UBP36_HUMAN
ID UBP36_HUMAN Reviewed; 1123 AA.
AC Q9P275; Q05C98; Q05DD0; Q6IQ38; Q8NDM8; Q9NVC8;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 4.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 36 {ECO:0000305};
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 36;
DE AltName: Full=Ubiquitin thioesterase 36;
DE AltName: Full=Ubiquitin-specific-processing protease 36;
GN Name=USP36 {ECO:0000312|HGNC:HGNC:20062}; Synonyms=KIAA1453;
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 [LARGE SCALE MRNA], AND VARIANTS ARG-806; CYS-828 AND
RP 959-LYS-LYS-960 DEL.
RC TISSUE=Brain;
RX PubMed=10819331; DOI=10.1093/dnares/7.2.143;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:143-150(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ILE-271; ARG-806 AND
RP PRO-887.
RC TISSUE=Cervix, Placenta, and Skin;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-954, AND VARIANTS ARG-806 AND
RP CYS-828.
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] OF 494-1123.
RC TISSUE=Testis;
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 SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=12429849; DOI=10.1091/mbc.e02-05-0271;
RA Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C.,
RA Greco A., Hochstrasser D.F., Diaz J.-J.;
RT "Functional proteomic analysis of human nucleolus.";
RL Mol. Biol. Cell 13:4100-4109(2002).
RN [6]
RP TISSUE SPECIFICITY, AND ENZYME ACTIVITY.
RX PubMed=14715245; DOI=10.1016/j.bbrc.2003.12.050;
RA Quesada V., Diaz-Perales A., Gutierrez-Fernandez A., Garabaya C., Cal S.,
RA Lopez-Otin C.;
RT "Cloning and enzymatic analysis of 22 novel human ubiquitin-specific
RT proteases.";
RL Biochem. Biophys. Res. Commun. 314:54-62(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-952, 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-464; SER-582 AND SER-667, 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 [9]
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 [10]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-131, AND ACTIVE SITE.
RX PubMed=19208757; DOI=10.1242/jcs.044461;
RA Endo A., Matsumoto M., Inada T., Yamamoto A., Nakayama K.I., Kitamura N.,
RA Komada M.;
RT "Nucleolar structure and function are regulated by the deubiquitylating
RT enzyme USP36.";
RL J. Cell Sci. 122:678-686(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-667 AND SER-682, 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-582; SER-713; SER-742 AND
RP SER-952, AND IDENTIFICATION BY 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 [13]
RP FUNCTION, ACTIVE SITE, AND MUTAGENESIS OF CYS-131.
RX PubMed=21268071; DOI=10.1002/jcb.22940;
RA Kim M.S., Ramakrishna S., Lim K.H., Kim J.H., Baek K.H.;
RT "Protein stability of mitochondrial superoxide dismutase SOD2 is regulated
RT by USP36.";
RL J. Cell. Biochem. 112:498-508(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-742, 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 [15]
RP FUNCTION.
RX PubMed=22622177; DOI=10.4161/auto.19381;
RA Taillebourg E., Gregoire I., Viargues P., Jacomin A.C., Thevenon D.,
RA Faure M., Fauvarque M.O.;
RT "The deubiquitinating enzyme USP36 controls selective autophagy activation
RT by ubiquitinated proteins.";
RL Autophagy 8:767-779(2012).
RN [16]
RP FUNCTION.
RX PubMed=22902402; DOI=10.1016/j.celrep.2012.07.009;
RA Richardson L.A., Reed B.J., Charette J.M., Freed E.F., Fredrickson E.K.,
RA Locke M.N., Baserga S.J., Gardner R.G.;
RT "A conserved deubiquitinating enzyme controls cell growth by regulating RNA
RT polymerase I stability.";
RL Cell Rep. 2:372-385(2012).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-429; SER-464; SER-546;
RP SER-582; SER-667; SER-682; SER-713 AND SER-952, AND IDENTIFICATION BY MASS
RP 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 [18]
RP FUNCTION, SUBCELLULAR LOCATION, ACTIVE SITE, AND MUTAGENESIS OF CYS-131.
RX PubMed=25775507; DOI=10.1073/pnas.1411713112;
RA Sun X.X., He X., Yin L., Komada M., Sears R.C., Dai M.S.;
RT "The nucleolar ubiquitin-specific protease USP36 deubiquitinates and
RT stabilizes c-Myc.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:3734-3739(2015).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, ACTIVE SITE, INTERACTION WITH NEDD4L AND
RP NTRK1, MUTAGENESIS OF CYS-131, AND UBIQUITINATION.
RX PubMed=27445338; DOI=10.1074/jbc.m116.722637;
RA Anta B., Martin-Rodriguez C., Gomis-Perez C., Calvo L., Lopez-Benito S.,
RA Calderon-Garcia A.A., Vicente-Garcia C., Villarroel A., Arevalo J.C.;
RT "Ubiquitin-specific Protease 36 (USP36) Controls Neuronal Precursor Cell-
RT expressed Developmentally Down-regulated 4-2 (Nedd4-2) Actions over the
RT Neurotrophin Receptor TrkA and Potassium Voltage-gated Channels 7.2/3
RT (Kv7.2/3).";
RL J. Biol. Chem. 291:19132-19145(2016).
RN [20]
RP FUNCTION, ACTIVE SITE, AND MUTAGENESIS OF CYS-131.
RX PubMed=29274341; DOI=10.1016/j.bbrc.2017.12.107;
RA DeVine T., Sears R.C., Dai M.S.;
RT "The ubiquitin-specific protease USP36 is a conserved histone H2B
RT deubiquitinase.";
RL Biochem. Biophys. Res. Commun. 495:2363-2368(2018).
RN [21]
RP FUNCTION.
RX PubMed=29273634; DOI=10.1074/jbc.m117.788430;
RA Fraile J.M., Campos-Iglesias D., Rodriguez F., Astudillo A.,
RA Vilarrasa-Blasi R., Verdaguer-Dot N., Prado M.A., Paulo J.A., Gygi S.P.,
RA Martin-Subero J.I., Freije J.M.P., Lopez-Otin C.;
RT "Loss of the deubiquitinase USP36 destabilizes the RNA helicase DHX33 and
RT causes preimplantation lethality in mice.";
RL J. Biol. Chem. 293:2183-2194(2018).
CC -!- FUNCTION: Deubiquitinase essential for the regulation of nucleolar
CC structure and function. Required for cell and organism viability. Plays
CC an important role in ribosomal RNA processing and protein synthesis,
CC which is mediated, at least in part, through deubiquitination of DHX33,
CC NPM1 and FBL, regulating their protein stability (PubMed:29273634,
CC PubMed:19208757, PubMed:22902402). Functions as a transcriptional
CC repressor by deubiquiting histone H2B at the promoters of genes
CC critical for cellular differentiation, such as CDKN1A, thereby
CC preventing histone H3 'Lys-4' trimethylation (H3K4) (PubMed:29274341).
CC Specifically deubiquitinates MYC in the nucleolus, leading to prevent
CC MYC degradation by the proteasome: acts by specifically interacting
CC with isoform 3 of FBXW7 (FBW7gamma) in the nucleolus and counteracting
CC ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does
CC not interact with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm
CC (PubMed:25775507). Interacts to and regulates the actions of E3
CC ubiquitin-protein ligase NEDD4L over substrates such as NTRK1, KCNQ2
CC and KCNQ3, affecting their expression an functions (PubMed:27445338).
CC Deubiquitinates SOD2, regulates SOD2 protein stability
CC (PubMed:21268071). Deubiquitinase activity is required to control
CC selective autophagy activation by ubiquitinated proteins
CC (PubMed:22622177). {ECO:0000269|PubMed:19208757,
CC ECO:0000269|PubMed:21268071, ECO:0000269|PubMed:22622177,
CC ECO:0000269|PubMed:22902402, ECO:0000269|PubMed:25775507,
CC ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:29273634,
CC ECO:0000269|PubMed:29274341}.
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:14715245};
CC -!- SUBUNIT: Interacts with isoform 3 of FBXW7; the interaction inhibits
CC MYC degradation induced by SCF(FBW7) complex (PubMed:25775507).
CC Interacts with NTRK1; USP36 does not deubiquitinate NTRK1
CC (PubMed:27445338). Interacts with NEDD4L (via domains WW1, 3 and 4);
CC the interaction inhibits ubiquitination of, at least, NTRK1, KCNQ2 and
CC KCNQ3 by NEDD4L (PubMed:27445338). {ECO:0000269|PubMed:25775507,
CC ECO:0000269|PubMed:27445338}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:12429849,
CC ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:25775507,
CC ECO:0000269|PubMed:27445338}. Cytoplasm {ECO:0000269|PubMed:27445338}.
CC -!- TISSUE SPECIFICITY: Broadly expressed. {ECO:0000269|PubMed:14715245}.
CC -!- PTM: Polyubiquitinated by NEDD4L, no effect on USP36 protein levels.
CC Both proteins interact with and regulate each other's ubiquitination
CC levels. {ECO:0000269|PubMed:27445338}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH16487.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=BAA95977.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB040886; BAA95977.1; ALT_INIT; mRNA.
DR EMBL; BC016487; AAH16487.1; ALT_SEQ; mRNA.
DR EMBL; BC027992; AAH27992.1; -; mRNA.
DR EMBL; BC071582; AAH71582.1; -; mRNA.
DR EMBL; AK001671; BAA91825.1; -; mRNA.
DR EMBL; AL833835; CAD38695.1; -; mRNA.
DR CCDS; CCDS32755.1; -.
DR RefSeq; NP_001308220.1; NM_001321291.1.
DR RefSeq; XP_005257599.1; XM_005257542.2.
DR RefSeq; XP_005257600.1; XM_005257543.2.
DR RefSeq; XP_016880389.1; XM_017024900.1.
DR AlphaFoldDB; Q9P275; -.
DR SMR; Q9P275; -.
DR BioGRID; 121651; 139.
DR IntAct; Q9P275; 43.
DR MINT; Q9P275; -.
DR STRING; 9606.ENSP00000441214; -.
DR BindingDB; Q9P275; -.
DR ChEMBL; CHEMBL4630861; -.
DR MEROPS; C19.042; -.
DR CarbonylDB; Q9P275; -.
DR iPTMnet; Q9P275; -.
DR PhosphoSitePlus; Q9P275; -.
DR SwissPalm; Q9P275; -.
DR BioMuta; USP36; -.
DR DMDM; 124056592; -.
DR SWISS-2DPAGE; Q9P275; -.
DR EPD; Q9P275; -.
DR jPOST; Q9P275; -.
DR MassIVE; Q9P275; -.
DR MaxQB; Q9P275; -.
DR PaxDb; Q9P275; -.
DR PeptideAtlas; Q9P275; -.
DR PRIDE; Q9P275; -.
DR Antibodypedia; 1709; 250 antibodies from 29 providers.
DR DNASU; 57602; -.
DR Ensembl; ENST00000312010.10; ENSP00000310590.6; ENSG00000055483.20.
DR Ensembl; ENST00000449938.7; ENSP00000401119.4; ENSG00000055483.20.
DR Ensembl; ENST00000542802.7; ENSP00000441214.1; ENSG00000055483.20.
DR Ensembl; ENST00000589225.5; ENSP00000467280.1; ENSG00000055483.20.
DR Ensembl; ENST00000592231.6; ENSP00000465698.2; ENSG00000055483.20.
DR GeneID; 57602; -.
DR KEGG; hsa:57602; -.
DR MANE-Select; ENST00000449938.7; ENSP00000401119.4; NM_001385174.1; NP_001372103.1.
DR UCSC; uc002jvz.2; human.
DR CTD; 57602; -.
DR DisGeNET; 57602; -.
DR GeneCards; USP36; -.
DR HGNC; HGNC:20062; USP36.
DR HPA; ENSG00000055483; Low tissue specificity.
DR MIM; 612543; gene.
DR neXtProt; NX_Q9P275; -.
DR OpenTargets; ENSG00000055483; -.
DR PharmGKB; PA134949090; -.
DR VEuPathDB; HostDB:ENSG00000055483; -.
DR eggNOG; KOG1865; Eukaryota.
DR GeneTree; ENSGT00940000157948; -.
DR InParanoid; Q9P275; -.
DR OMA; SETCLPQ; -.
DR OrthoDB; 929408at2759; -.
DR PhylomeDB; Q9P275; -.
DR TreeFam; TF315281; -.
DR PathwayCommons; Q9P275; -.
DR SignaLink; Q9P275; -.
DR BioGRID-ORCS; 57602; 563 hits in 1094 CRISPR screens.
DR ChiTaRS; USP36; human.
DR GeneWiki; USP36; -.
DR GenomeRNAi; 57602; -.
DR Pharos; Q9P275; Tbio.
DR PRO; PR:Q9P275; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9P275; protein.
DR Bgee; ENSG00000055483; Expressed in sural nerve and 180 other tissues.
DR ExpressionAtlas; Q9P275; baseline and differential.
DR Genevisible; Q9P275; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:FlyBase.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0016578; P:histone deubiquitination; IMP:UniProtKB.
DR GO; GO:0016242; P:negative regulation of macroautophagy; IMP:UniProtKB.
DR GO; GO:0007000; P:nucleolus organization; ISS:UniProtKB.
DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; HMP:ParkinsonsUK-UCL.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; HMP:ParkinsonsUK-UCL.
DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB.
DR GO; GO:2000232; P:regulation of rRNA processing; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
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 Cytoplasm; Hydrolase; Nucleus; Phosphoprotein; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..1123
FT /note="Ubiquitin carboxyl-terminal hydrolase 36"
FT /id="PRO_0000080666"
FT DOMAIN 122..423
FT /note="USP"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 67..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 430..577
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 589..999
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 70..89
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 432..446
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 457..471
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 487..501
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 549..577
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 605..681
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 742..758
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 765..788
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 858..872
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 886..906
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 917..932
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 964..979
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 131
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093,
FT ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:21268071,
FT ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:27445338,
FT ECO:0000269|PubMed:29274341"
FT ACT_SITE 382
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT MOD_RES 429
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 464
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 546
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 582
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 667
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 682
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 713
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 742
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 952
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT VARIANT 271
FT /note="V -> I (in dbSNP:rs3744793)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_037277"
FT VARIANT 489
FT /note="I -> M (in dbSNP:rs3744795)"
FT /id="VAR_037278"
FT VARIANT 775
FT /note="R -> Q (in dbSNP:rs9889908)"
FT /id="VAR_037279"
FT VARIANT 806
FT /note="Q -> R (in dbSNP:rs3088040)"
FT /evidence="ECO:0000269|PubMed:10819331,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_037280"
FT VARIANT 814
FT /note="K -> N (in dbSNP:rs3744797)"
FT /id="VAR_037281"
FT VARIANT 828
FT /note="R -> C (in dbSNP:rs1057040)"
FT /evidence="ECO:0000269|PubMed:10819331,
FT ECO:0000269|PubMed:14702039"
FT /id="VAR_037282"
FT VARIANT 887
FT /note="R -> P (in dbSNP:rs61760231)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_058034"
FT VARIANT 959..960
FT /note="Missing (in dbSNP:rs866027510)"
FT /evidence="ECO:0000269|PubMed:10819331"
FT /id="VAR_080193"
FT MUTAGEN 131
FT /note="C->A,S: Abolishes deubiquitinase activity. No effect
FT on NTRK1 ubiquitination levels."
FT /evidence="ECO:0000269|PubMed:19208757,
FT ECO:0000269|PubMed:21268071, ECO:0000269|PubMed:25775507,
FT ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:29274341"
FT CONFLICT 82
FT /note="R -> G (in Ref. 2; AAH71582)"
FT /evidence="ECO:0000305"
FT CONFLICT 573
FT /note="D -> G (in Ref. 3; BAA91825)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1123 AA; 122908 MW; 65CD93C1B8655319 CRC64;
MPIVDKLKEA LKPGRKDSAD DGELGKLLAS SAKKVLLQKI EFEPASKSFS YQLEALKSKY
VLLNPKTEGA SRHKSGDDPP ARRQGSEHTY ESCGDGVPAP QKVLFPTERL SLRWERVFRV
GAGLHNLGNT CFLNATIQCL TYTPPLANYL LSKEHARSCH QGSFCMLCVM QNHIVQAFAN
SGNAIKPVSF IRDLKKIARH FRFGNQEDAH EFLRYTIDAM QKACLNGCAK LDRQTQATTL
VHQIFGGYLR SRVKCSVCKS VSDTYDPYLD VALEIRQAAN IVRALELFVK ADVLSGENAY
MCAKCKKKVP ASKRFTIHRT SNVLTLSLKR FANFSGGKIT KDVGYPEFLN IRPYMSQNNG
DPVMYGLYAV LVHSGYSCHA GHYYCYVKAS NGQWYQMNDS LVHSSNVKVV LNQQAYVLFY
LRIPGSKKSP EGLISRTGSS SLPGRPSVIP DHSKKNIGNG IISSPLTGKR QDSGTMKKPH
TTEEIGVPIS RNGSTLGLKS QNGCIPPKLP SGSPSPKLSQ TPTHMPTILD DPGKKVKKPA
PPQHFSPRTA QGLPGTSNSN SSRSGSQRQG SWDSRDVVLS TSPKLLATAT ANGHGLKGND
ESAGLDRRGS SSSSPEHSAS SDSTKAPQTP RSGAAHLCDS QETNCSTAGH SKTPPSGADS
KTVKLKSPVL SNTTTEPAST MSPPPAKKLA LSAKKASTLW RATGNDLRPP PPSPSSDLTH
PMKTSHPVVA STWPVHRARA VSPAPQSSSR LQPPFSPHPT LLSSTPKPPG TSEPRSCSSI
STALPQVNED LVSLPHQLPE ASEPPQSPSE KRKKTFVGEP QRLGSETRLP QHIREATAAP
HGKRKRKKKK RPEDTAASAL QEGQTQRQPG SPMYRREGQA QLPAVRRQED GTQPQVNGQQ
VGCVTDGHHA SSRKRRRKGA EGLGEEGGLH QDPLRHSCSP MGDGDPEAME ESPRKKKKKK
RKQETQRAVE EDGHLKCPRS AKPQDAVVPE SSSCAPSANG WCPGDRMGLS QAPPVSWNGE
RESDVVQELL KYSSDKAYGR KVLTWDGKMS AVSQDAIEDS RQARTETVVD DWDEEFDRGK
EKKIKKFKRE KRRNFNAFQK LQTRRNFWSV THPAKAASLS YRR
