PSEN2

Presenilin 2 (Alzheimer disease 4)
Identifiers
Symbols	PSEN2; AD3L; AD4; PS2; STM2
External IDs	OMIM: 600759 MGI: 109284 HomoloGene: 386
Gene ontology
Molecular function	• protein binding; • peptidase activity;
Cellular component	• kinetochore; • integral to nuclear inner membrane; • endoplasmic reticulum; • Golgi apparatus; • integral to plasma membrane; • membrane; • integral to membrane;
Biological process	• cell fate specification; • membrane protein ectodomain proteolysis; • chromosome organization and biogenesis (sensu Eukaryota); • chromosome segregation; • Notch receptor processing; • intracellular signaling cascade; • apoptotic program; • protein processing; • embryonic limb morphogenesis; • anagen; • amyloid precursor protein catabolic process; • positive regulation of apoptosis; • positive regulation of enzyme activity;
RNA expression pattern
	More reference expression data
Orthologs
NP_000438 (protein)	NP_035313 (protein)

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

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 (Sep 1995). "A familial Alzheimer's disease locus on chromosome 1". Science 269 (5226): 970-3. 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): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
^ Mah, A L; Perry G, Smith M A, Monteiro M J (Nov. 2000). "Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation". J. Cell Biol. (UNITED STATES) 151 (4): 847-62. ISSN 0021-9525. PMID 11076969.
^ Tanahashi, H; Tabira T (Sep. 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 (Feb. 1998). "Interaction of presenilins with the filamin family of actin-binding proteins". J. Neurosci. (UNITED STATES) 18 (3): 914-22. ISSN 0270-6474. PMID 9437013.
^ Passer, B J; Pellegrini L, Vito P, Ganjei J K, D'Adamio L (Aug. 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): 24007-13. ISSN 0021-9258. PMID 10446169.
^ Lee, Sheu-Fen; Shah Sanjiv, Li Hongqiao, Yu Cong, Han Weiping, Yu Gang (Nov. 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): 45013-9. 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 (Sep. 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 10993060.
^ Morohashi, Yuichi; Hatano Noriyuki, Ohya Susumu, Takikawa Rie, Watabiki Tomonari, Takasugi Nobumasa, Imaizumi Yuji, Tomita Taisuke, Iwatsubo Takeshi (Apr. 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): 14965-75. 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 (Jun. 1999). "A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein". J. Cell Biol. (UNITED STATES) 145 (6): 1277-92. ISSN 0021-9525. PMID 10366599.
^ Buxbaum, J D; Choi E K, Luo Y, Lilliehook C, Crowley A C, Merriam D E, Wasco W (Oct. 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): 1177-81. doi:10.1038/2673. ISSN 1078-8956. PMID 9771743.
^ Choi, E K; Zaidi N F, Miller J S, Crowley A C, Merriam D E, Lilliehook C, Buxbaum J D, Wasco W (Jun. 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): 19197-204. 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): 183–90. 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. PMID 9683324.
Nishimura M, Yu G, St George-Hyslop PH (1999). "Biology of presenilins as causative molecules for Alzheimer disease.". Clin. Genet. 55 (4): 219–25. 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): 507–14. 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): 136–40. doi:10.1038/sj.embor.7400896. 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): 141–6. doi:10.1038/sj.embor.7400897. PMID 17268505.

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 (Sep 1995). "A familial Alzheimer's disease locus on chromosome 1". Science 269 (5226): 970-3. 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): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.

[pmid11076969-3] Mah, A L; Perry G, Smith M A, Monteiro M J (Nov. 2000). "Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation". J. Cell Biol. (UNITED STATES) 151 (4): 847-62. ISSN 0021-9525. PMID 11076969.

[pmid11001931-4] Tanahashi, H; Tabira T (Sep. 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 (Feb. 1998). "Interaction of presenilins with the filamin family of actin-binding proteins". J. Neurosci. (UNITED STATES) 18 (3): 914-22. ISSN 0270-6474. PMID 9437013.

[pmid10446169-6] Passer, B J; Pellegrini L, Vito P, Ganjei J K, D'Adamio L (Aug. 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): 24007-13. ISSN 0021-9258. PMID 10446169.

[pmid12297508-7] Lee, Sheu-Fen; Shah Sanjiv, Li Hongqiao, Yu Cong, Han Weiping, Yu Gang (Nov. 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): 45013-9. 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 (Sep. 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 10993060.

[pmid11847232-9] Morohashi, Yuichi; Hatano Noriyuki, Ohya Susumu, Takikawa Rie, Watabiki Tomonari, Takasugi Nobumasa, Imaizumi Yuji, Tomita Taisuke, Iwatsubo Takeshi (Apr. 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): 14965-75. 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 (Jun. 1999). "A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein". J. Cell Biol. (UNITED STATES) 145 (6): 1277-92. ISSN 0021-9525. PMID 10366599.

[pmid9771752-12] Buxbaum, J D; Choi E K, Luo Y, Lilliehook C, Crowley A C, Merriam D E, Wasco W (Oct. 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): 1177-81. doi:10.1038/2673. ISSN 1078-8956. PMID 9771743.

[pmid11278424-13] Choi, E K; Zaidi N F, Miller J S, Crowley A C, Merriam D E, Lilliehook C, Buxbaum J D, Wasco W (Jun. 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): 19197-204. doi:10.1074/jbc.M008597200. ISSN 0021-9258. PMID 11278424.

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PSEN2

From Wikipedia, the free encyclopedia

[edit] Interactions

[edit] References

[edit] Further reading

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