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Q5VVQ6 (OTU1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 81. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ubiquitin thioesterase OTU1

EC=3.4.19.12
Alternative name(s):
DUBA-8
HIV-1-induced protease 7
Short name=HIN-7
Short name=HsHIN7
OTU domain-containing protein 2
Gene names
Name:YOD1
Synonyms:DUBA8, HIN7, OTUD2
ORF Names:PRO0907
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length348 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolase that can remove conjugated ubiquitin from proteins and participates in endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by triming the ubiquitin chain on the associated substrate to facilitate their threading through the VCP/p97 pore. Ubiquitin moieties on substrates may present a steric impediment to the threading process when the substrate is transferred to the VCP pore and threaded through VCP's axial channel. Mediates deubiquitination of 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains. Also able to hydrolyze 'Lys-11'-linked ubiquitin chains. Cleaves both polyubiquitin and di-ubiquitin. Ref.7 Ref.9

Catalytic activity

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). Ref.7 Ref.9

Subunit structure

Interacts with VCP; the interaction is direct. Interacts with FAF2/UBXD8. Interacts with DERL1; however interaction is dependent on the UBAX-like region, suggesting that it may be indirect. Ref.7

Domain

The UBAX-like region mediates the interaction with VCP. According to Ref.7, it corresponds to a UBX domain, which is a hallmark for VCP-associated proteins. However, no canonical UBX is detected by prediction tools such as Pfam or PROSITE.

The C2H2-type zinc finger mediates specificity for 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains but not for 'Lys-11'-linked ubiquitin chains. Selectivity for 'Lys-11'-linked ubiquitin chains is provided by recognition of the sequence surrounding 'Lys-11' in ubiquitin. The S2 site region provides specificity for longer 'Lys-11'-linked ubiquitin chains (Ref.9).

Sequence similarities

Contains 1 C2H2-type zinc finger.

Contains 1 OTU domain.

Sequence caution

The sequence AAF71033.1 differs from that shown. Reason: Erroneous translation. Wrong choice of frame.

The sequence EAW93510.1 differs from that shown. Reason: Erroneous gene model prediction.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5VVQ6-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q5VVQ6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: MFGPAKGRHF...KAKDGTHVLQ → METLHIIYSEAKSFTVE
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 348348Ubiquitin thioesterase OTU1
PRO_0000282356

Regions

Domain149 – 274126OTU
Zinc finger318 – 34225C2H2-type
Region50 – 12879UBX-like
Region154 – 1607Cys-loop By similarity
Region213 – 22311Variable-loop By similarity
Region263 – 2675His-loop By similarity
Region291 – 2966S2 site

Sites

Active site1571 By similarity
Active site1601Nucleophile Probable
Active site2671 By similarity
Binding site2661Substrate; via carbonyl oxygen

Natural variations

Alternative sequence1 – 6161MFGPA…THVLQ → METLHIIYSEAKSFTVE in isoform 2.
VSP_024122

Experimental info

Mutagenesis1601C → S: Abolishes deubiquitinase activity without affecting interaction with VCP. Specifically blocks a step in the course of dislocation and/or degradation of endoplasmic reticulum-resident proteins destined for proteasomal degradation. Ref.7
Mutagenesis2921I → Q: Does not affect activity or specificity. Impairs ability to cleave longer 'Lys-11'-linked ubiquitin chains; when associated with Q-295. Ref.9
Mutagenesis2951V → Q: Does not affect activity or specificity. Impairs ability to cleave longer 'Lys-11'-linked ubiquitin chains; when associated with Q-292. Ref.9
Mutagenesis3361H → A: Reduced activity toward 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked ubiquitin without affecting activity toward 'Lys-11'-linked ubiquitin; when associated with A-342. Ref.9
Mutagenesis3421H → A: Reduced activity toward 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked ubiquitin without affecting activity toward 'Lys-11'-linked ubiquitin; when associated with A-336. Ref.9
Sequence conflict81R → G in CAD89975. Ref.5
Sequence conflict901L → F in BAC87233. Ref.1

Secondary structure

................................... 348
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 7, 2004. Version 1.
Checksum: 91DBD25BE85B1CCC

FASTA34838,322
        10         20         30         40         50         60 
MFGPAKGRHF GVHPAPGFPG GVSQQAAGTK AGPAGAWPVG SRTDTMWRLR CKAKDGTHVL 

        70         80         90        100        110        120 
QGLSSRTRVR ELQGQIAAIT GIAPGGQRIL VGYPPECLDL SNGDTILEDL PIQSGDMLII 

       130        140        150        160        170        180 
EEDQTRPRSS PAFTKRGASS YVRETLPVLT RTVVPADNSC LFTSVYYVVE GGVLNPACAP 

       190        200        210        220        230        240 
EMRRLIAQIV ASDPDFYSEA ILGKTNQEYC DWIKRDDTWG GAIEISILSK FYQCEICVVD 

       250        260        270        280        290        300 
TQTVRIDRFG EDAGYTKRVL LIYDGIHYDP LQRNFPDPDT PPLTIFSSND DIVLVQALEL 

       310        320        330        340 
ADEARRRRQF TDVNRFTLRC MVCQKGLTGQ AEAREHAKET GHTNFGEV 

« Hide

Isoform 2 [UniParc].

Checksum: 8055467E0FD819CA
Show »

FASTA30433,979

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Testis.
[2]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain and Testis.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-348.
Tissue: Spinal cord.
[6]"Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs."
Yu Y., Zhang C., Zhou G., Wu S., Qu X., Wei H., Xing G., Dong C., Zhai Y., Wan J., Ouyang S., Li L., Zhang S., Zhou K., Zhang Y., Wu C., He F.
Genome Res. 11:1392-1403(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 267-348.
Tissue: Fetal liver.
[7]"The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER."
Ernst R., Mueller B., Ploegh H.L., Schlieker C.
Mol. Cell 36:28-38(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME ACTIVITY, INTERACTION WITH FAF2; DERL1 AND VCP, MUTAGENESIS OF CYS-160.
[8]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis."
Mevissen T.E., Hospenthal M.K., Geurink P.P., Elliott P.R., Akutsu M., Arnaudo N., Ekkebus R., Kulathu Y., Wauer T., El Oualid F., Freund S.M., Ovaa H., Komander D.
Cell 154:169-184(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) OF 132-314 IN COMPLEX WITH UBIQUITINATED SUBSTRATE, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ILE-292; VAL-295; HIS-336 AND HIS-342.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK128014 mRNA. Translation: BAC87233.1.
AL445493 Genomic DNA. Translation: CAH70775.1.
AL445493 Genomic DNA. Translation: CAH70776.1.
CH471100 Genomic DNA. Translation: EAW93509.1.
CH471100 Genomic DNA. Translation: EAW93510.1. Sequence problems.
BC137166 mRNA. Translation: AAI37167.1.
BC137167 mRNA. Translation: AAI37168.1.
AL833081 mRNA. Translation: CAD89975.1.
AF116608 mRNA. Translation: AAF71033.1. Sequence problems.
RefSeqNP_001263249.1. NM_001276320.1.
NP_061036.3. NM_018566.3.
UniGeneHs.567533.
Hs.745490.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4BOQX-ray1.47A132-314[»]
4BOSX-ray2.35A/B147-314[»]
4BOZX-ray3.03A/D132-314[»]
ProteinModelPortalQ5VVQ6.
SMRQ5VVQ6. Positions 47-132, 135-309.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120666. 18 interactions.
IntActQ5VVQ6. 2 interactions.
STRING9606.ENSP00000326813.

Protein family/group databases

MEROPSC85.007.

PTM databases

PhosphoSiteQ5VVQ6.

Polymorphism databases

DMDM74747276.

Proteomic databases

PaxDbQ5VVQ6.
PRIDEQ5VVQ6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000315927; ENSP00000326813; ENSG00000180667. [Q5VVQ6-1]
ENST00000367084; ENSP00000356051; ENSG00000180667. [Q5VVQ6-2]
ENST00000391927; ENSP00000375793; ENSG00000180667. [Q5VVQ6-2]
GeneID55432.
KEGGhsa:55432.
UCSCuc001hfe.1. human. [Q5VVQ6-1]
uc001hff.1. human. [Q5VVQ6-2]

Organism-specific databases

CTD55432.
GeneCardsGC01M207217.
HGNCHGNC:25035. YOD1.
HPAHPA028400.
HPA028439.
MIM612023. gene.
neXtProtNX_Q5VVQ6.
PharmGKBPA142670552.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5539.
HOGENOMHOG000193461.
HOVERGENHBG097006.
InParanoidQ5VVQ6.
KOK13719.
OMAFDGIHYD.
OrthoDBEOG7J1808.
PhylomeDBQ5VVQ6.
TreeFamTF323700.

Gene expression databases

BgeeQ5VVQ6.
CleanExHS_YOD1.
GenevestigatorQ5VVQ6.

Family and domain databases

InterProIPR003323. OTU.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
[Graphical view]
PfamPF02338. OTU. 1 hit.
[Graphical view]
SMARTSM00355. ZnF_C2H2. 1 hit.
[Graphical view]
PROSITEPS50802. OTU. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi55432.
NextBio59830.
PROQ5VVQ6.
SOURCESearch...

Entry information

Entry nameOTU1_HUMAN
AccessionPrimary (citable) accession number: Q5VVQ6
Secondary accession number(s): B2RNX3 expand/collapse secondary AC list , Q5VVQ5, Q6ZRS6, Q86T63, Q9P1L8
Entry history
Integrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: December 7, 2004
Last modified: April 16, 2014
This is version 81 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM