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Q7TQI3 (OTUB1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Otub1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length271 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4

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. Ref.4

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

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.

Subunit structure

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

Subcellular location

Cytoplasm By similarity.

Sequence similarities

Belongs to the peptidase C65 family.

Contains 1 OTU domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 271270Ubiquitin thioesterase OTUB1
PRO_0000221009

Regions

Domain80 – 271192OTU
Region130 – 1389Ubiquitin-conjugating enzyme E2 binding By similarity
Region169 – 1779Ubiquitin-conjugating enzyme E2 binding By similarity
Region189 – 1957Free ubiquitin binding By similarity
Region206 – 2138Ubiquitin-conjugating enzyme E2 binding By similarity
Region214 – 2218Free ubiquitin binding By similarity
Region245 – 2517Free ubiquitin binding By similarity

Sites

Active site881 By similarity
Active site911Nucleophile By similarity
Active site2651 By similarity
Binding site2211Free ubiquitin By similarity
Binding site2351Free ubiquitin By similarity
Binding site2371Free ubiquitin By similarity
Binding site2611Free ubiquitin By similarity
Binding site2661Free ubiquitin By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue161Phosphoserine By similarity

Experimental info

Sequence conflict1861E → D in BAE20433. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q7TQI3 [UniParc].

Last modified March 1, 2004. Version 2.
Checksum: 32F78EE1DC5FD679

FASTA27131,270
        10         20         30         40         50         60 
MAAEEPQQQK QEPLGSDSEG VNCLAYDEAI MAQQDRIQQE IAVQNPLVSE RLELSVLYKE 

        70         80         90        100        110        120 
YAEDDNIYQQ KIKDLHKKYS YIRKTRPDGN CFYRAFGFSH LEALLDDSKE LQRFKAVSAK 

       130        140        150        160        170        180 
SKEDLVSQGF TEFTIEDFHN TFMDLIEQVE KQTSVADLLA SFNDQSTSDY LVVYLRLLTS 

       190        200        210        220        230        240 
GYLQRESKFF EHFIEGGRTV KEFCQQEVEP MCKESDHIHI IALAQALSVS IQVEYMDRGE 

       250        260        270 
GGTTNPHVFP EGSEPKVYLL YRPGHYDILY K 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Two isoforms of otubain 1 regulate T cell anergy via GRAIL."
Soares L., Seroogy C., Skrenta H., Anandasabapathy N., Lovelace P., Chung C.D., Engleman E., Fathman C.G.
Nat. Immunol. 5:45-54(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS29520.1.
RefSeqNP_598911.1. NM_134150.2.
UniGeneMm.203921.

3D structure databases

ProteinModelPortalQ7TQI3.
SMRQ7TQI3. Positions 25-271.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid223228. 4 interactions.
IntActQ7TQI3. 3 interactions.
MINTMINT-1854563.
STRING10090.ENSMUSP00000025679.

Protein family/group databases

MEROPSC65.001.

PTM databases

PhosphoSiteQ7TQI3.

2D gel databases

REPRODUCTION-2DPAGEQ7TQI3.

Proteomic databases

MaxQBQ7TQI3.
PaxDbQ7TQI3.
PRIDEQ7TQI3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000025679; ENSMUSP00000025679; ENSMUSG00000024767.
GeneID107260.
KEGGmmu:107260.
UCSCuc008gki.1. mouse.

Organism-specific databases

CTD55611.
MGIMGI:2147616. Otub1.

Phylogenomic databases

eggNOGNOG267426.
GeneTreeENSGT00390000006979.
HOGENOMHOG000019496.
HOVERGENHBG053383.
InParanoidQ7TQI3.
KOK09602.
OMAVEPMYKE.
OrthoDBEOG71K64D.
PhylomeDBQ7TQI3.
TreeFamTF314145.

Gene expression databases

ArrayExpressQ7TQI3.
BgeeQ7TQI3.
CleanExMM_OTUB1.
GenevestigatorQ7TQI3.

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

ChiTaRSOTUB1. mouse.
NextBio358648.
PROQ7TQI3.
SOURCESearch...

Entry information

Entry nameOTUB1_MOUSE
AccessionPrimary (citable) accession number: Q7TQI3
Secondary accession number(s): Q3ULV9 expand/collapse secondary AC list , Q3V408, Q8C326, Q8R5F2
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: July 9, 2014
This is version 102 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot