Q9XT97 · PSN1_BOVIN
- ProteinPresenilin-1
- GenePSEN1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids478 (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, and by regulating cytosolic CTNNB1 levels. 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). Under conditions of apoptosis or calcium influx, cleaves CDH1. 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 (By similarity).
Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity).
Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2 (By similarity).
The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is therefore involved in calcium homeostasis. Involved in the regulation of neurite outgrowth (By similarity).
Is a regulator of presynaptic facilitation, spike transmission and synaptic vesicles replenishment in a process that depends on gamma-secretase activity. It acts through the control of SYT7 presynaptic expression (By similarity).
Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity).
Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2 (By similarity).
The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is therefore involved in calcium homeostasis. Involved in the regulation of neurite outgrowth (By similarity).
Is a regulator of presynaptic facilitation, spike transmission and synaptic vesicles replenishment in a process that depends on gamma-secretase activity. It acts through the control of SYT7 presynaptic expression (By similarity).
Features
Showing features for active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 258 | |||||
Sequence: D | ||||||
Site | 292-293 | Cleavage; alternate | ||||
Sequence: TM | ||||||
Site | 293-294 | Cleavage; alternate | ||||
Sequence: MV | ||||||
Site | 299-300 | Cleavage | ||||
Sequence: MA | ||||||
Site | 356-357 | Cleavage; by caspase | ||||
Sequence: DS | ||||||
Active site | 396 | |||||
Sequence: D |
GO annotations
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
- Cleaved into 3 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos
Accessions
- Primary accessionQ9XT97
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Golgi apparatus membrane ; Multi-pass membrane protein
Cell membrane ; Multi-pass membrane protein
Early endosome membrane ; Multi-pass membrane protein
Note: Translocates with bound NOTCH1 from the endoplasmic reticulum and/or Golgi to the cell surface. Colocalizes with CDH1/2 at sites of cell-cell contact. Colocalizes with CTNNB1 in the endoplasmic reticulum and the proximity of the plasma membrane. Also present in azurophil granules of neutrophils. Colocalizes with UBQLN1 in the cell membrane and in cytoplasmic juxtanuclear structures called aggresomes.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-83 | Cytoplasmic | ||||
Sequence: MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDSRERHEHGNERRRRGNTESVSNGRAPSSSQQVVEQEEEEDEELTLKYGAKHV | ||||||
Transmembrane | 84-104 | Helical | ||||
Sequence: IMLFVPVTLCMVVVVATIKSV | ||||||
Topological domain | 105-133 | Lumenal | ||||
Sequence: SFYTRKDGQLIYTPFTEDTETVAQRALHS | ||||||
Transmembrane | 134-154 | Helical | ||||
Sequence: ILNAVIMISVIVIMTILLVVL | ||||||
Topological domain | 155-167 | Cytoplasmic | ||||
Sequence: YKYRCYKVIHAWL | ||||||
Transmembrane | 168-190 | Helical | ||||
Sequence: IVSSLLLLFFFSFIYLGEVFKTY | ||||||
Topological domain | 191-195 | Lumenal | ||||
Sequence: NVAMD | ||||||
Transmembrane | 196-217 | Helical | ||||
Sequence: YISVALLIWNFGVVGMIAIHWK | ||||||
Topological domain | 218-221 | Cytoplasmic | ||||
Sequence: GPLR | ||||||
Transmembrane | 222-242 | Helical | ||||
Sequence: LQQAYLIMISALMALVFIKYL | ||||||
Topological domain | 243-249 | Lumenal | ||||
Sequence: PEWTAWL | ||||||
Transmembrane | 250-273 | Helical | ||||
Sequence: ILAVISVYDLVAVLCPKGPLRMLV | ||||||
Topological domain | 274-391 | Cytoplasmic | ||||
Sequence: ETAQERNETLFPALIYSSTMVWLVNMAEGDPEAQRKVSKNSNYNAQRPANSPVTTTGTESESQDPVTESDDGGFSEEWEAQRDSRLGPHHSTAESRSAVQDLSSSILASEDPEERGVK | ||||||
Transmembrane | 392-412 | Helical | ||||
Sequence: LGLGDFIFYSVLVGKASATAS | ||||||
Topological domain | 413-418 | Lumenal | ||||
Sequence: GDWNTT | ||||||
Transmembrane | 419-439 | Helical | ||||
Sequence: IACFVAILIGLCLTLLLLAIF | ||||||
Topological domain | 440-443 | Cytoplasmic | ||||
Sequence: KKAL | ||||||
Transmembrane | 444-464 | Helical | ||||
Sequence: PALPVSITFGLIFYFATDYLV | ||||||
Topological domain | 465-478 | Lumenal | ||||
Sequence: QPFMDQLAFHQFYI |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000025589 | 1-299 | Presenilin-1 NTF subunit | |||
Sequence: MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDSRERHEHGNERRRRGNTESVSNGRAPSSSQQVVEQEEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTEDTETVAQRALHSILNAVIMISVIVIMTILLVVLYKYRCYKVIHAWLIVSSLLLLFFFSFIYLGEVFKTYNVAMDYISVALLIWNFGVVGMIAIHWKGPLRLQQAYLIMISALMALVFIKYLPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNM | ||||||
Modified residue | 52 | Phosphoserine | ||||
Sequence: S | ||||||
Chain | PRO_0000025590 | 300-478 | Presenilin-1 CTF subunit | |||
Sequence: AEGDPEAQRKVSKNSNYNAQRPANSPVTTTGTESESQDPVTESDDGGFSEEWEAQRDSRLGPHHSTAESRSAVQDLSSSILASEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCLTLLLLAIFKKALPALPVSITFGLIFYFATDYLVQPFMDQLAFHQFYI | ||||||
Modified residue | 311 | Phosphoserine; by PKA | ||||
Sequence: S | ||||||
Modified residue | 340 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 342 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 357 | Phosphoserine; by PKC | ||||
Sequence: S | ||||||
Chain | PRO_0000236051 | 357-478 | Presenilin-1 CTF12 | |||
Sequence: SRLGPHHSTAESRSAVQDLSSSILASEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCLTLLLLAIFKKALPALPVSITFGLIFYFATDYLVQPFMDQLAFHQFYI | ||||||
Modified residue | 378 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 382 | Phosphoserine | ||||
Sequence: S |
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 caspase-3 to produce the fragment, PS1-CTF12.
After endoproteolysis, the C-terminal fragment (CTF) is phosphorylated on serine residues by PKA and/or PKC. Phosphorylation on Ser-357 inhibits endoproteolysis.
Keywords
- PTM
Proteomic databases
Expression
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. Other components which are associated with the complex include SLC25A64, SLC5A7 and PHB. As part of the gamma-secretase complex, interacts with CRB2 (via transmembrane domain) (By similarity).
Predominantly heterodimer of a N-terminal (NTF) and a C-terminal (CTF) endoproteolytical fragment. Associates with proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP). Associates with NOTCH1. Associates with cadherin/catenin adhesion complexes through direct binding to CDH1 or CDH2. Interaction with CDH1 stabilizes the complex and stimulates cell-cell aggregation. Interaction with CDH2 is essential for trafficking of CDH2 from the endoplasmic reticulum to the plasma membrane. Interacts with CTNND2, CTNNB1, CTNND1, JUP, HERPUD1, FLNA, FLNB, MTCH1, PKP4 and PARL. Interacts through its N-terminus with GFAP (By similarity).
Interacts with DOCK3 (By similarity).
Interacts with UBQLN1 (By similarity).
Predominantly heterodimer of a N-terminal (NTF) and a C-terminal (CTF) endoproteolytical fragment. Associates with proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP). Associates with NOTCH1. Associates with cadherin/catenin adhesion complexes through direct binding to CDH1 or CDH2. Interaction with CDH1 stabilizes the complex and stimulates cell-cell aggregation. Interaction with CDH2 is essential for trafficking of CDH2 from the endoplasmic reticulum to the plasma membrane. Interacts with CTNND2, CTNNB1, CTNND1, JUP, HERPUD1, FLNA, FLNB, MTCH1, PKP4 and PARL. Interacts through its N-terminus with GFAP (By similarity).
Interacts with DOCK3 (By similarity).
Interacts with UBQLN1 (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for compositional bias, region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-27 | Polar residues | ||||
Sequence: MTELPAPLSYFQNAQMSEDNHLSNTVR | ||||||
Region | 1-68 | Disordered | ||||
Sequence: MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDSRERHEHGNERRRRGNTESVSNGRAPSSSQQVVEQEE | ||||||
Compositional bias | 28-49 | Basic and acidic residues | ||||
Sequence: SQNDSRERHEHGNERRRRGNTE | ||||||
Region | 289-291 | Important for cleavage of target proteins | ||||
Sequence: YSS | ||||||
Region | 307-347 | Disordered | ||||
Sequence: QRKVSKNSNYNAQRPANSPVTTTGTESESQDPVTESDDGGF | ||||||
Compositional bias | 309-336 | Polar residues | ||||
Sequence: KVSKNSNYNAQRPANSPVTTTGTESESQ | ||||||
Region | 333-461 | Required for interaction with CTNNB1 | ||||
Sequence: SESQDPVTESDDGGFSEEWEAQRDSRLGPHHSTAESRSAVQDLSSSILASEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCLTLLLLAIFKKALPALPVSITFGLIFYFATD | ||||||
Region | 383-410 | Required for interaction with CTNND2 | ||||
Sequence: EDPEERGVKLGLGDFIFYSVLVGKASAT | ||||||
Region | 388-392 | Important for cleavage of target proteins | ||||
Sequence: RGVKL | ||||||
Region | 443-445 | Important for cleavage of target proteins | ||||
Sequence: LPA | ||||||
Motif | 444-446 | PAL | ||||
Sequence: PAL | ||||||
Region | 475-478 | Interaction with MTCH1 | ||||
Sequence: QFYI |
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
- Length478
- Mass (Da)53,654
- Last updated1999-11-01 v1
- Checksum59E3FC0A1010D906
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-27 | Polar residues | ||||
Sequence: MTELPAPLSYFQNAQMSEDNHLSNTVR | ||||||
Compositional bias | 28-49 | Basic and acidic residues | ||||
Sequence: SQNDSRERHEHGNERRRRGNTE | ||||||
Compositional bias | 309-336 | Polar residues | ||||
Sequence: KVSKNSNYNAQRPANSPVTTTGTESESQ |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF038936 EMBL· GenBank· DDBJ | AAD39023.1 EMBL· GenBank· DDBJ | mRNA |