UBP2_BOVIN
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 03-AUG-2022, entry version 98.
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 ARNTL/BMAL1.
CC {ECO:0000250|UniProtKB:O75604, 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.ENSBTAP00000012857; -.
DR MEROPS; C19.013; -.
DR PaxDb; Q2KHV7; -.
DR Ensembl; ENSBTAT00000012857; ENSBTAP00000012857; ENSBTAG00000009749.
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 OrthoDB; 1283205at2759; -.
DR TreeFam; TF106277; -.
DR Proteomes; UP000009136; Chromosome 15.
DR Bgee; ENSBTAG00000009749; Expressed in infraspinatus muscle and 100 other tissues.
DR ExpressionAtlas; Q2KHV7; baseline and differential.
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: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 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
