UBP10_HUMAN
ID UBP10_HUMAN Reviewed; 798 AA.
AC Q14694; B2RDJ8; B4DS84; Q9BWG7; Q9NSL7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 10;
DE EC=3.4.19.12 {ECO:0000269|PubMed:20096447};
DE AltName: Full=Deubiquitinating enzyme 10;
DE AltName: Full=Ubiquitin thioesterase 10;
DE AltName: Full=Ubiquitin-specific-processing protease 10;
GN Name=USP10; Synonyms=KIAA0190;
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), FUNCTION, TISSUE SPECIFICITY,
RP INTERACTION WITH G3BP, AND MUTAGENESIS OF CYS-424.
RX PubMed=11439350; DOI=10.1038/sj.onc.1204553;
RA Soncini C., Berdo I., Draetta G.;
RT "Ras-GAP SH3 domain binding protein (G3BP) is a modulator of USP10, a novel
RT human ubiquitin specific protease.";
RL Oncogene 20:3869-3879(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Bone marrow;
RX PubMed=8724849; DOI=10.1093/dnares/3.1.17;
RA Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. V. The
RT coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 3:17-24(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain, and Placenta;
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 MRNA] (ISOFORM 1), AND VARIANT VAL-200.
RC TISSUE=Melanoma, and Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS PRO-203
RP AND LEU-204.
RC 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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-576, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-365 AND SER-370, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-576, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Prostate cancer;
RX PubMed=17487921; DOI=10.1002/elps.200600782;
RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.;
RT "Toward a global characterization of the phosphoproteome in prostate cancer
RT cells: identification of phosphoproteins in the LNCaP cell line.";
RL Electrophoresis 28:2027-2034(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-576, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17693683; DOI=10.1074/mcp.m700120-mcp200;
RA Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S., Li S.-J.,
RA Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R.;
RT "Quantitative phosphoproteome profiling of Wnt3a-mediated signaling
RT network: indicating the involvement of ribonucleoside-diphosphate reductase
RT M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal
RT transduction.";
RL Mol. Cell. Proteomics 6:1952-1967(2007).
RN [11]
RP FUNCTION, AND INTERACTION WITH SNX3.
RX PubMed=18632802; DOI=10.1152/ajprenal.00001.2008;
RA Boulkroun S., Ruffieux-Daidie D., Vitagliano J.J., Poirot O., Charles R.P.,
RA Lagnaz D., Firsov D., Kellenberger S., Staub O.;
RT "Vasopressin-inducible ubiquitin-specific protease 10 increases ENaC cell
RT surface expression by deubiquitylating and stabilizing sorting nexin 3.";
RL Am. J. Physiol. 295:F889-F900(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-100; SER-226 AND SER-370, 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-576, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [14]
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 [15]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CFTR, AND MUTAGENESIS OF
RP CYS-424.
RX PubMed=19398555; DOI=10.1074/jbc.m109.001685;
RA Bomberger J.M., Barnaby R.L., Stanton B.A.;
RT "The deubiquitinating enzyme USP10 regulates the post-endocytic sorting of
RT cystic fibrosis transmembrane conductance regulator in airway epithelial
RT cells.";
RL J. Biol. Chem. 284:18778-18789(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-563 AND SER-576, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INDUCTION, INTERACTION
RP WITH TP53, PHOSPHORYLATION AT THR-42 AND SER-337, AND MUTAGENESIS OF THR-42
RP AND SER-337.
RX PubMed=20096447; DOI=10.1016/j.cell.2009.12.032;
RA Yuan J., Luo K., Zhang L., Cheville J.C., Lou Z.;
RT "USP10 regulates p53 localization and stability by deubiquitinating p53.";
RL Cell 140:384-396(2010).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT THR-24; SER-365; SER-370 AND SER-576, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [19]
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 [20]
RP FUNCTION, ACTIVITY REGULATION, UBIQUITINATION, AND MUTAGENESIS OF CYS-424.
RX PubMed=21962518; DOI=10.1016/j.cell.2011.08.037;
RA Liu J., Xia H., Kim M., Xu L., Li Y., Zhang L., Cai Y., Norberg H.V.,
RA Zhang T., Furuya T., Jin M., Zhu Z., Wang H., Yu J., Li Y., Hao Y.,
RA Choi A., Ke H., Ma D., Yuan J.;
RT "Beclin1 controls the levels of p53 by regulating the deubiquitination
RT activity of USP10 and USP13.";
RL Cell 147:223-234(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-576, 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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-370; SER-547 AND SER-576, AND
RP IDENTIFICATION BY 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 [23]
RP INTERACTION WITH G3BP1 AND G3BP2.
RX PubMed=23279204; DOI=10.1111/gtc.12023;
RA Matsuki H., Takahashi M., Higuchi M., Makokha G.N., Oie M., Fujii M.;
RT "Both G3BP1 and G3BP2 contribute to stress granule formation.";
RL Genes Cells 18:135-146(2013).
RN [24]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TBX21, AND MUTAGENESIS OF
RP CYS-424.
RX PubMed=24845384; DOI=10.1016/j.bbrc.2014.05.037;
RA Pan L., Chen Z., Wang L., Chen C., Li D., Wan H., Li B., Shi G.;
RT "Deubiquitination and stabilization of T-bet by USP10.";
RL Biochem. Biophys. Res. Commun. 449:289-294(2014).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321 AND SER-365, AND
RP IDENTIFICATION BY 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 [26]
RP FUNCTION, IDENTIFICATION IN A DEUBIQUITINATION COMPLEX WITH TANK AND
RP ZC3H12A, AND INTERACTION WITH IKBKG; TANK; TRAF6 AND ZC3H12A.
RX PubMed=25861989; DOI=10.1074/jbc.m115.643767;
RA Wang W., Huang X., Xin H.B., Fu M., Xue A., Wu Z.H.;
RT "TRAF family member-associated NF-kappaB activator (TANK) inhibits
RT genotoxic nuclear factor kappaB activation by facilitating deubiquitinase
RT USP10-dependent deubiquitination of TRAF6 ligase.";
RL J. Biol. Chem. 290:13372-13385(2015).
CC -!- FUNCTION: Hydrolase that can remove conjugated ubiquitin from target
CC proteins such as p53/TP53, BECN1, SNX3 and CFTR. Acts as an essential
CC regulator of p53/TP53 stability: in unstressed cells, specifically
CC deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2
CC action and stabilize p53/TP53. Following DNA damage, translocates to
CC the nucleus and deubiquitinates p53/TP53, leading to regulate the
CC p53/TP53-dependent DNA damage response. Component of a regulatory loop
CC that controls autophagy and p53/TP53 levels: mediates deubiquitination
CC of BECN1, a key regulator of autophagy, leading to stabilize the
CC PIK3C3/VPS34-containing complexes. In turn, PIK3C3/VPS34-containing
CC complexes regulate USP10 stability, suggesting the existence of a
CC regulatory system by which PIK3C3/VPS34-containing complexes regulate
CC p53/TP53 protein levels via USP10 and USP13. Does not deubiquitinate
CC MDM2. Deubiquitinates CFTR in early endosomes, enhancing its endocytic
CC recycling. Involved in a TANK-dependent negative feedback response to
CC attenuate NF-kappaB activation via deubiquitinating IKBKG or TRAF6 in
CC response to interleukin-1-beta (IL1B) stimulation or upon DNA damage
CC (PubMed:25861989). Deubiquitinates TBX21 leading to its stabilization
CC (PubMed:24845384). {ECO:0000269|PubMed:11439350,
CC ECO:0000269|PubMed:18632802, ECO:0000269|PubMed:19398555,
CC ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:21962518,
CC ECO:0000269|PubMed:24845384, ECO:0000269|PubMed:25861989}.
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:20096447};
CC -!- ACTIVITY REGULATION: Specifically inhibited by spautin-1 (specific and
CC potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP10
CC and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-
CC containing complexes. {ECO:0000269|PubMed:21962518}.
CC -!- SUBUNIT: Found in a deubiquitination complex with TANK, USP10 and
CC ZC3H12A; this complex inhibits genotoxic stress- or interleukin-1-beta
CC (IL1B)-mediated NF-kappaB activation by promoting IKBKG or TRAF6
CC deubiquitination (PubMed:25861989). Interacts with IKBKG; this
CC interaction increases in response to DNA damage (PubMed:25861989).
CC Interacts with TANK; this interaction increases in response to DNA
CC damage (PubMed:25861989). Interacts with TRAF6; this interaction
CC increases in response to DNA damage (PubMed:25861989). Interacts with
CC ZC3H12A; this interaction increases in response to DNA damage
CC (PubMed:25861989). Interacts with G3BP1 (via NTF2-like domain) and
CC G3BP2 (via NTF2-like domain) (PubMed:11439350, PubMed:23279204).
CC Interacts with p53/TP53 (PubMed:20096447). Interacts with SNX3
CC (PubMed:18632802). Interacts with CFTR (PubMed:19398555). Interacts
CC with TBX21 (PubMed:24845384). {ECO:0000269|PubMed:11439350,
CC ECO:0000269|PubMed:18632802, ECO:0000269|PubMed:19398555,
CC ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:24845384,
CC ECO:0000269|PubMed:25861989}.
CC -!- INTERACTION:
CC Q14694; Q13283: G3BP1; NbExp=11; IntAct=EBI-2510389, EBI-1047359;
CC Q14694; Q9UN86: G3BP2; NbExp=9; IntAct=EBI-2510389, EBI-1044298;
CC Q14694; Q9UN86-2: G3BP2; NbExp=3; IntAct=EBI-2510389, EBI-11035716;
CC Q14694; P14136: GFAP; NbExp=3; IntAct=EBI-2510389, EBI-744302;
CC Q14694; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-2510389, EBI-1055254;
CC Q14694; P63244: RACK1; NbExp=3; IntAct=EBI-2510389, EBI-296739;
CC Q14694; Q5D1E8: ZC3H12A; NbExp=5; IntAct=EBI-2510389, EBI-747793;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20096447}. Nucleus
CC {ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:24845384}. Early
CC endosome {ECO:0000269|PubMed:19398555}. Note=Cytoplasmic in normal
CC conditions (PubMed:20096447). After DNA damage, translocates to the
CC nucleus following phosphorylation by ATM (PubMed:20096447).
CC {ECO:0000269|PubMed:20096447}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q14694-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14694-2; Sequence=VSP_038869;
CC Name=3;
CC IsoId=Q14694-3; Sequence=VSP_038868;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:11439350}.
CC -!- INDUCTION: Following DNA damage. Down-regulated in renal cell
CC carcinomas. {ECO:0000269|PubMed:20096447}.
CC -!- PTM: Phosphorylated by ATM following DNA damage, leading to
CC stablization and translocation it to the nucleus.
CC {ECO:0000269|PubMed:20096447}.
CC -!- PTM: Ubiquitinated. Deubiquitinated by USP13.
CC {ECO:0000269|PubMed:21962518}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP10 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD97644.1; Type=Erroneous initiation; Evidence={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; D80012; BAA11507.1; -; mRNA.
DR EMBL; AK299618; BAG61546.1; -; mRNA.
DR EMBL; AK315570; BAG37945.1; -; mRNA.
DR EMBL; AL162049; CAB82392.2; -; mRNA.
DR EMBL; BX537402; CAD97644.1; ALT_INIT; mRNA.
DR EMBL; AC009116; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC025280; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000263; AAH00263.1; -; mRNA.
DR CCDS; CCDS45537.1; -. [Q14694-1]
DR CCDS; CCDS62004.1; -. [Q14694-3]
DR RefSeq; NP_001259004.1; NM_001272075.1. [Q14694-3]
DR RefSeq; NP_005144.2; NM_005153.2. [Q14694-1]
DR AlphaFoldDB; Q14694; -.
DR SMR; Q14694; -.
DR BioGRID; 114554; 226.
DR ELM; Q14694; -.
DR IntAct; Q14694; 49.
DR MINT; Q14694; -.
DR STRING; 9606.ENSP00000457411; -.
DR BindingDB; Q14694; -.
DR ChEMBL; CHEMBL3407323; -.
DR MEROPS; C19.018; -.
DR GlyGen; Q14694; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q14694; -.
DR PhosphoSitePlus; Q14694; -.
DR SwissPalm; Q14694; -.
DR BioMuta; USP10; -.
DR DMDM; 2501458; -.
DR EPD; Q14694; -.
DR jPOST; Q14694; -.
DR MassIVE; Q14694; -.
DR MaxQB; Q14694; -.
DR PaxDb; Q14694; -.
DR PeptideAtlas; Q14694; -.
DR PRIDE; Q14694; -.
DR ProteomicsDB; 60132; -. [Q14694-1]
DR ProteomicsDB; 60133; -. [Q14694-2]
DR ProteomicsDB; 60134; -. [Q14694-3]
DR Antibodypedia; 1716; 394 antibodies from 38 providers.
DR DNASU; 9100; -.
DR Ensembl; ENST00000219473.12; ENSP00000219473.7; ENSG00000103194.16. [Q14694-1]
DR Ensembl; ENST00000570191.5; ENSP00000457411.1; ENSG00000103194.16. [Q14694-3]
DR GeneID; 9100; -.
DR KEGG; hsa:9100; -.
DR MANE-Select; ENST00000219473.12; ENSP00000219473.7; NM_005153.3; NP_005144.2.
DR UCSC; uc002fii.4; human. [Q14694-1]
DR CTD; 9100; -.
DR DisGeNET; 9100; -.
DR GeneCards; USP10; -.
DR HGNC; HGNC:12608; USP10.
DR HPA; ENSG00000103194; Low tissue specificity.
DR MIM; 609818; gene.
DR neXtProt; NX_Q14694; -.
DR OpenTargets; ENSG00000103194; -.
DR PharmGKB; PA37234; -.
DR VEuPathDB; HostDB:ENSG00000103194; -.
DR eggNOG; KOG1871; Eukaryota.
DR GeneTree; ENSGT00550000074994; -.
DR HOGENOM; CLU_008279_4_1_1; -.
DR InParanoid; Q14694; -.
DR OMA; TPRTCDS; -.
DR OrthoDB; 1078977at2759; -.
DR PhylomeDB; Q14694; -.
DR TreeFam; TF323203; -.
DR PathwayCommons; Q14694; -.
DR Reactome; R-HSA-5656169; Termination of translesion DNA synthesis.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR SignaLink; Q14694; -.
DR SIGNOR; Q14694; -.
DR BioGRID-ORCS; 9100; 453 hits in 1104 CRISPR screens.
DR ChiTaRS; USP10; human.
DR GeneWiki; USP10; -.
DR GenomeRNAi; 9100; -.
DR Pharos; Q14694; Tchem.
DR PRO; PR:Q14694; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q14694; protein.
DR Bgee; ENSG00000103194; Expressed in ventricular zone and 198 other tissues.
DR ExpressionAtlas; Q14694; baseline and differential.
DR Genevisible; Q14694; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
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:0002039; F:p53 binding; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; IDA:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; IMP:UniProtKB.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IMP:UniProtKB.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IDA:UniProtKB.
DR GO; GO:0019985; P:translesion synthesis; TAS:Reactome.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR InterPro; IPR009818; Ataxin-2_C.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR028767; USP10.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR PANTHER; PTHR13328:SF5; PTHR13328:SF5; 1.
DR Pfam; PF07145; PAM2; 1.
DR Pfam; PF00443; UCH; 1.
DR SUPFAM; SSF54001; SSF54001; 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; Autophagy; Cytoplasm; DNA damage;
KW DNA repair; Endosome; Hydrolase; Nucleus; Phosphoprotein; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation;
KW Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:20068231"
FT CHAIN 2..798
FT /note="Ubiquitin carboxyl-terminal hydrolase 10"
FT /id="PRO_0000080629"
FT DOMAIN 415..795
FT /note="USP"
FT REGION 2..100
FT /note="Interaction with p53/TP53"
FT /evidence="ECO:0000269|PubMed:20096447"
FT REGION 139..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 194..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 307..337
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 551..594
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 204..222
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 322..337
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 424
FT /note="Nucleophile"
FT ACT_SITE 749
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 24
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 42
FT /note="Phosphothreonine; by ATM"
FT /evidence="ECO:0000269|PubMed:20096447"
FT MOD_RES 100
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 211
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P52479"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 337
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:20096447"
FT MOD_RES 365
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569"
FT MOD_RES 370
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 547
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 563
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 576
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:17487921, ECO:0007744|PubMed:17693683,
FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..6
FT /note="MALHSP -> MPWLPSPGIG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038868"
FT VAR_SEQ 1
FT /note="M -> MCSKDTVLSVCALYWRKGIQSHTPLIGAWRRGKQREQPEDRGVPMKR
FT AA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8724849"
FT /id="VSP_038869"
FT VARIANT 200
FT /note="M -> V (in dbSNP:rs1862792)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_015859"
FT VARIANT 203
FT /note="S -> P (in dbSNP:rs2326391)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_015860"
FT VARIANT 204
FT /note="V -> L (in dbSNP:rs1812061)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_015861"
FT MUTAGEN 42
FT /note="T->A: Abolishes phosphorylation by ATM; when
FT associated with A-337."
FT /evidence="ECO:0000269|PubMed:20096447"
FT MUTAGEN 42
FT /note="T->E: Phospho-mimetic mutant that translocates to
FT the nucleus in absence of genotoxic stress; when associated
FT with D-337."
FT /evidence="ECO:0000269|PubMed:20096447"
FT MUTAGEN 337
FT /note="S->A: Abolishes phosphorylation by ATM; when
FT associated with A-42."
FT /evidence="ECO:0000269|PubMed:20096447"
FT MUTAGEN 337
FT /note="S->D: Phospho-mimetic mutant that translocates to
FT the nucleus in absence of genotoxic stress; when associated
FT with E-42."
FT /evidence="ECO:0000269|PubMed:20096447"
FT MUTAGEN 424
FT /note="C->A: Abolishes de-ubiquitinating activity."
FT /evidence="ECO:0000269|PubMed:11439350,
FT ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:21962518,
FT ECO:0000269|PubMed:24845384"
FT CONFLICT 108
FT /note="A -> V (in Ref. 3; BAG61546)"
FT /evidence="ECO:0000305"
FT CONFLICT 263
FT /note="T -> A (in Ref. 3; BAG61546)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 798 AA; 87134 MW; E6BA77E2B5CE2B3F CRC64;
MALHSPQYIF GDFSPDEFNQ FFVTPRSSVE LPPYSGTVLC GTQAVDKLPD GQEYQRIEFG
VDEVIEPSDT LPRTPSYSIS STLNPQAPEF ILGCTASKIT PDGITKEASY GSIDCQYPGS
ALALDGSSNV EAEVLENDGV SGGLGQRERK KKKKRPPGYY SYLKDGGDDS ISTEALVNGH
ANSAVPNSVS AEDAEFMGDM PPSVTPRTCN SPQNSTDSVS DIVPDSPFPG ALGSDTRTAG
QPEGGPGADF GQSCFPAEAG RDTLSRTAGA QPCVGTDTTE NLGVANGQIL ESSGEGTATN
GVELHTTESI DLDPTKPESA SPPADGTGSA SGTLPVSQPK SWASLFHDSK PSSSSPVAYV
ETKYSPPAIS PLVSEKQVEV KEGLVPVSED PVAIKIAELL ENVTLIHKPV SLQPRGLINK
GNWCYINATL QALVACPPMY HLMKFIPLYS KVQRPCTSTP MIDSFVRLMN EFTNMPVPPK
PRQALGDKIV RDIRPGAAFE PTYIYRLLTV NKSSLSEKGR QEDAEEYLGF ILNGLHEEML
NLKKLLSPSN EKLTISNGPK NHSVNEEEQE EQGEGSEDEW EQVGPRNKTS VTRQADFVQT
PITGIFGGHI RSVVYQQSSK ESATLQPFFT LQLDIQSDKI RTVQDALESL VARESVQGYT
TKTKQEVEIS RRVTLEKLPP VLVLHLKRFV YEKTGGCQKL IKNIEYPVDL EISKELLSPG
VKNKNFKCHR TYRLFAVVYH HGNSATGGHY TTDVFQIGLN GWLRIDDQTV KVINQYQVVK
PTAERTAYLL YYRRVDLL
