UniProt Accession

 OTUB1_HUMAN; Q96FW1; Q32Q78; Q96II3; Q9NXQ4; Q9P0B8 

Genbank Protein ID

 AY177200; AF161381; AK000120; AP000721; BC007519; BC010368; BC107701 

Genbank Nucleotide ID

 AAO27702.1; AAF28941.1; BAA90956.1; AAH07519.1; AAH10368.1; AAI07702.1 

Protein Name

 Ubiquitin thioesterase OTUB1 

Protein Synonyms/Alias

 Deubiquitinating enzyme OTUB1; OTU domain-containing ubiquitin aldehyde-binding protein 1; Otubain-1; hOTU1; Ubiquitin-specific-processing protease OTUB1 

Gene Name

 OTUB1 

Gene Synonyms/Alias

 OTB1; OTU1; HSPC263 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
245	IEGGRTVKEFCQQEV	ubiquitination	[1]

Reference

 [1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 

Functional Description

 Hydrolase that can specifically remove '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, a crucial inductor of CD4 T-cell anergy. Isoform 1 destabilizes RNF128, leading to prevent anergy. In contrast, isoform 2 stabilizes RNF128 and promotes anergy. 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. 

Sequence Annotation

 DOMAIN 80 271 OTU.
 REGION 130 138 Ubiquitin-conjugating enzyme E2 binding.
 REGION 169 177 Ubiquitin-conjugating enzyme E2 binding.
 REGION 189 195 Free ubiquitin binding.
 REGION 206 213 Ubiquitin-conjugating enzyme E2 binding.
 REGION 214 221 Free ubiquitin binding.
 REGION 245 251 Free ubiquitin binding.
 ACT_SITE 88 88
 ACT_SITE 91 91 Nucleophile.
 ACT_SITE 265 265
 BINDING 221 221 Free ubiquitin.
 BINDING 235 235 Free ubiquitin.
 BINDING 237 237 Free ubiquitin.
 BINDING 261 261 Free ubiquitin.
 BINDING 266 266 Free ubiquitin.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 16 16 Phosphoserine.  

Keyword

 3D-structure; Acetylation; Adaptive immunity; Alternative splicing; Complete proteome; Cytoplasm; Direct protein sequencing; DNA damage; DNA repair; Hydrolase; Immunity; Phosphoprotein; Protease; Reference proteome; Thiol protease; Ubl conjugation pathway. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 271 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
 GO:0019784; F:NEDD8-specific protease activity; IDA:UniProtKB.
 GO:0008242; F:omega peptidase activity; IEA:InterPro.
 GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
 GO:0004843; F:ubiquitin-specific protease activity; IDA:UniProtKB.
 GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
 GO:2000780; P:negative regulation of double-strand break repair; IMP:UniProtKB.
 GO:1901315; P:negative regulation of histone H2A K63-linked ubiquitination; IDA:UniProtKB.
 GO:0071108; P:protein K48-linked deubiquitination; IDA:UniProtKB.
 GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
 GO:0006974; P:response to DNA damage stimulus; IDA:UniProtKB. 

Interpro

 IPR003323; OTU.
 IPR019400; Peptidase_C65_otubain.
 IPR016615; Ubiquitin_thioesterase_Otubain. 

Pfam

 PF10275; Peptidase_C65 

SMART

  

PROSITE

 PS50802; OTU 

PRINTS