O12976 · PSN1_XENLA
- ProteinPresenilin-1
- Genepsen1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids433 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 223 | |||||
Sequence: D | ||||||
Site | 257-258 | Cleavage; alternate | ||||
Sequence: TM | ||||||
Site | 258-259 | Cleavage; alternate | ||||
Sequence: MI | ||||||
Site | 264-265 | Cleavage | ||||
Sequence: MA | ||||||
Active site | 351 | |||||
Sequence: D |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | axon | |
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | gamma-secretase complex | |
Cellular Component | Golgi apparatus | |
Cellular Component | Golgi membrane | |
Cellular Component | membrane | |
Cellular Component | mitochondrion | |
Cellular Component | plasma membrane | |
Cellular Component | synapse | |
Molecular Function | aspartic endopeptidase activity, intramembrane cleaving | |
Biological Process | amyloid precursor protein metabolic process | |
Biological Process | amyloid-beta formation | |
Biological Process | membrane protein ectodomain proteolysis | |
Biological Process | Notch signaling pathway | |
Biological Process | protein processing | |
Biological Process | regulation of canonical Wnt signaling pathway |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended namePresenilin-1
- EC number
- Short namesPS-1
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Amphibia > Batrachia > Anura > Pipoidea > Pipidae > Xenopodinae > Xenopus > Xenopus
Accessions
- Primary accessionO12976
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Golgi apparatus membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-48 | Cytoplasmic | ||||
Sequence: MNDTSERRSNENSESQSNGQTQSSSQQVLEQDEEEDEELTLKYGAKHV | ||||||
Transmembrane | 49-69 | Helical | ||||
Sequence: IMLFVPVTLCMVVVVATIKSV | ||||||
Topological domain | 70-98 | Lumenal | ||||
Sequence: SFYTRFDGQLIYTPFTEDTESVGQRALNS | ||||||
Transmembrane | 99-119 | Helical | ||||
Sequence: ILNATIMISVIIVMTILLVVL | ||||||
Topological domain | 120-132 | Cytoplasmic | ||||
Sequence: YKYRCYKVIHGWL | ||||||
Transmembrane | 133-155 | Helical | ||||
Sequence: IISSLLLLFFFSYIYLGEVFKTY | ||||||
Topological domain | 156-160 | Lumenal | ||||
Sequence: NVAVD | ||||||
Transmembrane | 161-182 | Helical | ||||
Sequence: YITLALLIWNFGVVGMICIHWK | ||||||
Topological domain | 183-186 | Cytoplasmic | ||||
Sequence: GPLL | ||||||
Transmembrane | 187-207 | Helical | ||||
Sequence: LQQAYLIMISALMALVFIKYL | ||||||
Topological domain | 208-214 | Lumenal | ||||
Sequence: PEWTTWL | ||||||
Transmembrane | 215-238 | Helical | ||||
Sequence: ILAVISVYDLVAVLSPKGPLRMLV | ||||||
Topological domain | 239-346 | Cytoplasmic | ||||
Sequence: ETAQERNETLFPALIYSSTMIWLVNMADGDPGLKQSASTKTYNTQAPTAHPRSDSAASDDNGGFDTTWEDHRNAQIGPINSTPESRVAVQALPSNSPPSEDPEERGVK | ||||||
Transmembrane | 347-367 | Helical | ||||
Sequence: LGLGDFIFYSVLVGKASATAS | ||||||
Topological domain | 368-373 | Lumenal | ||||
Sequence: GDWNTT | ||||||
Transmembrane | 374-394 | Helical | ||||
Sequence: LACFVAILIGLCLTLLLLAIF | ||||||
Topological domain | 395-398 | Cytoplasmic | ||||
Sequence: KKAL | ||||||
Transmembrane | 399-419 | Helical | ||||
Sequence: PALPISITFGLVFYFATDYLV | ||||||
Topological domain | 420-433 | Lumenal | ||||
Sequence: QPFMDQLAFHQFYI |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000073898 | 1-433 | Presenilin-1 | |||
Sequence: MNDTSERRSNENSESQSNGQTQSSSQQVLEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRFDGQLIYTPFTEDTESVGQRALNSILNATIMISVIIVMTILLVVLYKYRCYKVIHGWLIISSLLLLFFFSYIYLGEVFKTYNVAVDYITLALLIWNFGVVGMICIHWKGPLLLQQAYLIMISALMALVFIKYLPEWTTWLILAVISVYDLVAVLSPKGPLRMLVETAQERNETLFPALIYSSTMIWLVNMADGDPGLKQSASTKTYNTQAPTAHPRSDSAASDDNGGFDTTWEDHRNAQIGPINSTPESRVAVQALPSNSPPSEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTLACFVAILIGLCLTLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI | ||||||
Glycosylation | 371 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
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
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
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-31 | Disordered | ||||
Sequence: MNDTSERRSNENSESQSNGQTQSSSQQVLEQ | ||||||
Compositional bias | 11-28 | Polar residues | ||||
Sequence: ENSESQSNGQTQSSSQQV | ||||||
Region | 254-256 | Important for cleavage of target proteins | ||||
Sequence: YSS | ||||||
Compositional bias | 273-300 | Polar residues | ||||
Sequence: QSASTKTYNTQAPTAHPRSDSAASDDNG | ||||||
Region | 273-307 | Disordered | ||||
Sequence: QSASTKTYNTQAPTAHPRSDSAASDDNGGFDTTWE | ||||||
Region | 343-347 | Important for cleavage of target proteins | ||||
Sequence: RGVKL | ||||||
Region | 398-400 | Important for cleavage of target proteins | ||||
Sequence: LPA | ||||||
Motif | 399-401 | PAL | ||||
Sequence: PAL |
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
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length433
- Mass (Da)48,301
- Last updated1997-07-01 v1
- Checksum71CCEE3F6BB9C0AF
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 11-28 | Polar residues | ||||
Sequence: ENSESQSNGQTQSSSQQV | ||||||
Compositional bias | 273-300 | Polar residues | ||||
Sequence: QSASTKTYNTQAPTAHPRSDSAASDDNG |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
D84427 EMBL· GenBank· DDBJ | BAA19570.1 EMBL· GenBank· DDBJ | mRNA | ||
BC077762 EMBL· GenBank· DDBJ | AAH77762.1 EMBL· GenBank· DDBJ | mRNA |