ID   UBP37_PIG               Reviewed;         982 AA.
AC   F1SRY5;
DT   21-SEP-2011, integrated into UniProtKB/Swiss-Prot.
DT   03-MAY-2011, sequence version 1.
DT   27-MAR-2024, entry version 61.
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   Sus scrofa (Pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX   NCBI_TaxID=9823;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Landrace;
RG   Swine Genome Sequencing Consortium.;
RL   Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
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-631 by CDK2 during G1/S phase but not during
CC       mitosis; phosphorylation at Ser-631 is required for deubiquitinase
CC       activity. Also polyubiquitinated during early G1 phase, without leading
CC       to degradation. Phosphorylated at Ser-115 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; CU570813; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   AlphaFoldDB; F1SRY5; -.
DR   SMR; F1SRY5; -.
DR   STRING; 9823.ENSSSCP00000017157; -.
DR   PaxDb; 9823-ENSSSCP00000017157; -.
DR   eggNOG; KOG1868; Eukaryota.
DR   InParanoid; F1SRY5; -.
DR   TreeFam; TF323032; -.
DR   Proteomes; UP000008227; Unplaced.
DR   Proteomes; UP000314985; Unplaced.
DR   Proteomes; UP000694570; Unplaced.
DR   Proteomes; UP000694571; Unplaced.
DR   Proteomes; UP000694720; Unplaced.
DR   Proteomes; UP000694722; Unplaced.
DR   Proteomes; UP000694723; Unplaced.
DR   Proteomes; UP000694724; Unplaced.
DR   Proteomes; UP000694725; Unplaced.
DR   Proteomes; UP000694726; Unplaced.
DR   Proteomes; UP000694727; Unplaced.
DR   Proteomes; UP000694728; Unplaced.
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: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; 3.
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..982
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 37"
FT                   /id="PRO_0000412646"
FT   DOMAIN          343..954
FT                   /note="USP"
FT   DOMAIN          707..726
FT                   /note="UIM 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT   DOMAIN          809..828
FT                   /note="UIM 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT   DOMAIN          831..850
FT                   /note="UIM 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT   REGION          128..162
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          183..307
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          672..705
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          720..798
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           161..169
FT                   /note="D-box 3"
FT                   /evidence="ECO:0000250"
FT   MOTIF           224..226
FT                   /note="KEN box 2"
FT                   /evidence="ECO:0000250"
FT   MOTIF           785..787
FT                   /note="KEN box 3"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        128..148
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        183..200
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        201..227
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        228..304
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        677..702
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        723..740
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        775..792
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        909
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   MOD_RES         115
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q86T82"
FT   MOD_RES         171
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q86T82"
FT   MOD_RES         213
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q86T82"
FT   MOD_RES         631
FT                   /note="Phosphoserine; by CDK2"
FT                   /evidence="ECO:0000250|UniProtKB:Q86T82"
FT   MOD_RES         653
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q86T82"
FT   MOD_RES         655
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q86T82"
FT   MOD_RES         773
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q86T82"
SQ   SEQUENCE   982 AA;  110483 MW;  3B09ABDE42E07AFF CRC64;
     MSPLKIQGPI RIRSMQTGIT KWKEGSFEIV EKENKVSLVV HYNTGGIPRI FQLSHNIKNV
     VLRPSGAKQS RLMLTLQDNS FLSIDKVPSK DAEEMRLFLD AVHQNRLNAV AMKPSQGSGS
     FGAILGSRTS QKETHRQLSY SDNQVSSKRG SLETKDDIPF RKVLGNPGRA SIKTAAGSGI
     TATRTIPSLT STSTPLRSGL LENRTEKRKR MLSSGSELNE DYPKENDSSS NNKAMTDPSR
     KYLTSSREKQ LSLKQSEENR TSGLLPLQSS SFYGSRAASK DYSPSSTNLD RTNISSQTPS
     AKRSLGFLPQ PAPLSVKKLR CNQDYTGWNK PRLPLSSHQQ QLQGFSNLGN TCYMNAILQS
     LFSLQSFAND LLKQGIPWKK IPLNALISRR FAHLLVKKDI CNSETKKDLL KKVKNAISAT
     AERFSGYMQN DAHEFLSQCL DQLKEDMEKL NKTWKTEPVP GEENSPDVTA TRVYTCPVIT
     NLEFEVQHSI ICKACGEIIP KREQFNDLSI DLPRRKKPLP PRSIQDSLDL FFRAEELEYS
     CEKCGGKCAL VRHKFNRLPR ILILHLKRYS FNVALSLNNK IGQQVIIPRY LTLSSHCTEN
     TKPPFNLGWS AQMAISRPLK ASQMVNSCIT SPSTPSKNFT FKSKSSLALS LDSDSEDELK
     RSVALSQRLC EISSSEQQQE DLEKDSKSCK LEPDKSELEN SGFDAMSEEE LLAAVLEISK
     REASPSPSHE DDDKPTSSPD TGFAEDDIQE MPENPDPMET EKPKTITEPD PASFTEITKD
     CDENKENKTP EGSQGEVDWL QQYDMERERE EQELQQALAQ SLQEQEAWEQ KEDDDLKRAT
     ELSLQEFNNS FLDSLGSDED SGNEDVLDME YTEAEAEELK RNAETGNLPH SYRLISVVSH
     IGSTSSSGHY ISDVYDIKKQ AWFTYNDLEV SKIQEASVQS DRDRSGYIFF YMHKEIFDEL
     LETEKNSQAL SMEVGKTTRQ AS
//