ID   UBP37_BOVIN             Reviewed;         981 AA.
AC   F1N5V1;
DT   21-SEP-2011, integrated into UniProtKB/Swiss-Prot.
DT   03-MAY-2011, sequence version 1.
DT   27-MAR-2024, entry version 69.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 37;
DE            EC=3.4.19.12 {ECO:0000250|UniProtKB:Q86T82};
DE   AltName: Full=Deubiquitinating enzyme 37;
DE   AltName: Full=Ubiquitin thioesterase 37;
DE   AltName: Full=Ubiquitin-specific-processing protease 37;
GN   Name=USP37;
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 GENOMIC DNA].
RX   PubMed=19390049; DOI=10.1126/science.1169588;
RG   The bovine genome sequencing and analysis consortium;
RT   "The genome sequence of taurine cattle: a window to ruminant biology and
RT   evolution.";
RL   Science 324:522-528(2009).
CC   -!- FUNCTION: Deubiquitinase that plays a role in different processes
CC       including cell cycle regulation, DNA replication or DNA damage
CC       response. Antagonizes the anaphase-promoting complex (APC/C) during
CC       G1/S transition by mediating deubiquitination of cyclin-A (CCNA1 and
CC       CCNA2), thereby promoting S phase entry. Specifically mediates
CC       deubiquitination of 'Lys-11'-linked polyubiquitin chains, a specific
CC       ubiquitin-linkage type mediated by the APC/C complex. Phosphorylation
CC       at Ser-628 during G1/S phase maximizes the deubiquitinase activity,
CC       leading to prevent degradation of cyclin-A (CCNA1 and CCNA2). Plays an
CC       important role in the regulation of DNA replication by stabilizing the
CC       licensing factor CDT1. Plays also an essential role beyond S-phase
CC       entry to promote the efficiency and fidelity of replication by
CC       deubiquitinating checkpoint kinase 1/CHK1, promoting its stability.
CC       Sustains the DNA damage response (DDR) by deubiquitinating and
CC       stabilizing the ATP-dependent DNA helicase BLM. Mechanistically, DNA
CC       double-strand breaks (DSB) promotes ATM-mediated phosphorylation of
CC       USP37 and enhances the binding between USP37 and BLM. Promotes cell
CC       migration by deubiquitinating and stabilizing the epithelial-
CC       mesenchymal transition (EMT)-inducing transcription factor SNAI. Plays
CC       a role in the regulation of mitotic spindle assembly and mitotic
CC       progression by associating with chromatin-associated WAPL and
CC       stabilizing it through deubiquitination.
CC       {ECO:0000250|UniProtKB:Q86T82}.
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:Q86T82};
CC   -!- SUBUNIT: Interacts with FZR1/CDH1. Interacts with CDT1.
CC       {ECO:0000250|UniProtKB:Q86T82}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q86T82}.
CC       Chromosome {ECO:0000250|UniProtKB:Q86T82}.
CC   -!- DOMAIN: The KEN box 3 is required for interaction with FZR1/CDH1 and is
CC       essential for APC(CDH1)-mediated ubiquitination.
CC       {ECO:0000250|UniProtKB:Q86T82}.
CC   -!- PTM: Polyubiquitinated via 'Lys-11'-linked ubiquitin by the APC(CDH1)
CC       complex during late mitosis, leading to its degradation. Able to
CC       mediate auto-deubiquitination. {ECO:0000250|UniProtKB:Q86T82}.
CC   -!- PTM: Phosphorylated at Ser-630 by CDK2 during G1/S phase but not during
CC       mitosis; phosphorylation at Ser-630 is required for deubiquitinase
CC       activity. Also polyubiquitinated during early G1 phase, without leading
CC       to degradation. Phosphorylated at Ser-114 by ATM following DNA damage,
CC       which in turn increases its deubiquitination activity towards BLM.
CC       {ECO:0000250|UniProtKB:Q86T82}.
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR   EMBL; AAFC03077731; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AAFC03103854; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AAFC03103857; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; NP_001258921.1; NM_001271992.1.
DR   RefSeq; XP_010800620.1; XM_010802318.2.
DR   RefSeq; XP_010800621.1; XM_010802319.2.
DR   RefSeq; XP_010800622.1; XM_010802320.2.
DR   AlphaFoldDB; F1N5V1; -.
DR   SMR; F1N5V1; -.
DR   IntAct; F1N5V1; 1.
DR   STRING; 9913.ENSBTAP00000057573; -.
DR   PaxDb; 9913-ENSBTAP00000038058; -.
DR   Ensembl; ENSBTAT00000081874.1; ENSBTAP00000057573.1; ENSBTAG00000016572.5.
DR   GeneID; 407168; -.
DR   KEGG; bta:407168; -.
DR   CTD; 57695; -.
DR   VEuPathDB; HostDB:ENSBTAG00000016572; -.
DR   VGNC; VGNC:36726; USP37.
DR   eggNOG; KOG1868; Eukaryota.
DR   GeneTree; ENSGT00940000158091; -.
DR   HOGENOM; CLU_012557_0_0_1; -.
DR   InParanoid; F1N5V1; -.
DR   OMA; CGEVVNK; -.
DR   OrthoDB; 227085at2759; -.
DR   TreeFam; TF323032; -.
DR   Reactome; R-BTA-5689880; Ub-specific processing proteases.
DR   Proteomes; UP000009136; Chromosome 2.
DR   Bgee; ENSBTAG00000016572; Expressed in semen and 110 other cell types or tissues.
DR   ExpressionAtlas; F1N5V1; baseline and differential.
DR   GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR   GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISS:UniProtKB.
DR   GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR   GO; GO:0035871; P:protein K11-linked deubiquitination; ISS:UniProtKB.
DR   GO; GO:0071108; P:protein K48-linked deubiquitination; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0006275; P:regulation of DNA replication; ISS:UniProtKB.
DR   CDD; cd02257; Peptidase_C19; 2.
DR   CDD; cd13312; PH_USP37_like; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 2.
DR   Gene3D; 2.30.29.180; Ubiquitin carboxyl-terminal hydrolase 26/29/37, pleckstrin homology-like domain; 1.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR001394; Peptidase_C19_UCH.
DR   InterPro; IPR003903; UIM_dom.
DR   InterPro; IPR032069; USP37-like_PH.
DR   InterPro; IPR038093; USP37-like_PH_sf.
DR   InterPro; IPR018200; USP_CS.
DR   InterPro; IPR028889; USP_dom.
DR   PANTHER; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR21646:SF23; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE USP2; 1.
DR   Pfam; PF00443; UCH; 1.
DR   Pfam; PF16674; UCH_N; 1.
DR   Pfam; PF02809; UIM; 3.
DR   SMART; SM00726; UIM; 4.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   PROSITE; PS50330; UIM; 3.
DR   PROSITE; PS00972; USP_1; 1.
DR   PROSITE; PS00973; USP_2; 1.
DR   PROSITE; PS50235; USP_3; 1.
PE   3: Inferred from homology;
KW   Cell cycle; Cell division; Chromosome; Hydrolase; Mitosis; Nucleus;
KW   Phosphoprotein; Protease; Reference proteome; Repeat; Thiol protease;
KW   Ubl conjugation; Ubl conjugation pathway.
FT   CHAIN           1..981
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 37"
FT                   /id="PRO_0000412644"
FT   DOMAIN          343..953
FT                   /note="USP"
FT   DOMAIN          706..725
FT                   /note="UIM 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT   DOMAIN          808..827
FT                   /note="UIM 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT   DOMAIN          830..849
FT                   /note="UIM 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT   REGION          111..306
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          670..705
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          721..797
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           32..34
FT                   /note="KEN box 1"
FT                   /evidence="ECO:0000250"
FT   MOTIF           71..79
FT                   /note="D-box 1"
FT                   /evidence="ECO:0000250"
FT   MOTIF           96..105
FT                   /note="D-box 2"
FT                   /evidence="ECO:0000250"
FT   MOTIF           160..168
FT                   /note="D-box 3"
FT                   /evidence="ECO:0000250"
FT   MOTIF           223..225
FT                   /note="KEN box 2"
FT                   /evidence="ECO:0000250"
FT   MOTIF           784..786
FT                   /note="KEN box 3"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        111..147
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        182..199
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        200..226
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        227..303
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        676..701
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        722..739
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        774..791
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        352
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:Q86T82,
FT                   ECO:0000255|PROSITE-ProRule:PRU10092, ECO:0000255|PROSITE-
FT                   ProRule:PRU10093"
FT   ACT_SITE        908
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   MOD_RES         114
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q86T82"
FT   MOD_RES         170
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q86T82"
FT   MOD_RES         212
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q86T82"
FT   MOD_RES         630
FT                   /note="Phosphoserine; by CDK2"
FT                   /evidence="ECO:0000250|UniProtKB:Q86T82"
FT   MOD_RES         652
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q86T82"
FT   MOD_RES         654
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q86T82"
FT   MOD_RES         772
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q86T82"
SQ   SEQUENCE   981 AA;  110398 MW;  4F678FE4C1D0B5E3 CRC64;
     MSPLKIHGPI RIRSMQTGIT KWKEGSFEVV EKENKVSLVV HYNTGGIPRI FQLSHNIKNV
     VLRPSGAKQS RLMLTLQDNS FLSIDKVPSK DAEEMRLFLD AVHQNRLNAA MKPSQGSGSF
     GAILGSRTSQ KETNRQLSYS DNQVSSKRGS LETKDDTPFR KVLGNPSRGS IKAAAGNGVT
     PARTIPSLTS TSTPLRSGLL ENRTEKRKRM LSSGSELNED YPKENDSSSN NKAMTDPSRK
     YLTSSREKQL SLKQSEENRT SGLLPLQSSS FYGSRTAAKD YSPGSTNLDR TNISSQTPSA
     KRSLGFLPQP APLSVKKLRC NQDYTGWNKP RVPLSSHQQQ QLQGFSNLGN TCYMNAILQS
     LFSLQSFAND LLKQGIPWKK IPLNALIRRF AHLLVKKDIC NSETKKDLLK KVKNAISATA
     ERFSGYMQND AHEFLSQCLD QLKEDMEKLN KTWKIEPVPG EENSPDISAT RVYTCPVITN
     LEFEVQHSII CKVCGEIIPK REQFNDLSID LPRRKKPLPP RSIQDSLDLF FRAEELEYSC
     EKCGGKCALV RHKFNRLPRI LILHLKRYSF NVALSLNNKI GQQVIIPRYL TLSSHCTENT
     KPPFNLGWSA QMAVSRPLKA SQMVNSCITS PSTPSKNFTF KSKTSLALSL DSDSEDELKR
     SVALSHRLCE MSGSEQQQED LEKDSKSCRI EPDKSELENS GFDGMSEEEL LAAVLEISKR
     EASPSLSHED DDKPTSSPDT GFAEDDIQEM PENPDSVETE KPKTITEPDP ASFTEITKDC
     DENKENKTPE GSQGEVDWLQ QYDMEREREE QELQQALAQS LQEQEAWEQK EDDDLKRATE
     LSLQEFNNSF VDSLGSDEDS GNEDVLDMEY TEAEAEELKR NAETGNLPHS YRLISVVSHI
     GSTSSSGHYI SDVYDIKKQA WFTYNDLEVS KIQEASVQSD RDRSGYIFFY MHKEIFDELL
     ETEKNSQALN LEVGKTTRQV S
//