ID   UBP2_BOVIN              Reviewed;         606 AA.
AC   Q2KHV7;
DT   10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT   07-MAR-2006, sequence version 1.
DT   24-JAN-2024, entry version 105.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 2;
DE            EC=3.4.19.12;
DE   AltName: Full=41 kDa ubiquitin-specific protease;
DE   AltName: Full=Deubiquitinating enzyme 2;
DE   AltName: Full=Ubiquitin thioesterase 2;
DE   AltName: Full=Ubiquitin-specific-processing protease 2;
GN   Name=USP2; Synonyms=UBP41;
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=Heart ventricle;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Hydrolase that deubiquitinates polyubiquitinated target
CC       proteins such as MDM2, MDM4 and CCND1. Possesses both ubiquitin-
CC       specific peptidase and isopeptidase activities. Deubiquitinates MDM2
CC       without reversing MDM2-mediated p53/TP53 ubiquitination and thus
CC       indirectly promotes p53/TP53 degradation and limits p53 activity. Has
CC       no deubiquitinase activity against p53/TP53. Prevents MDM2-mediated
CC       degradation of MDM4. Plays a role in the G1/S cell-cycle progression in
CC       normal and cancer cells. Plays a role in the regulation of myogenic
CC       differentiation of embryonic muscle cells. Regulates the circadian
CC       clock by modulating its intrinsic circadian rhythm and its capacity to
CC       respond to external cues. Associates with clock proteins and
CC       deubiquitinates core clock component PER1 but does not affect its
CC       overall stability. Regulates the nucleocytoplasmic shuttling and
CC       nuclear retention of PER1 and its repressive role on the clock
CC       transcription factors CLOCK and BMAL1. {ECO:0000250|UniProtKB:O75604,
CC       ECO:0000250|UniProtKB:O88623}.
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   -!- ACTIVITY REGULATION: Cleavage is inhibited by ubiquitin in a dosage-
CC       dependent manner. Cleavage is blocked by ubiquitin aldehyde.
CC       {ECO:0000250|UniProtKB:O75604, ECO:0000250|UniProtKB:Q5U349}.
CC   -!- SUBUNIT: Homooligomer. Found in trimeric complex with MDM2 and MDM4 and
CC       USP2. Interacts with CCND1; the interaction is direct and promotes its
CC       stabilization by antagonizing ubiquitin-dependent degradation.
CC       Interacts (via N-terminus and C-terminus) with MDM2. Interacts with
CC       MDM4 and PER1. Interacts with KCNQ1; counteracts the NEDD4L-specific
CC       down-regulation of I(Ks) and restores plasma membrane localization of
CC       KCNQ1 (By similarity). {ECO:0000250|UniProtKB:O75604,
CC       ECO:0000250|UniProtKB:O88623, ECO:0000250|UniProtKB:Q5U349}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O88623}.
CC       Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:O88623}.
CC       Note=Localizes in the spermatid head in late-elongating spermatids in
CC       the thin area between the outer acrosomal membrane and the plasma
CC       membrane. {ECO:0000250|UniProtKB:Q5U349}.
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. USP2 subfamily.
CC       {ECO:0000305}.
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DR   EMBL; BC112866; AAI12867.1; -; mRNA.
DR   RefSeq; NP_001039728.1; NM_001046263.1.
DR   AlphaFoldDB; Q2KHV7; -.
DR   SMR; Q2KHV7; -.
DR   STRING; 9913.ENSBTAP00000060377; -.
DR   MEROPS; C19.013; -.
DR   PaxDb; 9913-ENSBTAP00000012857; -.
DR   Ensembl; ENSBTAT00000012857.6; ENSBTAP00000012857.5; ENSBTAG00000009749.6.
DR   GeneID; 522980; -.
DR   KEGG; bta:522980; -.
DR   CTD; 9099; -.
DR   VEuPathDB; HostDB:ENSBTAG00000009749; -.
DR   VGNC; VGNC:54894; USP2.
DR   eggNOG; KOG1868; Eukaryota.
DR   GeneTree; ENSGT00940000161289; -.
DR   HOGENOM; CLU_008279_1_2_1; -.
DR   InParanoid; Q2KHV7; -.
DR   TreeFam; TF106277; -.
DR   Reactome; R-BTA-5357786; TNFR1-induced proapoptotic signaling.
DR   Reactome; R-BTA-5357905; Regulation of TNFR1 signaling.
DR   Reactome; R-BTA-5357956; TNFR1-induced NF-kappa-B signaling pathway.
DR   Proteomes; UP000009136; Chromosome 15.
DR   Bgee; ENSBTAG00000009749; Expressed in infraspinatus muscle and 100 other cell types or tissues.
DR   ExpressionAtlas; Q2KHV7; baseline.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0048512; P:circadian behavior; ISS:UniProtKB.
DR   GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR   GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
DR   GO; GO:0045475; P:locomotor rhythm; ISS:UniProtKB.
DR   GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR   GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISS:UniProtKB.
DR   GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR   GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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:SF17; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 2; 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   Biological rhythms; Cell cycle; Cytoplasm; Hydrolase; Metal-binding;
KW   Myogenesis; Protease; Reference proteome; Thiol protease;
KW   Ubl conjugation pathway; Zinc; Zinc-finger.
FT   CHAIN           1..606
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 2"
FT                   /id="PRO_0000395965"
FT   DOMAIN          268..600
FT                   /note="USP"
FT   REGION          1..201
FT                   /note="Necessary for interaction with MDM4"
FT                   /evidence="ECO:0000250|UniProtKB:O75604"
FT   REGION          53..112
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          207..228
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          404..504
FT                   /note="Necessary for interaction with MDM4"
FT                   /evidence="ECO:0000250|UniProtKB:O75604"
FT   COMPBIAS        98..112
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        277
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   ACT_SITE        558
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   BINDING         426
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:O75604"
FT   BINDING         429
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:O75604"
FT   BINDING         477
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:O75604"
FT   BINDING         480
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:O75604"
SQ   SEQUENCE   606 AA;  68101 MW;  4713919E8BDEE909 CRC64;
     MSQLSSTLKR YTESARFTDA PFTKSSYGTY TPSSYGTNLA ASFLEKEKFG FKPSPPTSYL
     TRPRTYGPPS ILDYDRGRPL LRPDVIGGGK RAESQTRGTE RPSGSGLSGG SGFSYGVTTS
     SVSYLPVSAR DQGVTLTQKK SNSQSDLARD FSSLQTSDSY RLDSGNLGRS PMLARTRKEL
     CALQGLYQAA SRSEYLADYL ENYGRKASAP QVPTPTPPSR APEVLSPTYR PSGRYSLWEK
     GKGQALVSSR SSSPGRDTMN SKSAQGLAGL RNLGNTCFMN SILQCLSNTR ELRDYCLQRL
     YLRDLSHSSR AHTALMEEFA KLIQTIWTSS PNDVVSPSEF KTQIQRYAPR FVGYNQQDAQ
     EFLRFLLDGL HNEVNRVIAR PKSNTENLDH LPDDEKGRQM WRKYLEREDS RIGDLFVGQL
     KSSLTCTDCG YCSTVFDPFW DLSLPITKRG YPEVTLMDCM RLFTKEDVLD GDEKPTCCRC
     RARKRCIKKF SIQRFPKILV LHLKRFSESR IRTSKLTAFV NFPLRDLDLR EFASENTNHA
     VYNLYAVSNH SGTTMGGHYT AYCRSPVTGE WHTFNDSSVS PMSSSQVRTS DAYLLFYELA
     SPPSRM
//