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Protein

Ubiquitin thioesterase OTUB1

Gene

Otub1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hydrolase that can specifically remove compared to 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation. Regulator of T-cell anergy, a phenomenon that occurs when T-cells are rendered unresponsive to antigen rechallenge and no longer respond to their cognate antigen. Acts via its interaction with RNF128/GRAIL. Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128. Deubiquitinates estrogen receptor alpha (ESR1). Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains. Not able to cleave di-ubiquitin. Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin.1 Publication
Plays a key non-catalytic role in DNA repair regulation by inhibiting activity of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites. Inhibits RNF168 independently of ubiquitin thioesterase activity by binding and inhibiting UBE2N/UBC13, the E2 partner of RNF168, thereby limiting spreading of 'Lys-63'-linked histone H2A and H2AX marks. Inhibition occurs by binding to free ubiquitin: free ubiquitin acts as an allosteric regulator that increases affinity for UBE2N/UBC13 and disrupts interaction with UBE2V1. The OTUB1-UBE2N/UBC13-free ubiquitin complex adopts a configuration that mimics a cleaved 'Lys48'-linked di-ubiquitin chain (By similarity).By similarity

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).

Enzyme regulationi

By free ubiquitin: binding of free ubiquitin triggers conformational changes in the OTU domain and formation of a ubiquitin-binding helix in the N-terminus, promoting binding of the conjugated donor ubiquitin in UBE2N/UBC13 to OTUB1.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei88 – 881By similarity
Active sitei91 – 911NucleophileBy similarity
Binding sitei221 – 2211Free ubiquitinBy similarity
Binding sitei235 – 2351Free ubiquitinBy similarity
Binding sitei237 – 2371Free ubiquitinBy similarity
Binding sitei261 – 2611Free ubiquitinBy similarity
Active sitei265 – 2651By similarity
Binding sitei266 – 2661Free ubiquitinBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Adaptive immunity, DNA damage, DNA repair, Immunity, Ubl conjugation pathway

Protein family/group databases

MEROPSiC65.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin thioesterase OTUB1 (EC:3.4.19.12)
Alternative name(s):
Deubiquitinating enzyme OTUB1
OTU domain-containing ubiquitin aldehyde-binding protein 1
Otubain-1
Ubiquitin-specific-processing protease OTUB1
Gene namesi
Name:Otub1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:2147616. Otub1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 271270Ubiquitin thioesterase OTUB1PRO_0000221009Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei16 – 161PhosphoserineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ7TQI3.
PaxDbiQ7TQI3.
PRIDEiQ7TQI3.

2D gel databases

REPRODUCTION-2DPAGEQ7TQI3.

PTM databases

PhosphoSiteiQ7TQI3.

Expressioni

Gene expression databases

BgeeiQ7TQI3.
CleanExiMM_OTUB1.
ExpressionAtlasiQ7TQI3. baseline and differential.
GenevisibleiQ7TQI3. MM.

Interactioni

Subunit structurei

Interacts with RNF128. Forms a ternary complex with RNF128 and USP8. Interacts with FUS, ESR1 and GNB2L1/RACK1. Interacts with UBE2N/UBC13 (By similarity).By similarity

Protein-protein interaction databases

BioGridi223228. 4 interactions.
IntActiQ7TQI3. 3 interactions.
MINTiMINT-1854563.
STRINGi10090.ENSMUSP00000025679.

Structurei

3D structure databases

ProteinModelPortaliQ7TQI3.
SMRiQ7TQI3. Positions 25-271.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini80 – 271192OTUPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni130 – 1389Ubiquitin-conjugating enzyme E2 bindingBy similarity
Regioni169 – 1779Ubiquitin-conjugating enzyme E2 bindingBy similarity
Regioni189 – 1957Free ubiquitin bindingBy similarity
Regioni206 – 2138Ubiquitin-conjugating enzyme E2 bindingBy similarity
Regioni214 – 2218Free ubiquitin bindingBy similarity
Regioni245 – 2517Free ubiquitin bindingBy similarity

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiNOG267426.
GeneTreeiENSGT00390000006979.
HOGENOMiHOG000019496.
HOVERGENiHBG053383.
InParanoidiQ7TQI3.
KOiK09602.
OMAiRVEYMDR.
OrthoDBiEOG71K64D.
PhylomeDBiQ7TQI3.
TreeFamiTF314145.

Family and domain databases

InterProiIPR003323. OTU_dom.
IPR030298. OTUB1.
IPR016615. Otubain.
IPR019400. Peptidase_C65_otubain.
[Graphical view]
PANTHERiPTHR12931:SF16. PTHR12931:SF16. 1 hit.
PfamiPF10275. Peptidase_C65. 1 hit.
[Graphical view]
PIRSFiPIRSF013503. Ubiquitin_thioesterase_Otubain. 1 hit.
PROSITEiPS50802. OTU. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q7TQI3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAEEPQQQK QEPLGSDSEG VNCLAYDEAI MAQQDRIQQE IAVQNPLVSE
60 70 80 90 100
RLELSVLYKE YAEDDNIYQQ KIKDLHKKYS YIRKTRPDGN CFYRAFGFSH
110 120 130 140 150
LEALLDDSKE LQRFKAVSAK SKEDLVSQGF TEFTIEDFHN TFMDLIEQVE
160 170 180 190 200
KQTSVADLLA SFNDQSTSDY LVVYLRLLTS GYLQRESKFF EHFIEGGRTV
210 220 230 240 250
KEFCQQEVEP MCKESDHIHI IALAQALSVS IQVEYMDRGE GGTTNPHVFP
260 270
EGSEPKVYLL YRPGHYDILY K
Length:271
Mass (Da):31,270
Last modified:March 1, 2004 - v2
Checksum:i32F78EE1DC5FD679
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti186 – 1861E → D in BAE20433 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK027996 mRNA. Translation: BAE20433.1.
AK140070 mRNA. Translation: BAE24227.1.
AK145273 mRNA. Translation: BAE26339.1.
AK145970 mRNA. Translation: BAE26795.1.
BC022575 mRNA. Translation: AAH22575.1.
BC054410 mRNA. Translation: AAH54410.1.
CCDSiCCDS29520.1.
RefSeqiNP_598911.1. NM_134150.2.
UniGeneiMm.203921.

Genome annotation databases

EnsembliENSMUST00000025679; ENSMUSP00000025679; ENSMUSG00000024767.
GeneIDi107260.
KEGGimmu:107260.
UCSCiuc008gki.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK027996 mRNA. Translation: BAE20433.1.
AK140070 mRNA. Translation: BAE24227.1.
AK145273 mRNA. Translation: BAE26339.1.
AK145970 mRNA. Translation: BAE26795.1.
BC022575 mRNA. Translation: AAH22575.1.
BC054410 mRNA. Translation: AAH54410.1.
CCDSiCCDS29520.1.
RefSeqiNP_598911.1. NM_134150.2.
UniGeneiMm.203921.

3D structure databases

ProteinModelPortaliQ7TQI3.
SMRiQ7TQI3. Positions 25-271.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi223228. 4 interactions.
IntActiQ7TQI3. 3 interactions.
MINTiMINT-1854563.
STRINGi10090.ENSMUSP00000025679.

Protein family/group databases

MEROPSiC65.001.

PTM databases

PhosphoSiteiQ7TQI3.

2D gel databases

REPRODUCTION-2DPAGEQ7TQI3.

Proteomic databases

MaxQBiQ7TQI3.
PaxDbiQ7TQI3.
PRIDEiQ7TQI3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000025679; ENSMUSP00000025679; ENSMUSG00000024767.
GeneIDi107260.
KEGGimmu:107260.
UCSCiuc008gki.1. mouse.

Organism-specific databases

CTDi55611.
MGIiMGI:2147616. Otub1.

Phylogenomic databases

eggNOGiNOG267426.
GeneTreeiENSGT00390000006979.
HOGENOMiHOG000019496.
HOVERGENiHBG053383.
InParanoidiQ7TQI3.
KOiK09602.
OMAiRVEYMDR.
OrthoDBiEOG71K64D.
PhylomeDBiQ7TQI3.
TreeFamiTF314145.

Miscellaneous databases

ChiTaRSiOtub1. mouse.
NextBioi358648.
PROiQ7TQI3.
SOURCEiSearch...

Gene expression databases

BgeeiQ7TQI3.
CleanExiMM_OTUB1.
ExpressionAtlasiQ7TQI3. baseline and differential.
GenevisibleiQ7TQI3. MM.

Family and domain databases

InterProiIPR003323. OTU_dom.
IPR030298. OTUB1.
IPR016615. Otubain.
IPR019400. Peptidase_C65_otubain.
[Graphical view]
PANTHERiPTHR12931:SF16. PTHR12931:SF16. 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. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Corpora quadrigemina, Embryo, Mammary gland and Placenta.
  2. "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].
    Strain: FVB/N.
    Tissue: Colon and Mammary tumor.
  3. Lubec G., Klug S.
    Submitted (MAR-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 189-198, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Hippocampus.
  4. Cited for: FUNCTION.
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiOTUB1_MOUSE
AccessioniPrimary (citable) accession number: Q7TQI3
Secondary accession number(s): Q3ULV9
, Q3V408, Q8C326, Q8R5F2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: June 24, 2015
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. 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.