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'''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 protein]]s such as the [[Notch pathway|Notch protein]] and [[amyloid precursor protein]] (APP). The gamma secretase complex consists of PEN-2, [[APH-1]], [[nicastrin]], and the catalytic subunit [[presenilin]].<ref name="Kaether">Kaether C, Haass C, Steiner H | '''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 protein]]s such as the [[Notch pathway|Notch protein]] and [[amyloid precursor protein]] (APP). The gamma secretase complex consists of PEN-2, [[APH-1]], [[nicastrin]], and the catalytic subunit [[presenilin]].<ref name="Kaether">{{cite journal | vauthors = Kaether C, Haass C, Steiner H | title = Assembly, trafficking and function of gamma-secretase | journal = Neuro-Degenerative Diseases | volume = 3 | issue = 4-5 | pages = 275–83 | date = 2006 | pmid = 17047368 | doi = 10.1159/000095267 | url = }}</ref> 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 (anatomy)|lumen]] of the [[endoplasmic reticulum]] and later the extracellular environment.<ref name="Francis">{{cite journal | vauthors = Francis R, McGrath G, Zhang J, Ruddy DA, Sym M, Apfeld J, Nicoll M, Maxwell M, Hai B, Ellis MC, Parks AL, Xu W, Li J, Gurney M, Myers RL, Himes CS, Hiebsch R, Ruble C, Nye JS, Curtis D | title = aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation | journal = Developmental Cell | volume = 3 | issue = 1 | pages = 85–97 | date = July 2002 | pmid = 12110170 | doi = }}</ref> Biochemical studies have shown that a conserved [[sequence motif]] [[aspartate|D]]-[[tyrosine|Y]]-[[leucine|L]]-[[serine|S]]-[[phenylalanine|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.<ref name="Hasegawa">{{cite journal | vauthors = Hasegawa H, Sanjo N, Chen F, Gu YJ, Shier C, Petit A, Kawarai T, Katayama T, Schmidt SD, Mathews PM, Schmitt-Ulms G, Fraser PE, St George-Hyslop P | title = Both the sequence and length of the C terminus of PEN-2 are critical for intermolecular interactions and function of presenilin complexes | journal = The Journal of Biological Chemistry | volume = 279 | issue = 45 | pages = 46455–63 | date = November 2004 | pmid = 15322109 | doi = 10.1074/jbc.M406289200 }}</ref> | ||
==References== | ==References== | ||
<references /> | |||
==External links== | ==External links== | ||
* {{MeshName|presenilin+enhancer+2,+human}} | * {{MeshName|presenilin+enhancer+2,+human}} | ||
{{ | {{DEFAULTSORT:Pen-2}} | ||
[[Category:Alzheimer's disease]] | [[Category:Alzheimer's disease]] | ||
[[Category:Proteins]] | [[Category:Proteins]] | ||
{{ | |||
{{gene-19-stub}} | |||
[[de:PEN-2]] | |||
Latest revision as of 14:18, 3 July 2018
| presenilin enhancer 2 homolog (C. elegans) | |
|---|---|
| Identifiers | |
| Symbol | PSENEN |
| Entrez | 55851 |
| HUGO | 30100 |
| OMIM | 607632 |
| RefSeq | NM_172341 |
| UniProt | Q9NZ42 |
| Other data | |
| Locus | Chr. 19 q13.12 |
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]
References
- ↑ Kaether C, Haass C, Steiner H (2006). "Assembly, trafficking and function of gamma-secretase". Neuro-Degenerative Diseases. 3 (4–5): 275–83. doi:10.1159/000095267. PMID 17047368.
- ↑ Francis R, McGrath G, Zhang J, Ruddy DA, Sym M, Apfeld J, Nicoll M, Maxwell M, Hai B, Ellis MC, Parks AL, Xu W, Li J, Gurney M, Myers RL, Himes CS, Hiebsch R, Ruble C, Nye JS, Curtis D (July 2002). "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. PMID 12110170.
- ↑ Hasegawa H, Sanjo N, Chen F, Gu YJ, Shier C, Petit A, Kawarai T, Katayama T, Schmidt SD, Mathews PM, Schmitt-Ulms G, Fraser PE, St George-Hyslop P (November 2004). "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): 46455–63. doi:10.1074/jbc.M406289200. PMID 15322109.
External links
- presenilin+enhancer+2,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
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