High impact information on Thop1

• Therefore, PKA phosphorylation is suggested to play a regulatory role in EP24.15 enzyme activity [1].
• Cloning of the full-length mouse EP24.15 cDNA revealed 96.7% amino acid identity to the rat sequence, and conservation at serine 644, consistent with its putative functional role [1].
• The metalloendopeptidase EC (EP24.15) is a neuropeptide-metabolizing enzyme expressed predominantly in brain, pituitary, and testis, and is implicated in several physiological processes and diseases [1].
• Utilizing the mouse hypothalamic neuronal GT1-7 cell line, we demonstrate that EP24.15 exists within lipid rafts in the plasma membrane, and that the enzyme is localized to the exofacial leaflet of lipid rafts [2].
• The non-classical secretion inhibitor glyburide, a blocker of ATP-sensitive K+ channels, decreased the amount of constitutively released EP24.15 in cell media of GT1-7 cells [2].

Biological context of Thop1

• Regulation of cell-surface major histocompatibility complex class I expression by the endopeptidase EC3.4.24.15 (thimet oligopeptidase) [3].
• Conversely, stable retroviral silencing of endogenous EP24.15 by RNA interference induced a striking, long-term increase in surface MHC I [3].

Anatomical context of Thop1

• Further analysis revealed that an intracellular membrane marker and non-lipid raft, plasma membrane marker, failed to colocalize, supporting EP24.15/lipid raft association [4].
• For EP24.15 to have its greatest effect upon peptides in the periphery, it must be targeted and released into the extracellular space [4].
• Metalloendopeptidase EC 3.4.24.15 (EP24.15, thimet oligopeptidase) is a neuropeptide-metabolizing peptidase expressed throughout the body, but primarily in the brain, gonads, and pituitary [4].
• One of the most important oligopeptide-degrading and -binding proteins in the cytosol is the thimet oligopeptidase (EC 3.4.24.15), ubiquitously found in mammalian tissues [5].
• A catalytically inactive form of thimet oligopeptidase (EC 3.4.24.15; EP24.15) was used to isolate ACE substrates from adipose tissue [6].

Associations of Thop1 with chemical compounds

• Furthermore, EP24.15 immunoreactivity in lipid raft fractions generated from cells treated with methyl beta-cyclodextrin (MbetaCD) was greatly reduced [4].
• Western blot analysis of fractions taken from discontinuous sucrose density gradients carried out on crude plasma membrane fractions from AtT-20 cells reveals colocalization of EP24.15 and flotillin-1, a known lipid raft marker [4].
• The autophosphorylation is abolished in the presence of the thimet oligopeptidase substrates, as well as by the effect of a site directed inhibitor of this enzyme, and by the substitution of Glu474 for Asp at the metallo-peptidase motif [5].

References