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Protein

Ubiquitin thioesterase OTUB2

Gene

OTUB2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.3 Publications

Catalytic activityi

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).1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei48 – 481By similarity
Active sitei51 – 511NucleophileCurated
Active sitei224 – 2241
Sitei226 – 2261Required to orient and stabilize the active site H-224

GO - Molecular functioni

  1. ubiquitin-specific protease activity Source: UniProtKB

GO - Biological processi

  1. protein deubiquitination Source: UniProtKB
  2. protein K11-linked deubiquitination Source: UniProtKB
  3. protein K48-linked deubiquitination Source: UniProtKB
  4. protein K63-linked deubiquitination Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Protein family/group databases

MEROPSiC65.002.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:OTUB2
Synonyms:C14orf137, OTB2, OTU2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componentsi: Chromosome 14, Unplaced

Organism-specific databases

HGNCiHGNC:20351. OTUB2.

Subcellular locationi

GO - Cellular componenti

  1. nucleus Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi47 – 471G → P: Affects its ability to cleave 'K63'-linked ubiquitin. 1 Publication
Mutagenesisi51 – 511C → S: Loss of function in vitro. 1 Publication
Mutagenesisi226 – 2261N → A: Abolishes deubiquitinase activity. 1 Publication

Organism-specific databases

PharmGKBiPA134861658.

Polymorphism and mutation databases

BioMutaiOTUB2.
DMDMi44888285.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 234234Ubiquitin thioesterase OTUB2PRO_0000221010Add
BLAST

Proteomic databases

MaxQBiQ96DC9.
PaxDbiQ96DC9.
PeptideAtlasiQ96DC9.
PRIDEiQ96DC9.

PTM databases

PhosphoSiteiQ96DC9.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ96DC9.
CleanExiHS_OTUB2.
GenevestigatoriQ96DC9.

Organism-specific databases

HPAiHPA002329.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
ARRDC3Q96B673EBI-746259,EBI-2875665
CPSF6Q166303EBI-746259,EBI-358410
FAM168AQ925673EBI-746259,EBI-7957930
LZTS2Q9BRK43EBI-746259,EBI-741037
MID1O153443EBI-746259,EBI-2340316
MID2Q9UJV3-23EBI-746259,EBI-10172526
RELQ048643EBI-746259,EBI-307352
SIAH1Q8IUQ43EBI-746259,EBI-747107
TP53BP2Q13625-33EBI-746259,EBI-10175039
TRIM54Q9BYV23EBI-746259,EBI-2130429

Protein-protein interaction databases

BioGridi122461. 39 interactions.
IntActiQ96DC9. 13 interactions.
STRINGi9606.ENSP00000203664.

Structurei

Secondary structure

1
234
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi7 – 93Combined sources
Helixi15 – 217Combined sources
Helixi26 – 3510Combined sources
Turni36 – 383Combined sources
Beta strandi39 – 435Combined sources
Beta strandi47 – 493Combined sources
Helixi51 – 6414Combined sources
Helixi68 – 8720Combined sources
Helixi92 – 11019Combined sources
Helixi115 – 1228Combined sources
Helixi125 – 14420Combined sources
Helixi147 – 1504Combined sources
Helixi151 – 1533Combined sources
Helixi160 – 1678Combined sources
Helixi177 – 18711Combined sources
Beta strandi191 – 1966Combined sources
Beta strandi198 – 2003Combined sources
Beta strandi204 – 2096Combined sources
Beta strandi215 – 2239Combined sources
Beta strandi225 – 2306Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1TFFX-ray2.10A1-234[»]
4FJVX-ray2.05A/C1-234[»]
ProteinModelPortaliQ96DC9.
SMRiQ96DC9. Positions 2-232.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96DC9.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini40 – 231192OTUPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase C65 family.Curated
Contains 1 OTU domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG267426.
GeneTreeiENSGT00390000006979.
HOGENOMiHOG000019496.
HOVERGENiHBG053383.
InParanoidiQ96DC9.
KOiK09603.
OMAiATECDHV.
OrthoDBiEOG71K64D.
PhylomeDBiQ96DC9.
TreeFamiTF314145.

Family and domain databases

InterProiIPR003323. OTU.
IPR030299. OTUB2.
IPR016615. Otubain.
IPR019400. Peptidase_C65_otubain.
[Graphical view]
PANTHERiPTHR12931:SF3. PTHR12931:SF3. 1 hit.
PfamiPF10275. Peptidase_C65. 1 hit.
[Graphical view]
PIRSFiPIRSF013503. Ubiquitin_thioesterase_Otubain. 1 hit.
PROSITEiPS50802. OTU. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96DC9-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSETSFNLIS EKCDILSILR DHPENRIYRR KIEELSKRFT AIRKTKGDGN
60 70 80 90 100
CFYRALGYSY LESLLGKSRE IFKFKERVLQ TPNDLLAAGF EEHKFRNFFN
110 120 130 140 150
AFYSVVELVE KDGSVSSLLK VFNDQSASDH IVQFLRLLTS AFIRNRADFF
160 170 180 190 200
RHFIDEEMDI KDFCTHEVEP MATECDHIQI TALSQALSIA LQVEYVDEMD
210 220 230
TALNHHVFPE AATPSVYLLY KTSHYNILYA ADKH
Length:234
Mass (Da):27,213
Last modified:March 1, 2004 - v2
Checksum:iDF2DBD32A78F9929
GO
Isoform 2 (identifier: Q96DC9-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.

Show »
Length:73
Mass (Da):8,637
Checksum:iD3382B36FCD3C74A
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei74 – 234161Missing in isoform 2. 1 PublicationVSP_009465Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS9917.1. [Q96DC9-1]
RefSeqiNP_075601.1. NM_023112.3. [Q96DC9-1]
UniGeneiHs.278815.

Genome annotation databases

EnsembliENST00000203664; ENSP00000203664; ENSG00000089723. [Q96DC9-1]
ENST00000553723; ENSP00000451283; ENSG00000089723. [Q96DC9-2]
ENST00000617748; ENSP00000478628; ENSG00000277276. [Q96DC9-1]
GeneIDi78990.
KEGGihsa:78990.
UCSCiuc001yci.3. human. [Q96DC9-1]

Polymorphism and mutation databases

BioMutaiOTUB2.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS9917.1. [Q96DC9-1]
RefSeqiNP_075601.1. NM_023112.3. [Q96DC9-1]
UniGeneiHs.278815.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1TFFX-ray2.10A1-234[»]
4FJVX-ray2.05A/C1-234[»]
ProteinModelPortaliQ96DC9.
SMRiQ96DC9. Positions 2-232.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122461. 39 interactions.
IntActiQ96DC9. 13 interactions.
STRINGi9606.ENSP00000203664.

Protein family/group databases

MEROPSiC65.002.

PTM databases

PhosphoSiteiQ96DC9.

Polymorphism and mutation databases

BioMutaiOTUB2.
DMDMi44888285.

Proteomic databases

MaxQBiQ96DC9.
PaxDbiQ96DC9.
PeptideAtlasiQ96DC9.
PRIDEiQ96DC9.

Protocols and materials databases

DNASUi78990.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000203664; ENSP00000203664; ENSG00000089723. [Q96DC9-1]
ENST00000553723; ENSP00000451283; ENSG00000089723. [Q96DC9-2]
ENST00000617748; ENSP00000478628; ENSG00000277276. [Q96DC9-1]
GeneIDi78990.
KEGGihsa:78990.
UCSCiuc001yci.3. human. [Q96DC9-1]

Organism-specific databases

CTDi78990.
GeneCardsiGC14P094492.
HGNCiHGNC:20351. OTUB2.
HPAiHPA002329.
MIMi608338. gene.
neXtProtiNX_Q96DC9.
PharmGKBiPA134861658.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG267426.
GeneTreeiENSGT00390000006979.
HOGENOMiHOG000019496.
HOVERGENiHBG053383.
InParanoidiQ96DC9.
KOiK09603.
OMAiATECDHV.
OrthoDBiEOG71K64D.
PhylomeDBiQ96DC9.
TreeFamiTF314145.

Miscellaneous databases

ChiTaRSiOTUB2. human.
EvolutionaryTraceiQ96DC9.
GeneWikiiOTUB2.
GenomeRNAii78990.
NextBioi67574.
PROiQ96DC9.
SOURCEiSearch...

Gene expression databases

BgeeiQ96DC9.
CleanExiHS_OTUB2.
GenevestigatoriQ96DC9.

Family and domain databases

InterProiIPR003323. OTU.
IPR030299. OTUB2.
IPR016615. Otubain.
IPR019400. Peptidase_C65_otubain.
[Graphical view]
PANTHERiPTHR12931:SF3. PTHR12931:SF3. 1 hit.
PfamiPF10275. Peptidase_C65. 1 hit.
[Graphical view]
PIRSFiPIRSF013503. Ubiquitin_thioesterase_Otubain. 1 hit.
PROSITEiPS50802. OTU. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.
    , 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. Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), MUTAGENESIS OF ASN-226.

Entry informationi

Entry nameiOTUB2_HUMAN
AccessioniPrimary (citable) accession number: Q96DC9
Secondary accession number(s): Q6IA10, Q9H6T1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: April 29, 2015
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

In the structure described by PubMed:15258613, 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.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.