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   27-MAR-2024, entry version 191.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 36 {ECO:0000305};
DE            EC=2.3.2.- {ECO:0000269|PubMed:36912080};
DE            EC=3.4.19.12 {ECO:0000269|PubMed:14715245, ECO:0000269|PubMed:35989368};
DE   AltName: Full=Deubiquitinating enzyme 36 {ECO:0000303|PubMed:36912080};
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 CATALYTIC 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).
RN   [22]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=35989368; DOI=10.1038/s41388-022-02439-y;
RA   Ling H., Cao C.H., Han K., Lv Y.R., Ma X.D., Cao J.H., Chen J.W., Li S.,
RA   Lin J.L., Fang Y.J., Pan Z.Z., Xie D., Wang F.W.;
RT   "CEP63 upregulates YAP1 to promote colorectal cancer progression through
RT   stabilizing RNA binding protein FXR1.";
RL   Oncogene 41:4433-4445(2022).
RN   [23] {ECO:0000305}
RP   FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH EXOSC10, SUBCELLULAR
RP   LOCATION, INDUCTION, AND MUTAGENESIS OF CYS-131.
RX   PubMed=36912080; DOI=10.1093/nar/gkad140;
RA   Chen Y., Li Y., Dai R.S., Savage J.C., Shinde U., Klimek J., David L.L.,
RA   Young E.A., Hafner M., Sears R.C., Sun X.X., Dai M.S.;
RT   "The ubiquitin-specific protease USP36 SUMOylates EXOSC10 and promotes the
RT   nucleolar RNA exosome function in rRNA processing.";
RL   Nucleic Acids Res. 51:3934-3949(2023).
CC   -!- FUNCTION: Deubiquitinase essential for the regulation of nucleolar
CC       structure and function (PubMed:29273634, PubMed:19208757,
CC       PubMed:22902402). Required for cell and organism viability
CC       (PubMed:29273634, PubMed:19208757, PubMed:22902402). Plays an important
CC       role in ribosomal RNA processing and protein synthesis, which is
CC       mediated, at least in part, through deubiquitination of DHX33, NPM1 and
CC       FBL, regulating their protein stability (PubMed:29273634,
CC       PubMed:19208757, PubMed:22902402, PubMed:36912080). Functions as a
CC       transcriptional repressor by deubiquiting histone H2B at the promoters
CC       of genes 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 (PubMed:25775507). In
CC       contrast, it does not interact with isoform 1 of FBXW7 (FBW7alpha) in
CC       the nucleoplasm (PubMed:25775507). Interacts to and regulates the
CC       actions of E3 ubiquitin-protein ligase NEDD4L over substrates such as
CC       NTRK1, KCNQ2 and KCNQ3, affecting their expression an functions
CC       (PubMed:27445338). Deubiquitinates SOD2, regulates SOD2 protein
CC       stability (PubMed:21268071). Deubiquitinase activity is required to
CC       control selective autophagy activation by ubiquitinated proteins
CC       (PubMed:22622177). Promotes CEP63 stabilization through 'Lys-48'-linked
CC       deubiquitination leading to increased stability (PubMed:35989368). Acts
CC       as a SUMO ligase to promote EXOSC10 sumoylation critical for the
CC       nucleolar RNA exosome function in rRNA processing (PubMed:36912080).
CC       Binds to pre-rRNAs (PubMed:36912080). {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, ECO:0000269|PubMed:35989368,
CC       ECO:0000269|PubMed:36912080}.
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         ECO:0000269|PubMed:35989368};
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). Interacts (via C-terminus) with
CC       EXOSC10 (via C-terminus); the interaction is facilitated by the
CC       association with RNA and promotes sumoylation of EXOSC10
CC       (PubMed:36912080). {ECO:0000269|PubMed:25775507,
CC       ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:36912080}.
CC   -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:12429849,
CC       ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:25775507,
CC       ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:36912080}. Cytoplasm
CC       {ECO:0000269|PubMed:27445338}.
CC   -!- TISSUE SPECIFICITY: Broadly expressed. {ECO:0000269|PubMed:14715245}.
CC   -!- INDUCTION: Down-regulated by ribosomal stress (at protein level).
CC       {ECO:0000269|PubMed:36912080}.
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   PDB; 8BS3; X-ray; 2.20 A; A=80-461.
DR   PDB; 8BS9; X-ray; 1.90 A; A/C=80-424.
DR   PDBsum; 8BS3; -.
DR   PDBsum; 8BS9; -.
DR   AlphaFoldDB; Q9P275; -.
DR   SMR; Q9P275; -.
DR   BioGRID; 121651; 155.
DR   IntAct; Q9P275; 45.
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   EPD; Q9P275; -.
DR   jPOST; Q9P275; -.
DR   MassIVE; Q9P275; -.
DR   MaxQB; Q9P275; -.
DR   PaxDb; 9606-ENSP00000441214; -.
DR   PeptideAtlas; Q9P275; -.
DR   Pumba; Q9P275; -.
DR   Antibodypedia; 1709; 287 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   AGR; HGNC:20062; -.
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; STWPVSK; -.
DR   OrthoDB; 227085at2759; -.
DR   PhylomeDB; Q9P275; -.
DR   TreeFam; TF315281; -.
DR   PathwayCommons; Q9P275; -.
DR   SignaLink; Q9P275; -.
DR   SIGNOR; Q9P275; -.
DR   BioGRID-ORCS; 57602; 573 hits in 1173 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 182 other cell types or tissues.
DR   ExpressionAtlas; Q9P275; baseline and differential.
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:0140936; F:histone H2B deubiquitinase activity; IMP:UniProtKB.
DR   GO; GO:1990380; F:K48-linked deubiquitinase activity; IDA:UniProtKB.
DR   GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR   GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR   GO; GO:0006325; P:chromatin organization; 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:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR   GO; GO:1901524; P:regulation of mitophagy; 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   CDD; cd02661; Peptidase_C19E; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 1.
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   PANTHER; PTHR24006; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR24006:SF653; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 36; 1.
DR   Pfam; PF00443; UCH; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   PROSITE; PS00972; USP_1; 1.
DR   PROSITE; PS00973; USP_2; 1.
DR   PROSITE; PS50235; USP_3; 1.
DR   SWISS-2DPAGE; Q9P275; -.
DR   Genevisible; Q9P275; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Hydrolase; Nucleus; Phosphoprotein; Protease;
KW   Reference proteome; RNA-binding; Thiol protease; Transferase;
KW   Ubl conjugation; 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                   ECO:0000269|PubMed:36912080"
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"
FT   STRAND          127..129
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   HELIX           131..141
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   HELIX           144..151
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   TURN            152..158
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   HELIX           166..178
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   TURN            179..182
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          183..185
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   HELIX           188..192
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   HELIX           194..197
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   HELIX           209..225
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   HELIX           233..236
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   HELIX           240..245
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          247..255
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   TURN            256..258
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          261..269
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          271..274
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   HELIX           281..288
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          292..294
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   HELIX           296..298
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          300..302
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   TURN            303..306
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          307..309
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          311..319
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          322..329
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          334..338
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          347..350
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   HELIX           352..354
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          355..357
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          359..361
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          364..380
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          382..388
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          394..398
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          401..404
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   HELIX           407..410
FT                   /evidence="ECO:0007829|PDB:8BS9"
FT   STRAND          415..422
FT                   /evidence="ECO:0007829|PDB:8BS9"
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
//