D"
FT HELIX 572..574
FT /evidence="ECO:0007829|PDB:5C6D"
FT TURN 575..577
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 580..584
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 588..597
FT /evidence="ECO:0007829|PDB:5C6D"
FT HELIX 602..613
FT /evidence="ECO:0007829|PDB:5C6D"
FT HELIX 617..619
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 620..628
FT /evidence="ECO:0007829|PDB:5C6D"
FT TURN 629..631
FT /evidence="ECO:0007829|PDB:5C56"
FT STRAND 633..635
FT /evidence="ECO:0007829|PDB:5C6D"
FT HELIX 640..643
FT /evidence="ECO:0007829|PDB:2YLM"
FT STRAND 645..647
FT /evidence="ECO:0007829|PDB:5C6D"
FT HELIX 648..651
FT /evidence="ECO:0007829|PDB:5C6D"
FT TURN 652..654
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 656..664
FT /evidence="ECO:0007829|PDB:5C6D"
FT HELIX 668..671
FT /evidence="ECO:0007829|PDB:5C56"
FT TURN 681..683
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 684..693
FT /evidence="ECO:0007829|PDB:5C6D"
FT TURN 694..697
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 698..708
FT /evidence="ECO:0007829|PDB:5C6D"
FT HELIX 714..716
FT /evidence="ECO:0007829|PDB:5C6D"
FT HELIX 717..724
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 732..739
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 742..745
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 749..752
FT /evidence="ECO:0007829|PDB:2YLM"
FT HELIX 753..756
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 757..759
FT /evidence="ECO:0007829|PDB:5C56"
FT STRAND 764..770
FT /evidence="ECO:0007829|PDB:5C6D"
FT HELIX 773..777
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 778..780
FT /evidence="ECO:0007829|PDB:5C6D"
FT HELIX 783..792
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 793..800
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 803..805
FT /evidence="ECO:0007829|PDB:4Z96"
FT STRAND 809..814
FT /evidence="ECO:0007829|PDB:5C6D"
FT HELIX 819..829
FT /evidence="ECO:0007829|PDB:5C6D"
FT HELIX 834..836
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 837..840
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 846..848
FT /evidence="ECO:0007829|PDB:5C6D"
FT HELIX 861..865
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 866..868
FT /evidence="ECO:0007829|PDB:5J7T"
FT STRAND 870..872
FT /evidence="ECO:0007829|PDB:5C6D"
FT STRAND 875..880
FT /evidence="ECO:0007829|PDB:5C6D"
FT HELIX 885..890
FT /evidence="ECO:0007829|PDB:5C56"
FT STRAND 894..899
FT /evidence="ECO:0007829|PDB:5C56"
FT STRAND 905..910
FT /evidence="ECO:0007829|PDB:5C56"
FT HELIX 918..928
FT /evidence="ECO:0007829|PDB:5C56"
FT STRAND 933..935
FT /evidence="ECO:0007829|PDB:4YOC"
FT STRAND 939..945
FT /evidence="ECO:0007829|PDB:5C56"
FT STRAND 948..953
FT /evidence="ECO:0007829|PDB:5C56"
FT HELIX 959..961
FT /evidence="ECO:0007829|PDB:5C56"
FT STRAND 969..974
FT /evidence="ECO:0007829|PDB:5C56"
FT HELIX 977..979
FT /evidence="ECO:0007829|PDB:5C56"
FT TURN 984..986
FT /evidence="ECO:0007829|PDB:5C56"
FT STRAND 987..998
FT /evidence="ECO:0007829|PDB:5C56"
FT STRAND 1003..1014
FT /evidence="ECO:0007829|PDB:5C56"
FT HELIX 1017..1027
FT /evidence="ECO:0007829|PDB:5C56"
FT HELIX 1032..1035
FT /evidence="ECO:0007829|PDB:5C56"
FT STRAND 1039..1044
FT /evidence="ECO:0007829|PDB:5C56"
FT STRAND 1047..1050
FT /evidence="ECO:0007829|PDB:5C56"
FT TURN 1053..1055
FT /evidence="ECO:0007829|PDB:5C56"
FT HELIX 1060..1062
FT /evidence="ECO:0007829|PDB:5C56"
FT STRAND 1070..1072
FT /evidence="ECO:0007829|PDB:2YLM"
FT STRAND 1076..1080
FT /evidence="ECO:0007829|PDB:5C56"
SQ SEQUENCE 1102 AA; 128302 MW; F1A5A5C421396E45 CRC64;
MNHQQQQQQQ KAGEQQLSEP EDMEMEAGDT DDPPRITQNP VINGNVALSD GHNTAEEDME
DDTSWRSEAT FQFTVERFSR LSESVLSPPC FVRNLPWKIM VMPRFYPDRP HQKSVGFFLQ
CNAESDSTSW SCHAQAVLKI INYRDDEKSF SRRISHLFFH KENDWGFSNF MAWSEVTDPE
KGFIDDDKVT FEVFVQADAP HGVAWDSKKH TGYVGLKNQG ATCYMNSLLQ TLFFTNQLRK
AVYMMPTEGD DSSKSVPLAL QRVFYELQHS DKPVGTKKLT KSFGWETLDS FMQHDVQELC
RVLLDNVENK MKGTCVEGTI PKLFRGKMVS YIQCKEVDYR SDRREDYYDI QLSIKGKKNI
FESFVDYVAV EQLDGDNKYD AGEHGLQEAE KGVKFLTLPP VLHLQLMRFM YDPQTDQNIK
INDRFEFPEQ LPLDEFLQKT DPKDPANYIL HAVLVHSGDN HGGHYVVYLN PKGDGKWCKF
DDDVVSRCTK EEAIEHNYGG HDDDLSVRHC TNAYMLVYIR ESKLSEVLQA VTDHDIPQQL
VERLQEEKRI EAQKRKERQE AHLYMQVQIV AEDQFCGHQG NDMYDEEKVK YTVFKVLKNS
SLAEFVQSLS QTMGFPQDQI RLWPMQARSN GTKRPAMLDN EADGNKTMIE LSDNENPWTI
FLETVDPELA ASGATLPKFD KDHDVMLFLK MYDPKTRSLN YCGHIYTPIS CKIRDLLPVM
CDRAGFIQDT SLILYEEVKP NLTERIQDYD VSLDKALDEL MDGDIIVFQK DDPENDNSEL
PTAKEYFRDL YHRVDVIFCD KTIPNDPGFV VTLSNRMNYF QVAKTVAQRL NTDPMLLQFF
KSQGYRDGPG NPLRHNYEGT LRDLLQFFKP RQPKKLYYQQ LKMKITDFEN RRSFKCIWLN
SQFREEEITL YPDKHGCVRD LLEECKKAVE LGEKASGKLR LLEIVSYKII GVHQEDELLE
CLSPATSRTF RIEEIPLDQV DIDKENEMLV TVAHFHKEVF GTFGIPFLLR IHQGEHFREV
MKRIQSLLDI QEKEFEKFKF AIVMMGRHQY INEDEYEVNL KDFEPQPGNM SHPRPWLGLD
HFNKAPKRSR YTYLEKAIKI HN
