OTUD5_MOUSE
ID OTUD5_MOUSE Reviewed; 566 AA.
AC Q3U2S4; Q3UE33; Q91YL5; Q9CV50; Q9JIG6;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=OTU domain-containing protein 5;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme A;
DE Short=DUBA;
GN Name=Otud5 {ECO:0000312|MGI:MGI:1859615}; Synonyms=DXImx46e, Sfc7;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, Spleen, and Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 191-566 (ISOFORMS 1/2).
RX PubMed=10857745; DOI=10.1006/geno.2000.6173;
RA Means G.D., Toy D.Y., Baum P.R., Derry J.M.J.;
RT "A transcript map of a 2-Mb BAC contig in the proximal portion of the mouse
RT X chromosome and regional mapping of the scurfy mutation.";
RL Genomics 65:213-223(2000).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165; TYR-175 AND SER-177, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=33523931; DOI=10.1126/sciadv.abe2116;
RG Undiagnosed Diseases Network;
RA Beck D.B., Basar M.A., Asmar A.J., Thompson J.J., Oda H., Uehara D.T.,
RA Saida K., Pajusalu S., Talvik I., D'Souza P., Bodurtha J., Mu W.,
RA Baranano K.W., Miyake N., Wang R., Kempers M., Tamada T., Nishimura Y.,
RA Okada S., Kosho T., Dale R., Mitra A., Macnamara E., Matsumoto N.,
RA Inazawa J., Walkiewicz M., Ounap K., Tifft C.J., Aksentijevich I.,
RA Kastner D.L., Rocha P.P., Werner A.;
RT "Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway
RT intolerant to genomic variation.";
RL Sci. Adv. 7:0-0(2021).
CC -!- FUNCTION: Deubiquitinating enzyme that functions as negative regulator
CC of the innate immune system. Acts via TRAF3 deubiquitination and
CC subsequent suppression of type I interferon (IFN) production. Has
CC peptidase activity towards 'Lys-48'- and 'Lys-63'-linked polyubiquitin
CC chains. Can also cleave 'Lys-11'-linked ubiquitin chains (in vitro).
CC Controls neuroectodermal differentiation through cleaving 'Lys-48'-
CC linked ubiquitin chains to counteract degradation of select chromatin
CC regulators such as ARID1A, HDAC2 and HCF1.
CC {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}.
CC -!- SUBUNIT: Interacts with TRAF3. {ECO:0000250|UniProtKB:Q96G74}.
CC -!- INTERACTION:
CC Q3U2S4-1; Q80TP3: Ubr5; NbExp=2; IntAct=EBI-16131219, EBI-2553642;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96G74}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3U2S4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3U2S4-2; Sequence=VSP_023196;
CC -!- PTM: Phosphorylation at Ser-177 is required for deubiquitinating
CC activity. {ECO:0000250|UniProtKB:Q96G74}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice die at the embryo stage.
CC {ECO:0000269|PubMed:33523931}.
CC -!- SIMILARITY: Belongs to the peptidase C85 family. {ECO:0000305}.
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DR EMBL; AK009620; BAB26396.1; -; mRNA.
DR EMBL; AK149777; BAE29078.1; -; mRNA.
DR EMBL; AK155131; BAE33066.1; -; mRNA.
DR EMBL; AK171874; BAE42712.1; -; mRNA.
DR EMBL; BC016529; AAH16529.1; -; mRNA.
DR EMBL; BC051111; AAH51111.1; -; mRNA.
DR EMBL; AF229642; AAF66952.1; -; mRNA.
DR EMBL; AL671978; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL671995; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS29975.1; -. [Q3U2S4-1]
DR CCDS; CCDS72335.1; -. [Q3U2S4-2]
DR RefSeq; NP_001277466.1; NM_001290537.1. [Q3U2S4-2]
DR RefSeq; NP_613070.2; NM_138604.3. [Q3U2S4-1]
DR AlphaFoldDB; Q3U2S4; -.
DR SMR; Q3U2S4; -.
DR BioGRID; 207706; 11.
DR DIP; DIP-61498N; -.
DR IntAct; Q3U2S4; 10.
DR STRING; 10090.ENSMUSP00000033494; -.
DR MEROPS; C85.001; -.
DR iPTMnet; Q3U2S4; -.
DR PhosphoSitePlus; Q3U2S4; -.
DR EPD; Q3U2S4; -.
DR jPOST; Q3U2S4; -.
DR MaxQB; Q3U2S4; -.
DR PaxDb; Q3U2S4; -.
DR PRIDE; Q3U2S4; -.
DR ProteomicsDB; 294134; -. [Q3U2S4-1]
DR ProteomicsDB; 294135; -. [Q3U2S4-2]
DR Antibodypedia; 409; 177 antibodies from 33 providers.
DR DNASU; 54644; -.
DR Ensembl; ENSMUST00000033494; ENSMUSP00000033494; ENSMUSG00000031154. [Q3U2S4-1]
DR Ensembl; ENSMUST00000115668; ENSMUSP00000111332; ENSMUSG00000031154. [Q3U2S4-2]
DR GeneID; 54644; -.
DR KEGG; mmu:54644; -.
DR UCSC; uc009smu.2; mouse. [Q3U2S4-1]
DR UCSC; uc009smv.2; mouse. [Q3U2S4-2]
DR CTD; 55593; -.
DR MGI; MGI:1859615; Otud5.
DR VEuPathDB; HostDB:ENSMUSG00000031154; -.
DR eggNOG; KOG2605; Eukaryota.
DR GeneTree; ENSGT00940000158963; -.
DR InParanoid; Q3U2S4; -.
DR OMA; REDKHFE; -.
DR PhylomeDB; Q3U2S4; -.
DR TreeFam; TF326812; -.
DR BioGRID-ORCS; 54644; 22 hits in 73 CRISPR screens.
DR ChiTaRS; Otud5; mouse.
DR PRO; PR:Q3U2S4; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q3U2S4; protein.
DR Bgee; ENSMUSG00000031154; Expressed in granulocyte and 256 other tissues.
DR ExpressionAtlas; Q3U2S4; baseline and differential.
DR Genevisible; Q3U2S4; MM.
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:MGI.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0061578; F:Lys63-specific deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0043374; P:CD8-positive, alpha-beta T cell differentiation; IMP:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IMP:MGI.
DR GO; GO:0014033; P:neural crest cell differentiation; ISS:UniProtKB.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; ISO:MGI.
DR GO; GO:1904515; P:positive regulation of TORC2 signaling; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:MGI.
DR GO; GO:0016579; P:protein deubiquitination; ISO:MGI.
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; IMP:MGI.
DR GO; GO:2000316; P:regulation of T-helper 17 type immune response; IMP:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0072540; P:T-helper 17 cell lineage commitment; IMP:MGI.
DR InterPro; IPR031084; OTU5.
DR InterPro; IPR003323; OTU_dom.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR PANTHER; PTHR12419:SF4; PTHR12419:SF4; 1.
DR Pfam; PF02338; OTU; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50802; OTU; 1.
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_0000278224"
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 145..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..499
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"
FT ACT_SITE 329
FT /evidence="ECO:0000250"
FT MOD_RES 64
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96G74"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 175
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 177
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
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 VAR_SEQ 118..160
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023196"
FT CONFLICT 199
FT /note="Missing (in Ref. 3; AAF66952)"
FT /evidence="ECO:0000305"
FT CONFLICT 306
FT /note="I -> F (in Ref. 3; AAF66952)"
FT /evidence="ECO:0000305"
FT CONFLICT 308
FT /note="T -> I (in Ref. 1; BAE33066)"
FT /evidence="ECO:0000305"
FT CONFLICT 436
FT /note="A -> V (in Ref. 3; AAF66952)"
FT /evidence="ECO:0000305"
FT CONFLICT 526
FT /note="F -> FA (in Ref. 1; BAE33066)"
FT /evidence="ECO:0000305"
FT CONFLICT 532
FT /note="D -> Y (in Ref. 1; BAE29078)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 566 AA; 60306 MW; 89AAD0FF58792EFB CRC64;
MTILPKKKPP PPDADPANEP PPPGPLPPAP RRGAGVGVGG GGTGVGGGER DRDSGVVGAR
PRASPPPQGP LPGPPGALHR WALAVPPGAV AGPRPQQASP PPCGGPGGPG GGPGDALGAT
TAGVGAAGVV VGVGGTVGVG 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 SSQFSAGGDR ATSPLVSLYP ALECRALIQQ MSPSAFGLND WDDDEILASV
LAVSQQEYLD SMKKNKVHRE PPPDKS
