PSEN2

Presenilin 2
Identifiers
Symbols	PSEN2 ; AD3L; AD4; CMD1V; PS2; STM2
External IDs	OMIM: 600759 MGI: 109284 HomoloGene: 386 ChEMBL: 3708 GeneCards: PSEN2 Gene
Gene ontology Molecular function • endopeptidase activity • aspartic-type endopeptidase activity • protein binding Cellular component • Golgi membrane • kinetochore • nucleus • nuclear inner membrane • mitochondrial inner membrane • lysosomal membrane • endoplasmic reticulum • endoplasmic reticulum membrane • Golgi apparatus • centrosome • cytosol • plasma membrane • integral component of plasma membrane • cell cortex • cell surface • membrane • apical plasma membrane • Z disc • axon • growth cone • neuromuscular junction • ciliary rootlet • ciliary basal body • neuronal cell body • dendritic shaft • protein complex • membrane raft • perinuclear region of cytoplasm Biological process • cell fate specification • somitogenesis • negative regulation of protein phosphorylation • hair follicle development • hematopoietic progenitor cell differentiation • T cell activation involved in immune response • myeloid leukocyte differentiation • membrane protein ectodomain proteolysis • calcium ion transport • regulation of epidermal growth factor-activated receptor activity • Notch signaling pathway • Notch receptor processing • axon guidance • memory • protein transport • protein processing • dorsal/ventral neural tube patterning • embryonic limb morphogenesis • forebrain development • membrane protein intracellular domain proteolysis • negative regulation of protein complex assembly • negative regulation of protein binding • endoplasmic reticulum calcium ion homeostasis • intracellular signal transduction • amyloid precursor protein catabolic process • positive regulation of apoptotic process • negative regulation of apoptotic process • positive regulation of catalytic activity • neurotrophin TRK receptor signaling pathway • ephrin receptor signaling pathway • regulation of synaptic plasticity • lung alveolus development • thymus development • brain morphogenesis • beta-amyloid metabolic process • positive regulation of coagulation • T cell receptor signaling pathway • cardiac muscle contraction • apoptotic signaling pathway • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5664	19165
Ensembl	ENSG00000143801	ENSMUSG00000010609
UniProt	P49810	Q61144
RefSeq (mRNA)	NM_000447	NM_001128605
RefSeq (protein)	NP_000438	NP_001122077
Location (UCSC)	Chr 1: 226.87 – 226.9 Mb	Chr 1: 180.23 – 180.26 Mb
PubMed search

Presenilin-2 is a protein that in humans is encoded by the PSEN2 gene.^[1]

Function

Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma-secretase activity or themselves are protease enzymes. Two alternative transcripts of PSEN2 have been identified.^[2]

In melanocytic cells PSEN2 gene expression may be regulated by MITF.^[3]

Interactions

PSEN2 has been shown to interact with:

• BCL2-like 1,^[4]
• CAPN1,^[5]
• CIB1,^[6]
• Calsenilin,^[7][8]
• FHL2,^[9]
• FLNB,^[10]
• KCNIP4,^[11]
• Nicastrin,^[12][13] and
• UBQLN1.^[14]

References

1. Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, Yu CE, Jondro PD, Schmidt SD, Wang K (September 1995). "Candidate gene for the chromosome 1 familial Alzheimer's disease locus". Science 269 (5226): 973–977. doi:10.1126/science.7638622. PMID 7638622.
2. "Entrez Gene: PSEN2 presenilin 2 (Alzheimer disease 4)".
3. Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–676. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
4. Passer BJ, Pellegrini L, Vito P, Ganjei JK, D'Adamio L (August 1999). "Interaction of Alzheimer's presenilin-1 and presenilin-2 with Bcl-X(L). A potential role in modulating the threshold of cell death". J. Biol. Chem. 274 (34): 24007–13. doi:10.1074/jbc.274.34.24007. PMID 10446169.
5. Shinozaki K, Maruyama K, Kume H, Tomita T, Saido TC, Iwatsubo T, Obata K (May 1998). "The presenilin 2 loop domain interacts with the mu-calpain C-terminal region". Int. J. Mol. Med. 1 (5): 797–9. doi:10.3892/ijmm.1.5.797. PMID 9852298.
6. Stabler SM, Ostrowski LL, Janicki SM, Monteiro MJ (June 1999). "A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein". J. Cell Biol. 145 (6): 1277–92. doi:10.1083/jcb.145.6.1277. PMC 2133148. PMID 10366599.
7. Buxbaum JD, Choi EK, Luo Y, Lilliehook C, Crowley AC, Merriam DE, Wasco W (October 1998). "Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment". Nat. Med. 4 (10): 1177–81. doi:10.1038/2673. PMID 9771752.
8. Choi EK, Zaidi NF, Miller JS, Crowley AC, Merriam DE, Lilliehook C, Buxbaum JD, Wasco W (June 2001). "Calsenilin is a substrate for caspase-3 that preferentially interacts with the familial Alzheimer's disease-associated C-terminal fragment of presenilin 2". J. Biol. Chem. 276 (22): 19197–204. doi:10.1074/jbc.M008597200. PMID 11278424.
9. Tanahashi H, Tabira T (September 2000). "Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein". Hum. Mol. Genet. 9 (15): 2281–9. doi:10.1093/oxfordjournals.hmg.a018919. PMID 11001931.
10. Zhang W, Han SW, McKeel DW, Goate A, Wu JY (February 1998). "Interaction of presenilins with the filamin family of actin-binding proteins". J. Neurosci. 18 (3): 914–22. PMC 2042137. PMID 9437013.
11. Morohashi Y, Hatano N, Ohya S, Takikawa R, Watabiki T, Takasugi N, Imaizumi Y, Tomita T, Iwatsubo T (April 2002). "Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4". J. Biol. Chem. 277 (17): 14965–75. doi:10.1074/jbc.M200897200. PMID 11847232.
12. Lee SF, Shah S, Li H, Yu C, Han W, Yu G (November 2002). "Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch". J. Biol. Chem. 277 (47): 45013–9. doi:10.1074/jbc.M208164200. PMID 12297508.
13. Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song YQ, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang DS, Holmes E, Milman P, Liang Y, Zhang DM, Xu DH, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer LS, Sorbi S, Bruni A, Fraser P, St George-Hyslop P (September 2000). "Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing". Nature 407 (6800): 48–54. doi:10.1038/35024009. PMID 10993067.
14. Mah AL, Perry G, Smith MA, Monteiro MJ (November 2000). "Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation". J. Cell Biol. 151 (4): 847–62. doi:10.1083/jcb.151.4.847. PMC 2169435. PMID 11076969.

Further reading

• Cruts M, Van Broeckhoven C (1998). "Presenilin mutations in Alzheimer's disease". Hum. Mutat. 11 (3): 183–190. doi:10.1002/(SICI)1098-1004(1998)11:3<183::AID-HUMU1>3.0.CO;2-J. PMID 9521418.
• McGeer PL, Kawamata T, McGeer EG (1998). "Localization and possible functions of presenilins in brain". Reviews in the neurosciences 9 (1): 1–15. doi:10.1515/REVNEURO.1998.9.1.1. PMID 9683324.
• Nishimura M, Yu G, St George-Hyslop PH (1999). "Biology of presenilins as causative molecules for Alzheimer disease". Clin. Genet. 55 (4): 219–225. doi:10.1034/j.1399-0004.1999.550401.x. PMID 10361981.
• da Costa CA (2006). "Recent insights on the pro-apoptotic phenotype elicited by presenilin 2 and its caspase and presenilinase-derived fragments". Current Alzheimer research 2 (5): 507–514. doi:10.2174/156720505774932278. PMID 16375654.
• Wolfe MS (2007). "When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease". EMBO Rep. 8 (2): 136–140. doi:10.1038/sj.embor.7400896. PMC 1796780. PMID 17268504.
• De Strooper B (2007). "Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease". EMBO Rep. 8 (2): 141–146. doi:10.1038/sj.embor.7400897. PMC 1796779. PMID 17268505.

External links

• GeneReviews/NCBI/NIH/UW entry on Early-Onset Familial Alzheimer Disease