ID   UBP21_MOUSE             Reviewed;         566 AA.
AC   Q9QZL6; Q9D0R1;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   24-JAN-2024, entry version 158.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 21 {ECO:0000305};
DE            EC=3.4.19.12 {ECO:0000269|PubMed:18172164};
DE   AltName: Full=Deubiquitinating enzyme 21 {ECO:0000303|PubMed:18172164};
DE   AltName: Full=Ubiquitin thioesterase 21 {ECO:0000303|PubMed:18172164};
DE   AltName: Full=Ubiquitin-specific-processing protease 21 {ECO:0000303|PubMed:18172164};
GN   Name=Usp21 {ECO:0000303|PubMed:18172164, ECO:0000312|MGI:MGI:1353665};
GN   Synonyms=Usp23 {ECO:0000303|PubMed:10786635};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=10786635; DOI=10.1016/s0167-4781(99)00233-x;
RA   Smith T.S., Southan C.;
RT   "Sequencing, tissue distribution and chromosomal assignment of a novel
RT   ubiquitin-specific protease USP23.";
RL   Biochim. Biophys. Acta 1490:184-188(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Embryo;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-221; HIS-519 AND
RP   ASP-535.
RX   PubMed=18172164; DOI=10.1101/gad.1609708;
RA   Nakagawa T., Kajitani T., Togo S., Masuko N., Ohdan H., Hishikawa Y.,
RA   Koji T., Matsuyama T., Ikura T., Muramatsu M., Ito T.;
RT   "Deubiquitylation of histone H2A activates transcriptional initiation via
RT   trans-histone cross-talk with H3K4 di- and trimethylation.";
RL   Genes Dev. 22:37-49(2008).
CC   -!- FUNCTION: Deubiquitinates histone H2A, a specific tag for epigenetic
CC       transcriptional repression, thereby acting as a coactivator
CC       (PubMed:18172164). Deubiquitination of histone H2A releaves the
CC       repression of di- and trimethylation of histone H3 at 'Lys-4',
CC       resulting in regulation of transcriptional initiation
CC       (PubMed:18172164). Regulates gene expression via histone H2A
CC       deubiquitination (PubMed:18172164). Deubiquitinates BAZ2A/TIP5 leading
CC       to its stabilization (By similarity). Also capable of removing NEDD8
CC       from NEDD8 conjugates but has no effect on Sentrin-1 conjugates (By
CC       similarity). Also acts as a negative regulator of the ribosome quality
CC       control (RQC) by mediating deubiquitination of 40S ribosomal proteins
CC       RPS10/eS10 and RPS20/uS10, thereby antagonizing ZNF598-mediated 40S
CC       ubiquitination (By similarity). {ECO:0000250|UniProtKB:Q9UK80,
CC       ECO:0000269|PubMed:18172164}.
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:18172164};
CC   -!- SUBUNIT: Interacts with BEND3. {ECO:0000250|UniProtKB:Q9UK80}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9UK80}. Nucleus
CC       {ECO:0000250|UniProtKB:Q9UK80}.
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. USP21 subfamily.
CC       {ECO:0000305}.
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DR   EMBL; AF177759; AAD54322.1; -; mRNA.
DR   EMBL; AK011148; BAB27431.1; -; mRNA.
DR   EMBL; BC021903; AAH21903.1; -; mRNA.
DR   CCDS; CCDS35774.1; -.
DR   RefSeq; NP_038947.2; NM_013919.4.
DR   AlphaFoldDB; Q9QZL6; -.
DR   SMR; Q9QZL6; -.
DR   BioGRID; 206018; 6.
DR   STRING; 10090.ENSMUSP00000106936; -.
DR   MEROPS; C19.034; -.
DR   iPTMnet; Q9QZL6; -.
DR   PhosphoSitePlus; Q9QZL6; -.
DR   MaxQB; Q9QZL6; -.
DR   PaxDb; 10090-ENSMUSP00000064002; -.
DR   DNASU; 30941; -.
DR   GeneID; 30941; -.
DR   KEGG; mmu:30941; -.
DR   AGR; MGI:1353665; -.
DR   CTD; 27005; -.
DR   MGI; MGI:1353665; Usp21.
DR   eggNOG; KOG1868; Eukaryota.
DR   InParanoid; Q9QZL6; -.
DR   OrthoDB; 227085at2759; -.
DR   Reactome; R-MMU-5357786; TNFR1-induced proapoptotic signaling.
DR   Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR   Reactome; R-MMU-5357956; TNFR1-induced NF-kappa-B signaling pathway.
DR   Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR   BioGRID-ORCS; 30941; 0 hits in 78 CRISPR screens.
DR   PRO; PR:Q9QZL6; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q9QZL6; Protein.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IC:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR   GO; GO:0008234; F:cysteine-type peptidase activity; IDA:UniProtKB.
DR   GO; GO:0019784; F:deNEDDylase activity; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR   GO; GO:0031175; P:neuron projection development; ISO:MGI.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0045815; P:transcription initiation-coupled chromatin remodeling; IDA:UniProtKB.
DR   CDD; cd02674; Peptidase_C19R; 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; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR21646:SF6; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 21; 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.
PE   1: Evidence at protein level;
KW   Activator; Chromatin regulator; Cytoplasm; Hydrolase; Metal-binding;
KW   Nucleus; Protease; Reference proteome; Thiol protease; Transcription;
KW   Transcription regulation; Ubl conjugation pathway; Zinc.
FT   CHAIN           1..566
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 21"
FT                   /id="PRO_0000080649"
FT   DOMAIN          212..559
FT                   /note="USP"
FT   REGION          1..103
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          146..169
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          324..349
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           134..152
FT                   /note="Nuclear export signal"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UK80"
FT   COMPBIAS        57..72
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        221
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000305|PubMed:18172164"
FT   ACT_SITE        519
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   BINDING         385
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UK80"
FT   BINDING         388
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UK80"
FT   BINDING         438
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UK80"
FT   BINDING         441
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UK80"
FT   MUTAGEN         221
FT                   /note="C->A: Abolishes ability to deubiquitinate histone
FT                   H2A and ability to regulate transcription."
FT                   /evidence="ECO:0000269|PubMed:18172164"
FT   MUTAGEN         519
FT                   /note="H->A: Abolishes ability to deubiquitinate histone
FT                   H2A and ability to regulate transcription."
FT                   /evidence="ECO:0000269|PubMed:18172164"
FT   MUTAGEN         535
FT                   /note="D->N: Abolishes ability to deubiquitinate histone
FT                   H2A and ability to regulate transcription."
FT                   /evidence="ECO:0000269|PubMed:18172164"
FT   CONFLICT        220
FT                   /note="T -> TLPQ (in Ref. 2; BAB27431)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        338
FT                   /note="R -> C (in Ref. 2; BAB27431)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   566 AA;  62673 MW;  F2E1828E9BDB1AFD CRC64;
     MPQASEHRLG RTREPPVNVQ PRVGAKIPFP PRARSKERRN PVPGPNSMLR PLPPRPGPPD
     ERLKKLELGR GRTSGSRPRG PLRADHGVPL PGSPPPAVAL PLPSRTNLAR SKSVSSGDLR
     PMGIALGGHR GAGELGAALS RLALRPEPPT LRRSTSLRRL GGFPGPPTLL SIRTEPPTSH
     GSFHMISARP SEPFYSDDKM AHHTLLLGSG HVGLRNLGNT CFLNAVLQCL SSTRPLRDFC
     LRRDFRQEVP GGGRAQELTE AFADVIGALW HPDSCEAVNP TRFRAVFQKY VPSFSGYSQQ
     DAQEFLKLLM ERLHLEINRR GRRAPPILAS GPVPSPPRRG GGALHEEPEL SDDDRANLMW
     KRYLEREDSK IVDLFVGQLK SCLKCQACGY RSTTFEVFCD LSLPIPKKGF AGGKVSLRDC
     FSLFTKEEEL ESENAPVCDR CRQKTRSTKK LTVQRFPRIL VLHLNRFSTS RGSIKKSSVG
     VDFPLQRLSL GDFASDKAGS PVYQLYALCN HSGSVHYGHY TALCRCQTGW HVYNDSRVSP
     VSENQVASSE GYVLFYQLMQ EPLRCL
//