ID   OTU7A_HUMAN             Reviewed;         926 AA.
AC   Q8TE49; Q8IWK5;
DT   31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2002, sequence version 1.
DT   27-MAR-2024, entry version 158.
DE   RecName: Full=OTU domain-containing protein 7A;
DE            EC=3.4.19.12;
DE   AltName: Full=Zinc finger protein Cezanne 2;
GN   Name=OTUD7A; Synonyms=C15orf16, CEZANNE2, OTUD7;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Evans P.C., Coadwell W.J., Kilshaw P.J.;
RT   "Isolation of a novel human gene, Cezanne 2.";
RL   Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-678 (ISOFORM 2).
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   FUNCTION.
RX   PubMed=20622874; DOI=10.1038/nsmb.1873;
RA   Bremm A., Freund S.M., Komander D.;
RT   "Lys11-linked ubiquitin chains adopt compact conformations and are
RT   preferentially hydrolyzed by the deubiquitinase Cezanne.";
RL   Nat. Struct. Mol. Biol. 17:939-947(2010).
RN   [4]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=23827681; DOI=10.1016/j.cell.2013.05.046;
RA   Mevissen T.E., Hospenthal M.K., Geurink P.P., Elliott P.R., Akutsu M.,
RA   Arnaudo N., Ekkebus R., Kulathu Y., Wauer T., El Oualid F., Freund S.M.,
RA   Ovaa H., Komander D.;
RT   "OTU deubiquitinases reveal mechanisms of linkage specificity and enable
RT   ubiquitin chain restriction analysis.";
RL   Cell 154:169-184(2013).
RN   [5]
RP   STRUCTURE BY NMR OF 11-83.
RG   Structural genomics consortium (SGC);
RT   "The amino-terminal UBA domain of OTUD7A.";
RL   Submitted (FEB-2012) to the PDB data bank.
CC   -!- FUNCTION: Has deubiquitinating activity towards 'Lys-11'-linked
CC       polyubiquitin chains. {ECO:0000269|PubMed:20622874,
CC       ECO:0000269|PubMed:23827681}.
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:0000269|PubMed:23827681};
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8TE49-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8TE49-2; Sequence=VSP_011430;
CC   -!- SIMILARITY: Belongs to the peptidase C64 family. {ECO:0000305}.
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DR   EMBL; AJ430383; CAD23047.1; -; mRNA.
DR   EMBL; BC035668; AAH35668.1; -; mRNA.
DR   CCDS; CCDS10026.1; -. [Q8TE49-1]
DR   CCDS; CCDS91972.1; -. [Q8TE49-2]
DR   RefSeq; NP_570971.1; NM_130901.2. [Q8TE49-1]
DR   PDB; 2L2D; NMR; -; A=11-83.
DR   PDBsum; 2L2D; -.
DR   AlphaFoldDB; Q8TE49; -.
DR   BMRB; Q8TE49; -.
DR   SMR; Q8TE49; -.
DR   BioGRID; 127799; 21.
DR   IntAct; Q8TE49; 4.
DR   STRING; 9606.ENSP00000305926; -.
DR   MEROPS; C64.002; -.
DR   GlyGen; Q8TE49; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q8TE49; -.
DR   PhosphoSitePlus; Q8TE49; -.
DR   BioMuta; OTUD7A; -.
DR   DMDM; 51701344; -.
DR   EPD; Q8TE49; -.
DR   jPOST; Q8TE49; -.
DR   MassIVE; Q8TE49; -.
DR   MaxQB; Q8TE49; -.
DR   PaxDb; 9606-ENSP00000305926; -.
DR   PeptideAtlas; Q8TE49; -.
DR   ProteomicsDB; 74392; -. [Q8TE49-1]
DR   ProteomicsDB; 74393; -. [Q8TE49-2]
DR   Antibodypedia; 22563; 109 antibodies from 19 providers.
DR   DNASU; 161725; -.
DR   Ensembl; ENST00000307050.6; ENSP00000305926.5; ENSG00000169918.10. [Q8TE49-2]
DR   Ensembl; ENST00000560598.2; ENSP00000453883.2; ENSG00000169918.10. [Q8TE49-1]
DR   Ensembl; ENST00000678495.1; ENSP00000503326.1; ENSG00000169918.10. [Q8TE49-1]
DR   GeneID; 161725; -.
DR   KEGG; hsa:161725; -.
DR   MANE-Select; ENST00000307050.6; ENSP00000305926.5; NM_001382637.1; NP_001369566.1. [Q8TE49-2]
DR   UCSC; uc001zfq.4; human. [Q8TE49-1]
DR   AGR; HGNC:20718; -.
DR   CTD; 161725; -.
DR   DisGeNET; 161725; -.
DR   GeneCards; OTUD7A; -.
DR   GeneReviews; OTUD7A; -.
DR   HGNC; HGNC:20718; OTUD7A.
DR   HPA; ENSG00000169918; Tissue enhanced (brain).
DR   MalaCards; OTUD7A; -.
DR   MIM; 612024; gene.
DR   neXtProt; NX_Q8TE49; -.
DR   OpenTargets; ENSG00000169918; -.
DR   PharmGKB; PA134877572; -.
DR   VEuPathDB; HostDB:ENSG00000169918; -.
DR   eggNOG; KOG4345; Eukaryota.
DR   GeneTree; ENSGT00940000158999; -.
DR   HOGENOM; CLU_013263_0_0_1; -.
DR   InParanoid; Q8TE49; -.
DR   OMA; RCAKQPE; -.
DR   OrthoDB; 2909231at2759; -.
DR   PhylomeDB; Q8TE49; -.
DR   TreeFam; TF323312; -.
DR   PathwayCommons; Q8TE49; -.
DR   Reactome; R-HSA-5689896; Ovarian tumor domain proteases.
DR   SignaLink; Q8TE49; -.
DR   SIGNOR; Q8TE49; -.
DR   BioGRID-ORCS; 161725; 21 hits in 1195 CRISPR screens.
DR   ChiTaRS; OTUD7A; human.
DR   EvolutionaryTrace; Q8TE49; -.
DR   GenomeRNAi; 161725; -.
DR   Pharos; Q8TE49; Tbio.
DR   PRO; PR:Q8TE49; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   RNAct; Q8TE49; Protein.
DR   Bgee; ENSG00000169918; Expressed in endothelial cell and 124 other cell types or tissues.
DR   ExpressionAtlas; Q8TE49; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR   GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR   GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IBA:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0035871; P:protein K11-linked deubiquitination; IDA:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd22773; OTU_OTUD7A; 1.
DR   CDD; cd14347; UBA_Cezanne_like; 1.
DR   Gene3D; 1.20.5.4770; -; 1.
DR   Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1.
DR   InterPro; IPR003323; OTU_dom.
DR   InterPro; IPR002653; Znf_A20.
DR   PANTHER; PTHR13367:SF9; OTU DOMAIN-CONTAINING PROTEIN 7A; 1.
DR   PANTHER; PTHR13367; UBIQUITIN THIOESTERASE; 1.
DR   Pfam; PF02338; OTU; 1.
DR   Pfam; PF01754; zf-A20; 1.
DR   SMART; SM00259; ZnF_A20; 1.
DR   SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1.
DR   PROSITE; PS50802; OTU; 1.
DR   PROSITE; PS51036; ZF_A20; 1.
DR   Genevisible; Q8TE49; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytoplasm; Hydrolase; Metal-binding;
KW   Methylation; Nucleus; Phosphoprotein; Protease; Reference proteome;
KW   Thiol protease; Ubl conjugation pathway; Zinc; Zinc-finger.
FT   CHAIN           1..926
FT                   /note="OTU domain-containing protein 7A"
FT                   /id="PRO_0000188789"
FT   DOMAIN          199..374
FT                   /note="OTU"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT   ZN_FING         884..919
FT                   /note="A20-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT   REGION          75..99
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          168..410
FT                   /note="TRAF-binding"
FT                   /evidence="ECO:0000250"
FT   REGION          183..449
FT                   /note="Catalytic"
FT                   /evidence="ECO:0000250"
FT   REGION          452..514
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          537..613
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          668..768
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           494..509
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        82..99
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        453..490
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        491..512
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        555..573
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        574..594
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        207
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        210
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        367
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         890
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT   BINDING         895
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT   BINDING         907
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT   BINDING         910
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT   MOD_RES         119
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8R554"
FT   MOD_RES         880
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8R554"
FT   VAR_SEQ         260
FT                   /note="E -> ESGLVYTE (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_011430"
FT   STRAND          13..15
FT                   /evidence="ECO:0007829|PDB:2L2D"
FT   STRAND          22..24
FT                   /evidence="ECO:0007829|PDB:2L2D"
FT   HELIX           27..38
FT                   /evidence="ECO:0007829|PDB:2L2D"
FT   HELIX           42..51
FT                   /evidence="ECO:0007829|PDB:2L2D"
FT   TURN            52..54
FT                   /evidence="ECO:0007829|PDB:2L2D"
FT   HELIX           56..68
FT                   /evidence="ECO:0007829|PDB:2L2D"
FT   STRAND          71..75
FT                   /evidence="ECO:0007829|PDB:2L2D"
SQ   SEQUENCE   926 AA;  100677 MW;  6E4623C2EB2C8058 CRC64;
     MVSSVLPNPT SAECWAALLH DPMTLDMDAV LSDFVRSTGA EPGLARDLLE GKNWDLTAAL
     SDYEQLRQVH TANLPHVFNE GRGPKQPERE PQPGHKVERP CLQRQDDIAQ EKRLSRGISH
     ASSAIVSLAR SHVASECNNE QFPLEMPIYT FQLPDLSVYS EDFRSFIERD LIEQATMVAL
     EQAGRLNWWS TVCTSCKRLL PLATTGDGNC LLHAASLGMW GFHDRDLVLR KALYTMMRTG
     AEREALKRRW RWQQTQQNKE EEWEREWTEL LKLASSEPRT HFSKNGGTGG GVDNSEDPVY
     ESLEEFHVFV LAHILRRPIV VVADTMLRDS GGEAFAPIPF GGIYLPLEVP PNRCHCSPLV
     LAYDQAHFSA LVSMEQRDQQ REQAVIPLTD SEHKLLPLHF AVDPGKDWEW GKDDNDNARL
     AHLILSLEAK LNLLHSYMNV TWIRIPSETR APLAQPESPT ASAGEDVQSL ADSLDSDRDS
     VCSNSNSNNG KNGKDKEKEK QRKEKDKTRA DSVANKLGSF SKTLGIKLKK NMGGLGGLVH
     GKMGRANSAN GKNGDSAERG KEKKAKSRKG SKEESGASAS TSPSEKTTPS PTDKAAGASP
     AEKGGGPRGD AWKYSTDVKL SLNILRAAMQ GERKFIFAGL LLTSHRHQFH EEMIGYYLTS
     AQERFSAEQE QRRRDAATAA AAAAAAAAAT AKRPPRRPET EGVPVPERAS PGPPTQLVLK
     LKERPSPGPA AGRAARAAAG GTASPGGGAR RASASGPVPG RSPPAPARQS VIHVQASGAR
     DEACAPAVGA LRPCATYPQQ NRSLSSQSYS PARAAALRTV NTVESLARAV PGALPGAAGT
     AGAAEHKSQT YTNGFGALRD GLEFADADAP TARSNGECGR GGPGPVQRRC QRENCAFYGR
     AETEHYCSYC YREELRRRRE ARGARP
//