OTUD3_HUMAN
ID OTUD3_HUMAN Reviewed; 398 AA.
AC Q5T2D3; O75047;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=OTU domain-containing protein 3;
DE EC=3.4.19.12;
GN Name=OTUD3; Synonyms=KIAA0459;
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].
RC TISSUE=Brain;
RX PubMed=9455484; DOI=10.1093/dnares/4.5.345;
RA Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D.,
RA Nomura N., Ohara O.;
RT "Characterization of cDNA clones in size-fractionated cDNA libraries from
RT human brain.";
RL DNA Res. 4:345-349(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-224, AND IDENTIFICATION BY
RP 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 [5]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 52-209, FUNCTION, CATALYTIC
RP ACTIVITY, AND MUTAGENESIS OF 178-ARG--GLU-181.
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).
CC -!- FUNCTION: Deubiquitinating enzyme that hydrolyzes 'Lys-6'- and 'Lys-
CC 11'-linked polyubiquitin. Also hydrolyzes heterotypic (mixed and
CC branched) and homotypic chains. {ECO:0000269|PubMed:23827681}.
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:23827681};
CC -!- INTERACTION:
CC Q5T2D3; Q9BPX1: HSD17B14; NbExp=3; IntAct=EBI-16170539, EBI-742664;
CC Q5T2D3; P60484-1: PTEN; NbExp=9; IntAct=EBI-16170539, EBI-15722967;
CC -!- DOMAIN: The UBA-like domain has no influence on ubiquitin hydrolysis.
CC {ECO:0000269|PubMed:23827681}.
CC -!- DOMAIN: Specificity is given by the S1' ubiquitin-binding site within
CC the OTU domain composed of the Cys-, His- and Variable-loops.
CC {ECO:0000269|PubMed:23827681}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA32304.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB007928; BAA32304.2; ALT_INIT; mRNA.
DR EMBL; AL391883; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS41279.1; -.
DR RefSeq; NP_056022.1; NM_015207.1.
DR PDB; 4BOU; X-ray; 1.55 A; A=52-209.
DR PDBsum; 4BOU; -.
DR AlphaFoldDB; Q5T2D3; -.
DR SMR; Q5T2D3; -.
DR BioGRID; 116856; 39.
DR DIP; DIP-61702N; -.
DR IntAct; Q5T2D3; 2.
DR STRING; 9606.ENSP00000364261; -.
DR BindingDB; Q5T2D3; -.
DR ChEMBL; CHEMBL4630831; -.
DR MEROPS; C85.003; -.
DR iPTMnet; Q5T2D3; -.
DR PhosphoSitePlus; Q5T2D3; -.
DR BioMuta; OTUD3; -.
DR EPD; Q5T2D3; -.
DR jPOST; Q5T2D3; -.
DR MassIVE; Q5T2D3; -.
DR MaxQB; Q5T2D3; -.
DR PaxDb; Q5T2D3; -.
DR PeptideAtlas; Q5T2D3; -.
DR PRIDE; Q5T2D3; -.
DR ProteomicsDB; 64331; -.
DR Antibodypedia; 29739; 84 antibodies from 18 providers.
DR DNASU; 23252; -.
DR Ensembl; ENST00000375120.4; ENSP00000364261.3; ENSG00000169914.6.
DR GeneID; 23252; -.
DR KEGG; hsa:23252; -.
DR MANE-Select; ENST00000375120.4; ENSP00000364261.3; NM_015207.2; NP_056022.1.
DR UCSC; uc001bcs.5; human.
DR CTD; 23252; -.
DR DisGeNET; 23252; -.
DR GeneCards; OTUD3; -.
DR HGNC; HGNC:29038; OTUD3.
DR HPA; ENSG00000169914; Low tissue specificity.
DR MIM; 611758; gene.
DR neXtProt; NX_Q5T2D3; -.
DR OpenTargets; ENSG00000169914; -.
DR PharmGKB; PA142671215; -.
DR VEuPathDB; HostDB:ENSG00000169914; -.
DR eggNOG; ENOG502QUTD; Eukaryota.
DR GeneTree; ENSGT00390000016392; -.
DR HOGENOM; CLU_056188_0_0_1; -.
DR InParanoid; Q5T2D3; -.
DR OMA; DVPFTQH; -.
DR OrthoDB; 1448656at2759; -.
DR PhylomeDB; Q5T2D3; -.
DR TreeFam; TF329594; -.
DR PathwayCommons; Q5T2D3; -.
DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases.
DR Reactome; R-HSA-8948751; Regulation of PTEN stability and activity.
DR SignaLink; Q5T2D3; -.
DR BioGRID-ORCS; 23252; 17 hits in 1115 CRISPR screens.
DR ChiTaRS; OTUD3; human.
DR GenomeRNAi; 23252; -.
DR Pharos; Q5T2D3; Tbio.
DR PRO; PR:Q5T2D3; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5T2D3; protein.
DR Bgee; ENSG00000169914; Expressed in oocyte and 136 other tissues.
DR Genevisible; Q5T2D3; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IDA:MGI.
DR GO; GO:0016579; P:protein deubiquitination; IBA:GO_Central.
DR GO; GO:0035871; P:protein K11-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:1990167; P:protein K27-linked deubiquitination; IDA:MGI.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; IDA:MGI.
DR GO; GO:0044313; P:protein K6-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:MGI.
DR InterPro; IPR003323; OTU_dom.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR Pfam; PF02338; OTU; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50802; OTU; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Phosphoprotein; Protease; Reference proteome;
KW Thiol protease; Ubl conjugation pathway.
FT CHAIN 1..398
FT /note="OTU domain-containing protein 3"
FT /id="PRO_0000058103"
FT DOMAIN 65..189
FT /note="OTU"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT DOMAIN 230..270
FT /note="UBA-like"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 70..76
FT /note="Cys-loop"
FT REGION 127..137
FT /note="Variable-loop"
FT REGION 177..182
FT /note="His-loop"
FT REGION 305..383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 14..45
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 313..345
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 346..380
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 73
FT /evidence="ECO:0000250"
FT ACT_SITE 76
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 182
FT /evidence="ECO:0000250"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 321
FT /note="N -> S (in dbSNP:rs2298110)"
FT /id="VAR_051258"
FT VARIANT 333
FT /note="A -> T (in dbSNP:rs10916668)"
FT /id="VAR_051259"
FT MUTAGEN 178..181
FT /note="RYGE->LSNG: Impaired activity."
FT /evidence="ECO:0000269|PubMed:23827681"
FT HELIX 56..62
FT /evidence="ECO:0007829|PDB:4BOU"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:4BOU"
FT HELIX 76..86
FT /evidence="ECO:0007829|PDB:4BOU"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:4BOU"
FT HELIX 92..105
FT /evidence="ECO:0007829|PDB:4BOU"
FT HELIX 107..110
FT /evidence="ECO:0007829|PDB:4BOU"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:4BOU"
FT HELIX 120..128
FT /evidence="ECO:0007829|PDB:4BOU"
FT HELIX 136..145
FT /evidence="ECO:0007829|PDB:4BOU"
FT STRAND 149..153
FT /evidence="ECO:0007829|PDB:4BOU"
FT STRAND 160..166
FT /evidence="ECO:0007829|PDB:4BOU"
FT STRAND 172..178
FT /evidence="ECO:0007829|PDB:4BOU"
FT TURN 179..181
FT /evidence="ECO:0007829|PDB:4BOU"
FT STRAND 182..188
FT /evidence="ECO:0007829|PDB:4BOU"
SQ SEQUENCE 398 AA; 45124 MW; 9C16E610CF1E3C5A CRC64;
MSRKQAAKSR PGSGSRKAEA ERKRDERAAR RALAKERRNR PESGGGGGCE EEFVSFANQL
QALGLKLREV PGDGNCLFRA LGDQLEGHSR NHLKHRQETV DYMIKQREDF EPFVEDDIPF
EKHVASLAKP GTFAGNDAIV AFARNHQLNV VIHQLNAPLW QIRGTEKSSV RELHIAYRYG
EHYDSVRRIN DNSEAPAHLQ TDFQMLHQDE SNKREKIKTK GMDSEDDLRD EVEDAVQKVC
NATGCSDFNL IVQNLEAENY NIESAIIAVL RMNQGKRNNA EENLEPSGRV LKQCGPLWEE
GGSGARIFGN QGLNEGRTEN NKAQASPSEE NKANKNQLAK VTNKQRREQQ WMEKKKRQEE
RHRHKALESR GSHRDNNRSE AEANTQVTLV KTFAALNI
