Reviewed, UniProtKB/Swiss-Prot Q96DC9 (OTUB2_HUMAN)

Names and origin

Protein names

Recommended name:
    Ubiquitin thioesterase OTUB2
    EC=3.1.2.-
Alternative name(s):
    Otubain-2
    OTU domain-containing ubiquitin aldehyde-binding protein 2
    Ubiquitin-specific-processing protease OTUB2
    Deubiquitinating enzyme OTUB2

Gene names

Name:	OTUB2
Synonyms:	C14orf137, OTB2, OTU2

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	234 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Hydrolase that can remove conjugated ubiquitin from proteins in vitro and may therefore play an important regulatory role at the level of protein turnover by preventing degradation. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains, with a preference for 'Lys-63'-linked polyubiquitin chains. Ref.1 Ref.6
Tissue specificity	Widely expressed. Expressed at higher level in brain. Ref.1
Miscellaneous	In the structure described by Ref.7, the Asp-48 active site of the catalytic triad is located too far to interact directly with the active site His-224. A possible explanation is that OTUB2 is in inactive conformation in absence of ubiquitin and a conformation change may move Asp-48 in the proximity of His-224 in presence of ubiquitin substrate.
Sequence similarities	Belongs to the peptidase C65 family. Contains 1 OTU domain.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protease Thiol protease
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cellular amino acid and derivative metabolic process Ref.1 Inferred from direct assay. Source: UniProtKB modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW protein K48-linked deubiquitination Ref.6 Inferred from direct assay. Source: UniProtKB protein K63-linked deubiquitination Ref.6 Inferred from direct assay. Source: UniProtKB
Molecular function	ubiquitin-specific protease activity Ref.6 Ref.7 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96DC9-1)

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: Q96DC9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     74-234: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 234

234

Ubiquitin thioesterase OTUB2

PRO_0000221010

Regions

Domain

40 – 231

192

OTU

Sites

Active site

48

1

By similarity

Active site

51

1

Active site

224

1

Site

226

1

Required to orient and stabilize the active site H-224

Natural variations

Alternative sequence

74 – 234

161

Missing in isoform 2.

VSP_009465

Experimental info

Mutagenesis

47

1

G → P: Affects its ability to cleave 'K63'-linked ubiquitin. Ref.6

Mutagenesis

51

1

C → S: Loss of function in vitro. Ref.1

Mutagenesis

226

1

N → A: Abolishes deubiquitinase activity. Ref.7

Secondary structure

1

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234

Helix Strand Turn

Details...

Helix

17 – 20

4

Helix

24 – 28

5

Helix

29 – 38

10

Beta strand

39 – 43

5

Helix

51 – 64

14

Helix

68 – 87

20

Helix

92 – 111

20

Helix

115 – 122

8

Helix

125 – 145

21

Helix

147 – 150

4

Helix

151 – 153

3

Helix

160 – 167

8

Helix

177 – 187

11

Beta strand

191 – 195

5

Beta strand

215 – 221

7

Beta strand

224 – 230

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2004. Version 2. Checksum: DF2DBD32A78F9929	FASTA	234	27,213
	10 20 30 40 50 60 MSETSFNLIS EKCDILSILR DHPENRIYRR KIEELSKRFT AIRKTKGDGN CFYRALGYSY 70 80 90 100 110 120 LESLLGKSRE IFKFKERVLQ TPNDLLAAGF EEHKFRNFFN AFYSVVELVE KDGSVSSLLK 130 140 150 160 170 180 VFNDQSASDH IVQFLRLLTS AFIRNRADFF RHFIDEEMDI KDFCTHEVEP MATECDHIQI 190 200 210 220 230 TALSQALSIA LQVEYVDEMD TALNHHVFPE AATPSVYLLY KTSHYNILYA ADKH
	Isoform 2. Checksum: D3382B36FCD3C74A	FASTA	73	8,637
	10 20 30 40 50 60 MSETSFNLIS EKCDILSILR DHPENRIYRR KIEELSKRFT AIRKTKGDGN CFYRALGYSY 70 LESLLGKSRE IFK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Otubains: a new family of cysteine proteases in the ubiquitin pathway." Balakirev M.Y., Tcherniuk S.O., Jaquinod M., Chroboczek J. EMBO Rep. 4:517-522(2003) [PubMed: 12704427] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF CYS-51. Tissue: Cervix carcinoma.
[2]	"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] (ISOFORM 1).
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed: 12508121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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 AND 2). Tissue: Eye and Lung.
[6]	"Structural basis and specificity of human otubain 1-mediated deubiquitination." Edelmann M.J., Iphoefer A., Akutsu M., Altun M., di Gleria K., Kramer H.B., Fiebiger E., Dhe-Paganon S., Kessler B.M. Biochem. J. 418:379-390(2009) [PubMed: 18954305] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLY-47.
[7]	"Crystal structure of human otubain 2." Nanao M.H., Tcherniuk S.O., Chroboczek J., Dideberg O., Dessen A., Balakirev M.Y. EMBO Rep. 5:783-788(2004) [PubMed: 15258613] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), MUTAGENESIS OF ASN-226.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY177201 mRNA. Translation: AAO27703.1.
AK025569 mRNA. Translation: BAB15172.1.
CR457345 mRNA. Translation: CAG33626.1.
AL079302 Genomic DNA. No translation available.
BC009615 mRNA. Translation: AAH09615.1.
BC068058 mRNA. Translation: AAH68058.1.

IPI

IPI00302895.
IPI00401454.

RefSeq

NP_075601.1.

UniGene

Hs.278815

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TFF	X-ray	2.10	A	1-234	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96DC9. 1 interaction.

STRING

Q96DC9.

Protein family/group databases

MEROPS

C65.002.

Proteomic databases

PeptideAtlas

Q96DC9.

PRIDE

Q96DC9.

Genome annotation databases

Ensembl

ENST00000203664; ENSP00000203664; ENSG00000089723; Homo sapiens. [Genome view]

GeneID

78990.

KEGG

hsa:78990.

UCSC

uc001yci.1. human.

Organism-specific databases

CTD

78990.

GeneCards

GC14P093562.

H-InvDB

HIX0011922.

HGNC

HGNC:20351. OTUB2.

HPA

HPA002329.

MIM

608338. gene.

PharmGKB

PA134861658.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07067.

HOGENOM

HBG521362.

HOVERGEN

Q96DC9.

InParanoid

Q96DC9.

OMA

FPEAATP.

OrthoDB

EOG9DJNFZ.

PhylomeDB

Q96DC9.

Gene expression databases

ArrayExpress

Q96DC9.

Bgee

Q96DC9.

CleanEx

HS_OTUB2.

Genevestigator

Q96DC9.

GermOnline

ENSG00000089723. Homo sapiens.

Family and domain databases

InterPro

IPR003323. OTU.
IPR019400. Peptidase_C65_otubain.
IPR016615. Ubiquitin_thioesterase_Otubain.
[Graphical view]

Pfam

PF10275. Peptidase_C65. 1 hit.
[Graphical view]

PIRSF

PIRSF013503. Ubiquitin_thioesterase_Otubain. 1 hit.

PROSITE

PS50802. OTU. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

67574.

SOURCE

Search...

Entry information

Entry name

OTUB2_HUMAN

Accession

Primary (citable) accession number: Q96DC9
Secondary accession number(s): Q6IA10, Q9H6T1

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2004
Last sequence update:	March 1, 2004
Last modified:	January 19, 2010
This is version 69 of the entry and version 2 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.