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 24-JAN-2024, entry version 118. 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|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 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 -!- 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. Phosphorylation at Ser-323, Ser-332 and Ser-503 by MTOR CC promotes its 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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.ENSMUSP00000111330; -. DR MEROPS; C85.001; -. DR iPTMnet; Q3U2S4; -. DR PhosphoSitePlus; Q3U2S4; -. DR EPD; Q3U2S4; -. DR jPOST; Q3U2S4; -. DR MaxQB; Q3U2S4; -. DR PaxDb; 10090-ENSMUSP00000033494; -. DR ProteomicsDB; 294134; -. [Q3U2S4-1] DR ProteomicsDB; 294135; -. [Q3U2S4-2] DR Pumba; Q3U2S4; -. DR Antibodypedia; 409; 197 antibodies from 33 providers. DR DNASU; 54644; -. DR Ensembl; ENSMUST00000033494.16; ENSMUSP00000033494.10; ENSMUSG00000031154.16. [Q3U2S4-1] DR Ensembl; ENSMUST00000115668.10; ENSMUSP00000111332.4; ENSMUSG00000031154.16. [Q3U2S4-2] DR GeneID; 54644; -. DR KEGG; mmu:54644; -. DR UCSC; uc009smu.2; mouse. [Q3U2S4-1] DR UCSC; uc009smv.2; mouse. [Q3U2S4-2] DR AGR; MGI:1859615; -. DR CTD; 55593; -. DR MGI; MGI:1859615; Otud5. DR VEuPathDB; HostDB:ENSMUSG00000031154; -. DR eggNOG; KOG2605; Eukaryota. DR GeneTree; ENSGT00940000158963; -. DR InParanoid; Q3U2S4; -. DR OMA; DSHQHTH; -. DR OrthoDB; 691582at2759; -. DR PhylomeDB; Q3U2S4; -. DR TreeFam; TF326812; -. DR BioGRID-ORCS; 54644; 23 hits in 78 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 260 other cell types or tissues. DR ExpressionAtlas; Q3U2S4; baseline and differential. 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: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; 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: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 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; Q3U2S4; MM. 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|UniProtKB:Q96G74" FT ACT_SITE 329 FT /evidence="ECO:0000250|UniProtKB:Q96G74" 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 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: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 //