ID   OTUD5_RAT               Reviewed;         566 AA.
AC   Q2YDU3;
DT   20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT   20-FEB-2007, sequence version 2.
DT   24-JAN-2024, entry version 110.
DE   RecName: Full=OTU domain-containing protein 5;
DE            EC=3.4.19.12 {ECO:0000250|UniProtKB:Q96G74};
DE   AltName: Full=Deubiquitinating enzyme A;
DE            Short=DUBA;
GN   Name=Otud5 {ECO:0000312|RGD:1563027};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Placenta;
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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64; SER-165 AND SER-177, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
CC   -!- FUNCTION: Deubiquitinating enzyme that functions as a negative
CC       regulator of the innate immune system. Has peptidase activity towards
CC       'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. Can also cleave
CC       'Lys-11'-linked ubiquitin chains (in vitro). Acts via TRAF3
CC       deubiquitination and subsequent suppression of type I interferon (IFN)
CC       production. Controls neuroectodermal differentiation through cleaving
CC       'Lys-48'-linked ubiquitin chains to counteract degradation of select
CC       chromatin regulators such as ARID1A, HDAC2 and HCF1. Acts as a positive
CC       regulator of mTORC1 and mTORC2 signaling following phosphorylation by
CC       MTOR: acts by mediating deubiquitination of BTRC, leading to its
CC       stability. {ECO:0000250|UniProtKB:Q96G74}.
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:Q96G74};
CC   -!- ACTIVITY REGULATION: Inhibited by N-ethyl-maleimide (NEM).
CC       {ECO:0000250|UniProtKB:Q96G74}.
CC   -!- SUBUNIT: Interacts with TRAF3. {ECO:0000250|UniProtKB:Q96G74}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96G74}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q2YDU3-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q2YDU3-2; Sequence=VSP_023197;
CC   -!- PTM: Phosphorylation at Ser-177 is required for deubiquitinating
CC       activity. Phosphorylation at Ser-323, Ser-332 and Ser-503 by MTOR
CC       promotes its activity. {ECO:0000250|UniProtKB:Q96G74}.
CC   -!- SIMILARITY: Belongs to the peptidase C85 family. {ECO:0000305}.
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DR   EMBL; AABR03119131; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC110054; AAI10055.1; -; mRNA.
DR   RefSeq; NP_001032585.1; NM_001037496.1. [Q2YDU3-2]
DR   AlphaFoldDB; Q2YDU3; -.
DR   SMR; Q2YDU3; -.
DR   STRING; 10116.ENSRNOP00000006233; -.
DR   MEROPS; C85.001; -.
DR   iPTMnet; Q2YDU3; -.
DR   PhosphoSitePlus; Q2YDU3; -.
DR   PaxDb; 10116-ENSRNOP00000039455; -.
DR   GeneID; 363452; -.
DR   KEGG; rno:363452; -.
DR   UCSC; RGD:1563027; rat. [Q2YDU3-1]
DR   AGR; RGD:1563027; -.
DR   CTD; 55593; -.
DR   RGD; 1563027; Otud5.
DR   eggNOG; KOG2605; Eukaryota.
DR   HOGENOM; CLU_021938_0_1_1; -.
DR   InParanoid; Q2YDU3; -.
DR   OrthoDB; 691582at2759; -.
DR   PhylomeDB; Q2YDU3; -.
DR   PRO; PR:Q2YDU3; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR   GO; GO:0101005; F:deubiquitinase activity; ISO:RGD.
DR   GO; GO:1990380; F:K48-linked deubiquitinase activity; ISS:UniProtKB.
DR   GO; GO:0061578; F:K63-linked deubiquitinase activity; ISS:UniProtKB.
DR   GO; GO:0043374; P:CD8-positive, alpha-beta T cell differentiation; ISO:RGD.
DR   GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
DR   GO; GO:0032700; P:negative regulation of interleukin-17 production; ISO:RGD.
DR   GO; GO:0014033; P:neural crest cell differentiation; ISS:UniProtKB.
DR   GO; GO:1904263; P:positive regulation of TORC1 signaling; ISO:RGD.
DR   GO; GO:1904515; P:positive regulation of TORC2 signaling; ISO:RGD.
DR   GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:RGD.
DR   GO; GO:0071108; P:protein K48-linked deubiquitination; ISS:UniProtKB.
DR   GO; GO:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB.
DR   GO; GO:0031647; P:regulation of protein stability; ISO:RGD.
DR   GO; GO:2000316; P:regulation of T-helper 17 type immune response; ISO:RGD.
DR   GO; GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
DR   GO; GO:0072540; P:T-helper 17 cell lineage commitment; ISO:RGD.
DR   CDD; cd22752; OTU_OTUD5-like; 1.
DR   Gene3D; 3.90.70.80; -; 1.
DR   InterPro; IPR003323; OTU_dom.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   PANTHER; PTHR12419; OTU DOMAIN CONTAINING PROTEIN; 1.
DR   PANTHER; PTHR12419:SF4; OTU DOMAIN-CONTAINING PROTEIN 5; 1.
DR   Pfam; PF02338; OTU; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   PROSITE; PS50802; OTU; 1.
DR   Genevisible; Q2YDU3; RN.
PE   1: Evidence at protein level;
KW   Alternative splicing; Hydrolase; Nucleus; Phosphoprotein; Protease;
KW   Reference proteome; Thiol protease; Ubl conjugation pathway.
FT   CHAIN           1..566
FT                   /note="OTU domain-containing protein 5"
FT                   /id="PRO_0000278225"
FT   DOMAIN          213..336
FT                   /note="OTU"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT   REGION          1..117
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          146..175
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          218..224
FT                   /note="Cys-loop"
FT                   /evidence="ECO:0000250"
FT   REGION          273..283
FT                   /note="Variable-loop"
FT                   /evidence="ECO:0000250"
FT   REGION          324..329
FT                   /note="His-loop"
FT                   /evidence="ECO:0000250"
FT   REGION          413..497
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..30
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        93..108
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        415..455
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        221
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        224
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:Q96G74"
FT   ACT_SITE        329
FT                   /evidence="ECO:0000250|UniProtKB:Q96G74"
FT   MOD_RES         64
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         165
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         175
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96G74"
FT   MOD_RES         177
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         195
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96G74"
FT   MOD_RES         323
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96G74"
FT   MOD_RES         332
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96G74"
FT   MOD_RES         370
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96G74"
FT   MOD_RES         447
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96G74"
FT   MOD_RES         502
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96G74"
FT   MOD_RES         503
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96G74"
FT   VAR_SEQ         118..160
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_023197"
SQ   SEQUENCE   566 AA;  60288 MW;  1B49AF4337634A07 CRC64;
     MTILPKKKPP PPDADPANEP PPPGPLPPAP RRGGGVGVGG GGTGVGGGER DRDSGVVGAR
     PRASPPPQGP LPGPPGALHR WALAVPPGAV AGPRPQQASP PPCGGPGGPG GGPGDALGAT
     TAGVGAAGVV VGVGGPVGVG GCCSGPGHSK RRRQAPGVGA VGGASPEREE VGAGYNSEDE
     YEAAAARIEA MDPATVEQQE HWFEKALRDK KGFIIKQMKE DGACLFRAVA DQVYGDQDMH
     EVVRKHCMDY LMKNADYFSN YVTEDFTTYI NRKRKNNCHG NHIEMQAMAE MYNRPVEVYQ
     YSTEPINTFH GIHQNEDEPI RVSYHRNIHY NSVVNPNKAT IGVGLGLPSF KPGFAEQSLM
     KNAIKTSEES WIEQQMLEDK KRATDWEATN EAIEEQVARE SYLQWLRDQE KQARQVRGPS
     QPRKASATCS SATAAASSGL EEWTSRSPRQ RSSASSPEHP ELHAELGIKP PSPGTVLALA
     KPPSPCAPGT SSQFSAGADR ATSPLVSLYP ALECRALIQQ MSPSAFGLND WDDDEILASV
     LAVSQQEYLD SMKKNKVHRD PPPDKS
//