P49768

※ Protein Information

Tag	Content
UniProt Accession	PSN1_HUMAN; P49768;
Entrez ID	5663
GenBank Protein ID	NM_000021.3; NM_007318.2; XM_005267864.2; XM_005267866.1; XM_011536971.2; XM_011536972.2; XM_011536973.1; XM_011536974.1;
GenBank Nucleotide ID	NP_000012.1; NP_015557.2; XP_005267921.1; XP_005267923.1; XP_011535273.1; XP_011535274.1; XP_011535275.1; XP_011535276.1;
Protein Name	Presenilin-1 (PS-1) (EC 3.4.23.-) (Protein S182) [Cleaved into: Presenilin-1 NTF subunit; Presenilin-1 CTF subunit; Presenilin-1 CTF12 (PS1-CTF12)]
Gene Name	PSEN1; AD3; PS1; PSNL1
Organism	Homo sapiens
NCBI Taxa ID	9606
Functional Description	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 (amyloid-beta precursor protein) (PubMed:15274632, PubMed:10545183, PubMed:10593990, PubMed:10206644, PubMed:10899933, PubMed:10811883, PubMed:12679784, PubMed:12740439, PubMed:25043039, PubMed:26280335). Requires the presence of the other members of the gamma-secretase complex for protease activity (PubMed:15274632, PubMed:25043039, PubMed:26280335). Plays a role in No(view all) Functional Description 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 (amyloid-beta precursor protein) (PubMed:15274632, PubMed:10545183, PubMed:10593990, PubMed:10206644, PubMed:10899933, PubMed:10811883, PubMed:12679784, PubMed:12740439, PubMed:25043039, PubMed:26280335). Requires the presence of the other members of the gamma-secretase complex for protease activity (PubMed:15274632, PubMed:25043039, PubMed:26280335). Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (PubMed:9738936, PubMed:10593990, PubMed:10899933, PubMed:10811883). Stimulates cell-cell adhesion via its interaction with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin) (PubMed:11953314). Under conditions of apoptosis or calcium influx, cleaves CDH1 (PubMed:11953314). This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling (PubMed:9738936, PubMed:11953314). Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity).
Sequence (Fasta)	MTELPAPLSY FQNAQMSEDN HLSNTVRSQN DNRERQEHND RRSLGHPEPL SNGRPQGNSR 60 QVVEQDEEED EELTLKYGAK HVIMLFVPVT LCMVVVVATI KSVSFYTRKD GQLIYTPFTE 120 DTETVGQRAL HSILNAAIMI SVIVVMTILL VVLYKYRCYK VIHAWLIISS LLLLFFFSFI 180 YLGEVFKTYN VAVDYITVAL LIWNFGVVGM ISIHWKGPLR LQQAYLIMIS ALMALVFIKY 240 LPEWTAWLIL AVISVYDLVA VLCPKGPLRM LVETAQERNE TLFPALIYSS TMVWLVNMAE 300 GDPEAQRRVS KNSKYNAEST ERESQDTVAE NDDGGFSEEW EAQRDSHLGP HRSTPESRAA 360 VQELSSSILA GEDPEERGVK LGLGDFIFYS VLVGKASATA SGDWNTTIAC FVAILIGLCL 420 TLLLLAIFKK ALPALPISIT FGLVFYFATD YLVQPFMDQL AFHQFYI 468 Fasta Sequence >P49768\|PSEN1; AD3; PS1; PSNL1\|Homo sapiens (Human) MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSRQVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTEDTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFIYLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKYLPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAEGDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAAVQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCLTLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI

※ PTM-Disease Association

Num	PTM	Disease	Type	PTM Site	PMID
1	Glycosylation	Alzheimer's disease	P		12850546
1	[Reference]: As protein glycosylation is a key post-translational event that occurs within the Golgi, we have investigated the effect of altered PS1 expression levels on the protein glycosylation pattern using the SH-SY5Y human neuroblastoma cell line.
2	Serine Phosphorylation	Alzheimer's disease	U	S310	28132667
2	[Reference]: Here, comprehensive analysis using FRET-based imaging reveals that activity-driven and Protein Kinase A-mediated PS1 phosphorylation at three domains (domain 1: T74, domain 2: S310 and S313, domain 3: S365, S366, and S367), with S367 being critical, is responsible for the PS1 pathogenic 'closed' conformation, and resulting increase in the A?42/40 ratio.?

※ Disease Cross-ref Annotation

Database	Annotation
CTD (Curated) (count: 16) (view all)	MESH:D000544 ; Alzheimer Disease MESH:C564330 ; Alzheimer Disease, Familial, 3, with Spastic Paraparesis and Apraxia MESH:D000686 ; Amyloidosis MESH:D001238 ; Asphyxia Neonatorum MESH:D002311 ; Cardiomyopathy, Dilated MESH:C566296 ; Cardiomyopathy, Dilated, 1u MESH:D003072 ; Cognition Disorders MESH:D004195 ; Disease Models, Animal MESH:D057180 ; Frontotemporal Dementia MESH:C538118 ; Hidradenitis suppurativa, familial MESH:D007859 ; Learning Disorders MESH:D008569 ; Memory Disorders MESH:D009410 ; Nerve Degeneration MESH:D019636 ; Neurodegenerative Diseases MESH:D020774 ; Pick Disease of the Brain MESH:D013163 ; Splenomegaly
HGMD (count: 190) (view all)	CD050904; Dementia with Lewy bodies and Alzheimer disease; Small deletions CD982906; Alzheimer disease; Small deletions CD012275; Alzheimer disease; Small deletions CD076892; Alzheimer disease; Small deletions CD030744; Alzheimer disease; Small deletions CD962718; Alzheimer disease ?; Small deletions CG994995; Alzheimer disease; Gross deletions CG015636; Alzheimer disease; Gross deletions CG005151; Alzheimer disease; Gross deletions CG024998; Frontotemporal dementia; Gross deletions CG024999; Frontotemporal dementia; Gross deletions CG025000; Frontotemporal dementia; Gross deletions CP005307; Alzheimer disease; Small indels CP025174; Alzheimer disease; Small indels CI013496; Alzheimer disease; Small insertions CI013497; Alzheimer disease; Small insertions CI064720; Alzheimer disease; Small insertions CM004059; Alzheimer disease; Missense/nonsense CM981649; Alzheimer disease; Missense/nonsense CM951065; Alzheimer disease; Missense/nonsense CM043330; Alzheimer disease; Missense/nonsense CM022058; Alzheimer disease; Missense/nonsense CM032995; Alzheimer disease; Missense/nonsense CM003610; Alzheimer disease; Missense/nonsense CM961198; Alzheimer disease; Missense/nonsense CM056038; Alzheimer disease; Missense/nonsense CM055499; Alzheimer disease, early onset; Missense/nonsense CM000202; Alzheimer disease; Missense/nonsense CM055497; Alzheimer disease; Missense/nonsense CM003611; Frontotemporal dementia; Missense/nonsense CM951066; Alzheimer disease; Missense/nonsense CM043767; Alzheimer disease; Missense/nonsense CM981650; Alzheimer disease; Missense/nonsense CM992204; Alzheimer disease; Missense/nonsense CM043768; Alzheimer disease; Missense/nonsense CM034890; Alzheimer disease; Missense/nonsense CM981651; Alzheimer disease; Missense/nonsense CM081762; Alzheimer disease, ataxic variant; Missense/nonsense CM024731; Alzheimer disease; Missense/nonsense CM961200; Alzheimer disease; Missense/nonsense CM981652; Alzheimer disease; Missense/nonsense CM961199; Alzheimer disease; Missense/nonsense CM993458; Alzheimer disease; Missense/nonsense CM994550; Alzheimer disease; Missense/nonsense CM055496; Alzheimer disease; Missense/nonsense CM971251; Alzheimer disease; Missense/nonsense CM024347; Alzheimer disease; Missense/nonsense CM981653; Alzheimer disease; Missense/nonsense CM951067; Alzheimer disease; Missense/nonsense CM961201; Alzheimer disease; Missense/nonsense CM951068; Alzheimer disease; Missense/nonsense CM054079; Alzheimer disease, early onset; Missense/nonsense CM951069; Alzheimer disease; Missense/nonsense CM033662; Alzheimer disease; Missense/nonsense CM961202; Alzheimer disease; Missense/nonsense CM961203; Alzheimer disease; Missense/nonsense CM981654; Alzheimer disease; Missense/nonsense CM004060; Alzheimer disease; Missense/nonsense CM004061; Alzheimer disease; Missense/nonsense CM951070; Alzheimer disease; Missense/nonsense CM951071; Alzheimer disease; Missense/nonsense CM991073; Alzheimer disease; Missense/nonsense CM003612; Alzheimer disease; Missense/nonsense CM043769; Alzheimer disease; Missense/nonsense CM030700; Alzheimer disease; Missense/nonsense CM951072; Alzheimer disease; Missense/nonsense CM951073; Alzheimer disease; Missense/nonsense CM003613; Alzheimer disease; Missense/nonsense CM991074; Alzheimer disease; Missense/nonsense CM055498; Alzheimer disease, early onset; Missense/nonsense CM043770; Alzheimer disease; Missense/nonsense CM003614; Alzheimer disease; Missense/nonsense CM994066; Alzheimer disease; Missense/nonsense CM981655; Alzheimer disease; Missense/nonsense CM054825; Alzheimer disease; Missense/nonsense CM981656; Alzheimer disease; Missense/nonsense CM991075; Alzheimer disease; Missense/nonsense CM045192; Alzheimer disease; Missense/nonsense CM024145; Alzheimer disease; Missense/nonsense CM023437; Alzheimer disease; Missense/nonsense CM004063; Alzheimer disease; Missense/nonsense CM004062; Alzheimer disease; Missense/nonsense CM004064; Alzheimer disease; Missense/nonsense CM041068; Frontotemporal dementia; Missense/nonsense CM972856; Alzheimer disease; Missense/nonsense CM054081; Alzheimer disease, early onset; Missense/nonsense CM004065; Alzheimer disease; Missense/nonsense CM023582; Alzheimer disease; Missense/nonsense CM004067; Alzheimer disease; Missense/nonsense CM004066; Alzheimer disease; Missense/nonsense CM004068; Alzheimer disease; Missense/nonsense CM981657; Alzheimer disease; Missense/nonsense CM991076; Alzheimer disease; Missense/nonsense CM961204; Alzheimer disease; Missense/nonsense CM004069; Alzheimer disease; Missense/nonsense CM034891; Alzheimer disease; Missense/nonsense CM083051; Alzheimer disease ?; Missense/nonsense CM054082; Alzheimer disease, early onset; Missense/nonsense CM023583; Presenile dementia and parkinsonism; Missense/nonsense CM003615; Alzheimer disease; Missense/nonsense CM992963; Alzheimer disease; Missense/nonsense CM004070; Alzheimer disease; Missense/nonsense CM034292; Alzheimer disease; Missense/nonsense CM043771; Alzheimer disease; Missense/nonsense CM066192; Frontotemporal dementia; Missense/nonsense CM030701; Alzheimer disease; Missense/nonsense CM981658; Alzheimer disease; Missense/nonsense CM951074; Alzheimer disease; Missense/nonsense CM971252; Alzheimer disease; Missense/nonsense CM994067; Alzheimer disease; Missense/nonsense CM014376; Alzheimer disease; Missense/nonsense CM004071; Alzheimer disease; Missense/nonsense CM030702; Alzheimer disease; Missense/nonsense CM961205; Alzheimer disease; Missense/nonsense CM014216; Alzheimer disease; Missense/nonsense CM030703; Alzheimer disease; Missense/nonsense CM065407; Alzheimer disease, early onset; Missense/nonsense CM951075; Alzheimer disease; Missense/nonsense CM083050; Alzheimer disease ?; Missense/nonsense CM034892; Alzheimer disease; Missense/nonsense CM961206; Alzheimer disease; Missense/nonsense CM034293; Alzheimer disease; Missense/nonsense CM951076; Alzheimer disease; Missense/nonsense CM083551; Alzheimer disease, early onset & spastic paraparesis; Missense/nonsense CM003616; Alzheimer disease; Missense/nonsense CM971253; Alzheimer disease; Missense/nonsense CM951077; Alzheimer disease; Missense/nonsense CM030704; Alzheimer disease; Missense/nonsense CM951078; Alzheimer disease; Missense/nonsense CM020747; Alzheimer disease; Missense/nonsense CM033803; Alzheimer disease; Missense/nonsense CM951079; Alzheimer disease; Missense/nonsense CM971254; Alzheimer disease; Missense/nonsense CM961207; Alzheimer disease; Missense/nonsense CM034893; Alzheimer disease; Missense/nonsense CM043067; Subcortical dementia and parkinsonism; Missense/nonsense CM983754; Alzheimer disease; Missense/nonsense CM004072; Alzheimer disease; Missense/nonsense CM030948; Alzheimer disease ?; Missense/nonsense CM971255; Alzheimer disease; Missense/nonsense CM043068; Language impairment; Missense/nonsense CM076445; Alzheimer disease, early onset; Missense/nonsense CM951080; Alzheimer disease; Missense/nonsense CM951081; Alzheimer disease; Missense/nonsense CM981659; Alzheimer disease; Missense/nonsense CM014377; Alzheimer disease; Missense/nonsense CM024732; Alzheimer disease; Missense/nonsense CM951082; Alzheimer disease; Missense/nonsense CM076446; Alzheimer disease, early onset; Missense/nonsense CM951083; Alzheimer disease; Missense/nonsense CM961208; Alzheimer disease; Missense/nonsense CM064173; Alzheimer disease; Missense/nonsense CM000421; Alzheimer disease, association with; Missense/nonsense CM065408; Cardiomyopathy, dilated, and heart failure; Missense/nonsense CM004073; Alzheimer disease; Missense/nonsense CM004074; Alzheimer disease; Missense/nonsense CM004075; Alzheimer disease; Missense/nonsense CM083052; Alzheimer disease ?; Missense/nonsense CM030705; Alzheimer disease; Missense/nonsense CM971256; Alzheimer disease; Missense/nonsense CM030706; Alzheimer disease; Missense/nonsense CM045311; Alzheimer disease; Missense/nonsense CM951084; Alzheimer disease; Missense/nonsense CM054084; Alzheimer disease, early onset; Missense/nonsense CM991077; Alzheimer disease; Missense/nonsense CM054083; Alzheimer disease, early onset; Missense/nonsense CM003617; Alzheimer disease; Missense/nonsense CM951085; Alzheimer disease; Missense/nonsense CM004076; Alzheimer disease; Missense/nonsense CM000422; Alzheimer disease; Missense/nonsense CM993459; Alzheimer disease; Missense/nonsense CM951086; Alzheimer disease; Missense/nonsense CM004077; Alzheimer disease; Missense/nonsense CM073284; Alzheimer disease; Missense/nonsense CM092720; Frontotemporal dementia; Missense/nonsense CM054080; Alzheimer disease, early onset; Missense/nonsense CM004078; Alzheimer disease; Missense/nonsense CM981660; Alzheimer disease; Missense/nonsense HM971956; Alzheimer disease; Missense/nonsense CM023971; Alzheimer disease; Missense/nonsense CM004079; Alzheimer disease; Missense/nonsense CM981661; Alzheimer disease; Missense/nonsense CM991078; Alzheimer disease; Missense/nonsense CM004080; Alzheimer disease; Missense/nonsense CR000233; Alzheimer disease; Regulatory CR000234; Alzheimer disease; Regulatory CR015066; Alzheimer disease, association with; Regulatory CS951519; Alzheimer disease; Splicing CS982328; Alzheimer disease; Splicing CS962745; Alzheimer disease, late-onset, protect., assoc. ?; Splicing
GWASdb (count: 2)	rs17124867; Multiple complex diseases; Null rs177413; Telomere length; Null

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 22) (view all)	102 VVVATIKSVSFYTRK dbPAF 104 VATIKSVSFYTRKDG dbPAF 107 IKSVSFYTRKDGQLI dbPAF 154 TILLVVLYKYRCYKV dbPAF 240 MALVFIKYLPEWTAW dbPAF 256 ILAVISVYDLVAVLC dbPAF 310 PEAQRRVSKNSKYNA dbPAF 319 NSKYNAESTERESQD dbPAF 320 SKYNAESTERESQDT dbPAF 324 AESTERESQDTVAEN dbPAF 337 ENDDGGFSEEWEAQR dbPAF 346 EWEAQRDSHLGPHRS dbPAF 353 SHLGPHRSTPESRAA dbPAF 354 HLGPHRSTPESRAAV dbPAF 357 PHRSTPESRAAVQEL dbPAF 365 RAAVQELSSSILAGE dbPAF 366 AAVQELSSSILAGED dbPAF 367 AVQELSSSILAGEDP dbPAF 43 QEHNDRRSLGHPEPL dbPAF 51 LGHPEPLSNGRPQGN dbPAF 59 NGRPQGNSRQVVEQD dbPAF 99 CMVVVVATIKSVSFY dbPAF
Ubiquitination (count: 4)	109 SVSFYTRKDGQLIYT PLMD 311 EAQRRVSKNSKYNAE PLMD 314 RRVSKNSKYNAESTE PLMD 76 EDEELTLKYGAKHVI PLMD

PTM

Modification Sites

Phosphorylation
(count: 22)
(view all)

102       VVVATIKSVSFYTRK     dbPAF
104       VATIKSVSFYTRKDG     dbPAF
107       IKSVSFYTRKDGQLI     dbPAF
154       TILLVVLYKYRCYKV     dbPAF
240       MALVFIKYLPEWTAW     dbPAF
256       ILAVISVYDLVAVLC     dbPAF

Ubiquitination
(count: 4)

109       SVSFYTRKDGQLIYT     PLMD
311       EAQRRVSKNSKYNAE     PLMD
314       RRVSKNSKYNAESTE     PLMD
76        EDEELTLKYGAKHVI     PLMD

※ Protein-Protein Interaction

Network

Interaction

Source

E9PG40	P49768	HPRD
F5GYI6	P49768	HPRD
O00548	P49768	HPRD
O43464	P49768	IntAct
O43768	P49768	IntAct
O60716	P49768	HPRD
O75369	P49768	HPRD; MINT
O75460	P49768	HPRD
O95551	P49768	IntAct
O96018	P49768	MINT
P00533	P49768	BioGRID
P02649	P49768	IntAct
P04406	P49768	IntAct
P05067	P49768	IntAct
P09429	P49768	BioGRID
P10415	P49768	HPRD
P10636	P49768	HPRD
P11172	P49768	IntAct
P12814	P49768	IntAct
P12830	P49768	MINT
P14136	P49768	HPRD
P14923	P49768	HPRD; IntAct
P16066	P49768	DIP
P17612	P49768	HPRD
P20336	P49768	IntAct
P21333	P49768	HPRD; DIP; MINT
P23528	P49768	IntAct
P24410	P49768	DIP
P27635	P49768	DIP
P27986	P49768	HPRD
P29466	P49768	HPRD
P31150	P49768	HPRD
P35221	P49768	HPRD
P35222	P49768	HPRD; IntAct
P42574	P49768	HPRD
P46531	P49768	HPRD
P49662	P49768	HPRD
P49755	P49768	IntAct
P49768	P49768	HPRD; IntAct
P49768	P49810	IntAct
P49768	P49841	MINT;HPRD
P49768	P50502	IntAct
P49768	P52799	HPRD
P49768	P55210	HPRD
P49768	P55212	HPRD
P49768	P55809	IntAct
P49768	P56817	HPRD
P49768	P62491	HPRD; MINT
P49768	P62805	BioGRID
P49768	Q00535	HPRD; IntAct
P49768	Q02410	HPRD; MINT
P49768	Q02817	BioGRID
P49768	Q04721	HPRD
P49768	Q05513	HPRD
P49768	Q07817	HPRD; MINT
P49768	Q14118	DIP
P49768	Q14126	DIP
P49768	Q14790	HPRD
P49768	Q15011	HPRD
P49768	Q16543	IntAct
P49768	Q63ZY3	IntAct
P49768	Q6EMK4	DIP
P49768	Q6P1Q9	HPRD
P49768	Q6UX71	DIP
P49768	Q8IZD9	HPRD
P49768	Q8NFT8	DIP
P49768	Q8WW43	HPRD
P49768	Q92542	HPRD; IntAct; MINT
P49768	Q92947	IntAct
P49768	Q969H0	HPRD
P49768	Q96BI3	HPRD;IntAct
P49768	Q96QH2	IntAct
P49768	Q96TA2	HPRD
P49768	Q96TC7	IntAct
P49768	Q99466	HPRD
P49768	Q99569	HPRD; MINT
P49768	Q99590	HPRD
P49768	Q99767	MINT
P49768	Q99828	HPRD
P49768	Q9BQ95	IntAct
P49768	Q9BUP0	IntAct
P49768	Q9NQB0	IntAct;HPRD
P49768	Q9NZ42	HPRD
P49768	Q9NZJ7	HPRD; IntAct
P49768	Q9UM47	HPRD
P49768	Q9UMF0	HPRD
P49768	Q9UMX0	HPRD; MINT
P49768	Q9UQB3	HPRD; DIP
P49768	Q9Y2J2	IntAct
P49768	Q9Y2W7	HPRD

PTMD Annotation Information

※ Protein Information

Functional Description

Fasta Sequence

※ PTM-Disease Association

※ Disease Cross-ref Annotation

※ PTM Sites

※ Protein-Protein Interaction