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1.A.54.1.2
Presenilin-2 (PS-2; STM-2; E5-2; AD3 LP; AD5 PSN-2) Ca2+ leak channel of 448 aas and 9 TMSs. Presenilins 1 and 2 (PS1 & PS2) are main genetic risk factors of familial Alzheimer's disease (AD) that produce the beta-amyloid (Abeta) peptides. They also function in calcium signaling (Dehury et al. 2019). Mutations in both cause AD. The 9-TMS channel structure is substantially controlled by major dynamics in the hydrophilic loop bridging TMS6 and TMS7, which functions as a "plug" in the PS2 membrane channel. TMS2, TMS6, TMS7 and TMS9 flexibility controls the size of this channel. Most pathogenic PS2 mutations reduce stability relative to random mutations (Dehury et al. 2019).

Accession Number:P49810
Protein Name:Presenilin-2 aka AD3LP aka AD5
Length:448
Molecular Weight:50140.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:9
Location1 / Topology2 / Orientation3: Endoplasmic reticulum membrane1 / Multi-pass membrane protein2
Substrate Ca2+

Cross database links:

Genevestigator: P49810
eggNOG: prNOG07613
RefSeq: NP_000438.2    NP_036618.2   
Entrez Gene ID: 5664   
Pfam: PF01080   
OMIM: 600759  gene
606889  phenotype
KEGG: hsa:5664   

Gene Ontology

GO:0005789 C:endoplasmic reticulum membrane
GO:0000139 C:Golgi membrane
GO:0005887 C:integral to plasma membrane
GO:0005515 F:protein binding
GO:0042987 P:amyloid precursor protein catabolic process
GO:0006915 P:apoptosis
GO:0008624 P:induction of apoptosis by extracellular sig...
GO:0007242 ?:?
GO:0006509 P:membrane protein ectodomain proteolysis
GO:0031293 P:membrane protein intracellular domain prote...
GO:0007220 P:Notch receptor processing
GO:0043085 P:positive regulation of catalytic activity

References (16)

[1] “Candidate gene for the chromosome 1 familial Alzheimer's disease locus.”  Levy-Lahad E.et.al.   7638622
[2] “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
[3] “Identification and expression analysis of a potential familial Alzheimer disease gene on chromosome 1 related to AD3.”  Li J.et.al.   8618867
[4] “Genomic structure and expression of STM2, the chromosome 1 familial Alzheimer disease gene.”  Levy-Lahad E.et.al.   8661049
[5] “The DNA sequence and biological annotation of human chromosome 1.”  Gregory S.G.et.al.   16710414
[6] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[7] “Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells.”  Kovacs D.M.et.al.   8574969
[8] “Interaction of presenilins with the filamin family of actin-binding proteins.”  Zhang W.et.al.   9437013
[9] “A loss of function mutation of presenilin-2 interferes with amyloid beta-peptide production and notch signaling.”  Steiner H.et.al.   10497236
[10] “The transmembrane aspartates in presenilin 1 and 2 are obligatory for gamma-secretase activity and amyloid beta-protein generation.”  Kimberly W.T.et.al.   10652302
[11] “Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein.”  Sai X.et.al.   11799129
[12] “Presenilin mutations in Alzheimer's disease.”  Cruts M.et.al.   9521418
[13] “Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.”  Gauci S.et.al.   19413330
[14] “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
[15] “A novel mutation in the predicted TM2 domain of the presenilin 2 gene in Spanish patient with late-onset Alzheimer's disease.”  Lao J.I.et.al.   10732806
[16] “High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes.”  Finckh U.et.al.   10631141

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MLTFMASDSE EEVCDERTSL MSAESPTPRS CQEGRQGPED GENTAQWRSQ ENEEDGEEDP 
61:	DRYVCSGVPG RPPGLEEELT LKYGAKHVIM LFVPVTLCMI VVVATIKSVR FYTEKNGQLI 
121:	YTPFTEDTPS VGQRLLNSVL NTLIMISVIV VMTIFLVVLY KYRCYKFIHG WLIMSSLMLL 
181:	FLFTYIYLGE VLKTYNVAMD YPTLLLTVWN FGAVGMVCIH WKGPLVLQQA YLIMISALMA 
241:	LVFIKYLPEW SAWVILGAIS VYDLVAVLCP KGPLRMLVET AQERNEPIFP ALIYSSAMVW 
301:	TVGMAKLDPS SQGALQLPYD PEMEEDSYDS FGEPSYPEVF EPPLTGYPGE ELEEEEERGV 
361:	KLGLGDFIFY SVLVGKAAAT GSGDWNTTLA CFVAILIGLC LTLLLLAVFK KALPALPISI 
421:	TFGLIFYFST DNLVRPFMDT LASHQLYI