OTUD1_HUMAN
ID OTUD1_HUMAN Reviewed; 481 AA.
AC Q5VV17;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=OTU domain-containing protein 1;
DE EC=3.4.19.12;
DE AltName: Full=DUBA-7;
GN Name=OTUD1; Synonyms=DUBA7, OTDC1;
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 GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 287-437, FUNCTION, AND CATALYTIC
RP ACTIVITY.
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 specifically hydrolyzes 'Lys-
CC 63'-linked polyubiquitin to monoubiquitin.
CC {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 -!- DOMAIN: The UIM repeat increases the specificity and efficiency of the
CC enzyme toward 'Lys-63'-linked polyubiquitin.
CC {ECO:0000269|PubMed:23827681}.
CC -!- DOMAIN: Specificity is not given by the S1' ubiquitin-binding site
CC within the OTU domain (composed of the Cys-, His- and Variable-loops).
CC {ECO:0000269|PubMed:23827681}.
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DR EMBL; AL512603; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS44366.1; -.
DR RefSeq; NP_001138845.1; NM_001145373.2.
DR PDB; 4BOP; X-ray; 2.10 A; A/B=287-437.
DR PDBsum; 4BOP; -.
DR AlphaFoldDB; Q5VV17; -.
DR SMR; Q5VV17; -.
DR BioGRID; 128638; 27.
DR IntAct; Q5VV17; 11.
DR STRING; 9606.ENSP00000365678; -.
DR BindingDB; Q5VV17; -.
DR ChEMBL; CHEMBL4630832; -.
DR MEROPS; C85.004; -.
DR iPTMnet; Q5VV17; -.
DR PhosphoSitePlus; Q5VV17; -.
DR BioMuta; OTUD1; -.
DR DMDM; 74747188; -.
DR EPD; Q5VV17; -.
DR MassIVE; Q5VV17; -.
DR MaxQB; Q5VV17; -.
DR PaxDb; Q5VV17; -.
DR PeptideAtlas; Q5VV17; -.
DR PRIDE; Q5VV17; -.
DR ProteomicsDB; 65434; -.
DR Antibodypedia; 51774; 82 antibodies from 14 providers.
DR DNASU; 220213; -.
DR Ensembl; ENST00000376495.5; ENSP00000365678.3; ENSG00000165312.7.
DR GeneID; 220213; -.
DR KEGG; hsa:220213; -.
DR MANE-Select; ENST00000376495.5; ENSP00000365678.3; NM_001145373.3; NP_001138845.1.
DR UCSC; uc001irr.3; human.
DR CTD; 220213; -.
DR DisGeNET; 220213; -.
DR GeneCards; OTUD1; -.
DR HGNC; HGNC:27346; OTUD1.
DR HPA; ENSG00000165312; Tissue enhanced (bone).
DR MIM; 612022; gene.
DR neXtProt; NX_Q5VV17; -.
DR OpenTargets; ENSG00000165312; -.
DR PharmGKB; PA134932304; -.
DR VEuPathDB; HostDB:ENSG00000165312; -.
DR eggNOG; KOG2605; Eukaryota.
DR GeneTree; ENSGT00510000049635; -.
DR HOGENOM; CLU_044163_1_0_1; -.
DR InParanoid; Q5VV17; -.
DR OMA; RGGDRCD; -.
DR OrthoDB; 955020at2759; -.
DR PhylomeDB; Q5VV17; -.
DR TreeFam; TF338508; -.
DR PathwayCommons; Q5VV17; -.
DR SignaLink; Q5VV17; -.
DR BioGRID-ORCS; 220213; 19 hits in 1119 CRISPR screens.
DR GenomeRNAi; 220213; -.
DR Pharos; Q5VV17; Tbio.
DR PRO; PR:Q5VV17; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q5VV17; protein.
DR Bgee; ENSG00000165312; Expressed in buccal mucosa cell and 191 other tissues.
DR Genevisible; Q5VV17; HS.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IBA:GO_Central.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB.
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; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation pathway.
FT CHAIN 1..481
FT /note="OTU domain-containing protein 1"
FT /id="PRO_0000271018"
FT DOMAIN 309..438
FT /note="OTU"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT DOMAIN 457..476
FT /note="UIM"
FT /evidence="ECO:0000305"
FT REGION 18..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 202..282
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 314..320
FT /note="Cys-loop"
FT REGION 369..379
FT /note="His-loop"
FT REGION 426..431
FT /note="Variable-loop"
FT COMPBIAS 228..257
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 317
FT /evidence="ECO:0000250"
FT ACT_SITE 320
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 431
FT /evidence="ECO:0000250"
FT HELIX 290..306
FT /evidence="ECO:0007829|PDB:4BOP"
FT STRAND 310..312
FT /evidence="ECO:0007829|PDB:4BOP"
FT HELIX 320..330
FT /evidence="ECO:0007829|PDB:4BOP"
FT HELIX 333..335
FT /evidence="ECO:0007829|PDB:4BOP"
FT HELIX 336..349
FT /evidence="ECO:0007829|PDB:4BOP"
FT HELIX 351..354
FT /evidence="ECO:0007829|PDB:4BOP"
FT HELIX 355..357
FT /evidence="ECO:0007829|PDB:4BOP"
FT HELIX 362..369
FT /evidence="ECO:0007829|PDB:4BOP"
FT HELIX 378..388
FT /evidence="ECO:0007829|PDB:4BOP"
FT STRAND 391..399
FT /evidence="ECO:0007829|PDB:4BOP"
FT STRAND 402..410
FT /evidence="ECO:0007829|PDB:4BOP"
FT STRAND 412..414
FT /evidence="ECO:0007829|PDB:4BOP"
FT STRAND 421..427
FT /evidence="ECO:0007829|PDB:4BOP"
FT TURN 428..430
FT /evidence="ECO:0007829|PDB:4BOP"
FT STRAND 431..436
FT /evidence="ECO:0007829|PDB:4BOP"
SQ SEQUENCE 481 AA; 51063 MW; 37B3AEB0B3851982 CRC64;
MQLYSSVCTH YPAGAPGPTA AAPAPPAAAT PFKVSLQPPG AAGAAPEPET GECQPAAAAE
HREAAAVPAA KMPAFSSCFE VVSGAAAPAS AAAGPPGASC KPPLPPHYTS TAQITVRALG
ADRLLLHGPD PVPGAAGSAA APRGRCLLLA PAPAAPVPPR RGSSAWLLEE LLRPDCPEPA
GLDATREGPD RNFRLSEHRQ ALAAAKHRGP AATPGSPDPG PGPWGEEHLA ERGPRGWERG
GDRCDAPGGD AARRPDPEAE APPAGSIEAA PSSAAEPVIV SRSDPRDEKL ALYLAEVEKQ
DKYLRQRNKY RFHIIPDGNC LYRAVSKTVY GDQSLHRELR EQTVHYIADH LDHFSPLIEG
DVGEFIIAAA QDGAWAGYPE LLAMGQMLNV NIHLTTGGRL ESPTVSTMIH YLGPEDSLRP
SIWLSWLSNG HYDAVFDHSY PNPEYDNWCK QTQVQRKRDE ELAKSMAISL SKMYIEQNAC
S
