PEN-2

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.[5] 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.[6] 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.[7]

PSENEN
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5A63, 5FN3, 5FN4, 5FN5, 5FN2
Identifiers
Aliases	PSENEN, MSTP064, PEN-2, PEN2, MDS033, presenilin enhancer gamma-secretase subunit, ACNINV2, presenilin enhancer, gamma-secretase subunit
External IDs	OMIM: 607632 MGI: 1913590 HomoloGene: 11952 GeneCards: PSENEN
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.12 Start 35,745,600 bp[1] End 35,747,519 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 B1 Start 30,561,863 bp[2] End 30,563,627 bp[2]
Gene ontology Molecular function • GO:0001948 protein binding Cellular component • Golgi apparatus • endoplasmic reticulum membrane • membrane • integral component of plasma membrane • Golgi cisterna membrane • endoplasmic reticulum • integral component of membrane • cell membrane • gamma-secretase complex • endosome membrane • mitochondrion • integral component of presynaptic membrane Biological process • Notch signaling pathway • protein processing • GO:0048554 positive regulation of catalytic activity • membrane protein ectodomain proteolysis • Notch receptor processing • amyloid precursor protein catabolic process • amyloid-beta formation • amyloid precursor protein metabolic process • Notch receptor processing, ligand-dependent • membrane protein intracellular domain proteolysis • positive regulation of apoptotic process • cellular protein metabolic process • ephrin receptor signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	55851	66340
Ensembl	ENSG00000205155	ENSMUSG00000036835
UniProt	Q9NZ42	Q9CQR7
RefSeq (mRNA)	NM_172341 NM_001281532	NM_025498 NM_001364016 NM_001364017
RefSeq (protein)	NP_001268461 NP_758844	NP_079774 NP_001350945 NP_001350946
Location (UCSC)	Chr 19: 35.75 – 35.75 Mb	Chr 7: 30.56 – 30.56 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

References

1. GRCh38: Ensembl release 89: ENSG00000205155 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000036835 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Kaether C, Haass C, Steiner H (2006). "Assembly, trafficking and function of gamma-secretase" (PDF). Neuro-Degenerative Diseases. 3 (4–5): 275–83. doi:10.1159/000095267. PMID 17047368.
6. 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. doi:10.1016/S1534-5807(02)00189-2. PMID 12110170.
7. 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)