Biology:PEN-2
 Generic protein structure example |
PSENEN, formally PEN-2 (presenilin enhancer 2), is a protein that is a regulatory component of the gamma secretase complex, a protease complex responsible for proteolysis of transmembrane proteins such as the Notch protein and amyloid precursor protein (APP). The gamma secretase complex consists of PEN-2, APH-1, nicastrin, and the catalytic subunit presenilin.[1] PEN-2 is a 101-amino acid integral membrane protein likely with a topology such that both the N-terminus and the C-terminus face first the lumen of the endoplasmic reticulum and later the extracellular environment.[2] Biochemical studies have shown that a conserved sequence motif D-Y-L-S-F at the C-terminus, as well as the overall length of the C-terminal tail, is required for the formation of an active gamma secretase complex.[3]
PEN-2 binds to metformin at therapeutic concentration and may be responsible for its AMPK-activating effects. PEN2-metformin in turn binds to ATP6AP1 to inhibit v-ATPase activity.[4]
References
- ↑ "Assembly, trafficking and function of gamma-secretase". Neuro-Degenerative Diseases 3 (4–5): 275–283. 2006. doi:10.1159/000095267. PMID 17047368. http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-16592-7.
- ↑ "aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation". Developmental Cell 3 (1): 85–97. July 2002. doi:10.1016/S1534-5807(02)00189-2. PMID 12110170.
- ↑ "Both the sequence and length of the C terminus of PEN-2 are critical for intermolecular interactions and function of presenilin complexes". The Journal of Biological Chemistry 279 (45): 46455–46463. November 2004. doi:10.1074/jbc.M406289200. PMID 15322109.
- ↑ "Low-dose metformin targets the lysosomal AMPK pathway through PEN2". Nature 603 (7899): 159–165. March 2022. doi:10.1038/s41586-022-04431-8. PMID 35197629. Bibcode: 2022Natur.603..159M.
External links
- presenilin+enhancer+2,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
de:PEN-2
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