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Showing Protein Presenilin-1 (HMDBP07957)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP07957
Secondary Accession Numbers
  • 13668
Name Presenilin-1
Synonyms
  1. PS-1
  2. PS1-CTF12
  3. Presenilin-1 CTF subunit
  4. Presenilin-1 CTF12
  5. Presenilin-1 NTF subunit
  6. Protein S182
Gene Name PSEN1
Protein Type Unknown
Biological Properties
General Function Involved in intracellular signaling pathway
Specific Function Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. Stimulates cell-cell adhesion though its association with the E-cadherin/catenin complex. Under conditions of apoptosis or calcium influx, cleaves E-cadherin promoting the disassembly of the E-cadherin/catenin complex and increasing the pool of cytoplasmic beta-catenin, thus negatively regulating Wnt signaling. May also play a role in hematopoiesis
Pathways Not Available
Reactions Not Available
GO Classification
Component
membrane
cell part
membrane part
intrinsic to membrane
integral to membrane
Process
intracellular signaling pathway
signaling
signaling pathway
Cellular Location
  1. Golgi apparatus membrane
  2. Endoplasmic reticulum membrane
  3. Multi-pass membrane protein
  4. Multi-pass membrane protein
  5. Cell surface
Gene Properties
Chromosome Location Chromosome:1
Locus 14q24.3
SNPs PSEN1
Gene Sequence 
>1404 bp
ATGACAGAGTTACCTGCACCGTTGTCCTACTTCCAGAATGCACAGATGTCTGAGGACAAC
CACCTGAGCAATACTGTACGTAGCCAGAATGACAATAGAGAACGGCAGGAGCACAACGAC
AGACGGAGCCTTGGCCACCCTGAGCCATTATCTAATGGACGACCCCAGGGTAACTCCCGG
CAGGTGGTGGAGCAAGATGAGGAAGAAGATGAGGAGCTGACATTGAAATATGGCGCCAAG
CATGTGATCATGCTCTTTGTCCCTGTGACTCTCTGCATGGTGGTGGTCGTGGCTACCATT
AAGTCAGTCAGCTTTTATACCCGGAAGGATGGGCAGCTAATCTATACCCCATTCACAGAA
GATACCGAGACTGTGGGCCAGAGAGCCCTGCACTCAATTCTGAATGCTGCCATCATGATC
AGTGTCATTGTTGTCATGACTATCCTCCTGGTGGTTCTGTATAAATACAGGTGCTATAAG
GTCATCCATGCCTGGCTTATTATATCATCTCTATTGTTGCTGTTCTTTTTTTCATTCATT
TACTTGGGGGAAGTGTTTAAAACCTATAACGTTGCTGTGGACTACATTACTGTTGCACTC
CTGATCTGGAATTTTGGTGTGGTGGGAATGATTTCCATTCACTGGAAAGGTCCACTTCGA
CTCCAGCAGGCATATCTCATTATGATTAGTGCCCTCATGGCCCTGGTGTTTATCAAGTAC
CTCCCTGAATGGACTGCGTGGCTCATCTTGGCTGTGATTTCAGTATATGATTTAGTGGCT
GTTTTGTGTCCGAAAGGTCCACTTCGTATGCTGGTTGAAACAGCTCAGGAGAGAAATGAA
ACGCTTTTTCCAGCTCTCATTTACTCCTCAACAATGGTGTGGTTGGTGAATATGGCAGAA
GGAGACCCGGAAGCTCAAAGGAGAGTATCCAAAAATTCCAAGTATAATGCAGAAAGCACA
GAAAGGGAGTCACAAGACACTGTTGCAGAGAATGATGATGGCGGGTTCAGTGAGGAATGG
GAAGCCCAGAGGGACAGTCATCTAGGGCCTCATCGCTCTACACCTGAGTCACGAGCTGCT
GTCCAGGAACTTTCCAGCAGTATCCTCGCTGGTGAAGACCCAGAGGAAAGGGGAGTAAAA
CTTGGATTGGGAGATTTCATTTTCTACAGTGTTCTGGTTGGTAAAGCCTCAGCAACAGCC
AGTGGAGACTGGAACACAACCATAGCCTGTTTCGTAGCCATATTAATTGGTTTGTGCCTT
ACATTATTACTCCTTGCCATTTTCAAGAAAGCATTGCCAGCTCTTCCAATCTCCATCACC
TTTGGGCTTGTTTTCTACTTTGCCACAGATTATCTTGTACAGCCTTTTATGGACCAATTA
GCATTCCATCAATTTTATATCTAG
Protein Properties
Number of Residues 467
Molecular Weight 52667.3
Theoretical pI 4.97
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 83-103
  • 133-153
  • 161-181
  • 191-211
  • 221-241
  • 244-264
  • 408-428
  • 433-453
Protein Sequence 
>Presenilin-1
MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSR
QVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTE
DTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFI
YLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKY
LPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAE
GDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAA
VQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCL
TLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI
GenBank ID Protein 4506163
UniProtKB/Swiss-Prot ID P49768
UniProtKB/Swiss-Prot Entry Name PSN1_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_000021.3
GeneCard ID PSEN1
GenAtlas ID PSEN1
HGNC ID HGNC:9508
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  4. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976 ]
  5. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  6. Heilig R, Eckenberg R, Petit JL, Fonknechten N, Da Silva C, Cattolico L, Levy M, Barbe V, de Berardinis V, Ureta-Vidal A, Pelletier E, Vico V, Anthouard V, Rowen L, Madan A, Qin S, Sun H, Du H, Pepin K, Artiguenave F, Robert C, Cruaud C, Bruls T, Jaillon O, Friedlander L, Samson G, Brottier P, Cure S, Segurens B, Aniere F, Samain S, Crespeau H, Abbasi N, Aiach N, Boscus D, Dickhoff R, Dors M, Dubois I, Friedman C, Gouyvenoux M, James R, Madan A, Mairey-Estrada B, Mangenot S, Martins N, Menard M, Oztas S, Ratcliffe A, Shaffer T, Trask B, Vacherie B, Bellemere C, Belser C, Besnard-Gonnet M, Bartol-Mavel D, Boutard M, Briez-Silla S, Combette S, Dufosse-Laurent V, Ferron C, Lechaplais C, Louesse C, Muselet D, Magdelenat G, Pateau E, Petit E, Sirvain-Trukniewicz P, Trybou A, Vega-Czarny N, Bataille E, Bluet E, Bordelais I, Dubois M, Dumont C, Guerin T, Haffray S, Hammadi R, Muanga J, Pellouin V, Robert D, Wunderle E, Gauguet G, Roy A, Sainte-Marthe L, Verdier J, Verdier-Discala C, Hillier L, Fulton L, McPherson J, Matsuda F, Wilson R, Scarpelli C, Gyapay G, Wincker P, Saurin W, Quetier F, Waterston R, Hood L, Weissenbach J: The DNA sequence and analysis of human chromosome 14. Nature. 2003 Feb 6;421(6923):601-7. Epub 2003 Jan 1. [PubMed:12508121 ]
  7. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. [PubMed:14759258 ]
  8. Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, Tsuda T, Mar L, Foncin JF, Bruni AC, Montesi MP, Sorbi S, Rainero I, Pinessi L, Nee L, Chumakov I, Pollen D, Brookes A, Sanseau P, Polinsky RJ, Wasco W, Da Silva HA, Haines JL, Perkicak-Vance MA, Tanzi RE, Roses AD, Fraser PE, Rommens JM, St George-Hyslop PH: Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature. 1995 Jun 29;375(6534):754-60. [PubMed:7596406 ]
  9. Finckh U, Muller-Thomsen T, Mann U, Eggers C, Marksteiner J, Meins W, Binetti G, Alberici A, Hock C, Nitsch RM, Gal A: High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. Am J Hum Genet. 2000 Jan;66(1):110-7. [PubMed:10631141 ]
  10. Nielsen AL, Holm IE, Johansen M, Bonven B, Jorgensen P, Jorgensen AL: A new splice variant of glial fibrillary acidic protein, GFAP epsilon, interacts with the presenilin proteins. J Biol Chem. 2002 Aug 16;277(33):29983-91. Epub 2002 Jun 10. [PubMed:12058025 ]
  11. Baki L, Marambaud P, Efthimiopoulos S, Georgakopoulos A, Wen P, Cui W, Shioi J, Koo E, Ozawa M, Friedrich VL Jr, Robakis NK: Presenilin-1 binds cytoplasmic epithelial cadherin, inhibits cadherin/p120 association, and regulates stability and function of the cadherin/catenin adhesion complex. Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2381-6. [PubMed:11226248 ]
  12. Serban G, Kouchi Z, Baki L, Georgakopoulos A, Litterst CM, Shioi J, Robakis NK: Cadherins mediate both the association between PS1 and beta-catenin and the effects of PS1 on beta-catenin stability. J Biol Chem. 2005 Oct 28;280(43):36007-12. Epub 2005 Aug 26. [PubMed:16126725 ]
  13. Sahara N, Yahagi Y, Takagi H, Kondo T, Okochi M, Usami M, Shirasawa T, Mori H: Identification and characterization of presenilin I-467, I-463 and I-374. FEBS Lett. 1996 Feb 26;381(1-2):7-11. [PubMed:8641442 ]
  14. Tsujimura A, Yasojima K, Hashimoto-Gotoh T: Cloning of Xenopus presenilin-alpha and -beta cDNAs and their differential expression in oogenesis and embryogenesis. Biochem Biophys Res Commun. 1997 Feb 13;231(2):392-6. [PubMed:9070286 ]
  15. Vidal R, Ghiso J, Wisniewski T, Frangione B: Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes. Identification of a novel splice variant. FEBS Lett. 1996 Sep 9;393(1):19-23. [PubMed:8804415 ]
  16. Fraering PC, Ye W, Strub JM, Dolios G, LaVoie MJ, Ostaszewski BL, van Dorsselaer A, Wang R, Selkoe DJ, Wolfe MS: Purification and characterization of the human gamma-secretase complex. Biochemistry. 2004 Aug 3;43(30):9774-89. [PubMed:15274632 ]
  17. Kovacs DM, Fausett HJ, Page KJ, Kim TW, Moir RD, Merriam DE, Hollister RD, Hallmark OG, Mancini R, Felsenstein KM, Hyman BT, Tanzi RE, Wasco W: Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells. Nat Med. 1996 Feb;2(2):224-9. [PubMed:8574969 ]
  18. Podlisny MB, Citron M, Amarante P, Sherrington R, Xia W, Zhang J, Diehl T, Levesque G, Fraser P, Haass C, Koo EH, Seubert P, St George-Hyslop P, Teplow DB, Selkoe DJ: Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue. Neurobiol Dis. 1997;3(4):325-37. [PubMed:9173929 ]
  19. Walter J, Grunberg J, Capell A, Pesold B, Schindzielorz A, Citron M, Mendla K, George-Hyslop PS, Multhaup G, Selkoe DJ, Haass C: Proteolytic processing of the Alzheimer disease-associated presenilin-1 generates an in vivo substrate for protein kinase C. Proc Natl Acad Sci U S A. 1997 May 13;94(10):5349-54. [PubMed:9144240 ]
  20. Grunberg J, Walter J, Loetscher H, Deuschle U, Jacobsen H, Haass C: Alzheimer's disease associated presenilin-1 holoprotein and its 18-20 kDa C-terminal fragment are death substrates for proteases of the caspase family. Biochemistry. 1998 Feb 24;37(8):2263-70. [PubMed:9485372 ]
  21. Murayama M, Tanaka S, Palacino J, Murayama O, Honda T, Sun X, Yasutake K, Nihonmatsu N, Wolozin B, Takashima A: Direct association of presenilin-1 with beta-catenin. FEBS Lett. 1998 Aug 14;433(1-2):73-7. [PubMed:9738936 ]
  22. Zhang W, Han SW, McKeel DW, Goate A, Wu JY: Interaction of presenilins with the filamin family of actin-binding proteins. J Neurosci. 1998 Feb 1;18(3):914-22. [PubMed:9437013 ]
  23. Steiner H, Romig H, Pesold B, Philipp U, Baader M, Citron M, Loetscher H, Jacobsen H, Haass C: Amyloidogenic function of the Alzheimer's disease-associated presenilin 1 in the absence of endoproteolysis. Biochemistry. 1999 Nov 2;38(44):14600-5. [PubMed:10545183 ]
  24. Xu X, Shi Yc, Wu X, Gambetti P, Sui D, Cui MZ: Identification of a novel PSD-95/Dlg/ZO-1 (PDZ)-like protein interacting with the C terminus of presenilin-1. J Biol Chem. 1999 Nov 12;274(46):32543-6. [PubMed:10551805 ]
  25. Ray WJ, Yao M, Mumm J, Schroeter EH, Saftig P, Wolfe M, Selkoe DJ, Kopan R, Goate AM: Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch. J Biol Chem. 1999 Dec 17;274(51):36801-7. [PubMed:10593990 ]
  26. Levesque G, Yu G, Nishimura M, Zhang DM, Levesque L, Yu H, Xu D, Liang Y, Rogaeva E, Ikeda M, Duthie M, Murgolo N, Wang L, VanderVere P, Bayne ML, Strader CD, Rommens JM, Fraser PE, St George-Hyslop P: Presenilins interact with armadillo proteins including neural-specific plakophilin-related protein and beta-catenin. J Neurochem. 1999 Mar;72(3):999-1008. [PubMed:10037471 ]
  27. Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT, Selkoe DJ: Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature. 1999 Apr 8;398(6727):513-7. [PubMed:10206644 ]
  28. Berezovska O, Jack C, McLean P, Aster JC, Hicks C, Xia W, Wolfe MS, Kimberly WT, Weinmaster G, Selkoe DJ, Hyman BT: Aspartate mutations in presenilin and gamma-secretase inhibitors both impair notch1 proteolysis and nuclear translocation with relative preservation of notch1 signaling. J Neurochem. 2000 Aug;75(2):583-93. [PubMed:10899933 ]
  29. Kulic L, Walter J, Multhaup G, Teplow DB, Baumeister R, Romig H, Capell A, Steiner H, Haass C: Separation of presenilin function in amyloid beta-peptide generation and endoproteolysis of Notch. Proc Natl Acad Sci U S A. 2000 May 23;97(11):5913-8. [PubMed:10811883 ]
  30. Mirinics ZK, Calafat J, Udby L, Lovelock J, Kjeldsen L, Rothermund K, Sisodia SS, Borregaard N, Corey SJ: Identification of the presenilins in hematopoietic cells with localization of presenilin 1 to neutrophil and platelet granules. Blood Cells Mol Dis. 2002 Jan-Feb;28(1):28-38. [PubMed:11987239 ]
  31. Sai X, Kawamura Y, Kokame K, Yamaguchi H, Shiraishi H, Suzuki R, Suzuki T, Kawaichi M, Miyata T, Kitamura T, De Strooper B, Yanagisawa K, Komano H: Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein. J Biol Chem. 2002 Apr 12;277(15):12915-20. Epub 2002 Jan 17. [PubMed:11799129 ]
  32. Uemura K, Kitagawa N, Kohno R, Kuzuya A, Kageyama T, Chonabayashi K, Shibasaki H, Shimohama S: Presenilin 1 is involved in maturation and trafficking of N-cadherin to the plasma membrane. J Neurosci Res. 2003 Oct 15;74(2):184-91. [PubMed:14515347 ]
  33. Edbauer D, Winkler E, Regula JT, Pesold B, Steiner H, Haass C: Reconstitution of gamma-secretase activity. Nat Cell Biol. 2003 May;5(5):486-8. [PubMed:12679784 ]
  34. Kimberly WT, LaVoie MJ, Ostaszewski BL, Ye W, Wolfe MS, Selkoe DJ: Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6382-7. Epub 2003 May 9. [PubMed:12740439 ]
  35. Fluhrer R, Friedlein A, Haass C, Walter J: Phosphorylation of presenilin 1 at the caspase recognition site regulates its proteolytic processing and the progression of apoptosis. J Biol Chem. 2004 Jan 16;279(3):1585-93. Epub 2003 Oct 22. [PubMed:14576165 ]
  36. Wrigley JD, Nunn EJ, Nyabi O, Clarke EE, Hunt P, Nadin A, De Strooper B, Shearman MS, Beher D: Conserved residues within the putative active site of gamma-secretase differentially influence enzyme activity and inhibitor binding. J Neurochem. 2004 Sep;90(6):1312-20. [PubMed:15341515 ]
  37. Wang J, Beher D, Nyborg AC, Shearman MS, Golde TE, Goate A: C-terminal PAL motif of presenilin and presenilin homologues required for normal active site conformation. J Neurochem. 2006 Jan;96(1):218-27. Epub 2005 Nov 23. [PubMed:16305624 ]
  38. Cruts M, Hendriks L, Van Broeckhoven C: The presenilin genes: a new gene family involved in Alzheimer disease pathology. Hum Mol Genet. 1996;5 Spec No:1449-55. [PubMed:8875251 ]
  39. Cruts M, Van Broeckhoven C: Presenilin mutations in Alzheimer's disease. Hum Mutat. 1998;11(3):183-90. [PubMed:9521418 ]
  40. Cruts M, Backhovens H, Wang SY, Van Gassen G, Theuns J, De Jonghe CD, Wehnert A, De Voecht J, De Winter G, Cras P, et al.: Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3. Hum Mol Genet. 1995 Dec;4(12):2363-71. [PubMed:8634711 ]
  41. Campion D, Flaman JM, Brice A, Hannequin D, Dubois B, Martin C, Moreau V, Charbonnier F, Didierjean O, Tardieu S, et al.: Mutations of the presenilin I gene in families with early-onset Alzheimer's disease. Hum Mol Genet. 1995 Dec;4(12):2373-7. [PubMed:8634712 ]
  42. Rogaev EI, Sherrington R, Rogaeva EA, Levesque G, Ikeda M, Liang Y, Chi H, Lin C, Holman K, Tsuda T, et al.: Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature. 1995 Aug 31;376(6543):775-8. [PubMed:7651536 ]
  43. Authors unspecified: The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families. Nat Genet. 1995 Oct;11(2):219-22. [PubMed:7550356 ]
  44. Kamino K, Sato S, Sakaki Y, Yoshiiwa A, Nishiwaki Y, Takeda M, Tanabe H, Nishimura T, Ii K, St George-Hyslop PH, Miki T, Ogihara T: Three different mutations of presenilin 1 gene in early-onset Alzheimer's disease families. Neurosci Lett. 1996 Apr 26;208(3):195-8. [PubMed:8733303 ]
  45. Crook R, Ellis R, Shanks M, Thal LJ, Perez-Tur J, Baker M, Hutton M, Haltia T, Hardy J, Galasko D: Early-onset Alzheimer's disease with a presenilin-1 mutation at the site corresponding to the Volga German presenilin-2 mutation. Ann Neurol. 1997 Jul;42(1):124-8. [PubMed:9225696 ]
  46. Lendon CL, Martinez A, Behrens IM, Kosik KS, Madrigal L, Norton J, Neuman R, Myers A, Busfield F, Wragg M, Arcos M, Arango Viana JC, Ossa J, Ruiz A, Goate AM, Lopera F: E280A PS-1 mutation causes Alzheimer's disease but age of onset is not modified by ApoE alleles. Hum Mutat. 1997;10(3):186-95. [PubMed:9298817 ]
  47. Kwok JB, Taddei K, Hallupp M, Fisher C, Brooks WS, Broe GA, Hardy J, Fulham MJ, Nicholson GA, Stell R, St George Hyslop PH, Fraser PE, Kakulas B, Clarnette R, Relkin N, Gandy SE, Schofield PR, Martins RN: Two novel (M233T and R278T) presenilin-1 mutations in early-onset Alzheimer's disease pedigrees and preliminary evidence for association of presenilin-1 mutations with a novel phenotype. Neuroreport. 1997 Apr 14;8(6):1537-42. [PubMed:9172170 ]
  48. Ramirez-Duenas MG, Rogaeva EA, Leal CA, Lin C, Ramirez-Casillas GA, Hernandez-Romo JA, St George-Hyslop PH, Cantu JM: A novel Leu171Pro mutation in presenilin-1 gene in a Mexican family with early onset Alzheimer disease. Ann Genet. 1998;41(3):149-53. [PubMed:9833068 ]
  49. Mattila KM, Forsell C, Pirttila T, Rinne JO, Lehtimaki T, Roytta M, Lilius L, Eerola A, St George-Hyslop PH, Frey H, Lannfelt L: The Glu318Gly mutation of the presenilin-1 gene does not necessarily cause Alzheimer's disease. Ann Neurol. 1998 Dec;44(6):965-7. [PubMed:9851443 ]
  50. Aldudo J, Bullido MJ, Frank A, Valdivieso F: Missense mutation E318G of the presenilin-1 gene appears to be a nonpathogenic polymorphism. Ann Neurol. 1998 Dec;44(6):985-6. [PubMed:9851450 ]
  51. Cruts M, van Duijn CM, Backhovens H, Van den Broeck M, Wehnert A, Serneels S, Sherrington R, Hutton M, Hardy J, St George-Hyslop PH, Hofman A, Van Broeckhoven C: Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease. Hum Mol Genet. 1998 Jan;7(1):43-51. [PubMed:9384602 ]
  52. Poorkaj P, Sharma V, Anderson L, Nemens E, Alonso ME, Orr H, White J, Heston L, Bird TD, Schellenberg GD: Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene. Hum Mutat. 1998;11(3):216-21. [PubMed:9521423 ]
  53. Besancon R, Lorenzi A, Cruts M, Radawiec S, Sturtz F, Broussolle E, Chazot G, van Broeckhoven C, Chamba G, Vandenberghe A: Missense mutation in exon 11 (Codon 378) of the presenilin-1 gene in a French family with early-onset Alzheimer's disease and transmission study by mismatch enhanced allele specific amplification. Mutations in brief no. 141. Online. besancon@rockefeller1.univ.lyon1.fr. Hum Mutat. 1998;11(6):481. [PubMed:10200054 ]
  54. Dumanchin C, Brice A, Campion D, Hannequin D, Martin C, Moreau V, Agid Y, Martinez M, Clerget-Darpoux F, Frebourg T: De novo presenilin 1 mutations are rare in clinically sporadic, early onset Alzheimer's disease cases. French Alzheimer's Disease Study Group. J Med Genet. 1998 Aug;35(8):672-3. [PubMed:9719376 ]
  55. Wisniewski T, Dowjat WK, Buxbaum JD, Khorkova O, Efthimiopoulos S, Kulczycki J, Lojkowska W, Wegiel J, Wisniewski HM, Frangione B: A novel Polish presenilin-1 mutation (P117L) is associated with familial Alzheimer's disease and leads to death as early as the age of 28 years. Neuroreport. 1998 Jan 26;9(2):217-21. [PubMed:9507958 ]
  56. Taddei K, Kwok JB, Kril JJ, Halliday GM, Creasey H, Hallupp M, Fisher C, Brooks WS, Chung C, Andrews C, Masters CL, Schofield PR, Martins RN: Two novel presenilin-1 mutations (Ser169Leu and Pro436Gln) associated with very early onset Alzheimer's disease. Neuroreport. 1998 Oct 5;9(14):3335-9. [PubMed:9831473 ]
  57. Dermaut B, Cruts M, Slooter AJ, Van Gestel S, De Jonghe C, Vanderstichele H, Vanmechelen E, Breteler MM, Hofman A, van Duijn CM, Van Broeckhoven C: The Glu318Gly substitution in presenilin 1 is not causally related to Alzheimer disease. Am J Hum Genet. 1999 Jan;64(1):290-2. [PubMed:9915968 ]
  58. Campion D, Dumanchin C, Hannequin D, Dubois B, Belliard S, Puel M, Thomas-Anterion C, Michon A, Martin C, Charbonnier F, Raux G, Camuzat A, Penet C, Mesnage V, Martinez M, Clerget-Darpoux F, Brice A, Frebourg T: Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. Am J Hum Genet. 1999 Sep;65(3):664-70. [PubMed:10441572 ]
  59. Palmer MS, Beck JA, Campbell TA, Humphries CB, Roques PK, Fox NC, Harvey R, Rossor MN, Collinge J: Pathogenic presenilin 1 mutations (P436S & I143F) in early-onset Alzheimer's disease in the UK. Mutations in brief no. 223. Online. Hum Mutat. 1999;13(3):256. [PubMed:10090481 ]
  60. Sugiyama N, Suzuki K, Matsumura T, Kawanishi C, Onishi H, Yamada Y, Iseki E, Kosaka K: A novel missense mutation (G209R) in exon 8 of the presenilin 1 gene in a Japanese family with presenile familial Alzheimer's disease. Mutation in brief no. 254. Online. Hum Mutat. 1999;14(1):90. [PubMed:10447269 ]
  61. Aldudo J, Bullido MJ, Valdivieso F: DGGE method for the mutational analysis of the coding and proximal promoter regions of the Alzheimer's disease presenilin-1 gene: two novel mutations. Hum Mutat. 1999;14(5):433-9. [PubMed:10533070 ]
  62. Ezquerra M, Carnero C, Blesa R, Gelpi JL, Ballesta F, Oliva R: A presenilin 1 mutation (Ser169Pro) associated with early-onset AD and myoclonic seizures. Neurology. 1999 Feb;52(3):566-70. [PubMed:10025789 ]
  63. Smith MJ, Gardner RJ, Knight MA, Forrest SM, Beyreuther K, Storey E, McLean CA, Cotton RG, Cappal R, Masters CL: Early-onset Alzheimer's disease caused by a novel mutation at codon 219 of the presenilin-1 gene. Neuroreport. 1999 Feb 25;10(3):503-7. [PubMed:10208579 ]
  64. Romero I, Jorgensen P, Bolwig G, Fraser PE, Rogaeva E, Mann D, Havsager AM, Jorgensen AL: A presenilin-1 Thr116Asn substitution in a family with early-onset Alzheimer's disease. Neuroreport. 1999 Aug 2;10(11):2255-60. [PubMed:10439444 ]
  65. Yasuda M, Maeda S, Kawamata T, Tamaoka A, Yamamoto Y, Kuroda S, Maeda K, Tanaka C: Novel presenilin-1 mutation with widespread cortical amyloid deposition but limited cerebral amyloid angiopathy. J Neurol Neurosurg Psychiatry. 2000 Feb;68(2):220-3. [PubMed:10644793 ]
  66. Lewis PA, Perez-Tur J, Golde TE, Hardy J: The presenilin 1 C92S mutation increases abeta 42 production. Biochem Biophys Res Commun. 2000 Oct 14;277(1):261-3. [PubMed:11027672 ]
  67. Raux G, Gantier R, Thomas-Anterion C, Boulliat J, Verpillat P, Hannequin D, Brice A, Frebourg T, Campion D: Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation. Neurology. 2000 Nov 28;55(10):1577-8. [PubMed:11094121 ]
  68. Athan ES, Williamson J, Ciappa A, Santana V, Romas SN, Lee JH, Rondon H, Lantigua RA, Medrano M, Torres M, Arawaka S, Rogaeva E, Song YQ, Sato C, Kawarai T, Fafel KC, Boss MA, Seltzer WK, Stern Y, St George-Hyslop P, Tycko B, Mayeux R: A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families. JAMA. 2001 Nov 14;286(18):2257-63. [PubMed:11710891 ]
  69. Matsubara-Tsutsui M, Yasuda M, Yamagata H, Nomura T, Taguchi K, Kohara K, Miyoshi K, Miki T: Molecular evidence of presenilin 1 mutation in familial early onset dementia. Am J Med Genet. 2002 Apr 8;114(3):292-8. [PubMed:11920851 ]
  70. Moehlmann T, Winkler E, Xia X, Edbauer D, Murrell J, Capell A, Kaether C, Zheng H, Ghetti B, Haass C, Steiner H: Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of their effect on Abeta 42 production. Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8025-30. Epub 2002 Jun 4. [PubMed:12048239 ]
  71. Bertoli Avella AM, Marcheco Teruel B, Llibre Rodriguez JJ, Gomez Viera N, Borrajero Martinez I, Severijnen EA, Joosse M, van Duijn CM, Heredero Baute L, Heutink P: A novel presenilin 1 mutation (L174 M) in a large Cuban family with early onset Alzheimer disease. Neurogenetics. 2002 Oct;4(2):97-104. [PubMed:12484344 ]
  72. Kwok JB, Halliday GM, Brooks WS, Dolios G, Laudon H, Murayama O, Hallupp M, Badenhop RF, Vickers J, Wang R, Naslund J, Takashima A, Gandy SE, Schofield PR: Presenilin-1 mutation L271V results in altered exon 8 splicing and Alzheimer's disease with non-cored plaques and no neuritic dystrophy. J Biol Chem. 2003 Feb 28;278(9):6748-54. Epub 2002 Dec 19. [PubMed:12493737 ]
  73. Cornier AS, Staehling-Hampton K, Delventhal KM, Saga Y, Caubet JF, Sasaki N, Ellard S, Young E, Ramirez N, Carlo SE, Torres J, Emans JB, Turnpenny PD, Pourquie O: Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome. Am J Hum Genet. 2008 Jun;82(6):1334-41. doi: 10.1016/j.ajhg.2008.04.014. Epub 2008 May 15. [PubMed:18485326 ]