ID UBP7_MOUSE Reviewed; 1103 AA. AC Q6A4J8; Q3UX92; Q496Y5; Q8BW01; DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot. DT 13-SEP-2004, sequence version 1. DT 27-MAR-2024, entry version 154. DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 7; DE EC=3.4.19.12 {ECO:0000269|PubMed:14719112, ECO:0000269|PubMed:21268065}; DE AltName: Full=Deubiquitinating enzyme 7; DE AltName: Full=Herpesvirus-associated ubiquitin-specific protease; DE Short=mHAUSP; DE AltName: Full=Ubiquitin thioesterase 7; DE AltName: Full=Ubiquitin-specific-processing protease 7; GN Name=Usp7; Synonyms=Hausp; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, RP TISSUE SPECIFICITY, INTERACTION WITH TP53, AND MUTAGENESIS OF CYS-224. RX PubMed=14719112; RA Lim S.-K., Shin J.-M., Kim Y.-S., Baek K.-H.; RT "Identification and characterization of murine mHAUSP encoding a RT deubiquitinating enzyme that regulates the status of p53 ubiquitination."; RL Int. J. Oncol. 24:357-364(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-545 (ISOFORM 2), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 832-1103. RC STRAIN=C57BL/6J; TISSUE=Egg, and Stomach; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 214-1103 (ISOFORM 3). RC STRAIN=C57BL/6J; TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19; SER-50 AND SER-54, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [6] RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE. RX PubMed=19946331; DOI=10.1038/onc.2009.427; RA Kon N., Kobayashi Y., Li M., Brooks C.L., Ludwig T., Gu W.; RT "Inactivation of HAUSP in vivo modulates p53 function."; RL Oncogene 29:1270-1279(2010). RN [7] RP FUNCTION, INTERACTION WITH DNMT1 AND UHRF1, AND MUTAGENESIS OF CYS-224. RX PubMed=21268065; DOI=10.1002/jcb.22998; RA Qin W., Leonhardt H., Spada F.; RT "Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA RT methyltransferase Dnmt1."; RL J. Cell. Biochem. 112:439-444(2011). RN [8] RP FUNCTION. 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 [9] RP TISSUE SPECIFICITY. 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 [10] RP FUNCTION, AND INTERACTION WITH EPOP. RX PubMed=27863226; DOI=10.1016/j.molcel.2016.10.019; RA Liefke R., Karwacki-Neisius V., Shi Y.; RT "EPOP interacts with elongin BC and USP7 to modulate the chromatin RT landscape."; RL Mol. Cell 64:659-672(2016). RN [11] RP ERRATUM OF PUBMED:27863226. RX PubMed=28061330; DOI=10.1016/j.molcel.2016.12.006; RA Liefke R., Karwacki-Neisius V., Shi Y.; RL Mol. Cell 65:202-202(2017). RN [12] RP FUNCTION. 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). 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:21268065, PubMed:14719112, PubMed:19946331). Together with CC DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase CC activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 CC ubiquitination and proteasomal degradation. Deubiquitinates p53/TP53, CC preventing degradation of p53/TP53, and enhances p53/TP53-dependent CC transcription regulation, cell growth repression and apoptosis. CC Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even CC in the presence of excess MDM2, and also induces p53/TP53-dependent CC cell growth repression and apoptosis. Deubiquitination of FOXO4 in CC presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits CC FOXO4-induced transcriptional activity. In association with DAXX, is CC involved in the deubiquitination and translocation of PTEN from the CC nucleus to the cytoplasm, both processes that are counteracted by PML. CC Deubiquitinates KMT2E preventing KMT2E proteasomal-mediated degradation CC (By similarity). Involved in cell proliferation during early embryonic CC development. Involved in transcription-coupled nucleotide excision CC repair (TC-NER) in response to UV damage: recruited to DNA damage sites CC following interaction with KIAA1530/UVSSA and promotes deubiquitination CC of ERCC6, preventing UV-induced degradation of ERCC6 (By similarity). 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 Deubiquitinates alkylation repair enzyme ALKBH3. OTUD4 recruits USP7 CC and USP9X to stabilize ALKBH3, thereby promoting the repair of CC alkylated DNA lesions (By similarity). Acts as a chromatin regulator CC via its association with the Polycomb group (PcG) multiprotein PRC1- CC like complex; may act by deubiquitinating components of the PRC1-like CC complex (By similarity). Able to mediate deubiquitination of histone CC H2B; it is however unsure whether this activity takes place in vivo CC (PubMed:27863226). Exhibits a preference towards 'Lys-48'-linked CC ubiquitin chains. Increases regulatory T-cells (Treg) suppressive CC capacity by deubiquitinating and stabilizing the transcription factor CC FOXP3 which is crucial for Treg cell function (PubMed:23973222). Plays CC a role in the maintenance of the circadian clock periodicity via CC deubiquitination and stabilization of the CRY1 and CRY2 proteins CC (PubMed:27123980). Deubiquitinates REST, thereby stabilizing REST and CC promoting the maintenance of neural progenitor cells (By similarity). CC Deubiquitinates SIRT7, inhibiting SIRT7 histone deacetylase activity CC and regulating gluconeogenesis (By similarity). Involved in the CC regulation of WASH-dependent actin polymerization at the surface of CC endosomes and the regulation of endosomal protein recycling (By CC similarity). It maintains optimal WASH complex activity and precise F- CC actin levels via deubiquitination of TRIM27 and WASHC1 (By similarity). CC Mediates the deubiquitination of phosphorylated DEPTOR, promoting its CC stability and leading to decreased mTORC1 signaling (By similarity). CC {ECO:0000250|UniProtKB:Q93009, ECO:0000269|PubMed:23973222, CC ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:27863226}. 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:14719112, CC ECO:0000269|PubMed:21268065}; CC -!- SUBUNIT: Monomer. Homodimer. Part of a complex with DAXX, MDM2, RASSF1 CC and USP7. Part of a complex with DAXX, MDM2 and USP7. Interacts with CC MDM2; the interaction is independent of p53/TP53. Interacts with DAXX; CC the interaction is direct and independent of MDM2 and p53/TP53. CC Component of a complex composed of KMT2E, OGT and USP7; the complex CC stabilizes KMT2E, preventing KMT2E ubiquitination and proteasomal- CC mediated degradation (By similarity). Interacts (via MATH domain) with CC KMT2E (By similarity). Interacts with OGT (By similarity). Interacts CC with FOXO4; the interaction is enhanced in presence of hydrogen CC peroxide and occurs independently of p53/TP53. Interacts with p53/TP53; CC the interaction is enhanced in response to DNA damage; the interaction CC is impaired by TSPYL5. Interacts with PTEN; the interaction is direct. CC Interacts with ATXN1 and the strength of interaction is influenced by CC the length of the poly-Gln region in ATXN1. A weaker interaction seen CC with mutants having longer poly-Gln regions. Interacts with CC KIAA1530/UVSSA. Interacts with MEX3C and antagonizes its ability to CC degrade mRNA (By similarity). Interacts with DNMT1 and UHRF1 CC (PubMed:21268065). Interacts with FOXP3 (By similarity). Interacts (via CC MATH domain) with RNF220 (By similarity). Associated component of the CC Polycomb group (PcG) multiprotein PRC1-like complex (By similarity). CC Interacts with EPOP (PubMed:27863226). Interacts with OTUD4 and USP9X; CC the interaction is direct (By similarity). Interacts with CRY2 (By CC similarity). Interacts with REST (By similarity). Interacts with ERCC6 CC (By similarity). Part of a complex consisting of USP7, MAGEL2 and CC TRIM27; directly interacts with MAGEL2; directly interacts with TRIM27 CC (By similarity). {ECO:0000250|UniProtKB:Q93009, CC ECO:0000269|PubMed:14719112, ECO:0000269|PubMed:21268065, CC ECO:0000269|PubMed:27863226}. CC -!- INTERACTION: CC Q6A4J8; O08586: Pten; NbExp=2; IntAct=EBI-1216254, EBI-1186266; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q93009}. Cytoplasm CC {ECO:0000250|UniProtKB:Q93009}. Nucleus, PML body CC {ECO:0000250|UniProtKB:Q93009}. Chromosome CC {ECO:0000250|UniProtKB:Q93009}. 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. {ECO:0000250|UniProtKB:Q93009}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q6A4J8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6A4J8-2; Sequence=VSP_021952; CC Name=3; CC IsoId=Q6A4J8-3; Sequence=VSP_021953, VSP_021954; CC -!- TISSUE SPECIFICITY: Widely expressed. High expression is detected in CC brain, bone marrow, thymus and testis. {ECO:0000269|PubMed:14719112, CC ECO:0000269|PubMed:26365382}. CC -!- DEVELOPMENTAL STAGE: Expressed in embryo at 3.5 and from 7.5 to 10.5 CC dpc (at protein level). CC -!- DOMAIN: The C-terminus plays a role in its oligomerization. CC {ECO:0000250}. CC -!- PTM: Polyneddylated. {ECO:0000250}. CC -!- PTM: Not sumoylated. {ECO:0000250}. CC -!- PTM: Polyubiquitinated. Ubiquitinated at Lys-870 (By similarity). CC {ECO:0000250}. CC -!- DISRUPTION PHENOTYPE: Led to early embryonic lethality. Show CC disorganized germinal layers without the formation of a proamniotic CC cavity. Many of the surviving cells were trophoblastic giant cells with CC large nuclei. {ECO:0000269|PubMed:19946331}. CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}. 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; AF548565; AAQ12339.1; -; mRNA. DR EMBL; AK075830; BAC35992.1; -; mRNA. DR EMBL; AK135814; BAE22671.1; -; mRNA. DR EMBL; BC100666; AAI00667.1; -; mRNA. DR CCDS; CCDS49755.1; -. [Q6A4J8-1] DR RefSeq; NP_001003918.2; NM_001003918.2. DR AlphaFoldDB; Q6A4J8; -. DR BMRB; Q6A4J8; -. DR SMR; Q6A4J8; -. DR BioGRID; 232963; 66. DR DIP; DIP-38603N; -. DR IntAct; Q6A4J8; 6. DR MINT; Q6A4J8; -. DR STRING; 10090.ENSMUSP00000124093; -. DR MEROPS; C19.016; -. DR GlyConnect; 2806; 2 N-Linked glycans (2 sites). DR GlyCosmos; Q6A4J8; 2 sites, 2 glycans. DR GlyGen; Q6A4J8; 3 sites, 2 N-linked glycans (2 sites), 1 O-linked glycan (1 site). DR iPTMnet; Q6A4J8; -. DR PhosphoSitePlus; Q6A4J8; -. DR SwissPalm; Q6A4J8; -. DR EPD; Q6A4J8; -. DR jPOST; Q6A4J8; -. DR MaxQB; Q6A4J8; -. DR PaxDb; 10090-ENSMUSP00000124093; -. DR PeptideAtlas; Q6A4J8; -. DR ProteomicsDB; 297711; -. [Q6A4J8-1] DR ProteomicsDB; 297712; -. [Q6A4J8-2] DR ProteomicsDB; 297713; -. [Q6A4J8-3] DR Pumba; Q6A4J8; -. DR DNASU; 252870; -. DR GeneID; 252870; -. DR KEGG; mmu:252870; -. DR UCSC; uc007ycx.1; mouse. [Q6A4J8-1] DR AGR; MGI:2182061; -. DR CTD; 7874; -. DR MGI; MGI:2182061; Usp7. DR eggNOG; KOG1863; Eukaryota. DR InParanoid; Q6A4J8; -. DR OrthoDB; 51419at2759; -. DR PhylomeDB; Q6A4J8; -. DR Reactome; R-MMU-5689880; Ub-specific processing proteases. DR Reactome; R-MMU-6781823; Formation of TC-NER Pre-Incision Complex. DR Reactome; R-MMU-6782135; Dual incision in TC-NER. DR Reactome; R-MMU-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER. DR Reactome; R-MMU-6804757; Regulation of TP53 Degradation. DR Reactome; R-MMU-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes. DR Reactome; R-MMU-8948747; Regulation of PTEN localization. DR BioGRID-ORCS; 252870; 25 hits in 120 CRISPR screens. DR ChiTaRS; Usp7; mouse. DR PRO; PR:Q6A4J8; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; Q6A4J8; Protein. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0016605; C:PML body; ISO:MGI. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0001741; C:XY body; IDA:MGI. 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; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:1990380; F:K48-linked deubiquitinase activity; ISS:UniProtKB. DR GO; GO:0002039; F:p53 binding; ISO:MGI. DR GO; GO:0035520; P:monoubiquitinated protein deubiquitination; ISO:MGI. DR GO; GO:0044027; P:negative regulation of gene expression via CpG island methylation; ISO:MGI. DR GO; GO:0045721; P:negative regulation of gluconeogenesis; ISS:UniProtKB. DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:MGI. DR GO; GO:1904262; P:negative regulation of TORC1 signaling; ISO:MGI. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI. DR GO; GO:1901537; P:positive regulation of DNA demethylation; ISS:UniProtKB. DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB. DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB. DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; ISS:UniProtKB. DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB. DR GO; GO:1905279; P:regulation of retrograde transport, endosome to Golgi; ISO:MGI. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. DR GO; GO:0075342; P:symbiont-mediated disruption of host cell PML body; ISO:MGI. DR GO; GO:0140673; P:transcription elongation-coupled chromatin remodeling; IMP:UniProtKB. DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; ISS:UniProtKB. DR CDD; cd03772; MATH_HAUSP; 1. DR CDD; cd02659; peptidase_C19C; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 1. 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. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Biological rhythms; Chromosome; KW Cytoplasm; Developmental protein; DNA damage; DNA repair; Hydrolase; KW Isopeptide bond; Nucleus; Phosphoprotein; Protease; Reference proteome; KW Thiol protease; Ubl conjugation; Ubl conjugation pathway. FT CHAIN 1..1103 FT /note="Ubiquitin carboxyl-terminal hydrolase 7" FT /id="PRO_0000268006" FT DOMAIN 69..196 FT /note="MATH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00129" FT DOMAIN 215..522 FT /note="USP" FT REGION 1..209 FT /note="Interaction with TSPYL5" FT /evidence="ECO:0000250|UniProtKB:Q93009" FT REGION 1..41 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 46..65 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 54..209 FT /note="Interaction with p53/TP53 and MDM2" FT /evidence="ECO:0000250|UniProtKB:Q93009" FT REGION 71..206 FT /note="Necessary for nuclear localization" FT /evidence="ECO:0000250|UniProtKB:Q93009" FT COMPBIAS 1..17 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 224 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, FT ECO:0000255|PROSITE-ProRule:PRU10093, FT ECO:0000269|PubMed:14719112, ECO:0000269|PubMed:21268065" FT ACT_SITE 465 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, FT ECO:0000255|PROSITE-ProRule:PRU10093" FT MOD_RES 19 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19144319, FT ECO:0007744|PubMed:21183079" FT MOD_RES 50 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 54 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 870 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q93009" FT MOD_RES 964 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q93009" FT MOD_RES 1085 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q93009" FT MOD_RES 1097 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q93009" FT CROSSLNK 870 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:Q93009" FT CROSSLNK 870 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); alternate" FT /evidence="ECO:0000250|UniProtKB:Q93009" FT CROSSLNK 883 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q93009" FT VAR_SEQ 1..27 FT /note="MNHQQQQQQQQKAGEQQLSEPEDMEME -> MASSTSPPRSPSGGILTQDTI FT YFPQSNIISELLPWYLRYTPPEVPSTSVITKFILVNCPWNEGIEYQ (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_021952" FT VAR_SEQ 974 FT /note="E -> ECLQ (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_021953" FT VAR_SEQ 1094..1103 FT /note="YLEKAIKIHN -> LGLC (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_021954" FT MUTAGEN 224 FT /note="C->S: Loss of p53/TP53-deubiquitinating activity." FT /evidence="ECO:0000269|PubMed:14719112, FT ECO:0000269|PubMed:21268065" FT CONFLICT 162 FT /note="E -> K (in Ref. 2; BAE22671)" FT /evidence="ECO:0000305" SQ SEQUENCE 1103 AA; 128475 MW; 989DFE733F0D961E CRC64; MNHQQQQQQQ QKAGEQQLSE PEDMEMEAGD TDDPPRITQN PVINGNVTLS DGHSNAEEDM EDDTSWRSEA TFQFTVERFS RLSESVLSPP CFVRNLPWKI MVMPRFYPDR PHQKSVGFFL QCNAESDSTS WSCHAQAVLK IINYRDDDKS FSRRISHLFF HEENDWGFSN FMAWSEVTDP EKGFIDDDKV TFEVFVQADA PHGVAWDSKK HTGYVGLKNQ GATCYMNSLL QTLFFTNQLR KAVYMMPTEG DDSSKSVPLA LQRVFYELQH SDKPVGTKKL TKSFGWETLD SFMQHDVQEL CRVLLDNVEN KMKGTCVEGT IPKLFRGKMV SYIQCKDVDY RSDRREDYYD IQLSIKGKKN IFESFVDYVA VEQLDGDNKY DAGEHGLQEA EKGVKFLTLP PVLHLQLMRF MYDPQTDQNI KINDRFEFPE QLPLDEFLQK TDPKDPANYI LHAVLVHSGD NHGGHYVVYL NPKGDGKWCK FDDDVVSRCT KEEAIEHNYG GHDDDLSVRH CTNAYMLVYI RESKLSEVLQ AVTDHDIPQQ LVERLQEEKR IEAQKRKERQ EAHLYMQVQI VAEDQFCGHQ GNDMYDEEKV RYTVFKVLKN SSLAEFVQSL SQTMGFPQDQ IRLWPMQARS NGTKRPAMLD NEADGNKTMI ELSDNENPWT IFLETVDPEL AASGATLPKF DKDHDVMLFL KMYDPKTRSL NYCGHIYTPI SCKIRDLLPV MCDRAGFIQD TSLILYEEVK PNLTERIQDY DVSLDKALDE LMDGDIIVFQ KDDPENDNSE LPTAKEYFRD LYHRVDVIFC DKTIPNDPGF VVTLSNRMNY FQVAKTVAQR LNTDPMLLQF FKSQGYRDGP GNPLRHNYEG TLRDLLQFFK PRQPKKLYYQ QLKMKITDFE NRRSFKCIWL NSQFREEEIT LYPDKHGCVR DLLEECKKAV ELGDKASGRL RLLEIVSYKI IGVHQEDELL ECLSPATSRT FRIEEIPLDQ VDIDKENEML ITVAHFHKEV FGTFGIPFLL RIHQGEHFRE VMKRIQSLLD IQEKEFEKFK FAIVMMGRHQ YINEDEYEVN LKDFEPQPGN MSHPRPWLGL DHFNKAPKRS RYTYLEKAIK IHN //