CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008201
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Presenilin-1 
Protein Synonyms/Alias
 PS-1; Protein S182; Presenilin-1 NTF subunit; Presenilin-1 CTF subunit; Presenilin-1 CTF12; PS1-CTF12 
Gene Name
 PSEN1 
Gene Synonyms/Alias
 AD3; PS1; PSNL1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
105SVSFYTRKDGQLIYTubiquitination[1]
310RRVSKNSKYNAESTEubiquitination[1]
Reference
 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 
Functional Description
 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. 
Sequence Annotation
 REGION 322 450 Required for interaction with CTNNB1.
 REGION 372 399 Required for interaction with CTNND2.
 REGION 464 467 Interaction with MTCH1.
 MOTIF 433 435 PAL.
 ACT_SITE 257 257 Probable.
 ACT_SITE 385 385 Probable.
 MOD_RES 43 43 Phosphoserine.
 MOD_RES 310 310 Phosphoserine; by PKA.
 MOD_RES 346 346 Phosphoserine; by PKC.
 MOD_RES 365 365 Phosphoserine (By similarity).
 MOD_RES 367 367 Phosphoserine.  
Keyword
 3D-structure; Alternative splicing; Alzheimer disease; Amyloidosis; Apoptosis; Cardiomyopathy; Cell adhesion; Complete proteome; Direct protein sequencing; Disease mutation; Endoplasmic reticulum; Golgi apparatus; Hydrolase; Membrane; Neurodegeneration; Notch signaling pathway; Phosphoprotein; Polymorphism; Protease; Reference proteome; Transmembrane; Transmembrane helix. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 467 AA 
Protein Sequence
MTELPAPLSY FQNAQMSEDN HLSNTNDNRE RQEHNDRRSL GHPEPLSNGR PQGNSRQVVE 60
QDEEEDEELT LKYGAKHVIM LFVPVTLCMV VVVATIKSVS FYTRKDGQLI YTPFTEDTET 120
VGQRALHSIL NAAIMISVIV VMTILLVVLY KYRCYKVIHA WLIISSLLLL FFFSFIYLGE 180
VFKTYNVAVD YITVALLIWN FGVVGMISIH WKGPLRLQQA YLIMISALMA LVFIKYLPEW 240
TAWLILAVIS VYDLVAVLCP KGPLRMLVET AQERNETLFP ALIYSSTMVW LVNMAEGDPE 300
AQRRVSKNSK YNAESTERES QDTVAENDDG GFSEEWEAQR DSHLGPHRST PESRAAVQEL 360
SSSILAGEDP EERGVKLGLG DFIFYSVLVG KASATASGDW NTTIACFVAI LIGLCLTLLL 420
LAIFKKALPA LPISITFGLV FYFATDYLVQ PFMDQLAFHQ FYI 463 
Gene Ontology
 GO:0016324; C:apical plasma membrane; IBA:RefGenome.
 GO:0030424; C:axon; IBA:RefGenome.
 GO:0005938; C:cell cortex; IBA:RefGenome.
 GO:0009986; C:cell surface; IBA:RefGenome.
 GO:0005813; C:centrosome; IDA:UniProtKB.
 GO:0035253; C:ciliary rootlet; IBA:RefGenome.
 GO:0031410; C:cytoplasmic vesicle; IEA:Compara.
 GO:0043198; C:dendritic shaft; IBA:RefGenome.
 GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
 GO:0070765; C:gamma-secretase complex; IDA:UniProtKB.
 GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
 GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
 GO:0030426; C:growth cone; IBA:RefGenome.
 GO:0005887; C:integral to plasma membrane; IDA:HGNC.
 GO:0000776; C:kinetochore; IDA:UniProtKB.
 GO:0005765; C:lysosomal membrane; IBA:RefGenome.
 GO:0045121; C:membrane raft; IBA:RefGenome.
 GO:0005743; C:mitochondrial inner membrane; IBA:RefGenome.
 GO:0031594; C:neuromuscular junction; IBA:RefGenome.
 GO:0043025; C:neuronal cell body; IBA:RefGenome.
 GO:0005640; C:nuclear outer membrane; IDA:MGI.
 GO:0048471; C:perinuclear region of cytoplasm; IBA:RefGenome.
 GO:0005791; C:rough endoplasmic reticulum; IDA:UniProtKB.
 GO:0005790; C:smooth endoplasmic reticulum; IDA:UniProtKB.
 GO:0030018; C:Z disc; IBA:RefGenome.
 GO:0004190; F:aspartic-type endopeptidase activity; IEA:InterPro.
 GO:0045296; F:cadherin binding; IBA:RefGenome.
 GO:0005262; F:calcium channel activity; IMP:UniProtKB.
 GO:0004175; F:endopeptidase activity; IDA:MGI.
 GO:0000186; P:activation of MAPKK activity; IEA:Compara.
 GO:0042987; P:amyloid precursor protein catabolic process; TAS:HGNC.
 GO:0042640; P:anagen; IEA:Compara.
 GO:0000045; P:autophagic vacuole assembly; IEA:Compara.
 GO:0050435; P:beta-amyloid metabolic process; IBA:RefGenome.
 GO:0001568; P:blood vessel development; IEA:Compara.
 GO:0048854; P:brain morphogenesis; IEA:Compara.
 GO:0021870; P:Cajal-Retzius cell differentiation; IEA:Compara.
 GO:0001708; P:cell fate specification; IEA:Compara.
 GO:0016337; P:cell-cell adhesion; IMP:MGI.
 GO:0021795; P:cerebral cortex cell migration; IEA:Compara.
 GO:0015871; P:choline transport; IEA:Compara.
 GO:0021904; P:dorsal/ventral neural tube patterning; IEA:Compara.
 GO:0030326; P:embryonic limb morphogenesis; IEA:Compara.
 GO:0050673; P:epithelial cell proliferation; IEA:Compara.
 GO:0001947; P:heart looping; IEA:Compara.
 GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Compara.
 GO:0035556; P:intracellular signal transduction; IEA:InterPro.
 GO:0015813; P:L-glutamate transport; IEA:Compara.
 GO:0006509; P:membrane protein ectodomain proteolysis; IDA:HGNC.
 GO:0007613; P:memory; IEA:Compara.
 GO:0006839; P:mitochondrial transport; IEA:Compara.
 GO:0002573; P:myeloid leukocyte differentiation; IEA:Compara.
 GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
 GO:0050771; P:negative regulation of axonogenesis; IEA:Compara.
 GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; IEA:Compara.
 GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Compara.
 GO:2000059; P:negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IEA:Compara.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0051444; P:negative regulation of ubiquitin-protein ligase activity; IEA:Compara.
 GO:0051402; P:neuron apoptotic process; IEA:Compara.
 GO:0048666; P:neuron development; IEA:Compara.
 GO:0001764; P:neuron migration; IEA:Compara.
 GO:0007220; P:Notch receptor processing; TAS:HGNC.
 GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
 GO:0043065; P:positive regulation of apoptotic process; IEA:Compara.
 GO:0043085; P:positive regulation of catalytic activity; IDA:HGNC.
 GO:0050820; P:positive regulation of coagulation; IEA:Compara.
 GO:0043406; P:positive regulation of MAP kinase activity; IEA:Compara.
 GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Compara.
 GO:0001921; P:positive regulation of receptor recycling; IEA:Compara.
 GO:0009791; P:post-embryonic development; IEA:Compara.
 GO:0006486; P:protein glycosylation; IEA:Compara.
 GO:0016485; P:protein processing; IDA:HGNC.
 GO:0015031; P:protein transport; IEA:Compara.
 GO:0042325; P:regulation of phosphorylation; IDA:UniProtKB.
 GO:0043393; P:regulation of protein binding; IEA:Compara.
 GO:0060075; P:regulation of resting membrane potential; IEA:Compara.
 GO:0048167; P:regulation of synaptic plasticity; IEA:Compara.
 GO:0051966; P:regulation of synaptic transmission, glutamatergic; IEA:Compara.
 GO:0006974; P:response to DNA damage stimulus; IEA:Compara.
 GO:0006979; P:response to oxidative stress; IEA:Compara.
 GO:0048705; P:skeletal system morphogenesis; IEA:Compara.
 GO:0043589; P:skin morphogenesis; IEA:Compara.
 GO:0051563; P:smooth endoplasmic reticulum calcium ion homeostasis; IBA:RefGenome.
 GO:0001756; P:somitogenesis; IEA:Compara.
 GO:0016080; P:synaptic vesicle targeting; IEA:Compara.
 GO:0002286; P:T cell activation involved in immune response; IEA:Compara.
 GO:0050852; P:T cell receptor signaling pathway; IEA:Compara.
 GO:0048538; P:thymus development; IEA:Compara. 
Interpro
 IPR002031; Pept_A22A_PS1.
 IPR006639; Peptidase_A22.
 IPR001108; Peptidase_A22A. 
Pfam
 PF01080; Presenilin 
SMART
 SM00730; PSN 
PROSITE
  
PRINTS
 PR01072; PRESENILIN.
 PR01073; PRESENILIN1.