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|---|---|
| Accession Number: | P49768 |
| Protein Name: | Presenilin-1 aka Protein S182 |
| Length: | 467 |
| Molecular Weight: | 52668.00 |
| Species: | Homo sapiens (Human) [9606] |
| Number of TMSs: | 9 |
| Location1 / Topology2 / Orientation3: | Endoplasmic reticulum membrane1 / Multi-pass membrane protein2 |
| Substrate | inorganic cation, calcium(2+), peptide |
Cross database links:
| DIP: | DIP-1134N |
|---|---|
| RefSeq: | NP_000012.1 NP_015557.2 |
| Entrez Gene ID: | 5663 |
| Pfam: | PF01080 |
| OMIM: |
104311 gene 600274 phenotype 607822 phenotype |
| KEGG: | hsa:5663 |
Gene Ontology
GO:0009986
C:cell surface
GO:0005789
C:endoplasmic reticulum membrane
GO:0000139
C:Golgi membrane
GO:0005639
C:integral to nuclear inner membrane
GO:0005887
C:integral to plasma membrane
GO:0000776
C:kinetochore
GO:0005640
C:nuclear outer membrane
GO:0008013
F:beta-catenin binding
GO:0030165
F:PDZ domain binding
GO:0042987
P:amyloid precursor protein catabolic process
GO:0006916
P:anti-apoptosis
GO:0016337
P:cell-cell adhesion
GO:0007059
P:chromosome segregation
GO:0008624
P:induction of apoptosis by extracellular sig...
GO:0006509
P:membrane protein ectodomain proteolysis
GO:0031293
P:membrane protein intracellular domain prote...
GO:0007220
P:Notch receptor processing
| |
References (74)[1] “Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease.” Sherrington R.et.al. 7596406 [2] “Identification and characterization of presenilin I-467, I-463 and I-374.” Sahara N.et.al. 8641442 [3] “Complete sequencing and characterization of 21,243 full-length human cDNAs.” Ota T.et.al. 14702039 [4] “The DNA sequence and analysis of human chromosome 14.” Heilig R.et.al. 12508121 [5] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).” The MGC Project Teamet.al. 15489334 [6] “Cloning of Xenopus presenilin-alpha and -beta cDNAs and their differential expression in oogenesis and embryogenesis.” Tsujimura A.et.al. 9070286 [7] “Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes. Identification of a novel splice variant.” Vidal R.et.al. 8804415 [8] “Purification and characterization of the human gamma-secretase complex.” Fraering P.C.et.al. 15274632 [9] “Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells.” Kovacs D.M.et.al. 8574969 [10] “Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue.” Podlisny M.B.et.al. 9173929 [11] “Proteolytic processing of the Alzheimer disease-associated presenilin-1 generates an in vivo substrate for protein kinase C.” Walter J.et.al. 9144240 [12] “Alzheimer's disease associated presenilin-1 holoprotein and its 18-20 kDa C-terminal fragment are death substrates for proteases of the caspase family.” Gruenberg J.et.al. 9485372 [13] “Direct association of presenilin-1 with beta-catenin.” Murayama M.et.al. 9738936 [14] “Interaction of presenilins with the filamin family of actin-binding proteins.” Zhang W.et.al. 9437013 [15] “Amyloidogenic function of the Alzheimer's disease-associated presenilin 1 in the absence of endoproteolysis.” Steiner H.et.al. 10545183 [16] “Identification of a novel PSD-95/Dlg/ZO-1 (PDZ)-like protein interacting with the C terminus of presenilin-1.” Xu X.et.al. 10551805 [17] “Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch.” Ray W.J.et.al. 10593990 [18] “Presenilins interact with armadillo proteins including neural-specific plakophilin-related protein and beta-catenin.” Levesque G.et.al. 10037471 [19] “Presenilin-1 forms complexes with the cadherin/catenin cell-cell adhesion system and is recruited to intercellular and synaptic contacts.” Georgakopoulos A.et.al. 10635315 [20] “Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity.” Wolfe M.S.et.al. 10206644 [21] “Aspartate mutations in presenilin and gamma-secretase inhibitors both impair notch1 proteolysis and nuclear translocation with relative preservation of notch1 signaling.” Berezovska O.et.al. 10899933 [22] “Separation of presenilin function in amyloid beta-peptide generation and endoproteolysis of Notch.” Kulic L.et.al. 10811883 [23] “Presenilin-1 binds cytoplasmic epithelial cadherin, inhibits cadherin/p120 association, and regulates stability and function of the cadherin/catenin adhesion complex.” Baki L.et.al. 11226248 [24] “Identification of the presenilins in hematopoietic cells with localization of presenilin 1 to neutrophil and platelet granules.” Mirinics Z.K.et.al. 11987239 [25] “Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein.” Sai X.et.al. 11799129 [26] “A new splice variant of glial fibrillary acidic protein GFAPepsilon, interacts with the presenilin proteins.” Nielsen A.L.et.al. 12058025 [27] “Presenilin 1 is involved in maturation and trafficking of N-cadherin to the plasma membrane.” Uemura K.et.al. 14515347 [28] “Reconstitution of gamma-secretase activity.” Edbauer D.et.al. 12679784 [29] “Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2.” Kimberly W.T.et.al. 12740439 [30] “An unappreciated role for RNA surveillance.” Hillman R.T.et.al. 14759258 [31] “Phosphorylation of presenilin 1 at the caspase recognition site regulates its proteolytic processing and the progression of apoptosis.” Fluhrer R.et.al. 14576165 [32] “Conserved residues within the putative active site of gamma-secretase differentially influence enzyme activity and inhibitor binding.” Wrigley J.D.et.al. 15341515 [33] “Cadherins mediate both the association between PS1 and beta-catenin and the effects of PS1 on beta-catenin stability.” Serban G.et.al. 16126725 [34] “Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.” Olsen J.V.et.al. 17081983 [35] “C-terminal PAL motif of presenilin and presenilin homologues required for normal active site conformation.” Wang J.et.al. 16305624 [36] “The presenilin genes: a new gene family involved in Alzheimer disease pathology.” Cruts M.et.al. 8875251 [37] “Presenilin mutations in Alzheimer's disease.” Cruts M.et.al. 9521418 [38] “Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.” Daub H.et.al. 18691976 [39] “Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.” Mayya V.et.al. 19690332 [40] “Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3.” Cruts M.et.al. 8634711 [41] “Mutations of the presenilin I gene in families with early-onset Alzheimer's disease.” Campion D.et.al. 8634712 [42] “Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene.” Rogaev E.I.et.al. 7651536 [43] “The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families.” Clark R.F.et.al. 7550356 [44] “Three different mutations of presenilin 1 gene in early-onset Alzheimer's disease families.” Kamino K.et.al. 8733303 [45] “Early-onset Alzheimer's disease with a presenilin-1 mutation at the site corresponding to the Volga German presenilin-2 mutation.” Crook R.et.al. 9225696 [46] “E280A PS-1 mutation causes Alzheimer's disease but age of onset is not modified by ApoE alleles.” Lendon C.L.et.al. 9298817 [47] “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.” Kwok J.B.J.et.al. 9172170 [48] “A novel Leu171Pro mutation in presenilin-1 gene in a Mexican family with early onset Alzheimer disease.” Ramirez-Duenas M.G.et.al. 9833068 [49] “The Glu318Gly mutation of the presenilin-1 gene does not necessarily cause Alzheimer's disease.” Mattila K.M.et.al. 9851443 [50] “Missense mutation E318G of the presenilin-1 gene appears to be a nonpathogenic polymorphism.” Aldudo J.et.al. 9851450 [51] “Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease.” Cruts M.et.al. 9384602 [52] “Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene.” Poorkaj P.et.al. 9521423 [53] “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.” Besancon R.et.al. 10200054 [54] “De novo presenilin 1 mutations are rare in clinically sporadic, early onset Alzheimer's disease cases.” Dumanchin C.et.al. 9719376 [55] “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.” Wisniewski T.et.al. 9507958 [56] “Two novel presenilin-1 mutations (Ser169Leu and Pro436Gln) associated with very early onset Alzheimer's disease.” Taddei K.et.al. 9831473 [57] “The Glu318Gly substitution in presenilin 1 is not causally related to Alzheimer disease.” Dermaut B.et.al. 9915968 [58] “Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum.” Campion D.et.al. 10441572 [59] “Pathogenic presenilin 1 mutations (P436S and I143F) in early-onset Alzheimer's disease in the UK.” Palmer M.S.et.al. 10090481 [60] “A novel missense mutation (G209R) in exon 8 of the presenilin 1 gene in a Japanese family with presenile familial Alzheimer's disease.” Sugiyama N.et.al. 10447269 [61] “DGGE method for the mutational analysis of the coding and proximal promoter regions of the Alzheimer's disease presenilin-1 gene: two novel mutations.” Aldudo J.et.al. 10533070 [62] “A presenilin 1 mutation (Ser169Pro) associated with early-onset AD and myoclonic seizures.” Ezquerra M.et.al. 10025789 [63] “Early-onset Alzheimer's disease caused by a novel mutation at codon 219 of the presenilin-1 gene.” Smith M.J.et.al. 10208579 [64] “A presenilin-1 Thr116Asn substitution in a family with early-onset Alzheimer's disease.” Romero I.et.al. 10439444 [65] “High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes.” Finckh U.et.al. 10631141 [66] “Novel presenilin-1 mutation with widespread cortical amyloid deposition but limited cerebral amyloid angiopathy.” Yasuda M.et.al. 10644793 [67] “The presenilin 1 C92S mutation increases abeta 42 production.” Lewis P.A.et.al. 11027672 [68] “Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation.” Raux G.et.al. 11094121 [69] “A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families.” Athan E.S.et.al. 11710891 [70] “Molecular evidence of presenilin 1 mutation in familial early onset dementia.” Matsubara-Tsutsui M.et.al. 11920851 [71] “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.” Moehlmann T.et.al. 12048239 [72] “A novel presenilin 1 mutation (L174 M) in a large Cuban family with early onset Alzheimer disease.” Bertoli-Avella A.M.et.al. 12484344 | |
| Structure: | |
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External Searches:
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Analyze:
| Predict TMSs (Predict number of transmembrane segments) | ||||
| FASTA formatted sequence |
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1: MTELPAPLSY FQNAQMSEDN HLSNTVRSQN DNRERQEHND RRSLGHPEPL SNGRPQGNSR 61: QVVEQDEEED EELTLKYGAK HVIMLFVPVT LCMVVVVATI KSVSFYTRKD GQLIYTPFTE 121: DTETVGQRAL HSILNAAIMI SVIVVMTILL VVLYKYRCYK VIHAWLIISS LLLLFFFSFI 181: YLGEVFKTYN VAVDYITVAL LIWNFGVVGM ISIHWKGPLR LQQAYLIMIS ALMALVFIKY 241: LPEWTAWLIL AVISVYDLVA VLCPKGPLRM LVETAQERNE TLFPALIYSS TMVWLVNMAE 301: GDPEAQRRVS KNSKYNAEST ERESQDTVAE NDDGGFSEEW EAQRDSHLGP HRSTPESRAA 361: VQELSSSILA GEDPEERGVK LGLGDFIFYS VLVGKASATA SGDWNTTIAC FVAILIGLCL 421: TLLLLAIFKK ALPALPISIT FGLVFYFATD YLVQPFMDQL AFHQFYI