Reviewed, UniProtKB/Swiss-Prot Q96G74 (OTUD5_HUMAN)

Names and origin

Protein names

Recommended name:
    OTU domain-containing protein 5
    EC=3.1.2.15
Alternative name(s):
    Deubiquinating enzyme A
      Short name=DUBA

Gene names

Name:

OTUD5

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	571 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Negative regulator of innate immune system. Has deubiquitinating activity that is directed towards 'Lys-63'-linked polyubiquitin chains. Acts via TRAF3 deubiquitination and subsequent suppression of type I interferon (IFN) production. Ref.5
Catalytic activity	Ubiquitin C-terminal thioester + H2O = ubiquitin + a thiol.
Enzyme regulation	Inhibited by N-ethyl-maleimide (NEM).
Subunit structure	Interacts with TRAF3. Ref.5
Tissue specificity	Expressed in various tissues, including the liver and placenta, as well as in peripheral blood leukocytes. Ref.5
Induction	By bacterial lipopolysaccharides (LPS) in bone marrow-derived macrophages.
Sequence similarities	Belongs to the peptidase C85 family. Contains 1 OTU domain.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cysteine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin thiolesterase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96G74-1)

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: Q96G74-2)

The sequence of this isoform differs from the canonical sequence as follows:
     17-40: Missing.
     304-308: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q96G74-3)

The sequence of this isoform differs from the canonical sequence as follows:
     304-308: Missing.
     563-566: HRDP → PCRC
     567-571: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 571	571	OTU domain-containing protein 5		PRO_0000278223
Regions
	Domain	213 – 341	129	OTU
	Compositional bias	5 – 113	109	Pro-rich
	Compositional bias	33 – 174	142	Gly-rich
Sites
	Active site	221	1	Potential
	Active site	224	1	Potential
	Active site	334	1	Potential
Amino acid modifications
	Modified residue	64	1	Phosphoserine Ref.4 Ref.6 Ref.7
	Modified residue	165	1	Phosphoserine Ref.7 Ref.8 Ref.9
	Modified residue	175	1	Phosphotyrosine Ref.8
	Modified residue	177	1	Phosphoserine Ref.7 Ref.9
	Modified residue	452	1	Phosphoserine Ref.7
	Modified residue	507	1	Phosphothreonine Ref.8
	Modified residue	508	1	Phosphoserine Ref.8
Natural variations
	Alternative sequence	17 – 40	24	Missing in isoform 2.		VSP_023195
	Alternative sequence	304 – 308	5	Missing in isoform 2 and isoform 3.		VSP_023192
	Alternative sequence	563 – 566	4	HRDP → PCRC in isoform 3.		VSP_023193
	Alternative sequence	567 – 571	5	Missing in isoform 3.		VSP_023194
Experimental info
	Mutagenesis	224	1	C → S: Loss of suppression of IFN production. Ref.5
	Mutagenesis	542	1	L → A: Loss of 'K-48'- and 'K-63'-linked polyubiquitin chain binding. Partial loss of TRAF3 deubiquitination; when associated with A-549. Ref.5
	Mutagenesis	549	1	S → A: Loss of 'K-48'- and 'K-63'-linked polyubiquitin chain binding. Partial loss of TRAF3 deubiquitination; when associated with A-542. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: F4B2B385B84ABC46	FASTA	571	60,626
	10 20 30 40 50 60 MTILPKKKPP PPDADPANEP PPPGPMPPAP RRGGGVGVGG GGTGVGGGDR DRDSGVVGAR 70 80 90 100 110 120 PRASPPPQGP LPGPPGALHR WALAVPPGAV AGPRPQQASP PPCGGPGGPG GGPGDALGAA 130 140 150 160 170 180 AAGVGAAGVV VGVGGAVGVG GCCSGPGHSK RRRQAPGVGA VGGGSPEREE VGAGYNSEDE 190 200 210 220 230 240 YEAAAARIEA MDPATVEQQE HWFEKALRDK KGFIIKQMKE DGACLFRAVA DQVYGDQDMH 250 260 270 280 290 300 EVVRKHCMDY LMKNADYFSN YVTEDFTTYI NRKRKNNCHG NHIEMQAMAE MYNRPVEVYQ 310 320 330 340 350 360 YSTGTSAVEP INTFHGIHQN EDEPIRVSYH RNIHYNSVVN PNKATIGVGL GLPSFKPGFA 370 380 390 400 410 420 EQSLMKNAIK TSEESWIEQQ MLEDKKRATD WEATNEAIEE QVARESYLQW LRDQEKQARQ 430 440 450 460 470 480 VRGPSQPRKA SATCSSATAA ASSGLEEWTS RSPRQRSSAS SPEHPELHAE LGMKPPSPGT 490 500 510 520 530 540 VLALAKPPSP CAPGTSSQFS AGADRATSPL VSLYPALECR ALIQQMSPSA FGLNDWDDDE 550 560 570 ILASVLAVSQ QEYLDSMKKN KVHRDPPPDK S
	Isoform 2. Checksum: FB641E44937EC3F2	FASTA	542	58,007
	10 20 30 40 50 60 MTILPKKKPP PPDADPGGTG VGGGDRDRDS GVVGARPRAS PPPQGPLPGP PGALHRWALA 70 80 90 100 110 120 VPPGAVAGPR PQQASPPPCG GPGGPGGGPG DALGAAAAGV GAAGVVVGVG GAVGVGGCCS 130 140 150 160 170 180 GPGHSKRRRQ APGVGAVGGG SPEREEVGAG YNSEDEYEAA AARIEAMDPA TVEQQEHWFE 190 200 210 220 230 240 KALRDKKGFI IKQMKEDGAC LFRAVADQVY GDQDMHEVVR KHCMDYLMKN ADYFSNYVTE 250 260 270 280 290 300 DFTTYINRKR KNNCHGNHIE MQAMAEMYNR PVEVYQYSTE PINTFHGIHQ NEDEPIRVSY 310 320 330 340 350 360 HRNIHYNSVV NPNKATIGVG LGLPSFKPGF AEQSLMKNAI KTSEESWIEQ QMLEDKKRAT 370 380 390 400 410 420 DWEATNEAIE EQVARESYLQ WLRDQEKQAR QVRGPSQPRK ASATCSSATA AASSGLEEWT 430 440 450 460 470 480 SRSPRQRSSA SSPEHPELHA ELGMKPPSPG TVLALAKPPS PCAPGTSSQF SAGADRATSP 490 500 510 520 530 540 LVSLYPALEC RALIQQMSPS AFGLNDWDDD EILASVLAVS QQEYLDSMKK NKVHRDPPPD KS
	Isoform 3. Checksum: 9C931880385CF8CB	FASTA	561	59,640
	10 20 30 40 50 60 MTILPKKKPP PPDADPANEP PPPGPMPPAP RRGGGVGVGG GGTGVGGGDR DRDSGVVGAR 70 80 90 100 110 120 PRASPPPQGP LPGPPGALHR WALAVPPGAV AGPRPQQASP PPCGGPGGPG GGPGDALGAA 130 140 150 160 170 180 AAGVGAAGVV VGVGGAVGVG GCCSGPGHSK RRRQAPGVGA VGGGSPEREE VGAGYNSEDE 190 200 210 220 230 240 YEAAAARIEA MDPATVEQQE HWFEKALRDK KGFIIKQMKE DGACLFRAVA DQVYGDQDMH 250 260 270 280 290 300 EVVRKHCMDY LMKNADYFSN YVTEDFTTYI NRKRKNNCHG NHIEMQAMAE MYNRPVEVYQ 310 320 330 340 350 360 YSTEPINTFH GIHQNEDEPI RVSYHRNIHY NSVVNPNKAT IGVGLGLPSF KPGFAEQSLM 370 380 390 400 410 420 KNAIKTSEES WIEQQMLEDK KRATDWEATN EAIEEQVARE SYLQWLRDQE KQARQVRGPS 430 440 450 460 470 480 QPRKASATCS SATAAASSGL EEWTSRSPRQ RSSASSPEHP ELHAELGMKP PSPGTVLALA 490 500 510 520 530 540 KPPSPCAPGT SSQFSAGADR ATSPLVSLYP ALECRALIQQ MSPSAFGLND WDDDEILASV 550 560 LAVSQQEYLD SMKKNKVPCR C

References

[1]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). Tissue: Kidney and Skin.
[2]	"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: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 140-571 (ISOFORM 2). Tissue: Amygdala.
[3]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 176-571 (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 253-571 (ISOFORM 1). Tissue: Small intestine.
[4]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64, MASS SPECTROMETRY. Tissue: Epithelium.
[5]	"DUBA: a deubiquitinase that regulates type I interferon production." Kayagaki N., Phung Q., Chan S., Chaudhari R., Quan C., O'Rourke K.M., Eby M., Pietras E., Cheng G., Bazan J.F., Zhang Z., Arnott D., Dixit V.M. Science 318:1628-1632(2007) [PubMed: 17991829] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH TRAF3, MUTAGENESIS OF CYS-224; LEU-542 AND SER-549.
[6]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64, MASS SPECTROMETRY.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64; SER-165; SER-177 AND SER-452, MASS SPECTROMETRY.
[8]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165; TYR-175; THR-507 AND SER-508, MASS SPECTROMETRY.
[9]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165 AND SER-177, MASS SPECTROMETRY. Tissue: T-cell.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC009917 mRNA. Translation: AAH09917.1. BC028225 mRNA. Translation: AAH28225.1. BC098440 mRNA. Translation: AAH98440.1. AL137509 mRNA. Translation: CAB70778.1. AK022612 mRNA. Translation: BAB14131.1. Different initiation. AK026260 mRNA. Translation: BAB15416.1. Different initiation.
IPI	IPI00640364. IPI00641956. IPI00940013.
PIR	T46265.
RefSeq	NP_001129629.1. NP_001129630.1. NP_060072.1.
UniGene	Hs.496098
3D structure databases
SMR	Q96G74. Positions 208-340.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96G74. 1 interaction.
Protein family/group databases
MEROPS	C85.001.
PTM databases
PhosphoSite	Q96G74.
Proteomic databases
PRIDE	Q96G74.
Genome annotation databases
Ensembl	ENST00000156084; ENSP00000156084; ENSG00000068308; Homo sapiens. [Genome view]
GeneID	55593.
KEGG	hsa:55593.
UCSC	uc004dlt.2. human. uc004dlu.1. human.
Organism-specific databases
CTD	55593.
GeneCards	GC0XM048665.
HGNC	HGNC:25402. OTUD5.
HPA	HPA017375.
MIM	300713. gene.
PharmGKB	PA142671217.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG04829.
HOGENOM	HBG717174.
HOVERGEN	Q96G74.
InParanoid	Q96G74.
OMA	SPPPCGG.
PhylomeDB	Q96G74.
Gene expression databases
ArrayExpress	Q96G74.
Bgee	Q96G74.
CleanEx	HS_OTUD5.
Genevestigator	Q96G74.
Family and domain databases
InterPro	IPR003323. OTU. [Graphical view]
Pfam	PF02338. OTU. 1 hit. [Graphical view]
PROSITE	PS50802. OTU. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	60126.
SOURCE	Search...

Entry information

Entry name

OTUD5_HUMAN

Accession

Primary (citable) accession number: Q96G74
Secondary accession number(s): Q4KMN9 , Q8N6T5, Q9H650, Q9H9U0, Q9NT65

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 20, 2007
Last sequence update:	December 1, 2001
Last modified:	January 19, 2010
This is version 58 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.