Q96G74 (OTUD5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
OTU domain-containing protein 5
EC=3.4.19.12

Alternative name(s):
Deubiquitinating enzyme A
Short name=DUBA

Gene names

Name:

OTUD5

Organism

Homo sapiens (Human)

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	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).
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.
Sequence caution	The sequence BAB14131.1 differs from that shown. Reason: Erroneous initiation. The sequence BAB15416.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	innate immune response Traceable author statement. Source: Reactome negative regulation of type I interferon production Traceable author statement. Source: Reactome proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	cysteine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW
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

Nucleophile Probable

Active site

334

1

Probable

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

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

571

Helix Strand Turn

Details...

Helix

193 – 211

19

Beta strand

214 – 216

3

Helix

224 – 233

10

Helix

237 – 239

3

Helix

240 – 253

14

Helix

255 – 258

4

Helix

282 – 292

11

Beta strand

296 – 301

6

Beta strand

311 – 314

4

Beta strand

325 – 330

6

Turn

331 – 333

3

Beta strand

334 – 339

6

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 [UniParc]. 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 [UniParc]. 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

	« Hide 'large scale' referencesShow 'large scale' 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: Cervix carcinoma.
[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. Tissue: Cervix carcinoma.
[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. Tissue: Cervix carcinoma.
[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. Tissue: Embryonic kidney.
[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: Leukemic T-cell.
[10]	"The catalytic domain of human OTUD5." Structural genomics consortium (SGC) Submitted (DEC-2010) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 172-339.
+	Additional computationally mapped references.

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. NM_001136157.1.
NP_001129630.1. NM_001136158.1.
NP_060072.1. NM_017602.3.

UniGene

Hs.496098.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3PFY	X-ray	1.70	A	172-339	[»]

ProteinModelPortal

Q96G74.

SMR

Q96G74. Positions 191-341.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96G74. 16 interactions.

MINT

MINT-1408843.

STRING

Q96G74.

Protein family/group databases

MEROPS

C85.001.

PTM databases

PhosphoSite

Q96G74.

Polymorphism databases

DMDM

74731791.

Proteomic databases

PRIDE

Q96G74.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000156084; ENSP00000156084; ENSG00000068308.

GeneID

55593.

KEGG

hsa:55593.

UCSC

uc004dlt.2. human.
uc004dlu.1. human.

Organism-specific databases

CTD

55593.

GeneCards

GC0XM048779.

H-InvDB

HIX0016789.

HGNC

HGNC:25402. OTUD5.

HPA

HPA017375.

MIM

300713. gene.

neXtProt

NX_Q96G74.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04829.

GeneTree

ENSGT00510000048473.

HOGENOM

HBG717174.

HOVERGEN

HBG060214.

InParanoid

Q96G74.

OMA

WEDDEIL.

OrthoDB

EOG4KWJSV.

PhylomeDB

Q96G74.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q96G74.

Bgee

Q96G74.

CleanEx

HS_OTUD5.

Genevestigator

Q96G74.

Family and domain databases

InterPro

IPR003323. OTU.
[Graphical view]

KO

K12655.

Pfam

PF02338. OTU. 1 hit.
[Graphical view]

PROSITE

PS50802. OTU. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

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 25, 2012
This is version 77 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.