O12976 · PSN1_XENLA

Function

function

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). Requires the presence of the other members of the gamma-secretase complex for protease activity. Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins.

Features

Showing features for active site, site.

143350100150200250300350400
TypeIDPosition(s)Description
Active site223
Site257-258Cleavage; alternate
Site258-259Cleavage; alternate
Site264-265Cleavage
Active site351

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentaxon
Cellular Componentendoplasmic reticulum
Cellular Componentendoplasmic reticulum membrane
Cellular Componentgamma-secretase complex
Cellular ComponentGolgi apparatus
Cellular ComponentGolgi membrane
Cellular Componentmembrane
Cellular Componentmitochondrion
Cellular Componentplasma membrane
Cellular Componentsynapse
Molecular Functionaspartic endopeptidase activity, intramembrane cleaving
Biological Processamyloid precursor protein metabolic process
Biological Processamyloid-beta formation
Biological Processmembrane protein ectodomain proteolysis
Biological ProcessNotch signaling pathway
Biological Processprotein processing
Biological Processregulation of canonical Wnt signaling pathway

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Presenilin-1
  • EC number
  • Short names
    PS-1
  • Alternative names
    • Presenilin alpha (PS-alpha)

Gene names

    • Name
      psen1

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Amphibia > Batrachia > Anura > Pipoidea > Pipidae > Xenopodinae > Xenopus > Xenopus

Accessions

  • Primary accession
    O12976
  • Secondary accessions
    • Q6DD65

Proteomes

Organism-specific databases

Subcellular Location

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-48Cytoplasmic
Transmembrane49-69Helical
Topological domain70-98Lumenal
Transmembrane99-119Helical
Topological domain120-132Cytoplasmic
Transmembrane133-155Helical
Topological domain156-160Lumenal
Transmembrane161-182Helical
Topological domain183-186Cytoplasmic
Transmembrane187-207Helical
Topological domain208-214Lumenal
Transmembrane215-238Helical
Topological domain239-346Cytoplasmic
Transmembrane347-367Helical
Topological domain368-373Lumenal
Transmembrane374-394Helical
Topological domain395-398Cytoplasmic
Transmembrane399-419Helical
Topological domain420-433Lumenal

Keywords

PTM/Processing

Features

Showing features for chain, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00000738981-433Presenilin-1
Glycosylation371N-linked (GlcNAc...) asparagine

Post-translational modification

Heterogeneous proteolytic processing generates N-terminal (NTF) and C-terminal (CTF) fragments of approximately 35 and 20 kDa, respectively. During apoptosis, the C-terminal fragment (CTF) is further cleaved by a caspase.

Keywords

PTM databases

Expression

Tissue specificity

Highest expression in ovaries and to a lesser extent in testis, intestine, kidney, brain, eye and lung. Weak expression in liver and heart. Present in trace amounts in skeletal muscle.

Developmental stage

Abundant in early stages of oogenesis. The expression is rapidly reduced between meiotic maturation and fertilization stages.

Gene expression databases

    • 399258Expressed in testis and 19 other cell types or tissues

Interaction

Subunit

Homodimer. The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity.

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region, compositional bias, motif.

TypeIDPosition(s)Description
Region1-31Disordered
Compositional bias11-28Polar residues
Region254-256Important for cleavage of target proteins
Compositional bias273-300Polar residues
Region273-307Disordered
Region343-347Important for cleavage of target proteins
Region398-400Important for cleavage of target proteins
Motif399-401PAL

Domain

The PAL motif is required for normal active site conformation.
Substrates, such as NOTCH1 and APP peptides, are bound between PSEN1 transmembrane domains and via the first lumenal loop and the cytoplasmic loop between the sixth and seventh transmembrane domains. Substrate binding causes a conformation change and formation of an intermolecular antiparallel beta-sheet between PSEN1 and its substrates.

Sequence similarities

Belongs to the peptidase A22A family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    433
  • Mass (Da)
    48,301
  • Last updated
    1997-07-01 v1
  • Checksum
    71CCEE3F6BB9C0AF
MNDTSERRSNENSESQSNGQTQSSSQQVLEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRFDGQLIYTPFTEDTESVGQRALNSILNATIMISVIIVMTILLVVLYKYRCYKVIHGWLIISSLLLLFFFSYIYLGEVFKTYNVAVDYITLALLIWNFGVVGMICIHWKGPLLLQQAYLIMISALMALVFIKYLPEWTTWLILAVISVYDLVAVLSPKGPLRMLVETAQERNETLFPALIYSSTMIWLVNMADGDPGLKQSASTKTYNTQAPTAHPRSDSAASDDNGGFDTTWEDHRNAQIGPINSTPESRVAVQALPSNSPPSEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTLACFVAILIGLCLTLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias11-28Polar residues
Compositional bias273-300Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
D84427
EMBL· GenBank· DDBJ
BAA19570.1
EMBL· GenBank· DDBJ
mRNA
BC077762
EMBL· GenBank· DDBJ
AAH77762.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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