Ubiquitin thioesterase OTUB1 - Rattus norvegicus (Rat)

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B2RYG6 (OTUB1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 44. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

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 names

Name:

Otub1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	271 AA.
Sequence status	Complete.
Protein existence	Evidence 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 By similarity. 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.
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.
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. UniProtKB Q96FW1
Subcellular location	Cytoplasm Ref.3.
Sequence similarities	Belongs to the peptidase C65 family. Contains 1 OTU domain.

Ontologies

Keywords
Biological process	Adaptive immunity DNA damage DNA repair Immunity Ubl conjugation pathway
Cellular component	Cytoplasm
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of double-strand break repair Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of histone H2A K63-linked ubiquitination Inferred from sequence or structural similarity. Source: UniProtKB protein K48-linked deubiquitination Inferred from sequence or structural similarity. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: UniProtKB-KW response to DNA damage stimulus Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	NEDD8-specific protease activity Inferred from sequence or structural similarity. Source: UniProtKB omega peptidase activity Inferred from electronic annotation. Source: InterPro ubiquitin binding Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-specific protease activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 271

271

Ubiquitin thioesterase OTUB1

PRO_0000349125

Regions

Domain

80 – 271

192

OTU

Region

130 – 138

Ubiquitin-conjugating enzyme E2 binding By similarity

Region

169 – 177

Ubiquitin-conjugating enzyme E2 binding By similarity

Region

189 – 195

Free ubiquitin binding By similarity

Region

206 – 213

Ubiquitin-conjugating enzyme E2 binding By similarity

Region

214 – 221

Free ubiquitin binding By similarity

Region

245 – 251

Free ubiquitin binding By similarity

Sites

Active site

By similarity UniProtKB Q96FW1

Active site

Nucleophile By similarity UniProtKB Q96FW1

Active site

265

By similarity UniProtKB Q96FW1

Binding site

221

Free ubiquitin By similarity

Binding site

235

Free ubiquitin By similarity

Binding site

237

Free ubiquitin By similarity

Binding site

261

Free ubiquitin By similarity

Binding site

266

Free ubiquitin By similarity

Site

Required for proximal ubiquitin-binding By similarity

Amino acid modifications

Modified residue

Phosphoserine By similarity UniProtKB Q7TQI3

Sequences

Sequence

Length

Mass (Da)

Tools

B2RYG6 [UniParc].

Last modified July 1, 2008. Version 1.
Checksum: 32F78EE1DC5FD679
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FASTA

271

31,270

        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' referencesShow 'large scale' references »
[1]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Brown Norway.
[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]. Tissue: Prostate.
[3]	"Proteome profile of the mature rat olfactory bulb." Maurya D.K., Sundaram C.S., Bhargava P. Proteomics 9:2593-2599(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION.

Cross-references

Sequence databases
EMBL GenBank DDBJ	CH473953 Genomic DNA. Translation: EDM12666.1. BC166771 mRNA. Translation: AAI66771.1.
IPI	IPI00371462.
RefSeq	NP_001099802.1. NM_001106332.1.
UniGene	Rn.9218.
3D structure databases
ProteinModelPortal	B2RYG6.
SMR	B2RYG6. Positions 25-271.
ModBase	Search...
Protein family/group databases
MEROPS	C65.001.
PTM databases
PhosphoSite	B2RYG6.
2D gel databases
World-2DPAGE	0004:B2RYG6.
Proteomic databases
PaxDb	B2RYG6.
PRIDE	B2RYG6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000028752; ENSRNOP00000028752; ENSRNOG00000021175.
GeneID	293705.
KEGG	rno:293705.
UCSC	RGD:1311329. rat.
Organism-specific databases
CTD	55611.
RGD	1311329. Otub1.
Phylogenomic databases
eggNOG	NOG267426.
GeneTree	ENSGT00390000006979.
HOGENOM	HOG000019496.
HOVERGEN	HBG053383.
KO	K09602.
OMA	VVYLRLI.
OrthoDB	EOG47H5QS.
Gene expression databases
Genevestigator	B2RYG6.
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
NextBio	636821.

Entry information

Entry name

OTUB1_RAT

Accession

Primary (citable) accession number: B2RYG6

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 2, 2008
Last sequence update:	July 1, 2008
Last modified:	April 3, 2013
This is version 44 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein family/group databases

PTM databases

2D gel databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents