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Q96DC9 (OTUB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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 OTUB2

EC=3.4.19.12
Alternative name(s):
Deubiquitinating enzyme OTUB2
OTU domain-containing ubiquitin aldehyde-binding protein 2
Otubain-2
Ubiquitin-specific-processing protease OTUB2
Gene names
Name:OTUB2
Synonyms:C14orf137, OTB2, OTU2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length234 AA.
Sequence statusComplete.
Protein existenceEvidence 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 'Lys-11'-,'Lys-48'- and 'Lys-63'-linked polyubiquitin chains, with a preference for 'Lys-63'-linked polyubiquitin chains. Ref.1 Ref.6 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

Tissue specificity

Widely expressed. Expressed at higher level in brain. Ref.1

Miscellaneous

In the structure described by Ref.8, 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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 234234Ubiquitin thioesterase OTUB2
PRO_0000221010

Regions

Domain40 – 231192OTU

Sites

Active site481 By similarity
Active site511Nucleophile Probable
Active site2241
Site2261Required to orient and stabilize the active site H-224

Natural variations

Alternative sequence74 – 234161Missing in isoform 2.
VSP_009465

Experimental info

Mutagenesis471G → P: Affects its ability to cleave 'K63'-linked ubiquitin. Ref.6
Mutagenesis511C → S: Loss of function in vitro. Ref.1
Mutagenesis2261N → A: Abolishes deubiquitinase activity. Ref.8

Secondary structure

...................................... 234
Helix Strand Turn

Details...

Sequences

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

Last modified March 1, 2004. Version 2.
Checksum: DF2DBD32A78F9929

FASTA23427,213
        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 

« Hide

Isoform 2 [UniParc].

Checksum: D3382B36FCD3C74A
Show »

FASTA738,637

References

« Hide '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] [Europe PMC] [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. 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 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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF GLY-47.
[7]"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: FUNCTION, CATALYTIC ACTIVITY.
[8]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), MUTAGENESIS OF ASN-226.
+Additional computationally mapped references.

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.
RefSeqNP_075601.1. NM_023112.3.
UniGeneHs.278815.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1TFFX-ray2.10A1-234[»]
4FJVX-ray2.05A/C1-234[»]
ProteinModelPortalQ96DC9.
SMRQ96DC9. Positions 2-232.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122461. 29 interactions.
IntActQ96DC9. 4 interactions.
STRING9606.ENSP00000203664.

Protein family/group databases

MEROPSC65.002.

PTM databases

PhosphoSiteQ96DC9.

Polymorphism databases

DMDM44888285.

Proteomic databases

PaxDbQ96DC9.
PeptideAtlasQ96DC9.
PRIDEQ96DC9.

Protocols and materials databases

DNASU78990.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000203664; ENSP00000203664; ENSG00000089723. [Q96DC9-1]
ENST00000553723; ENSP00000451283; ENSG00000089723. [Q96DC9-2]
GeneID78990.
KEGGhsa:78990.
UCSCuc001yci.3. human. [Q96DC9-1]

Organism-specific databases

CTD78990.
GeneCardsGC14P094492.
HGNCHGNC:20351. OTUB2.
HPAHPA002329.
MIM608338. gene.
neXtProtNX_Q96DC9.
PharmGKBPA134861658.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG267426.
HOGENOMHOG000019496.
HOVERGENHBG053383.
InParanoidQ96DC9.
KOK09603.
OMAVFSEAAC.
OrthoDBEOG71K64D.
PhylomeDBQ96DC9.
TreeFamTF314145.

Gene expression databases

BgeeQ96DC9.
CleanExHS_OTUB2.
GenevestigatorQ96DC9.

Family and domain databases

InterProIPR003323. OTU.
IPR019400. Peptidase_C65_otubain.
IPR016615. Ubiquitin_thioesterase_Otubain.
[Graphical view]
PfamPF10275. Peptidase_C65. 1 hit.
[Graphical view]
PIRSFPIRSF013503. Ubiquitin_thioesterase_Otubain. 1 hit.
PROSITEPS50802. OTU. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSOTUB2. human.
EvolutionaryTraceQ96DC9.
GeneWikiOTUB2.
GenomeRNAi78990.
NextBio67574.
PROQ96DC9.
SOURCESearch...

Entry information

Entry nameOTUB2_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 106 of the entry and version 2 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

Peptidase families

Classification of peptidase families and list of entries

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 14

Human chromosome 14: entries, gene names and cross-references to MIM