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 27-MAR-2024, entry version 240. 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 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 [16] 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 [17] 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 [18] 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 [19] 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 [20] 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 [21] 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 [22] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH EPSTEIN-BARR VIRUS RP EBNA1 (MICROBIAL INFECTION). RX PubMed=20719947; DOI=10.1128/jvi.01183-10; RA Sivachandran N., Cao J.Y., Frappier L.; RT "Epstein-Barr virus nuclear antigen 1 Hijacks the host kinase CK2 to RT disrupt PML nuclear bodies."; RL J. Virol. 84:11113-11123(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 EPSTEIN-BARR VIRUS EBNA1 (MICROBIAL INFECTION). RX PubMed=24216761; DOI=10.1128/mcb.00968-13; RA Cao J.Y., Shire K., Landry C., Gish G.D., Pawson T., Frappier L.; RT "Identification of a novel protein interaction motif in the regulatory RT subunit of casein kinase 2."; RL Mol. Cell. Biol. 34:246-258(2014). RN [39] 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 [40] 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 [41] 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 [42] 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 [43] 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 [44] 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 [45] 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 [46] RP FUNCTION, AND INTERACTION WITH HERPES VIRUS 8/HHV-8 PROTEIN VIRF-1 RP (MICROBIAL INFECTION). RX PubMed=26786098; DOI=10.1074/jbc.m115.710632; RA Chavoshi S., Egorova O., Lacdao I.K., Farhadi S., Sheng Y., Saridakis V.; RT "Identification of Kaposi Sarcoma Herpesvirus (KSHV) vIRF1 Protein as a RT Novel Interaction Partner of Human Deubiquitinase USP7."; RL J. Biol. Chem. 291:6281-6291(2016). RN [47] 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 [48] 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 [49] RP INTERACTION WITH HERPES VIRUS 8/HHV-8 PROTEIN VIRF-1 AND VIRF-3 (MICROBIAL RP INFECTION). RX PubMed=29343584; DOI=10.1128/jvi.02003-17; RA Xiang Q., Ju H., Li Q., Mei S.C., Chen D., Choi Y.B., Nicholas J.; RT "Human Herpesvirus 8 Interferon Regulatory Factors 1 and 3 Mediate RT Replication and Latency Activities via Interactions with USP7 RT Deubiquitinase."; RL J. Virol. 92:0-0(2018). RN [50] RP INTERACTION WITH HERPES VIRUS 8/HHV-8 PROTEIN VIRF-2 (MICROBIAL INFECTION). RX PubMed=31666375; DOI=10.1128/jvi.01553-19; RA Xiang Q., Ju H., Nicholas J.; RT "USP7-Dependent Regulation of TRAF Activation and Signaling by a Viral RT Interferon Regulatory Factor Homologue."; RL J. Virol. 94:0-0(2020). RN [51] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=35216969; DOI=10.1016/j.jbc.2022.101750; RA Vega M., Chen Y., Shi Y., Gera J., Lichtenstein A.; RT "Turnover of the mTOR inhibitor, DEPTOR, and downstream AKT phosphorylation RT in multiple myeloma cells, is dependent on ERK1-mediated phosphorylation."; RL J. Biol. Chem. 298:101750-101750(2022). RN [52] 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 [53] 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 [54] 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 [55] 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 [56] 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). RN [57] RP VARIANT HAFOUS 143-TYR--ASN-1102 DEL, INVOLVEMENT IN HAFOUS, RP CHARACTERIZATION OF VARIANT HAFOUS 143-TYR--ASN-1102 DEL, INTERACTION WITH RP MAGEL2 AND TRIM27, MUTAGENESIS OF CYS-223, AND FUNCTION. RX PubMed=26365382; DOI=10.1016/j.molcel.2015.07.033; RA Hao Y.H., Fountain M.D. Jr., Fon Tacer K., Xia F., Bi W., Kang S.H., RA Patel A., Rosenfeld J.A., Le Caignec C., Isidor B., Krantz I.D., Noon S.E., RA Pfotenhauer J.P., Morgan T.M., Moran R., Pedersen R.C., Saenz M.S., RA Schaaf C.P., Potts P.R.; RT "USP7 Acts as a Molecular Rheostat to Promote WASH-Dependent Endosomal RT Protein Recycling and Is Mutated in a Human Neurodevelopmental Disorder."; RL Mol. Cell 59:956-969(2015). RN [58] RP VARIANTS HAFOUS ILE-225; LYS-345; PHE-373; ASP-392; GLY-485; RP 576-CYS--ASN-1102 DEL; PRO-757; THR-766 AND ASN-1080, AND INVOLVEMENT IN RP HAFOUS. RX PubMed=30679821; DOI=10.1038/s41436-019-0433-1; RA Fountain M.D., Oleson D.S., Rech M.E., Segebrecht L., Hunter J.V., RA McCarthy J.M., Lupo P.J., Holtgrewe M., Moran R., Rosenfeld J.A., RA Isidor B., Le Caignec C., Saenz M.S., Pedersen R.C., Morgan T.M., RA Pfotenhauer J.P., Xia F., Bi W., Kang S.L., Patel A., Krantz I.D., RA Raible S.E., Smith W., Cristian I., Torti E., Juusola J., Millan F., RA Wentzensen I.M., Person R.E., Kuery S., Bezieau S., Uguen K., Ferec C., RA Munnich A., van Haelst M., Lichtenbelt K.D., van Gassen K., Hagelstrom T., RA Chawla A., Perry D.L., Taft R.J., Jones M., Masser-Frye D., Dyment D., RA Venkateswaran S., Li C., Escobar L.F., Horn D., Spillmann R.C., Pena L., RA Wierzba J., Strom T.M., Parenti I., Kaiser F.J., Ehmke N., Schaaf C.P.; RT "Pathogenic variants in USP7 cause a neurodevelopmental disorder with RT speech delays, altered behavior, and neurologic anomalies."; RL Genet. Med. 21:1797-1807(2019). CC -!- FUNCTION: Hydrolase that deubiquitinates target proteins such as FOXO4, CC DEPTOR, KAT5, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and CC DAXX (PubMed:11923872, PubMed:15053880, PubMed:16964248, CC PubMed:18716620, PubMed:25283148, PubMed:25865756, PubMed:26678539, CC PubMed:28655758, PubMed:35216969). Together with DAXX, prevents MDM2 CC self-ubiquitination and enhances the E3 ligase activity of MDM2 towards CC p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal CC degradation (PubMed:15053880, PubMed:16845383, PubMed:18566590, CC PubMed:20153724). Deubiquitinates p53/TP53, preventing degradation of CC p53/TP53, and enhances p53/TP53-dependent transcription regulation, CC cell growth repression and apoptosis (PubMed:25283148). Deubiquitinates CC p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence CC of excess MDM2, and also induces p53/TP53-dependent cell growth CC repression and apoptosis (PubMed:11923872, PubMed:26786098). CC Deubiquitination of FOXO4 in presence of hydrogen peroxide is not CC dependent on p53/TP53 and inhibits FOXO4-induced transcriptional CC activity (PubMed:16964248). In association with DAXX, is involved in CC the deubiquitination and translocation of PTEN from the nucleus to the CC 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). Involved in the regulation of WASH-dependent actin CC polymerization at the surface of endosomes and the regulation of CC endosomal protein recycling (PubMed:26365382). It maintains optimal CC WASH complex activity and precise F-actin levels via deubiquitination CC of TRIM27 and WASHC1 (PubMed:26365382). Mediates the deubiquitination CC of phosphorylated DEPTOR, promoting its stability and leading to CC decreased mTORC1 signaling (PubMed:35216969). CC {ECO:0000269|PubMed:11923872, ECO:0000269|PubMed:15053880, CC ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:16964248, CC ECO:0000269|PubMed:18566590, ECO:0000269|PubMed:18716620, CC ECO:0000269|PubMed:20153724, ECO:0000269|PubMed:20601937, 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:22689415, CC ECO:0000269|PubMed:23973222, ECO:0000269|PubMed:25283148, CC ECO:0000269|PubMed:25865756, ECO:0000269|PubMed:25944111, CC ECO:0000269|PubMed:26365382, ECO:0000269|PubMed:26678539, CC ECO:0000269|PubMed:26786098, ECO:0000269|PubMed:27123980, CC ECO:0000269|PubMed:28655758, ECO:0000269|PubMed:35216969}. 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 -!- FUNCTION: (Microbial infection) Upon infection with Epstein-Barr virus, CC the interaction with viral EBNA1 increases the association of USP7 with CC PML proteins, which is required for the polyubiquitylation and CC degradation of PML. {ECO:0000269|PubMed:20719947, CC ECO:0000269|PubMed:24216761}. 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, ECO:0000269|PubMed:35216969}; 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 proteasomal-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 Part of a complex consisting of USP7, MAGEL2 and TRIM27; directly CC interacts with MAGEL2; directly interacts with TRIM27 CC (PubMed:26365382). {ECO:0000250|UniProtKB:Q6A4J8, CC ECO:0000269|PubMed:12093161, ECO:0000269|PubMed:16845383, CC ECO:0000269|PubMed:16964248, ECO:0000269|PubMed:18566590, CC ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:20601937, CC ECO:0000269|PubMed:21170034, 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:22863774, ECO:0000269|PubMed:25266658, CC ECO:0000269|PubMed:25283148, ECO:0000269|PubMed:25944111, CC ECO:0000269|PubMed:26030138, ECO:0000269|PubMed:26365382, 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 the interaction is independent and simultaneous to EBNA1 interaction CC with USP7 as well as necessary for PML nuclear bodies disruption by CC EBNA1 (PubMed:14506283, PubMed:24216761). EBNA1, USP7 and CSNK2B form a CC ternary complex. EBNA1 shows a 10-fold higher affinity than p53/TP53 CC and can compete with it for USP7 binding (PubMed:14506283). CC {ECO:0000269|PubMed:14506283, ECO:0000269|PubMed:24216761}. 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 -!- SUBUNIT: (Microbial infection) Interacts with herpes virus 8/HHV-8 CC proteins vIRF-1 and vIRF-3; these interactions may disrupt TP53 CC signaling pathway during viral infection by decreasing the availability CC of USP7 for deubiquitinating and stabilizing TP53. CC {ECO:0000269|PubMed:29343584, ECO:0000269|PubMed:31666375}. CC -!- SUBUNIT: (Microbial infection) Interacts with herpes virus 8/HHV-8 CC protein vIRF-2; this interaction modulates antiviral signaling via CC disruption of USP7 interactions with innate immune signaling proteins CC TRAF3 and TRAF6 thus affecting their ubiquitination. CC {ECO:0000269|PubMed:31666375}. CC -!- INTERACTION: 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=7; IntAct=EBI-302474, EBI-2341576; CC Q93009; Q9HC52: CBX8; NbExp=7; IntAct=EBI-302474, EBI-712912; CC Q93009; Q9UER7: DAXX; NbExp=15; IntAct=EBI-302474, EBI-77321; CC Q93009; Q9HCI5: MAGEE1; NbExp=2; IntAct=EBI-302474, EBI-949966; CC Q93009; P21145: MAL; NbExp=3; IntAct=EBI-302474, EBI-3932027; CC Q93009; Q00987: MDM2; NbExp=34; IntAct=EBI-302474, EBI-389668; CC Q93009; O15151: MDM4; NbExp=15; IntAct=EBI-302474, EBI-398437; CC Q93009; Q5U5Q3: MEX3C; NbExp=3; IntAct=EBI-302474, EBI-2864451; CC Q93009; Q99836: MYD88; NbExp=3; IntAct=EBI-302474, EBI-447677; CC Q93009; P35227: PCGF2; NbExp=5; IntAct=EBI-302474, EBI-2129767; 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; P84022: SMAD3; NbExp=2; IntAct=EBI-302474, EBI-347161; CC Q93009; P48431: SOX2; NbExp=3; IntAct=EBI-302474, EBI-6124081; CC Q93009; Q99426: TBCB; NbExp=2; IntAct=EBI-302474, EBI-764356; CC Q93009; P04637: TP53; NbExp=19; IntAct=EBI-302474, EBI-366083; CC Q93009; Q86VY4: TSPYL5; NbExp=4; IntAct=EBI-302474, EBI-3436472; 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 -!- DISEASE: Hao-Fountain syndrome (HAFOUS) [MIM:616863]: An autosomal CC dominant neurodevelopmental disorder characterized by global CC developmental delay, varying degrees of intellectual disability, autism CC spectrum disorder, poor or absent speech, and mild facial dysmorphism. CC Most patients develop seizures. Additional variable features include CC hypotonia, hypogonadism in males, and ocular anomalies. CC {ECO:0000269|PubMed:26365382, ECO:0000269|PubMed:30679821}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42773/USP7"; 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 PDB; 7VIJ; X-ray; 2.30 A; A=560-1083. DR PDB; 7XHH; X-ray; 2.10 A; A/B=207-554. DR PDB; 7XHK; X-ray; 2.30 A; B=211-553. DR PDB; 7XPY; X-ray; 2.35 A; A=560-1102. DR PDB; 8D4Z; X-ray; 2.26 A; A/B=207-560. 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 PDBsum; 7VIJ; -. DR PDBsum; 7XHH; -. DR PDBsum; 7XHK; -. DR PDBsum; 7XPY; -. DR PDBsum; 8D4Z; -. DR AlphaFoldDB; Q93009; -. DR BMRB; Q93009; -. DR SMR; Q93009; -. DR BioGRID; 113622; 837. DR CORUM; Q93009; -. DR DIP; DIP-29053N; -. DR ELM; Q93009; -. DR IntAct; Q93009; 248. DR MINT; Q93009; -. DR STRING; 9606.ENSP00000343535; -. DR BindingDB; Q93009; -. DR ChEMBL; CHEMBL2157850; -. DR MEROPS; C19.016; -. DR GlyCosmos; Q93009; 1 site, 1 glycan. DR GlyGen; Q93009; 2 sites, 1 O-linked glycan (2 sites). 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; 9606-ENSP00000343535; -. DR PeptideAtlas; Q93009; -. DR ProteomicsDB; 6915; -. DR ProteomicsDB; 75669; -. [Q93009-1] DR Pumba; Q93009; -. DR ABCD; Q93009; 3 sequenced antibodies. DR Antibodypedia; 2881; 851 antibodies from 43 providers. DR DNASU; 7874; -. DR Ensembl; ENST00000344836.9; ENSP00000343535.4; ENSG00000187555.17. [Q93009-1] DR Ensembl; ENST00000381886.8; ENSP00000371310.4; ENSG00000187555.17. [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 AGR; HGNC:12630; -. 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 MIM; 616863; phenotype. DR neXtProt; NX_Q93009; -. DR OpenTargets; ENSG00000187555; -. DR Orphanet; 500055; Hao-Fountain syndrome due to 16p13.2 microdeletion. DR Orphanet; 643538; Hao-Fountain syndrome due to USP7 mutation. DR PharmGKB; PA37255; -. DR VEuPathDB; HostDB:ENSG00000187555; -. DR eggNOG; KOG1863; Eukaryota. DR GeneTree; ENSGT00940000156053; -. DR InParanoid; Q93009; -. DR OMA; HTAHHRF; -. DR OrthoDB; 51419at2759; -. 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; 567 hits in 1208 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 208 other cell types or tissues. DR ExpressionAtlas; Q93009; baseline and differential. 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; IDA:UniProt. 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:K48-linked deubiquitinase activity; IDA:UniProtKB. DR GO; GO:0002039; F:p53 binding; IDA:UniProtKB. DR GO; GO:0035520; P:monoubiquitinated protein deubiquitination; IDA:MGI. DR GO; GO:0044027; P:negative regulation of gene expression via CpG island methylation; IMP:UniProtKB. DR GO; GO:0045721; P:negative regulation of gluconeogenesis; IDA:UniProtKB. 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:1904262; P:negative regulation of TORC1 signaling; IDA:UniProt. DR GO; GO:1901537; P:positive regulation of DNA demethylation; IDA:UniProtKB. DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB. DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; TAS:Reactome. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. 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: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:0075342; P:symbiont-mediated disruption of host cell PML body; IDA:UniProt. DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; IMP:UniProtKB. DR CDD; cd03772; MATH_HAUSP; 1. DR CDD; cd02659; peptidase_C19C; 1. DR DisProt; DP00941; -. DR Gene3D; 3.90.70.10; Cysteine proteinases; 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 PANTHER; PTHR24006; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1. DR PANTHER; PTHR24006:SF644; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 7; 1. 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; Cysteine proteinases; 1. DR SUPFAM; SSF49599; TRAF domain-like; 1. DR PROSITE; PS50144; MATH; 1. DR PROSITE; PS00972; USP_1; 1. DR PROSITE; PS00973; USP_2; 1. DR PROSITE; PS50235; USP_3; 1. DR Genevisible; Q93009; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Autism spectrum disorder; KW Biological rhythms; Chromosome; Cytoplasm; Developmental protein; KW Direct protein sequencing; Disease variant; DNA damage; DNA repair; KW Epilepsy; Host-virus interaction; Hydrolase; Intellectual disability; KW Isopeptide bond; Nucleus; Phosphoprotein; Protease; Reference proteome; KW Thiol protease; 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 VARIANT 143..1102 FT /note="Missing (in HAFOUS; when expressed in USP7-deficient FT cells does not rescue defective endosomal protein recycling FT and reduced F-actin levels)" FT /evidence="ECO:0000269|PubMed:26365382" FT /id="VAR_086825" FT VARIANT 225 FT /note="M -> I (in HAFOUS; dbSNP:rs1555465642)" FT /evidence="ECO:0000269|PubMed:30679821" FT /id="VAR_086826" FT VARIANT 345 FT /note="E -> K (in HAFOUS)" FT /evidence="ECO:0000269|PubMed:30679821" FT /id="VAR_086827" FT VARIANT 373 FT /note="L -> F (in HAFOUS)" FT /evidence="ECO:0000269|PubMed:30679821" FT /id="VAR_086828" FT VARIANT 392 FT /note="G -> D (in HAFOUS)" FT /evidence="ECO:0000269|PubMed:30679821" FT /id="VAR_086829" FT VARIANT 485 FT /note="V -> G (in HAFOUS)" FT /evidence="ECO:0000269|PubMed:30679821" FT /id="VAR_086830" FT VARIANT 576..1102 FT /note="Missing (in HAFOUS)" FT /evidence="ECO:0000269|PubMed:30679821" FT /id="VAR_086831" FT VARIANT 757 FT /note="L -> P (in HAFOUS; uncertain significance; the FT patient also carries a de novo clinically relevant variant FT in SLC2A1)" FT /evidence="ECO:0000269|PubMed:30679821" FT /id="VAR_086832" FT VARIANT 766 FT /note="I -> T (in HAFOUS)" FT /evidence="ECO:0000269|PubMed:30679821" FT /id="VAR_086833" FT VARIANT 1080 FT /note="D -> N (in HAFOUS)" FT /evidence="ECO:0000269|PubMed:30679821" FT /id="VAR_086834" 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. Reduced deubiquitination of FT TRIM27 and WASHC1." 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:26365382, ECO:0000269|PubMed:26678539, FT 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:7XHH" 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:7VIJ" 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:7VIJ" 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 667..671 FT /evidence="ECO:0007829|PDB:7VIJ" 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:7VIJ" FT STRAND 894..899 FT /evidence="ECO:0007829|PDB:7VIJ" FT STRAND 905..910 FT /evidence="ECO:0007829|PDB:7VIJ" FT HELIX 918..926 FT /evidence="ECO:0007829|PDB:7VIJ" FT STRAND 933..935 FT /evidence="ECO:0007829|PDB:4YOC" FT STRAND 939..945 FT /evidence="ECO:0007829|PDB:7VIJ" FT STRAND 948..953 FT /evidence="ECO:0007829|PDB:7VIJ" FT HELIX 959..961 FT /evidence="ECO:0007829|PDB:7VIJ" FT STRAND 965..967 FT /evidence="ECO:0007829|PDB:7XPY" FT STRAND 969..974 FT /evidence="ECO:0007829|PDB:7VIJ" FT HELIX 977..979 FT /evidence="ECO:0007829|PDB:7VIJ" FT TURN 984..986 FT /evidence="ECO:0007829|PDB:7VIJ" FT STRAND 987..998 FT /evidence="ECO:0007829|PDB:7VIJ" FT STRAND 1001..1012 FT /evidence="ECO:0007829|PDB:7VIJ" FT HELIX 1017..1028 FT /evidence="ECO:0007829|PDB:7VIJ" FT HELIX 1032..1037 FT /evidence="ECO:0007829|PDB:7VIJ" FT STRAND 1039..1044 FT /evidence="ECO:0007829|PDB:7VIJ" FT STRAND 1047..1050 FT /evidence="ECO:0007829|PDB:7VIJ" FT TURN 1053..1055 FT /evidence="ECO:0007829|PDB:7VIJ" FT HELIX 1060..1062 FT /evidence="ECO:0007829|PDB:7VIJ" FT STRAND 1070..1072 FT /evidence="ECO:0007829|PDB:7VIJ" FT STRAND 1076..1080 FT /evidence="ECO:0007829|PDB:7VIJ" 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 //