UBP36_MOUSE
ID UBP36_MOUSE Reviewed; 1098 AA.
AC B1AQJ2; Q6ZPQ7;
DT 07-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 36;
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; Synonyms=Kiaa1453;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-937.
RC TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pancreas;
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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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 Functions as a transcriptional repressor by deubiquiting histone H2B at
CC the promoters of genes critical for cellular differentiation, such as
CC CDKN1A, thereby preventing histone H3 'Lys-4' trimethylation (H3K4).
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 Interacts to and regulates the actions of E3 ubiquitin-protein ligase
CC NEDD4L over substrates such as NTRK1, KCNQ2 and KCNQ3, affecting their
CC expression an functions. Deubiquitinates SOD2, regulates SOD2 protein
CC stability. Deubiquitinase activity is required to control selective
CC autophagy activation by ubiquitinated proteins (By similarity).
CC {ECO:0000250|UniProtKB:Q9P275, ECO:0000269|PubMed:29273634}.
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;
CC -!- SUBUNIT: Interacts with isoform 3 of FBXW7; the interaction inhibits
CC MYC degradation induced by SCF(FBW7) complex. Interacts with NTRK1;
CC USP36 does not deubiquitinate NTRK1. Interacts with NEDD4L (via domains
CC WW1, 3 and 4); the interaction inhibits ubiquitination of, at least,
CC NTRK1, KCNQ2 and KCNQ3 by NEDD4L. {ECO:0000250|UniProtKB:Q9P275}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:Q9P275}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9P275}.
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:0000250|UniProtKB:Q9P275}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality (PubMed:29273634). Embryos
CC show apoptosis at the morula stage, blocking the transition from morula
CC to blastocysts during embryonic development (PubMed:29273634).
CC {ECO:0000269|PubMed:29273634}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC98173.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL591404; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK129363; BAC98173.1; ALT_INIT; mRNA.
DR CCDS; CCDS48998.1; -.
DR RefSeq; NP_001028700.1; NM_001033528.1.
DR RefSeq; XP_006534365.1; XM_006534302.3.
DR RefSeq; XP_006534366.1; XM_006534303.2.
DR RefSeq; XP_006534367.1; XM_006534304.3.
DR AlphaFoldDB; B1AQJ2; -.
DR SMR; B1AQJ2; -.
DR BioGRID; 215324; 1.
DR STRING; 10090.ENSMUSP00000101903; -.
DR iPTMnet; B1AQJ2; -.
DR PhosphoSitePlus; B1AQJ2; -.
DR EPD; B1AQJ2; -.
DR MaxQB; B1AQJ2; -.
DR PaxDb; B1AQJ2; -.
DR PeptideAtlas; B1AQJ2; -.
DR PRIDE; B1AQJ2; -.
DR ProteomicsDB; 298360; -.
DR Antibodypedia; 1709; 250 antibodies from 29 providers.
DR DNASU; 72344; -.
DR Ensembl; ENSMUST00000092382; ENSMUSP00000090036; ENSMUSG00000033909.
DR Ensembl; ENSMUST00000106296; ENSMUSP00000101903; ENSMUSG00000033909.
DR GeneID; 72344; -.
DR KEGG; mmu:72344; -.
DR UCSC; uc007mot.2; mouse.
DR CTD; 57602; -.
DR MGI; MGI:1919594; Usp36.
DR VEuPathDB; HostDB:ENSMUSG00000033909; -.
DR eggNOG; KOG1865; Eukaryota.
DR GeneTree; ENSGT00940000157948; -.
DR HOGENOM; CLU_008279_10_1_1; -.
DR InParanoid; B1AQJ2; -.
DR OMA; SETCLPQ; -.
DR OrthoDB; 929408at2759; -.
DR PhylomeDB; B1AQJ2; -.
DR TreeFam; TF315281; -.
DR BioGRID-ORCS; 72344; 25 hits in 75 CRISPR screens.
DR ChiTaRS; Usp36; mouse.
DR PRO; PR:B1AQJ2; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; B1AQJ2; protein.
DR Bgee; ENSMUSG00000033909; Expressed in rostral migratory stream and 233 other tissues.
DR ExpressionAtlas; B1AQJ2; baseline and differential.
DR Genevisible; B1AQJ2; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISO:MGI.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0016578; P:histone deubiquitination; ISS:UniProtKB.
DR GO; GO:0016242; P:negative regulation of macroautophagy; ISS:UniProtKB.
DR GO; GO:0007000; P:nucleolus organization; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IMP:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:2000232; P:regulation of rRNA processing; IMP: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..1098
FT /note="Ubiquitin carboxyl-terminal hydrolase 36"
FT /id="PRO_0000378494"
FT DOMAIN 122..423
FT /note="USP"
FT REGION 72..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 428..464
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 483..574
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 589..640
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 664..710
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 722..973
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 539..574
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 602..623
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 694..710
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 746..787
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 797..811
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 851..885
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 903..917
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 943..958
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 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:0000250|UniProtKB:Q9P275"
FT MOD_RES 463
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P275"
FT MOD_RES 547
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P275"
FT MOD_RES 578
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P275"
FT MOD_RES 663
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P275"
FT MOD_RES 678
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P275"
FT MOD_RES 709
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P275"
FT CONFLICT 452
FT /note="S -> P (in Ref. 2; BAC98173)"
FT /evidence="ECO:0000305"
FT CONFLICT 486
FT /note="V -> I (in Ref. 2; BAC98173)"
FT /evidence="ECO:0000305"
FT CONFLICT 541
FT /note="L -> P (in Ref. 2; BAC98173)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1098 AA; 119913 MW; 5853578D7BFD84DF CRC64;
MPIVDKLKEA LKPGRKDSAE DGDLGRLLAA SAKKVLLQRI EFEPASKSFS YQLESLKSKY
VLLSARAEGA SRHRSGDELQ ARKPGTERVS GSGGDGVPAP QKVLFPVERL SLRWERVFRV
GAGLHNLGNT CFLNSTIQCL TYTPPLANYL LSKEHARSCH QGGFCMLCLM QNHMVQAFAN
SGNAIKPVSF IRDLKKIARH FRFGNQEDAH EFLRYTIDAM QKACLNGYAK LDRQTQATTL
VHQIFGGYLR SRVKCSVCKS VSDTYDPYLD IALEIRQAAN IVRALELFVK SDVLSGENAY
MCAKCKKKVP ASKRFTIHRT SNVLTLSLKR FANFSGGKIT KDVGYPEFLN IRPYMSQSSG
DPVMYGLYAV LVHSGYSCHA GHYYCYVKAS NGQWYQMNDS LVHSSNVKVV LNQQAYVLFY
LRIPGSKKSP EGPVSRVGAT LPSRPKVVPE HSKKSPGNGV VPSPLMAKRQ DSVMMRKLPA
PEEVGVPVSR NGSLPGLKLQ NGCAPAKTPA GSPSPRLTPT PTHMPTILDE PGKKVKKSAP
LQSLTTSPTT SQGSPGTGES RSQRPGSWAS RDTIFSTSPK LLARAITNGH RLKGEGSGVD
LEKGDSSSSS PEHSASSDPA KAPQTAESRA AHACDSQGTN CPTAGHPKAL LNGVDAKMVK
LKSPALSSTT TEPTSLMSPP PAKKLALSAK KASTLRRATG NDIGSPSPSA FCDLTSPMKA
THPVVASTGP VSKTRTAAPA PRPSTHPHSA SLSSSSAKPL GTSEPQSCRP SAWTPLPQVN
GHFTSHLHQL PEASEALHSP SKKRKKTPNG DPQRLGIDTL LPQCLRGAPA AARRKRKKRC
SEGEGATAPK QEGQFQDQSW SSGSQKEEGT QPQVNGHQVS HILDSYHVSS RKRRKRKRSE
GLSQEATPSQ DLIQHSCSPV DHSEPEARTE LQKKKKKKRR KRKPEPQQDE ESKHPGDQRS
PRPSVTPVPA LSVNGHLPSD CLGLGQAPLV TWNRDQEPDV VQALLQDSSD KAYGKKVLTW
DGEPSAISQD AIKDSRLART QTVVDDWDEE FDRGKEKKIK KFKREKKRNF NAFQKLQSRR
NFWSVTHPAK VASLSYRR
