UniProt Accession

 UCHL3_HUMAN; P15374; B2R970; Q5TBK8; Q6IBE9 

Genbank Protein ID

 M30496; BT019359; CR456855; AK313665; AL137244; CH471093; BC018125 

Genbank Nucleotide ID

 AAA36791.1; AAV38166.1; CAG33136.1; BAG36417.1; CAI12419.1; EAW80542.1; AAH18125.1 

Protein Name

 Ubiquitin carboxyl-terminal hydrolase isozyme L3 

Protein Synonyms/Alias

 UCH-L3; Ubiquitin thioesterase L3 

Gene Name

 UCHL3 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
120	FESGSTLKKFLEESV	ubiquitination	[1]
121	ESGSTLKKFLEESVS	ubiquitination	[2, 3]
210	EDAIEVCKKFMERDP	ubiquitination	[4, 5]
211	DAIEVCKKFMERDPD	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [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] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [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] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 

Functional Description

 Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3", and exhibits a preference towards 'Lys-48'-linked Ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin- signaling and insulin-induced adipogenesis. Required for stress- response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders. 

Sequence Annotation

 REGION 8 13 Interaction with ubiquitin.
 REGION 152 159 Interaction with ubiquitin.
 REGION 219 224 Interaction with ubiquitin.
 ACT_SITE 95 95 Nucleophile.
 ACT_SITE 169 169 Proton donor (Probable).
 MOD_RES 130 130 Phosphoserine.  

Keyword

 3D-structure; Complete proteome; Cytoplasm; Hydrolase; Phosphoprotein; Protease; Reference proteome; Thiol protease; Ubl conjugation pathway. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 230 AA 

Protein Sequence

Gene Ontology

 GO:0005739; C:mitochondrion; IDA:HPA.
 GO:0005634; C:nucleus; IDA:HPA.
 GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
 GO:0008233; F:peptidase activity; IDA:UniProtKB.
 GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
 GO:0004221; F:ubiquitin thiolesterase activity; TAS:UniProtKB.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; NAS:UniProtKB. 

Interpro

 IPR001578; Peptidase_C12. 

Pfam

 PF01088; Peptidase_C12 

SMART

  

PROSITE

 PS00140; UCH_1 

PRINTS

 PR00707; UBCTHYDRLASE.