Q5VVQ6 (OTU1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	348 AA.
Sequence status	Complete.
Protein existence	Evidence 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 both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. Able to cleave both polyubiquitin and di-ubiquitin. Ref.7
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
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.
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.

Ontologies

Keywords
Biological process	Ubl conjugation pathway Unfolded protein response
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Protease Thiol protease
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ER-associated protein catabolic process Inferred from mutant phenotype Ref.7. Source: UniProtKB cellular amino acid metabolic process Inferred from sequence or structural similarity. Source: UniProtKB endoplasmic reticulum unfolded protein response Inferred from mutant phenotype Ref.7. Source: UniProtKB protein K48-linked deubiquitination Inferred from direct assay Ref.7PubMed 21376232. Source: UniProtKB protein K63-linked deubiquitination Inferred from direct assay Ref.7. Source: UniProtKB
Cellular_component	intracellular Inferred from electronic annotation. Source: InterPro
Molecular_function	ubiquitin-specific protease activity Inferred from direct assay Ref.7PubMed 21376232. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 348	348	Ubiquitin thioesterase OTU1		PRO_0000282356
Regions
	Domain	149 – 274	126	OTU
	Zinc finger	318 – 342	25	C2H2-type
	Region	50 – 128	79	UBX-like
Sites
	Active site	157	1	By similarity
	Active site	160	1	Nucleophile Probable
	Active site	342	1	By similarity
Natural variations
	Alternative sequence	1 – 61	61	MFGPA…THVLQ → METLHIIYSEAKSFTVE in isoform 2.		VSP_024122
Experimental info
	Mutagenesis	160	1	C → 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
	Sequence conflict	8	1	R → G in CAD89975. Ref.5
	Sequence conflict	90	1	L → F in BAC87233. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 7, 2004. Version 1. Checksum: 91DBD25BE85B1CCC	FASTA	348	38,322
	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
	Isoform 2 [UniParc]. Checksum: 8055467E0FD819CA	FASTA	304	33,979
	10 20 30 40 50 60 METLHIIYSE AKSFTVEGLS SRTRVRELQG QIAAITGIAP GGQRILVGYP PECLDLSNGD 70 80 90 100 110 120 TILEDLPIQS GDMLIIEEDQ TRPRSSPAFT KRGASSYVRE TLPVLTRTVV PADNSCLFTS 130 140 150 160 170 180 VYYVVEGGVL NPACAPEMRR LIAQIVASDP DFYSEAILGK TNQEYCDWIK RDDTWGGAIE 190 200 210 220 230 240 ISILSKFYQC EICVVDTQTV RIDRFGEDAG YTKRVLLIYD GIHYDPLQRN FPDPDTPPLT 250 260 270 280 290 300 IFSSNDDIVL VQALELADEA RRRRQFTDVN RFTLRCMVCQ KGLTGQAEAR EHAKETGHTN FGEV

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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].

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.
IPI	IPI00183503. IPI00644473.
RefSeq	NP_001263249.1. NM_001276320.1. NP_061036.3. NM_018566.3.
UniGene	Hs.567533. Hs.711982.
3D structure databases
ProteinModelPortal	Q5VVQ6.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q5VVQ6. 2 interactions.
STRING	9606.ENSP00000326813.
Protein family/group databases
MEROPS	C85.007.
PTM databases
PhosphoSite	Q5VVQ6.
Polymorphism databases
DMDM	74747276.
Proteomic databases
PaxDb	Q5VVQ6.
PRIDE	Q5VVQ6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000315927; ENSP00000326813; ENSG00000180667. ENST00000367084; ENSP00000356051; ENSG00000180667. ENST00000391927; ENSP00000375793; ENSG00000180667.
GeneID	55432.
KEGG	hsa:55432.
UCSC	uc001hfe.1. human. uc001hff.1. human.
Organism-specific databases
CTD	55432.
GeneCards	GC01M207217.
HGNC	HGNC:25035. YOD1.
HPA	HPA028400. HPA028439.
MIM	612023. gene.
neXtProt	NX_Q5VVQ6.
PharmGKB	PA142670552.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5539.
HOGENOM	HOG000193461.
HOVERGEN	HBG097006.
InParanoid	Q5VVQ6.
KO	K13719.
OMA	PIQSGDM.
Gene expression databases
Bgee	Q5VVQ6.
CleanEx	HS_YOD1.
Genevestigator	Q5VVQ6.
Family and domain databases
InterPro	IPR003323. OTU. IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. [Graphical view]
Pfam	PF02338. OTU. 1 hit. [Graphical view]
SMART	SM00355. ZnF_C2H2. 1 hit. [Graphical view]
PROSITE	PS50802. OTU. 1 hit. PS00028. ZINC_FINGER_C2H2_1. 1 hit. PS50157. ZINC_FINGER_C2H2_2. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	55432.
NextBio	59830.
SOURCE	Search...

Entry information

Entry name

OTU1_HUMAN

Accession

Primary (citable) accession number: Q5VVQ6
Secondary accession number(s): B2RNX3 , Q5VVQ5, Q6ZRS6, Q86T63, Q9P1L8

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 3, 2007
Last sequence update:	December 7, 2004
Last modified:	May 1, 2013
This is version 73 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.