Full text data of OTUD5
OTUD5
[Confidence: low (only semi-automatic identification from reviews)]
OTU domain-containing protein 5; 3.4.19.12 (Deubiquitinating enzyme A; DUBA)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
OTU domain-containing protein 5; 3.4.19.12 (Deubiquitinating enzyme A; DUBA)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q96G74
ID OTUD5_HUMAN Reviewed; 571 AA.
AC Q96G74; B4DGG7; Q4KMN9; Q8N6T5; Q9H650; Q9H9U0; Q9NT65;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-DEC-2001, sequence version 1.
DT 22-JAN-2014, entry version 96.
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;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 176-571 (ISOFORM 2), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 253-571 (ISOFORM 1).
RC TISSUE=Brain, and Small intestine;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Kidney, and Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 140-571 (ISOFORM 2).
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH TRAF3, AND MUTAGENESIS
RP OF CYS-224; LEU-542 AND SER-549.
RX PubMed=17991829; DOI=10.1126/science.1145918;
RA Kayagaki N., Phung Q., Chan S., Chaudhari R., Quan C., O'Rourke K.M.,
RA Eby M., Pietras E., Cheng G., Bazan J.F., Zhang Z., Arnott D.,
RA Dixit V.M.;
RT "DUBA: a deubiquitinase that regulates type I interferon production.";
RL Science 318:1628-1632(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165; SER-177 AND
RP SER-452, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165 AND SER-177, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64 AND SER-165, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP FUNCTION.
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.,
RA Freund S.M., Ovaa H., Komander D.;
RT "OTU deubiquitinases reveal mechanisms of linkage specificity and
RT enable ubiquitin chain restriction analysis.";
RL Cell 154:169-184(2013).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 172-339.
RG Structural genomics consortium (SGC);
RT "The catalytic domain of human OTUD5.";
RL Submitted (DEC-2010) to the PDB data bank.
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 172-351 IN COMPLEX WITH
RP UBIQUITIN, CATALYTIC ACTIVITY, FUNCTION, INDUCTION, PHOSPHORYLATION AT
RP SER-64; SER-165; TYR-175; SER-177 AND THR-507, MUTAGENESIS OF SER-177
RP AND CYS-224, ACTIVE SITE, AND MASS SPECTROMETRY.
RX PubMed=22245969; DOI=10.1038/nsmb.2206;
RA Huang O.W., Ma X., Yin J., Flinders J., Maurer T., Kayagaki N.,
RA Phung Q., Bosanac I., Arnott D., Dixit V.M., Hymowitz S.G.,
RA Starovasnik M.A., Cochran A.G.;
RT "Phosphorylation-dependent activity of the deubiquitinase DUBA.";
RL Nat. Struct. Mol. Biol. 19:171-175(2012).
CC -!- FUNCTION: Deubiquitinating enzyme that functions as negative
CC regulator of the innate immune system. Acts via TRAF3
CC deubiquitination and subsequent suppression of type I interferon
CC (IFN) production. Has peptidase activity towards 'Lys-48'- and
CC 'Lys-63'-linked polyubiquitin chains. Can also cleave 'Lys-11'-
CC linked ubiquitin chains (in vitro).
CC -!- CATALYTIC ACTIVITY: Thiol-dependent hydrolysis of ester,
CC thioester, amide, peptide and isopeptide bonds formed by the C-
CC terminal Gly of ubiquitin (a 76-residue protein attached to
CC proteins as an intracellular targeting signal).
CC -!- ENZYME REGULATION: Inhibited by N-ethyl-maleimide (NEM).
CC -!- SUBUNIT: Interacts with TRAF3.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q96G74-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96G74-2; Sequence=VSP_023195, VSP_023192;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q96G74-4; Sequence=VSP_045185, VSP_023192;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q96G74-3; Sequence=VSP_023192, VSP_023193, VSP_023194;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in various tissues, including the
CC liver and placenta, as well as in peripheral blood leukocytes.
CC -!- INDUCTION: Up-regulated by bacterial lipopolysaccharide (LPS) in
CC bone marrow-derived macrophages.
CC -!- PTM: Phosphorylation at Ser-177 is required for deubiquitinating
CC activity.
CC -!- SIMILARITY: Belongs to the peptidase C85 family.
CC -!- SIMILARITY: Contains 1 OTU domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14131.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAB15416.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AK294590; BAG57778.1; -; mRNA.
DR EMBL; AF207550; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009917; AAH09917.1; -; mRNA.
DR EMBL; BC028225; AAH28225.1; -; mRNA.
DR EMBL; BC098440; AAH98440.1; -; mRNA.
DR EMBL; AL137509; CAB70778.1; -; mRNA.
DR EMBL; AK022612; BAB14131.1; ALT_INIT; mRNA.
DR EMBL; AK026260; BAB15416.1; ALT_INIT; mRNA.
DR PIR; T46265; T46265.
DR RefSeq; NP_001129629.1; NM_001136157.1.
DR RefSeq; NP_001129630.1; NM_001136158.1.
DR RefSeq; NP_001129631.1; NM_001136159.1.
DR RefSeq; NP_060072.1; NM_017602.3.
DR RefSeq; XP_005272680.1; XM_005272623.1.
DR RefSeq; XP_005278098.1; XM_005278041.1.
DR UniGene; Hs.496098; -.
DR PDB; 3PFY; X-ray; 1.70 A; A=172-339.
DR PDB; 3TMO; X-ray; 2.20 A; A=172-351.
DR PDB; 3TMP; X-ray; 1.91 A; A/C/E/G=172-351.
DR PDBsum; 3PFY; -.
DR PDBsum; 3TMO; -.
DR PDBsum; 3TMP; -.
DR ProteinModelPortal; Q96G74; -.
DR SMR; Q96G74; 173-341.
DR IntAct; Q96G74; 16.
DR MINT; MINT-1408843; -.
DR STRING; 9606.ENSP00000156084; -.
DR MEROPS; C85.001; -.
DR PhosphoSite; Q96G74; -.
DR DMDM; 74731791; -.
DR PaxDb; Q96G74; -.
DR PRIDE; Q96G74; -.
DR Ensembl; ENST00000156084; ENSP00000156084; ENSG00000068308.
DR Ensembl; ENST00000428668; ENSP00000401629; ENSG00000068308.
DR Ensembl; ENST00000594822; ENSP00000472254; ENSG00000267983.
DR Ensembl; ENST00000597676; ENSP00000471884; ENSG00000267983.
DR GeneID; 55593; -.
DR KEGG; hsa:55593; -.
DR UCSC; uc011mmp.2; human.
DR CTD; 55593; -.
DR GeneCards; GC0XM048779; -.
DR HGNC; HGNC:25402; OTUD5.
DR HPA; HPA017375; -.
DR MIM; 300713; gene.
DR neXtProt; NX_Q96G74; -.
DR PharmGKB; PA142671217; -.
DR eggNOG; NOG286112; -.
DR HOGENOM; HOG000231360; -.
DR HOVERGEN; HBG060214; -.
DR InParanoid; Q96G74; -.
DR KO; K12655; -.
DR OMA; WEDDEIL; -.
DR PhylomeDB; Q96G74; -.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; OTUD5; human.
DR GenomeRNAi; 55593; -.
DR NextBio; 60126; -.
DR PRO; PR:Q96G74; -.
DR ArrayExpress; Q96G74; -.
DR Bgee; Q96G74; -.
DR CleanEx; HS_OTUD5; -.
DR Genevestigator; Q96G74; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004843; F:deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0032480; P:negative regulation of type I interferon production; TAS:Reactome.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:UniProtKB.
DR InterPro; IPR003323; OTU.
DR Pfam; PF02338; OTU; 1.
DR PROSITE; PS50802; OTU; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Hydrolase;
KW Phosphoprotein; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation pathway.
FT CHAIN 1 571 OTU domain-containing protein 5.
FT /FTId=PRO_0000278223.
FT DOMAIN 213 341 OTU.
FT REGION 218 224 Cys-loop (By similarity).
FT REGION 273 283 Variable-loop (By similarity).
FT REGION 329 334 His-loop (By similarity).
FT COMPBIAS 5 113 Pro-rich.
FT COMPBIAS 33 174 Gly-rich.
FT ACT_SITE 221 221 Potential.
FT ACT_SITE 224 224 Nucleophile.
FT ACT_SITE 334 334 Probable.
FT MOD_RES 64 64 Phosphoserine.
FT MOD_RES 165 165 Phosphoserine.
FT MOD_RES 175 175 Phosphotyrosine.
FT MOD_RES 177 177 Phosphoserine.
FT MOD_RES 452 452 Phosphoserine.
FT MOD_RES 507 507 Phosphothreonine.
FT VAR_SEQ 1 217 Missing (in isoform 4).
FT /FTId=VSP_045185.
FT VAR_SEQ 17 40 Missing (in isoform 2).
FT /FTId=VSP_023195.
FT VAR_SEQ 304 308 Missing (in isoform 2, isoform 3 and
FT isoform 4).
FT /FTId=VSP_023192.
FT VAR_SEQ 563 566 HRDP -> PCRC (in isoform 3).
FT /FTId=VSP_023193.
FT VAR_SEQ 567 571 Missing (in isoform 3).
FT /FTId=VSP_023194.
FT MUTAGEN 177 177 S->D,E: Loss of deubiquitinase activity.
FT Abolishes activation by protein kinases.
FT MUTAGEN 224 224 C->S: Loss of deubiquitinase activity.
FT Loss of suppression of IFN production.
FT MUTAGEN 542 542 L->A: Loss of 'K-48'- and 'K-63'-linked
FT polyubiquitin chain binding. Partial loss
FT of TRAF3 deubiquitination; when
FT associated with A-549.
FT MUTAGEN 549 549 S->A: Loss of 'K-48'- and 'K-63'-linked
FT polyubiquitin chain binding. Partial loss
FT of TRAF3 deubiquitination; when
FT associated with A-542.
FT HELIX 178 180
FT HELIX 181 186
FT HELIX 193 211
FT STRAND 214 216
FT HELIX 224 234
FT HELIX 237 239
FT HELIX 240 253
FT HELIX 255 258
FT HELIX 259 261
FT HELIX 266 273
FT HELIX 282 292
FT STRAND 296 301
FT STRAND 303 305
FT STRAND 311 314
FT STRAND 325 330
FT TURN 331 333
FT STRAND 334 339
SQ SEQUENCE 571 AA; 60626 MW; F4B2B385B84ABC46 CRC64;
MTILPKKKPP PPDADPANEP PPPGPMPPAP RRGGGVGVGG GGTGVGGGDR DRDSGVVGAR
PRASPPPQGP LPGPPGALHR WALAVPPGAV AGPRPQQASP PPCGGPGGPG GGPGDALGAA
AAGVGAAGVV VGVGGAVGVG GCCSGPGHSK RRRQAPGVGA VGGGSPEREE VGAGYNSEDE
YEAAAARIEA MDPATVEQQE HWFEKALRDK KGFIIKQMKE DGACLFRAVA DQVYGDQDMH
EVVRKHCMDY LMKNADYFSN YVTEDFTTYI NRKRKNNCHG NHIEMQAMAE MYNRPVEVYQ
YSTGTSAVEP INTFHGIHQN EDEPIRVSYH RNIHYNSVVN PNKATIGVGL GLPSFKPGFA
EQSLMKNAIK TSEESWIEQQ MLEDKKRATD WEATNEAIEE QVARESYLQW LRDQEKQARQ
VRGPSQPRKA SATCSSATAA ASSGLEEWTS RSPRQRSSAS SPEHPELHAE LGMKPPSPGT
VLALAKPPSP CAPGTSSQFS AGADRATSPL VSLYPALECR ALIQQMSPSA FGLNDWDDDE
ILASVLAVSQ QEYLDSMKKN KVHRDPPPDK S
//
ID OTUD5_HUMAN Reviewed; 571 AA.
AC Q96G74; B4DGG7; Q4KMN9; Q8N6T5; Q9H650; Q9H9U0; Q9NT65;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-DEC-2001, sequence version 1.
DT 22-JAN-2014, entry version 96.
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;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 176-571 (ISOFORM 2), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 253-571 (ISOFORM 1).
RC TISSUE=Brain, and Small intestine;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Kidney, and Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 140-571 (ISOFORM 2).
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH TRAF3, AND MUTAGENESIS
RP OF CYS-224; LEU-542 AND SER-549.
RX PubMed=17991829; DOI=10.1126/science.1145918;
RA Kayagaki N., Phung Q., Chan S., Chaudhari R., Quan C., O'Rourke K.M.,
RA Eby M., Pietras E., Cheng G., Bazan J.F., Zhang Z., Arnott D.,
RA Dixit V.M.;
RT "DUBA: a deubiquitinase that regulates type I interferon production.";
RL Science 318:1628-1632(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165; SER-177 AND
RP SER-452, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165 AND SER-177, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64 AND SER-165, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP FUNCTION.
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.,
RA Freund S.M., Ovaa H., Komander D.;
RT "OTU deubiquitinases reveal mechanisms of linkage specificity and
RT enable ubiquitin chain restriction analysis.";
RL Cell 154:169-184(2013).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 172-339.
RG Structural genomics consortium (SGC);
RT "The catalytic domain of human OTUD5.";
RL Submitted (DEC-2010) to the PDB data bank.
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 172-351 IN COMPLEX WITH
RP UBIQUITIN, CATALYTIC ACTIVITY, FUNCTION, INDUCTION, PHOSPHORYLATION AT
RP SER-64; SER-165; TYR-175; SER-177 AND THR-507, MUTAGENESIS OF SER-177
RP AND CYS-224, ACTIVE SITE, AND MASS SPECTROMETRY.
RX PubMed=22245969; DOI=10.1038/nsmb.2206;
RA Huang O.W., Ma X., Yin J., Flinders J., Maurer T., Kayagaki N.,
RA Phung Q., Bosanac I., Arnott D., Dixit V.M., Hymowitz S.G.,
RA Starovasnik M.A., Cochran A.G.;
RT "Phosphorylation-dependent activity of the deubiquitinase DUBA.";
RL Nat. Struct. Mol. Biol. 19:171-175(2012).
CC -!- FUNCTION: Deubiquitinating enzyme that functions as negative
CC regulator of the innate immune system. Acts via TRAF3
CC deubiquitination and subsequent suppression of type I interferon
CC (IFN) production. Has peptidase activity towards 'Lys-48'- and
CC 'Lys-63'-linked polyubiquitin chains. Can also cleave 'Lys-11'-
CC linked ubiquitin chains (in vitro).
CC -!- CATALYTIC ACTIVITY: Thiol-dependent hydrolysis of ester,
CC thioester, amide, peptide and isopeptide bonds formed by the C-
CC terminal Gly of ubiquitin (a 76-residue protein attached to
CC proteins as an intracellular targeting signal).
CC -!- ENZYME REGULATION: Inhibited by N-ethyl-maleimide (NEM).
CC -!- SUBUNIT: Interacts with TRAF3.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q96G74-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96G74-2; Sequence=VSP_023195, VSP_023192;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q96G74-4; Sequence=VSP_045185, VSP_023192;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q96G74-3; Sequence=VSP_023192, VSP_023193, VSP_023194;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in various tissues, including the
CC liver and placenta, as well as in peripheral blood leukocytes.
CC -!- INDUCTION: Up-regulated by bacterial lipopolysaccharide (LPS) in
CC bone marrow-derived macrophages.
CC -!- PTM: Phosphorylation at Ser-177 is required for deubiquitinating
CC activity.
CC -!- SIMILARITY: Belongs to the peptidase C85 family.
CC -!- SIMILARITY: Contains 1 OTU domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14131.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAB15416.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AK294590; BAG57778.1; -; mRNA.
DR EMBL; AF207550; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009917; AAH09917.1; -; mRNA.
DR EMBL; BC028225; AAH28225.1; -; mRNA.
DR EMBL; BC098440; AAH98440.1; -; mRNA.
DR EMBL; AL137509; CAB70778.1; -; mRNA.
DR EMBL; AK022612; BAB14131.1; ALT_INIT; mRNA.
DR EMBL; AK026260; BAB15416.1; ALT_INIT; mRNA.
DR PIR; T46265; T46265.
DR RefSeq; NP_001129629.1; NM_001136157.1.
DR RefSeq; NP_001129630.1; NM_001136158.1.
DR RefSeq; NP_001129631.1; NM_001136159.1.
DR RefSeq; NP_060072.1; NM_017602.3.
DR RefSeq; XP_005272680.1; XM_005272623.1.
DR RefSeq; XP_005278098.1; XM_005278041.1.
DR UniGene; Hs.496098; -.
DR PDB; 3PFY; X-ray; 1.70 A; A=172-339.
DR PDB; 3TMO; X-ray; 2.20 A; A=172-351.
DR PDB; 3TMP; X-ray; 1.91 A; A/C/E/G=172-351.
DR PDBsum; 3PFY; -.
DR PDBsum; 3TMO; -.
DR PDBsum; 3TMP; -.
DR ProteinModelPortal; Q96G74; -.
DR SMR; Q96G74; 173-341.
DR IntAct; Q96G74; 16.
DR MINT; MINT-1408843; -.
DR STRING; 9606.ENSP00000156084; -.
DR MEROPS; C85.001; -.
DR PhosphoSite; Q96G74; -.
DR DMDM; 74731791; -.
DR PaxDb; Q96G74; -.
DR PRIDE; Q96G74; -.
DR Ensembl; ENST00000156084; ENSP00000156084; ENSG00000068308.
DR Ensembl; ENST00000428668; ENSP00000401629; ENSG00000068308.
DR Ensembl; ENST00000594822; ENSP00000472254; ENSG00000267983.
DR Ensembl; ENST00000597676; ENSP00000471884; ENSG00000267983.
DR GeneID; 55593; -.
DR KEGG; hsa:55593; -.
DR UCSC; uc011mmp.2; human.
DR CTD; 55593; -.
DR GeneCards; GC0XM048779; -.
DR HGNC; HGNC:25402; OTUD5.
DR HPA; HPA017375; -.
DR MIM; 300713; gene.
DR neXtProt; NX_Q96G74; -.
DR PharmGKB; PA142671217; -.
DR eggNOG; NOG286112; -.
DR HOGENOM; HOG000231360; -.
DR HOVERGEN; HBG060214; -.
DR InParanoid; Q96G74; -.
DR KO; K12655; -.
DR OMA; WEDDEIL; -.
DR PhylomeDB; Q96G74; -.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; OTUD5; human.
DR GenomeRNAi; 55593; -.
DR NextBio; 60126; -.
DR PRO; PR:Q96G74; -.
DR ArrayExpress; Q96G74; -.
DR Bgee; Q96G74; -.
DR CleanEx; HS_OTUD5; -.
DR Genevestigator; Q96G74; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004843; F:deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0032480; P:negative regulation of type I interferon production; TAS:Reactome.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:UniProtKB.
DR InterPro; IPR003323; OTU.
DR Pfam; PF02338; OTU; 1.
DR PROSITE; PS50802; OTU; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Hydrolase;
KW Phosphoprotein; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation pathway.
FT CHAIN 1 571 OTU domain-containing protein 5.
FT /FTId=PRO_0000278223.
FT DOMAIN 213 341 OTU.
FT REGION 218 224 Cys-loop (By similarity).
FT REGION 273 283 Variable-loop (By similarity).
FT REGION 329 334 His-loop (By similarity).
FT COMPBIAS 5 113 Pro-rich.
FT COMPBIAS 33 174 Gly-rich.
FT ACT_SITE 221 221 Potential.
FT ACT_SITE 224 224 Nucleophile.
FT ACT_SITE 334 334 Probable.
FT MOD_RES 64 64 Phosphoserine.
FT MOD_RES 165 165 Phosphoserine.
FT MOD_RES 175 175 Phosphotyrosine.
FT MOD_RES 177 177 Phosphoserine.
FT MOD_RES 452 452 Phosphoserine.
FT MOD_RES 507 507 Phosphothreonine.
FT VAR_SEQ 1 217 Missing (in isoform 4).
FT /FTId=VSP_045185.
FT VAR_SEQ 17 40 Missing (in isoform 2).
FT /FTId=VSP_023195.
FT VAR_SEQ 304 308 Missing (in isoform 2, isoform 3 and
FT isoform 4).
FT /FTId=VSP_023192.
FT VAR_SEQ 563 566 HRDP -> PCRC (in isoform 3).
FT /FTId=VSP_023193.
FT VAR_SEQ 567 571 Missing (in isoform 3).
FT /FTId=VSP_023194.
FT MUTAGEN 177 177 S->D,E: Loss of deubiquitinase activity.
FT Abolishes activation by protein kinases.
FT MUTAGEN 224 224 C->S: Loss of deubiquitinase activity.
FT Loss of suppression of IFN production.
FT MUTAGEN 542 542 L->A: Loss of 'K-48'- and 'K-63'-linked
FT polyubiquitin chain binding. Partial loss
FT of TRAF3 deubiquitination; when
FT associated with A-549.
FT MUTAGEN 549 549 S->A: Loss of 'K-48'- and 'K-63'-linked
FT polyubiquitin chain binding. Partial loss
FT of TRAF3 deubiquitination; when
FT associated with A-542.
FT HELIX 178 180
FT HELIX 181 186
FT HELIX 193 211
FT STRAND 214 216
FT HELIX 224 234
FT HELIX 237 239
FT HELIX 240 253
FT HELIX 255 258
FT HELIX 259 261
FT HELIX 266 273
FT HELIX 282 292
FT STRAND 296 301
FT STRAND 303 305
FT STRAND 311 314
FT STRAND 325 330
FT TURN 331 333
FT STRAND 334 339
SQ SEQUENCE 571 AA; 60626 MW; F4B2B385B84ABC46 CRC64;
MTILPKKKPP PPDADPANEP PPPGPMPPAP RRGGGVGVGG GGTGVGGGDR DRDSGVVGAR
PRASPPPQGP LPGPPGALHR WALAVPPGAV AGPRPQQASP PPCGGPGGPG GGPGDALGAA
AAGVGAAGVV VGVGGAVGVG GCCSGPGHSK RRRQAPGVGA VGGGSPEREE VGAGYNSEDE
YEAAAARIEA MDPATVEQQE HWFEKALRDK KGFIIKQMKE DGACLFRAVA DQVYGDQDMH
EVVRKHCMDY LMKNADYFSN YVTEDFTTYI NRKRKNNCHG NHIEMQAMAE MYNRPVEVYQ
YSTGTSAVEP INTFHGIHQN EDEPIRVSYH RNIHYNSVVN PNKATIGVGL GLPSFKPGFA
EQSLMKNAIK TSEESWIEQQ MLEDKKRATD WEATNEAIEE QVARESYLQW LRDQEKQARQ
VRGPSQPRKA SATCSSATAA ASSGLEEWTS RSPRQRSSAS SPEHPELHAE LGMKPPSPGT
VLALAKPPSP CAPGTSSQFS AGADRATSPL VSLYPALECR ALIQQMSPSA FGLNDWDDDE
ILASVLAVSQ QEYLDSMKKN KVHRDPPPDK S
//
MIM
300713
*RECORD*
*FIELD* NO
300713
*FIELD* TI
*300713 OTU DOMAIN-CONTAINING PROTEIN 5; OTUD5
;;DUBA
*FIELD* TX
Deubiquitinating enzymes (DUBs; see 603478) are proteases that
read morespecifically cleave ubiquitin (191339) linkages, negating the action of
ubiquitin ligases. DUBA belongs to a DUB subfamily characterized by an
ovarian tumor (OTU) domain.
CLONING
Kayagaki et al. (2007) identified deubiquitinating enzyme A (DUBA) in a
small interfering RNA (siRNA)-based screen as a regulator of type I
interferon (e.g., 147660) production. In addition to an OTU domain, DUBA
contains a ubiquitin action motif (UIM) at its carboxy terminus. The
2,759-basepair mRNA contains an open reading frame (ORF) predicting a
571-amino acid protein.
GENE FUNCTION
Kayagaki et al. (2007) demonstrated that reduction of DUBA augmented the
pattern recognition receptor (PRR)-induced type I interferon response in
transfected HEK293 cells, whereas ectopic expression of DUBA had the
converse effect. DUBA bound tumor necrosis factor receptor-associated
factor-3 (TRAF3; 601896), an adaptor protein essential for type I
interferon response. TRAF3 is an E3 ubiquitin ligase that preferentially
assembled lys63-linked polyubiquitin chains in cotransfection assays.
DUBA selectively cleaved the lys63-linked polyubiquitin chains on TRAF3,
resulting in its dissociation from the downstream signaling complex
containing TANK-binding kinase-1 (604834). A discrete ubiquitin
interaction motif within DUBA was required for efficient
deubiquitination of TRAF3 and optimal suppression of type I interferon.
Kayagaki et al. (2007) concluded that their data identified DUBA as a
negative regulator of innate immune responses.
MAPPING
The OTUD5 gene maps to chromosome Xp11.23 (Kayagaki et al., 2007).
*FIELD* RF
1. Kayagaki, N.; Phung, Q.; Chan, S.; Chaudhari, R.; Quan, C.; O'Rourke,
K. M.; Eby, M.; Pietras, E.; Cheng, G.; Bazan, J. F.; Zhang, Z.; Arnott,
D.; Dixit, V. M.: DUBA: a deubiquitinase that regulates type I interferon
production. Science 318: 1628-1632, 2007.
*FIELD* CD
Ada Hamosh: 5/6/2008
*FIELD* ED
alopez: 05/07/2008
alopez: 5/7/2008
alopez: 5/6/2008
*RECORD*
*FIELD* NO
300713
*FIELD* TI
*300713 OTU DOMAIN-CONTAINING PROTEIN 5; OTUD5
;;DUBA
*FIELD* TX
Deubiquitinating enzymes (DUBs; see 603478) are proteases that
read morespecifically cleave ubiquitin (191339) linkages, negating the action of
ubiquitin ligases. DUBA belongs to a DUB subfamily characterized by an
ovarian tumor (OTU) domain.
CLONING
Kayagaki et al. (2007) identified deubiquitinating enzyme A (DUBA) in a
small interfering RNA (siRNA)-based screen as a regulator of type I
interferon (e.g., 147660) production. In addition to an OTU domain, DUBA
contains a ubiquitin action motif (UIM) at its carboxy terminus. The
2,759-basepair mRNA contains an open reading frame (ORF) predicting a
571-amino acid protein.
GENE FUNCTION
Kayagaki et al. (2007) demonstrated that reduction of DUBA augmented the
pattern recognition receptor (PRR)-induced type I interferon response in
transfected HEK293 cells, whereas ectopic expression of DUBA had the
converse effect. DUBA bound tumor necrosis factor receptor-associated
factor-3 (TRAF3; 601896), an adaptor protein essential for type I
interferon response. TRAF3 is an E3 ubiquitin ligase that preferentially
assembled lys63-linked polyubiquitin chains in cotransfection assays.
DUBA selectively cleaved the lys63-linked polyubiquitin chains on TRAF3,
resulting in its dissociation from the downstream signaling complex
containing TANK-binding kinase-1 (604834). A discrete ubiquitin
interaction motif within DUBA was required for efficient
deubiquitination of TRAF3 and optimal suppression of type I interferon.
Kayagaki et al. (2007) concluded that their data identified DUBA as a
negative regulator of innate immune responses.
MAPPING
The OTUD5 gene maps to chromosome Xp11.23 (Kayagaki et al., 2007).
*FIELD* RF
1. Kayagaki, N.; Phung, Q.; Chan, S.; Chaudhari, R.; Quan, C.; O'Rourke,
K. M.; Eby, M.; Pietras, E.; Cheng, G.; Bazan, J. F.; Zhang, Z.; Arnott,
D.; Dixit, V. M.: DUBA: a deubiquitinase that regulates type I interferon
production. Science 318: 1628-1632, 2007.
*FIELD* CD
Ada Hamosh: 5/6/2008
*FIELD* ED
alopez: 05/07/2008
alopez: 5/7/2008
alopez: 5/6/2008