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
59	LELSVLYKEYAEDDN	ubiquitination	[1]
71	DDNIYQQKIKDLHKK	ubiquitination	[1, 2]
84	KKYSYIRKTRPDGNC	ubiquitination	[1, 2, 3]
109	EALLDDSKELQRFKA	ubiquitination	[1, 2, 4]
188	GYLQRESKFFEHFIE	acetylation	[5]
188	GYLQRESKFFEHFIE	ubiquitination	[2]

Reference

 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [4] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [5] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861] 

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