PSEN2

Presenilin 2 (Alzheimer disease 4)
Identifiers
Symbols	PSEN2; AD3L; AD4; CMD1V; PS2; STM2
External IDs	OMIM: 600759 MGI: 109284 HomoloGene: 386 GeneCards: PSEN2 Gene
Gene Ontology
Molecular function	• endopeptidase activity; • endopeptidase activity; • aspartic-type endopeptidase activity; • protein binding; • peptidase activity;
Cellular component	• Golgi membrane; • kinetochore; • membrane fraction; • nuclear inner membrane; • mitochondrial inner membrane; • lysosomal membrane; • endoplasmic reticulum; • endoplasmic reticulum membrane; • Golgi apparatus; • centrosome; • cytosol; • plasma membrane; • integral to plasma membrane; • cell cortex; • cell surface; • apical plasma membrane; • Z disc; • axon; • growth cone; • neuromuscular junction; • ciliary rootlet; • neuronal cell body; • dendritic shaft; • protein complex; • membrane raft; • perinuclear region of cytoplasm;
Biological process	• negative regulation of transcription from RNA polymerase II promoter; • response to hypoxia; • cell fate specification; • somitogenesis; • positive regulation of receptor recycling; • negative regulation of protein phosphorylation; • hair follicle development; • hemopoietic progenitor cell differentiation; • T cell activation involved in immune response; • myeloid leukocyte differentiation; • proteolysis; • membrane protein ectodomain proteolysis; • calcium ion transport; • apoptotic process; • anti-apoptosis; • negative regulation of epidermal growth factor-activated receptor activity; • Notch signaling pathway; • Notch receptor processing; • Notch receptor processing; • memory; • cell death; • induction of apoptosis by extracellular signals; • embryo development; • protein transport; • protein processing; • dorsal/ventral neural tube patterning; • embryonic limb morphogenesis; • forebrain development; • membrane protein intracellular domain proteolysis; • positive regulation of proteasomal ubiquitin-dependent protein catabolic process; • intracellular signal transduction; • locomotion; • anagen; • amyloid precursor protein catabolic process; • amyloid precursor protein catabolic process; • positive regulation of apoptotic process; • positive regulation of catalytic activity; • skin morphogenesis; • nerve growth factor 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; • negative regulation of ubiquitin-protein ligase activity; • cardiac muscle contraction; • negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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Presenilin-2 is a protein that in humans is encoded by the PSEN2 gene.^[1]

[edit] 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 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]

[edit] Interactions

PSEN2 has been shown to interact with UBQLN1,^[4] FHL2,^[5] FLNB,^[6] BCL2-like 1,^[7] Nicastrin,^[8]^[9] KCNIP4,^[10] CAPN1,^[11] CIB1^[12] and Calsenilin.^[13]^[14]

[edit] References

^ Levy-Lahad E, Wijsman EM, Nemens E, Anderson L, Goddard KA, Weber JL, Bird TD, Schellenberg GD (September 1995). "A familial Alzheimer's disease locus on chromosome 1". Science 269 (5226): 970–973. doi:10.1126/science.7638621. PMID 7638621.
^ "Entrez Gene: PSEN2 presenilin 2 (Alzheimer disease 4)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5664.
^ Hoek KS, Schlegel NC, Eichhoff OM et al (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.
^ Mah, A L; Perry G, Smith M A, Monteiro M J (November 2000). "Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation". J. Cell Biol. (UNITED STATES) 151 (4): 847–862. doi:10.1083/jcb.151.4.847. ISSN 0021-9525. PMC 2169435. PMID 11076969. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2169435.
^ Tanahashi, H; Tabira T (September 2000). "Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein". Hum. Mol. Genet. (ENGLAND) 9 (15): 2281–9. ISSN 0964-6906. PMID 11001931.
^ Zhang, W; Han S W, McKeel D W, Goate A, Wu J Y (February 1998). "Interaction of presenilins with the filamin family of actin-binding proteins". J. Neurosci. (UNITED STATES) 18 (3): 914–22. ISSN 0270-6474. PMC 2042137. PMID 9437013. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2042137.
^ Passer, B J; Pellegrini L, Vito P, Ganjei J K, 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. (UNITED STATES) 274 (34): 24007–24013. doi:10.1074/jbc.274.34.24007. ISSN 0021-9258. PMID 10446169.
^ Lee, Sheu-Fen; Shah Sanjiv, Li Hongqiao, Yu Cong, Han Weiping, Yu Gang (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. (United States) 277 (47): 45013–45019. doi:10.1074/jbc.M208164200. ISSN 0021-9258. PMID 12297508.
^ Yu, G; Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song Y Q, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang D S, Holmes E, Milman P, Liang Y, Zhang D M, Xu D H, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer L S, 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 (ENGLAND) 407 (6800): 48–54. doi:10.1038/35024009. ISSN 0028-0836. PMID 10993067.
^ Morohashi, Yuichi; Hatano Noriyuki, Ohya Susumu, Takikawa Rie, Watabiki Tomonari, Takasugi Nobumasa, Imaizumi Yuji, Tomita Taisuke, Iwatsubo Takeshi (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. (United States) 277 (17): 14965–14975. doi:10.1074/jbc.M200897200. ISSN 0021-9258. PMID 11847232.
^ Shinozaki, K; Maruyama K, Kume H, Tomita T, Saido T C, Iwatsubo T, Obata K (May 1998). "The presenilin 2 loop domain interacts with the mu-calpain C-terminal region". Int. J. Mol. Med. (GREECE) 1 (5): 797–9. ISSN 1107-3756. PMID 9852298.
^ Stabler, S M; Ostrowski L L, Janicki S M, Monteiro M J (June 1999). "A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein". J. Cell Biol. (UNITED STATES) 145 (6): 1277–1292. doi:10.1083/jcb.145.6.1277. ISSN 0021-9525. PMC 2133148. PMID 10366599. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2133148.
^ Buxbaum, J D; Choi E K, Luo Y, Lilliehook C, Crowley A C, Merriam D E, Wasco W (October 1998). "Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment". Nat. Med. (UNITED STATES) 4 (10): 1177–1181. doi:10.1038/2673. ISSN 1078-8956. PMID 9771752.
^ Choi, E K; Zaidi N F, Miller J S, Crowley A C, Merriam D E, Lilliehook C, Buxbaum J D, 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. (United States) 276 (22): 19197–19204. doi:10.1074/jbc.M008597200. ISSN 0021-9258. PMID 11278424.

[edit] 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; Kawamata; McGeer (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1796780.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1796779.

[edit] External links

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

This article on a gene on chromosome 1 is a stub. You can help Wikipedia by expanding it.

[pmid7638621-0] Levy-Lahad E, Wijsman EM, Nemens E, Anderson L, Goddard KA, Weber JL, Bird TD, Schellenberg GD (September 1995). "A familial Alzheimer's disease locus on chromosome 1". Science 269 (5226): 970–973. doi:10.1126/science.7638621. PMID 7638621.

[1] "Entrez Gene: PSEN2 presenilin 2 (Alzheimer disease 4)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5664.

[pmid19067971-2] Hoek KS, Schlegel NC, Eichhoff OM et al (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.

[pmid11076969-3] Mah, A L; Perry G, Smith M A, Monteiro M J (November 2000). "Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation". J. Cell Biol. (UNITED STATES) 151 (4): 847–862. doi:10.1083/jcb.151.4.847. ISSN 0021-9525. PMC 2169435. PMID 11076969. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2169435.

[pmid11001931-4] Tanahashi, H; Tabira T (September 2000). "Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein". Hum. Mol. Genet. (ENGLAND) 9 (15): 2281–9. ISSN 0964-6906. PMID 11001931.

[pmid9437013-5] Zhang, W; Han S W, McKeel D W, Goate A, Wu J Y (February 1998). "Interaction of presenilins with the filamin family of actin-binding proteins". J. Neurosci. (UNITED STATES) 18 (3): 914–22. ISSN 0270-6474. PMC 2042137. PMID 9437013. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2042137.

[pmid10446169-6] Passer, B J; Pellegrini L, Vito P, Ganjei J K, 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. (UNITED STATES) 274 (34): 24007–24013. doi:10.1074/jbc.274.34.24007. ISSN 0021-9258. PMID 10446169.

[pmid12297508-7] Lee, Sheu-Fen; Shah Sanjiv, Li Hongqiao, Yu Cong, Han Weiping, Yu Gang (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. (United States) 277 (47): 45013–45019. doi:10.1074/jbc.M208164200. ISSN 0021-9258. PMID 12297508.

[pmid10993067-8] Yu, G; Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song Y Q, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang D S, Holmes E, Milman P, Liang Y, Zhang D M, Xu D H, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer L S, 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 (ENGLAND) 407 (6800): 48–54. doi:10.1038/35024009. ISSN 0028-0836. PMID 10993067.

[pmid11847232-9] Morohashi, Yuichi; Hatano Noriyuki, Ohya Susumu, Takikawa Rie, Watabiki Tomonari, Takasugi Nobumasa, Imaizumi Yuji, Tomita Taisuke, Iwatsubo Takeshi (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. (United States) 277 (17): 14965–14975. doi:10.1074/jbc.M200897200. ISSN 0021-9258. PMID 11847232.

[pmid9852298-10] Shinozaki, K; Maruyama K, Kume H, Tomita T, Saido T C, Iwatsubo T, Obata K (May 1998). "The presenilin 2 loop domain interacts with the mu-calpain C-terminal region". Int. J. Mol. Med. (GREECE) 1 (5): 797–9. ISSN 1107-3756. PMID 9852298.

[pmid10366599-11] Stabler, S M; Ostrowski L L, Janicki S M, Monteiro M J (June 1999). "A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein". J. Cell Biol. (UNITED STATES) 145 (6): 1277–1292. doi:10.1083/jcb.145.6.1277. ISSN 0021-9525. PMC 2133148. PMID 10366599. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2133148.

[pmid9771752-12] Buxbaum, J D; Choi E K, Luo Y, Lilliehook C, Crowley A C, Merriam D E, Wasco W (October 1998). "Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment". Nat. Med. (UNITED STATES) 4 (10): 1177–1181. doi:10.1038/2673. ISSN 1078-8956. PMID 9771752.

[pmid11278424-13] Choi, E K; Zaidi N F, Miller J S, Crowley A C, Merriam D E, Lilliehook C, Buxbaum J D, 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. (United States) 276 (22): 19197–19204. doi:10.1074/jbc.M008597200. ISSN 0021-9258. PMID 11278424.

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PSEN2

Contents

[edit] Function

[edit] Interactions

[edit] References

[edit] Further reading

[edit] External links

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