UBP7_MOUSE
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 03-AUG-2022, entry version 145.
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, Pancreas,
RC 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 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 [10]
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 KAT5, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX
CC (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).
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 proteosomal-
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). {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: Expressed at high levels in brain, lung, thymus and
CC testis. Expressed at low levels in the liver.
CC {ECO:0000269|PubMed:14719112}.
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}.
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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; 28.
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 GlyGen; Q6A4J8; 2 sites, 2 N-linked glycans (2 sites).
DR iPTMnet; Q6A4J8; -.
DR PhosphoSitePlus; Q6A4J8; -.
DR EPD; Q6A4J8; -.
DR jPOST; Q6A4J8; -.
DR MaxQB; Q6A4J8; -.
DR PaxDb; Q6A4J8; -.
DR PeptideAtlas; Q6A4J8; -.
DR PRIDE; Q6A4J8; -.
DR ProteomicsDB; 297711; -. [Q6A4J8-1]
DR ProteomicsDB; 297712; -. [Q6A4J8-2]
DR ProteomicsDB; 297713; -. [Q6A4J8-3]
DR DNASU; 252870; -.
DR GeneID; 252870; -.
DR KEGG; mmu:252870; -.
DR UCSC; uc007ycx.1; mouse. [Q6A4J8-1]
DR CTD; 7874; -.
DR MGI; MGI:2182061; Usp7.
DR eggNOG; KOG1863; Eukaryota.
DR InParanoid; Q6A4J8; -.
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 114 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; IEA:UniProtKB-SubCell.
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:Lys48-specific deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0002039; F:p53 binding; ISO:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0035616; P:histone H2B conserved C-terminal lysine deubiquitination; IMP:UniProtKB.
DR GO; GO:0010216; P:maintenance of DNA methylation; ISO:MGI.
DR GO; GO:0035520; P:monoubiquitinated protein deubiquitination; ISO:MGI.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; 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:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
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:0006111; P:regulation of gluconeogenesis; 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:0006283; P:transcription-coupled nucleotide-excision repair; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 2.60.210.10; -; 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 Pfam; PF00917; MATH; 1.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF14533; USP7_C2; 1.
DR Pfam; PF12436; USP7_ICP0_bdg; 1.
DR SMART; SM00061; MATH; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50144; MATH; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW 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
