Q9W6T7 · PSN1_DANRE

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) (PubMed:10521267).
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 (By similarity).

Features

Showing features for active site, site.

145650100150200250300350400450
TypeIDPosition(s)Description
Active site246
Site280-281Cleavage; alternate
Site281-282Cleavage; alternate
Site287-288Cleavage
Active site374

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-beta formation
Biological Processbrain development
Biological Processcalcium ion homeostasis
Biological Processcanonical Wnt signaling pathway
Biological Processlymphangiogenesis
Biological Processmelanocyte differentiation
Biological Processmembrane protein ectodomain proteolysis
Biological ProcessNotch signaling pathway
Biological Processoptomotor response
Biological Processprotein processing
Biological Processregulation of canonical Wnt signaling pathway
Biological Processresponse to hypoxia
Biological Processsomite development
Biological Processswimming behavior

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Presenilin-1
  • EC number
  • Short names
    PS-1; Zf-PS1

Gene names

    • Name
      psen1

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Actinopterygii > Neopterygii > Teleostei > Ostariophysi > Cypriniformes > Danionidae > Danioninae > Danio

Accessions

  • Primary accession
    Q9W6T7

Proteomes

Organism-specific databases

Subcellular Location

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-70Cytoplasmic
Transmembrane71-91Helical
Topological domain92-121Lumenal
Transmembrane122-142Helical
Topological domain143-155Cytoplasmic
Transmembrane156-178Helical
Topological domain179-183Lumenal
Transmembrane184-205Helical
Topological domain206-209Cytoplasmic
Transmembrane210-230Helical
Topological domain231-237Lumenal
Transmembrane238-261Helical
Topological domain262-369Cytoplasmic
Transmembrane370-390Helical
Topological domain391-396Lumenal
Transmembrane397-417Helical
Topological domain418-421Cytoplasmic
Transmembrane422-442Helical
Topological domain443-456Lumenal

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis374Abolishes its endoproteolysis. Probably loss of function.

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00000738971-456Presenilin-1

Post-translational modification

Cleaved, probably through autocleavage.
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.

Proteomic databases

Expression

Developmental stage

Expressed both maternally and zygotically. Ubiquitously expressed during embryogenesis.

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 compositional bias, region, motif.

TypeIDPosition(s)Description
Compositional bias9-38Polar residues
Region9-56Disordered
Region277-279Important for cleavage of target proteins
Region332-365Disordered
Compositional bias333-347Polar residues
Region366-370Important for cleavage of target proteins
Region421-423Important for cleavage of target proteins
Motif422-424PAL

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
    456
  • Mass (Da)
    50,981
  • Last updated
    1999-11-01 v1
  • Checksum
    B90C42280C874F8D
MADLVQNAANNVLNDGMDTSRHTSSTAAPPSRNEVELNGQPPTAPPPQVVTDSEEDEDEELTLKYGAKHVIMLFIPVTLCMVVVVATIKSVSFYTQKDGQQLIYTPFREDTETVGQRALHSMLNAIIMISVIVVMTLVLVVLYKYRCYKVIQAWLFFSNLLLLFFFSLIYLGEVFKTYNVAMDYFTLALIIWNFGVVGMICIHWKGPLRLQQAYLIMISALMALVFIKYLPEWTAWLILAAISVYDLLAVLCPKGPLRILVETAQERNEAIFPALIYSSTMVWLFNMADSAETRNNSSHPVPQQENQVVAMAPTAQAEDDGGFTPAWVDHQQHQLGPMQSTEESRRQIQEMPSARPPPPADDDEERGVKLGLGDFIFYSMLVGKASATASGDWNTTLACFVAILIGLCLTLLLLAIFKKALPALPISITFGLVFYFATDNLVRPFMDQLAVHQFYI

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
F1Q8Y6F1Q8Y6_DANREpsen1456
F8W381F8W381_DANREpsen1455

Sequence caution

The sequence AAH54639.1 differs from that shown. Reason: Erroneous initiation Truncated N-terminus.

Features

Showing features for compositional bias, sequence conflict.

TypeIDPosition(s)Description
Compositional bias9-38Polar residues
Sequence conflict308in Ref. 2; AAH54639
Sequence conflict317in Ref. 2; AAH54639
Compositional bias333-347Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AJ132931
EMBL· GenBank· DDBJ
CAB40386.1
EMBL· GenBank· DDBJ
mRNA
BC054639
EMBL· GenBank· DDBJ
AAH54639.1
EMBL· GenBank· DDBJ
mRNA Different initiation

Genome annotation databases

Similar Proteins

Disclaimer

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