PEN-2

PSENEN
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; GeneCards: PSENEN
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	5A63, 5FN3, 5FN4, 5FN5, 5FN2
Gene location (Human)
Chr.	Chromosome 19 (human)
End	35,747,519 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	30,263,052 bp
RNA expression pattern
	Top expressed in
	right uterine tube; ; olfactory zone of nasal mucosa; ; right testis; ; left testis; ; granulocyte; ; mucosa of transverse colon; ; C1 segment; ; blood; ; hypothalamus; ; apex of heart;
	Top expressed in
	primary oocyte; ; secondary oocyte; ; zygote; ; thymus; ; urinary bladder; ; adrenal gland; ; white adipose tissue; ; granulocyte; ; islet of Langerhans; ; spleen;
	More reference expression data
	n/a
Gene ontology
Molecular function	protein binding;
Cellular component	Golgi apparatus; endoplasmic reticulum membrane; membrane; integral component of plasma membrane; Golgi cisterna membrane; endoplasmic reticulum; integral component of membrane; plasma membrane; gamma-secretase complex; endosome membrane; mitochondrion; integral component of presynaptic membrane;
Biological process	Notch signaling pathway; protein processing; 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; ephrin receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	55851
	66340
	ENSG00000205155
	ENSMUSG00000036835
	Q9NZ42
	Q9CQR7
	NM_172341; NM_001281532; NM_018468
	NM_025498; NM_001364016; NM_001364017
	NP_001268461; NP_758844
	NP_079774; NP_001350945; NP_001350946
	Wikidata
View/Edit Human	View/Edit Mouse

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. 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. 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.

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.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000205155 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000036835 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Kaether C, Haass C, Steiner H (2006). "Assembly, trafficking and function of gamma-secretase". Neuro-Degenerative Diseases. 3 (4–5): 275–283. doi:10.1159/000095267. PMID 17047368. S2CID 17324271.
↑ Francis R, McGrath G, Zhang J, Ruddy DA, Sym M, Apfeld J, et al. (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.
↑ Hasegawa H, Sanjo N, Chen F, Gu YJ, Shier C, Petit A, et al. (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): 46455–46463. doi:10.1074/jbc.M406289200. PMID 15322109.
↑ Ma T, Tian X, Zhang B, Li M, Wang Y, Yang C, et al. (March 2022). "Low-dose metformin targets the lysosomal AMPK pathway through PEN2". Nature. 603 (7899): 159–165. Bibcode:2022Natur.603..159M. doi:10.1038/s41586-022-04431-8. PMC 8891018. PMID 35197629.

External links

presenilin+enhancer+2,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article on a gene on human chromosome 19 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000205155 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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.

[Kaether-5] Kaether C, Haass C, Steiner H (2006). "Assembly, trafficking and function of gamma-secretase". Neuro-Degenerative Diseases. 3 (4–5): 275–283. doi:10.1159/000095267. PMID 17047368. S2CID 17324271.

[Francis-6] Francis R, McGrath G, Zhang J, Ruddy DA, Sym M, Apfeld J, et al. (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.

[Hasegawa-7] Hasegawa H, Sanjo N, Chen F, Gu YJ, Shier C, Petit A, et al. (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): 46455–46463. doi:10.1074/jbc.M406289200. PMID 15322109.

[pmid35197629-8] Ma T, Tian X, Zhang B, Li M, Wang Y, Yang C, et al. (March 2022). "Low-dose metformin targets the lysosomal AMPK pathway through PEN2". Nature. 603 (7899): 159–165. Bibcode:2022Natur.603..159M. doi:10.1038/s41586-022-04431-8. PMC 8891018. PMID 35197629.