OTUD5_HUMAN
ID OTUD5_HUMAN Reviewed; 571 AA.
AC Q96G74; B4DGG7; G5E9D7; Q4KMN9; Q8N6T5; Q9H650; Q9H9U0; Q9NT65;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=OTU domain-containing protein 5 {ECO:0000305};
DE EC=3.4.19.12 {ECO:0000269|PubMed:22245969};
DE AltName: Full=Deubiquitinating enzyme A;
DE Short=DUBA;
GN Name=OTUD5 {ECO:0000312|HGNC:HGNC:25402};
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 [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 176-571 (ISOFORM 5), AND NUCLEOTIDE SEQUENCE [LARGE
RP 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., 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., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., 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., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., 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., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., 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., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA 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 GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 140-571 (ISOFORM 5).
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., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
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 phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH TRAF3, AND MUTAGENESIS OF
RP 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., Dixit V.M.;
RT "DUBA: a deubiquitinase that regulates type I interferon production.";
RL Science 318:1628-1632(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165; SER-177 AND SER-452, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [10]
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., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165 AND SER-177, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
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., 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64; SER-165 AND SER-177, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
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 [17]
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 AND
RP CYS-224, ACTIVE SITE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=22245969; DOI=10.1038/nsmb.2206;
RA Huang O.W., Ma X., Yin J., Flinders J., Maurer T., Kayagaki N., Phung Q.,
RA Bosanac I., Arnott D., Dixit V.M., Hymowitz S.G., Starovasnik M.A.,
RA Cochran A.G.;
RT "Phosphorylation-dependent activity of the deubiquitinase DUBA.";
RL Nat. Struct. Mol. Biol. 19:171-175(2012).
RN [18]
RP FUNCTION, VARIANTS MCAND 161-VAL--GLY-163 DEL; ASN-256; TRP-274; PRO-352;
RP TRP-404; SER-494 AND TRP-520, CHARACTERIZATION OF VARIANTS MCAND
RP 161-VAL--GLY-163 DEL; ASN-256; TRP-274; PRO-352 AND SER-494, SUBCELLULAR
RP LOCATION, MUTAGENESIS OF CYS-224, AND PHOSPHORYLATION.
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 (PubMed:33523931).
CC {ECO:0000269|PubMed:17991829, ECO:0000269|PubMed:22245969,
CC ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:33523931}.
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:22245969};
CC -!- ACTIVITY REGULATION: Inhibited by N-ethyl-maleimide (NEM).
CC -!- SUBUNIT: Interacts with TRAF3. {ECO:0000269|PubMed:17991829,
CC ECO:0000269|PubMed:22245969}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:33523931}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q96G74-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96G74-2; Sequence=VSP_023195, VSP_023192;
CC Name=3;
CC IsoId=Q96G74-3; Sequence=VSP_023192, VSP_023193, VSP_023194;
CC Name=4;
CC IsoId=Q96G74-4; Sequence=VSP_045185, VSP_023192;
CC Name=5;
CC IsoId=Q96G74-5; Sequence=VSP_023192;
CC -!- TISSUE SPECIFICITY: Expressed in various tissues, including the liver
CC and placenta, as well as in peripheral blood leukocytes.
CC {ECO:0000269|PubMed:17991829}.
CC -!- INDUCTION: Up-regulated by bacterial lipopolysaccharide (LPS) in bone
CC marrow-derived macrophages. {ECO:0000269|PubMed:22245969}.
CC -!- PTM: Phosphorylation at Ser-177 is required for deubiquitinating
CC activity. {ECO:0000269|PubMed:22245969, ECO:0000269|PubMed:33523931}.
CC -!- DISEASE: Multiple congenital anomalies-neurodevelopmental syndrome, X-
CC linked (MCAND) [MIM:301056]: An X-linked recessive, congenital disorder
CC characterized by central nervous system, craniofacial, cardiac,
CC skeletal, and genitourinary anomalies. Clinical features include poor
CC growth, short stature, global developmental delay, impaired
CC intellectual development, microcephaly, hydrocephalus, hypotonia,
CC congenital heart defects, hypospadias, and other variable
CC abnormalities. Brain imaging typically shows ventriculomegaly and thin
CC corpus callosum. The severity of the disorder is highly variable,
CC ranging from death in early infancy to survival into the second or
CC third decade. {ECO:0000269|PubMed:33523931}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Dubious isoform produced through aberrant
CC splice sites. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Dubious isoform produced through aberrant
CC splice sites. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the peptidase C85 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14131.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB15416.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK022612; BAB14131.1; ALT_INIT; mRNA.
DR EMBL; AK026260; BAB15416.1; ALT_INIT; mRNA.
DR EMBL; AK294590; BAG57778.1; -; mRNA.
DR EMBL; AF207550; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471224; EAW50724.1; -; 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 CCDS; CCDS14313.1; -. [Q96G74-1]
DR CCDS; CCDS48104.1; -. [Q96G74-5]
DR CCDS; CCDS48105.1; -. [Q96G74-4]
DR PIR; T46265; T46265.
DR RefSeq; NP_001129629.1; NM_001136157.1. [Q96G74-5]
DR RefSeq; NP_001129630.1; NM_001136158.1. [Q96G74-5]
DR RefSeq; NP_001129631.1; NM_001136159.1. [Q96G74-4]
DR RefSeq; NP_060072.1; NM_017602.3. [Q96G74-1]
DR RefSeq; XP_006724600.1; XM_006724537.2. [Q96G74-1]
DR PDB; 3PFY; X-ray; 1.70 A; A=172-344.
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 AlphaFoldDB; Q96G74; -.
DR SMR; Q96G74; -.
DR BioGRID; 120738; 47.
DR DIP; DIP-53541N; -.
DR IntAct; Q96G74; 23.
DR MINT; Q96G74; -.
DR STRING; 9606.ENSP00000156084; -.
DR MEROPS; C85.001; -.
DR GlyGen; Q96G74; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96G74; -.
DR PhosphoSitePlus; Q96G74; -.
DR BioMuta; OTUD5; -.
DR DMDM; 74731791; -.
DR EPD; Q96G74; -.
DR jPOST; Q96G74; -.
DR MassIVE; Q96G74; -.
DR MaxQB; Q96G74; -.
DR PaxDb; Q96G74; -.
DR PeptideAtlas; Q96G74; -.
DR PRIDE; Q96G74; -.
DR ProteomicsDB; 33910; -.
DR ProteomicsDB; 4133; -.
DR ProteomicsDB; 76598; -. [Q96G74-1]
DR ProteomicsDB; 76599; -. [Q96G74-2]
DR ProteomicsDB; 76600; -. [Q96G74-3]
DR TopDownProteomics; Q96G74-2; -. [Q96G74-2]
DR Antibodypedia; 409; 177 antibodies from 33 providers.
DR DNASU; 55593; -.
DR Ensembl; ENST00000156084.8; ENSP00000156084.4; ENSG00000068308.15. [Q96G74-1]
DR Ensembl; ENST00000376488.8; ENSP00000365671.3; ENSG00000068308.15. [Q96G74-5]
DR Ensembl; ENST00000396743.7; ENSP00000379969.3; ENSG00000068308.15. [Q96G74-5]
DR Ensembl; ENST00000428668.2; ENSP00000401629.2; ENSG00000068308.15. [Q96G74-4]
DR GeneID; 55593; -.
DR KEGG; hsa:55593; -.
DR MANE-Select; ENST00000376488.8; ENSP00000365671.3; NM_001136157.2; NP_001129629.1. [Q96G74-5]
DR UCSC; uc004dlt.5; human. [Q96G74-1]
DR CTD; 55593; -.
DR DisGeNET; 55593; -.
DR GeneCards; OTUD5; -.
DR HGNC; HGNC:25402; OTUD5.
DR HPA; ENSG00000068308; Low tissue specificity.
DR MalaCards; OTUD5; -.
DR MIM; 300713; gene.
DR MIM; 301056; phenotype.
DR neXtProt; NX_Q96G74; -.
DR OpenTargets; ENSG00000068308; -.
DR PharmGKB; PA142671217; -.
DR VEuPathDB; HostDB:ENSG00000068308; -.
DR eggNOG; KOG2605; Eukaryota.
DR GeneTree; ENSGT00940000158963; -.
DR HOGENOM; CLU_021938_0_1_1; -.
DR InParanoid; Q96G74; -.
DR OMA; REDKHFE; -.
DR OrthoDB; 1448656at2759; -.
DR PhylomeDB; Q96G74; -.
DR TreeFam; TF326812; -.
DR PathwayCommons; Q96G74; -.
DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases.
DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling.
DR SignaLink; Q96G74; -.
DR SIGNOR; Q96G74; -.
DR BioGRID-ORCS; 55593; 105 hits in 721 CRISPR screens.
DR ChiTaRS; OTUD5; human.
DR GenomeRNAi; 55593; -.
DR Pharos; Q96G74; Tbio.
DR PRO; PR:Q96G74; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q96G74; protein.
DR Bgee; ENSG00000068308; Expressed in upper arm skin and 185 other tissues.
DR ExpressionAtlas; Q96G74; baseline and differential.
DR Genevisible; Q96G74; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0101005; F:deubiquitinase activity; IDA:MGI.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; IDA:MGI.
DR GO; GO:0061578; F:Lys63-specific deubiquitinase activity; IDA:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:FlyBase.
DR GO; GO:0032480; P:negative regulation of type I interferon production; TAS:Reactome.
DR GO; GO:0014033; P:neural crest cell differentiation; IMP:UniProtKB.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IMP:FlyBase.
DR GO; GO:1904515; P:positive regulation of TORC2 signaling; IMP:FlyBase.
DR GO; GO:0016579; P:protein deubiquitination; IDA:MGI.
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:0032496; P:response to lipopolysaccharide; IDA:UniProtKB.
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 3D-structure; Alternative splicing; Disease variant; Hydrolase;
KW Intellectual disability; Nucleus; Phosphoprotein; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation pathway.
FT CHAIN 1..571
FT /note="OTU domain-containing protein 5"
FT /id="PRO_0000278223"
FT DOMAIN 213..341
FT /note="OTU"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT REGION 1..111
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 329..334
FT /note="His-loop"
FT /evidence="ECO:0000250"
FT REGION 418..502
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 420..460
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:0000269|PubMed:22245969"
FT ACT_SITE 334
FT /evidence="ECO:0000305|PubMed:22245969"
FT MOD_RES 64
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22245969,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22245969,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 175
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:22245969"
FT MOD_RES 177
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22245969,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 452
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 507
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:22245969"
FT VAR_SEQ 1..217
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045185"
FT VAR_SEQ 17..40
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023195"
FT VAR_SEQ 304..308
FT /note="Missing (in isoform 2, isoform 3, isoform 4 and
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005"
FT /id="VSP_023192"
FT VAR_SEQ 563..566
FT /note="HRDP -> PCRC (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023193"
FT VAR_SEQ 567..571
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023194"
FT VARIANT 161..163
FT /note="Missing (in MCAND; reduced cleavage activity towards
FT 'K-48'-chains but not 'K-63'-chains; no effect on
FT phosphorylation)"
FT /evidence="ECO:0000269|PubMed:33523931"
FT /id="VAR_085336"
FT VARIANT 256
FT /note="D -> N (in MCAND; reduced cleavage activity towards
FT 'K-63'- and 'K-48'-chains; no effect on phosphorylation)"
FT /evidence="ECO:0000269|PubMed:33523931"
FT /id="VAR_085337"
FT VARIANT 274
FT /note="R -> W (in MCAND; partial mislocation at the
FT cytoplasm; reduced cleavage activity towards 'K-63'- and
FT 'K-48'-chains; no effect on phosphorylation)"
FT /evidence="ECO:0000269|PubMed:33523931"
FT /id="VAR_085338"
FT VARIANT 352
FT /note="L -> P (in MCAND; in mice embryo the mutation is
FT lethal; reduced cleavage activity towards 'K-48'-chains but
FT not 'K-63'-chains; no effect on nuclear location; no effect
FT on phosphorylation)"
FT /evidence="ECO:0000269|PubMed:33523931"
FT /id="VAR_085339"
FT VARIANT 404
FT /note="R -> W (in MCAND; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33523931"
FT /id="VAR_085340"
FT VARIANT 494
FT /note="G -> S (in MCAND; decreased mRNA and protein levels;
FT no effect on cleavage activity towards 'K-48'-chains but
FT not 'K-63'-chains; in mice embryo the mutation is lethal;
FT no effect on phosphorylation)"
FT /evidence="ECO:0000269|PubMed:33523931"
FT /id="VAR_085341"
FT VARIANT 520
FT /note="R -> W (in MCAND; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33523931"
FT /id="VAR_085342"
FT MUTAGEN 177
FT /note="S->D,E: Loss of deubiquitinase activity. Abolishes
FT activation by protein kinases."
FT /evidence="ECO:0000269|PubMed:22245969"
FT MUTAGEN 224
FT /note="C->S: Loss of deubiquitinase activity. Loss of
FT suppression of IFN production. No effect on nuclear
FT location."
FT /evidence="ECO:0000269|PubMed:17991829,
FT ECO:0000269|PubMed:22245969, ECO:0000269|PubMed:33523931"
FT MUTAGEN 542
FT /note="L->A: Loss of 'K-48'- and 'K-63'-linked
FT polyubiquitin chain binding. Partial loss of TRAF3
FT deubiquitination; when associated with A-549."
FT /evidence="ECO:0000269|PubMed:17991829"
FT MUTAGEN 549
FT /note="S->A: Loss of 'K-48'- and 'K-63'-linked
FT polyubiquitin chain binding. Partial loss of TRAF3
FT deubiquitination; when associated with A-542."
FT /evidence="ECO:0000269|PubMed:17991829"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:3TMP"
FT HELIX 181..186
FT /evidence="ECO:0007829|PDB:3TMP"
FT HELIX 193..211
FT /evidence="ECO:0007829|PDB:3PFY"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:3PFY"
FT HELIX 224..234
FT /evidence="ECO:0007829|PDB:3PFY"
FT HELIX 237..239
FT /evidence="ECO:0007829|PDB:3PFY"
FT HELIX 240..253
FT /evidence="ECO:0007829|PDB:3PFY"
FT HELIX 255..258
FT /evidence="ECO:0007829|PDB:3PFY"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:3TMP"
FT HELIX 266..273
FT /evidence="ECO:0007829|PDB:3TMP"
FT HELIX 282..292
FT /evidence="ECO:0007829|PDB:3PFY"
FT STRAND 296..301
FT /evidence="ECO:0007829|PDB:3PFY"
FT STRAND 303..305
FT /evidence="ECO:0007829|PDB:3TMO"
FT STRAND 311..314
FT /evidence="ECO:0007829|PDB:3PFY"
FT STRAND 325..330
FT /evidence="ECO:0007829|PDB:3PFY"
FT TURN 331..333
FT /evidence="ECO:0007829|PDB:3PFY"
FT STRAND 334..339
FT /evidence="ECO:0007829|PDB:3PFY"
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
