THOP1 cleaves oligopeptide fragment (8-16aa)

Stable Identifier
R-HSA-8940641
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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Thimet oligopeptidase (THOP1, EP24.15) is a zinc-dependent peptidase of the metallopeptidase M3 family (Pierotti et al. 1990). It was first described as a neuropeptide-degrading enzyme present in the soluble fraction of brain homogenates (Orlowski et al. 1983). However, its predominant location in the cytosol and nucleus suggests that extracellular degradation of neuropeptides and hormones is not its primary function (Fontenele-Neto et al. 2001). THOP1 can metabolize peptides within cells, thereby affecting antigen presentation and G protein-coupled receptor signal transduction. It was shown in vivo to participate in antigen presentation through MHC-I (Silva et al. 1999, Kim et al. 2003, Yorl et al. 2003) and in vitro to bind (Portaro et al. 1999) or degrade (Saric et al. 2001) some MHC-I associated peptides. THOP1 can degrade a broad range of intracellular peptides containing 5–17 amino acids (Oliveira et al. 2001, Berti et al. 2009). Substrate size is restricted because its catalytic center is located in a deep channel (Ray et al. 2004). THOP1 can both degrade existing peptides and generate new peptides, making it a versatile enzyme for regulating intracellular peptide function including antigen presentation (Berti et al. 2009, Russo et al. 2012).

Cytotoxic T lymphocytes (CTLs) recognize peptides presented by HLA class I molecules on the cell surface. The C terminus of these CTL epitopes is considered to be produced by the proteasome, but is complemented by THOP1 and other cytosolic endopeptidases such as Nardilysin (Kessler et al. 2011, Oliveira & van Hall 2015).
Literature References
PubMed ID Title Journal Year
2261476 Molecular cloning and primary structure of rat testes metalloendopeptidase EC 3.4.24.15

Roberts, JL, Glucksman, MJ, Pierotti, A, Orlowski, M, Dong, KW

Biochemistry 1990
Participants
Participates
Catalyst Activity

metalloendopeptidase activity of THOP1 [cytosol]

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