UBP21_MOUSE
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 03-AUG-2022, entry version 150.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 21;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 21;
DE AltName: Full=Ubiquitin thioesterase 21;
DE AltName: Full=Ubiquitin-specific-processing protease 21;
GN Name=Usp21; Synonyms=Usp23;
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 Deubiquitination of histone H2A releaves the repression of di- and
CC trimethylation of histone H3 at 'Lys-4', resulting in regulation of
CC transcriptional initiation. Regulates gene expression via histone H2A
CC deubiquitination. Also capable of removing NEDD8 from NEDD8 conjugates
CC but has no effect on Sentrin-1 conjugates. Deubiquitinates BAZ2A/TIP5
CC leading to its stabilization (By similarity).
CC {ECO:0000250|UniProtKB:Q9UK80, 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 and BAZ2A/TIP5.
CC {ECO:0000250|UniProtKB:Q9UK80}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
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; 4.
DR STRING; 10090.ENSMUSP00000064002; -.
DR MEROPS; C19.034; -.
DR iPTMnet; Q9QZL6; -.
DR PhosphoSitePlus; Q9QZL6; -.
DR MaxQB; Q9QZL6; -.
DR PaxDb; Q9QZL6; -.
DR PRIDE; Q9QZL6; -.
DR DNASU; 30941; -.
DR GeneID; 30941; -.
DR KEGG; mmu:30941; -.
DR CTD; 27005; -.
DR MGI; MGI:1353665; Usp21.
DR eggNOG; KOG1868; Eukaryota.
DR InParanoid; Q9QZL6; -.
DR OrthoDB; 561804at2759; -.
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 NFkappaB signaling pathway.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR BioGRID-ORCS; 30941; 0 hits in 72 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:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0016578; P:histone deubiquitination; IDA:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; 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 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"
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 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"
FT BINDING 388
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 438
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 441
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
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
