ID   UBP21_BOVIN             Reviewed;         565 AA.
AC   Q2KJ72;
DT   24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT   07-MAR-2006, sequence version 1.
DT   24-JAN-2024, entry version 94.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 21;
DE            EC=3.4.19.12 {ECO:0000250|UniProtKB:Q9UK80};
DE   AltName: Full=Deubiquitinating enzyme 21;
DE   AltName: Full=Ubiquitin thioesterase 21;
DE   AltName: Full=Ubiquitin-specific-processing protease 21;
GN   Name=USP21;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Thymus;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Deubiquitinating enzyme that hydrolyzes 'Lys-6'- and 'Lys-
CC       11'-linked polyubiquitin. Also hydrolyzes heterotypic (mixed and
CC       branched) and homotypic chains. Important regulator of energy
CC       metabolism. Glucose and fatty acids trigger its nuclear translocation
CC       by CBP-dependent acetylation. In the nucleus, deubiquitinates and
CC       stabilizes the nuclear receptor PPARD regulating the expression of
CC       various genes involved in glucose and lipid metabolism and oxidative
CC       phosphorylation. Also acts as a negative regulator of the ribosome
CC       quality control (RQC) by mediating deubiquitination of 40S ribosomal
CC       proteins RPS10/eS10 and RPS20/uS10, thereby antagonizing ZNF598-
CC       mediated 40S ubiquitination. {ECO:0000250|UniProtKB:Q5T2D3}.
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:0000250|UniProtKB:Q9UK80};
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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; BC105488; AAI05489.1; -; mRNA.
DR   RefSeq; NP_001039841.1; NM_001046376.2.
DR   AlphaFoldDB; Q2KJ72; -.
DR   SMR; Q2KJ72; -.
DR   STRING; 9913.ENSBTAP00000062274; -.
DR   MEROPS; C19.034; -.
DR   PaxDb; 9913-ENSBTAP00000029184; -.
DR   GeneID; 534273; -.
DR   KEGG; bta:534273; -.
DR   CTD; 27005; -.
DR   eggNOG; KOG1868; Eukaryota.
DR   InParanoid; Q2KJ72; -.
DR   OrthoDB; 227085at2759; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR   GO; GO:0008234; F:cysteine-type peptidase activity; ISS: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; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0045815; P:transcription initiation-coupled chromatin remodeling; ISS: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   2: Evidence at transcript 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..565
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 21"
FT                   /id="PRO_0000367508"
FT   DOMAIN          212..558
FT                   /note="USP"
FT   REGION          1..103
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          109..128
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          142..163
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..71
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        221
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   ACT_SITE        518
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   BINDING         384
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UK80"
FT   BINDING         387
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UK80"
FT   BINDING         437
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UK80"
FT   BINDING         440
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UK80"
SQ   SEQUENCE   565 AA;  62619 MW;  6AA35C030406094C CRC64;
     MPQASEHRLG RTREPPLNIQ PRVGSKLPFA PRARSKERRN PAPGPNPMLR PLPPRPGPPE
     ERLKKLELGR GRTSGPRPSG PLRADHGVPL PGSPPPTVAL PLPSRTNLAR SKSVSSGDLR
     PMGIALGGHR GTGELGAALS RLALRPEPPP LRRSTSLRRL GGFPGPPTLF SIRTEPPTPH
     GSFHVISARP SEPFYSDDKM AHHTLLLGSG HVGLRNLGNT CFLNALLQCL SSTRPLRDFC
     LRRDFRQEVP GGGRAQELTE AFADVIGALW HPDSCEAVNP TRFRAVFQKY VPSFSGYSQQ
     DAQEFLKLLM ERLHLEINRR GRRAPPILAS SPAPHPPRLG GALLEEPELS DDDRANLMWK
     RYLEREDSKI VDLFVGQLKS CLKCQACGYR STTFEVFCDL SLPIPKKGFA GGKVSLRDCF
     NLFTKEEELE SENAPVCDRC RQKTRSTKKL TVQRFPRILV LHLNRFSASR GSIKKSSVGV
     DFPLQRLSLG DFASDKAGSP VYQLYALCNH SGSVHYGHYT ALCRCQTGWH VYNDSRVSPV
     SENQVASSEG YVLFYQLMQE PPRCL
//