Presenilin-1

Details

Name
Presenilin-1
Synonyms
  • 3.4.23.-
  • AD3
  • Protein S182
  • PS-1
  • PS1
  • PSNL1
Gene Name
PSEN1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0054188|Presenilin-1
MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSR
QVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTE
DTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFI
YLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKY
LPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAE
GDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAA
VQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCL
TLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI
Number of residues
467
Molecular Weight
52667.34
Theoretical pI
Not Available
GO Classification
Functions
aspartic endopeptidase activity, intramembrane cleaving / aspartic-type endopeptidase activity / ATPase binding / beta-catenin binding / cadherin binding / calcium channel activity / endopeptidase activity / growth factor receptor binding / PDZ domain binding
Processes
amyloid precursor protein catabolic process / amyloid precursor protein metabolic process / amyloid-beta formation / amyloid-beta metabolic process / apoptotic signaling pathway / astrocyte activation / astrocyte activation involved in immune response / autophagosome assembly / blood vessel development / brain morphogenesis / Cajal-Retzius cell differentiation / calcium ion transport / cell fate specification / cell-cell adhesion / cellular response to amyloid-beta / cerebellum development / cerebral cortex cell migration / choline transport / DNA damage response / dorsal/ventral neural tube patterning / embryonic limb morphogenesis / endoplasmic reticulum calcium ion homeostasis / epithelial cell proliferation / heart looping / hematopoietic progenitor cell differentiation / intracellular signal transduction / L-glutamate import across plasma membrane / learning or memory / locomotion / membrane protein ectodomain proteolysis / memory / mitochondrial transport / myeloid dendritic cell differentiation / negative regulation of apoptotic process / negative regulation of apoptotic signaling pathway / negative regulation of axonogenesis / negative regulation of core promoter binding / negative regulation of gene expression / negative regulation of neuron apoptotic process / negative regulation of protein phosphorylation / negative regulation of transcription by RNA polymerase II / negative regulation of ubiquitin-dependent protein catabolic process / neural retina development / neuron apoptotic process / neuron cellular homeostasis / neuron development / neuron migration / neuron projection maintenance / Notch receptor processing / Notch signaling pathway / positive regulation of amyloid fibril formation / positive regulation of apoptotic process / positive regulation of catalytic activity / positive regulation of coagulation / positive regulation of dendritic spine development / positive regulation of DNA-templated transcription / positive regulation of gene expression / positive regulation of glycolytic process / positive regulation of L-glutamate import across plasma membrane / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / positive regulation of protein binding / positive regulation of protein import into nucleus / positive regulation of protein phosphorylation / positive regulation of receptor recycling / positive regulation of tumor necrosis factor production / post-embryonic development / protein catabolic process at postsynapse / protein processing / protein transport / regulation of canonical Wnt signaling pathway / regulation of gene expression / regulation of neuron projection development / regulation of phosphorylation / regulation of postsynapse organization / regulation of resting membrane potential / regulation of synaptic plasticity / regulation of synaptic transmission, glutamatergic / regulation of synaptic vesicle cycle / response to oxidative stress / sequestering of calcium ion / skeletal system morphogenesis / skin morphogenesis / smooth endoplasmic reticulum calcium ion homeostasis / somitogenesis / synapse organization / synaptic vesicle targeting / T cell activation involved in immune response / T cell receptor signaling pathway / thymus development
Components
aggresome / apical plasma membrane / azurophil granule membrane / cell cortex / cell junction / cell surface / centrosome / ciliary rootlet / dendritic shaft / early endosome membrane / endoplasmic reticulum / endoplasmic reticulum membrane / gamma-secretase complex / glutamatergic synapse / Golgi apparatus / Golgi membrane / growth cone / kinetochore / lysosomal membrane / membrane / membrane raft / mitochondrial inner membrane / mitochondrion / neuromuscular junction / neuron projection / neuronal cell body / nuclear membrane / nuclear outer membrane / nucleoplasm / nucleus / perinuclear region of cytoplasm / plasma membrane / postsynapse / presynaptic membrane / protein-containing complex / rough endoplasmic reticulum / sarcolemma / smooth endoplasmic reticulum / synaptic vesicle / Z disc
General 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:15274632, PubMed:10545183, PubMed:10593990, PubMed:10206644, PubMed:10899933, PubMed:10811883, PubMed:12679784, PubMed:12740439, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874, PubMed:28269784, PubMed:20460383). Requires the presence of the other members of the gamma-secretase complex for protease activity (PubMed:15274632, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874). 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 (PubMed:9738936, PubMed:10593990, PubMed:10899933, PubMed:10811883). 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) (PubMed:11953314). Under conditions of apoptosis or calcium influx, cleaves CDH1 (PubMed:11953314). 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 (PubMed:9738936, PubMed:11953314). Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity). Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2 (PubMed:17428795, PubMed:28269784). 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 (PubMed:25394380, PubMed:16959576). Involved in the regulation of neurite outgrowth (PubMed:15004326, PubMed:20460383). 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).
Specific Function
Aspartic endopeptidase activity, intramembrane cleaving
Pfam Domain Function
Transmembrane Regions
83-103 133-153 167-189 195-216 221-241 249-272 381-401 408-428 433-453
Cellular Location
Endoplasmic reticulum
Gene sequence
>lcl|BSEQ0054189|Presenilin-1 (PSEN1)
ATGACAGAGTTACCTGCACCGTTGTCCTACTTCCAGAATGCACAGATGTCTGAGGACAAC
CACCTGAGCAATACTGTACGTAGCCAGAATGACAATAGAGAACGGCAGGAGCACAACGAC
AGACGGAGCCTTGGCCACCCTGAGCCATTATCTAATGGACGACCCCAGGGTAACTCCCGG
CAGGTGGTGGAGCAAGATGAGGAAGAAGATGAGGAGCTGACATTGAAATATGGCGCCAAG
CATGTGATCATGCTCTTTGTCCCTGTGACTCTCTGCATGGTGGTGGTCGTGGCTACCATT
AAGTCAGTCAGCTTTTATACCCGGAAGGATGGGCAGCTAATCTATACCCCATTCACAGAA
GATACCGAGACTGTGGGCCAGAGAGCCCTGCACTCAATTCTGAATGCTGCCATCATGATC
AGTGTCATTGTTGTCATGACTATCCTCCTGGTGGTTCTGTATAAATACAGGTGCTATAAG
GTCATCCATGCCTGGCTTATTATATCATCTCTATTGTTGCTGTTCTTTTTTTCATTCATT
TACTTGGGGGAAGTGTTTAAAACCTATAACGTTGCTGTGGACTACATTACTGTTGCACTC
CTGATCTGGAATTTTGGTGTGGTGGGAATGATTTCCATTCACTGGAAAGGTCCACTTCGA
CTCCAGCAGGCATATCTCATTATGATTAGTGCCCTCATGGCCCTGGTGTTTATCAAGTAC
CTCCCTGAATGGACTGCGTGGCTCATCTTGGCTGTGATTTCAGTATATGATTTAGTGGCT
GTTTTGTGTCCGAAAGGTCCACTTCGTATGCTGGTTGAAACAGCTCAGGAGAGAAATGAA
ACGCTTTTTCCAGCTCTCATTTACTCCTCAACAATGGTGTGGTTGGTGAATATGGCAGAA
GGAGACCCGGAAGCTCAAAGGAGAGTATCCAAAAATTCCAAGTATAATGCAGAAAGCACA
GAAAGGGAGTCACAAGACACTGTTGCAGAGAATGATGATGGCGGGTTCAGTGAGGAATGG
GAAGCCCAGAGGGACAGTCATCTAGGGCCTCATCGCTCTACACCTGAGTCACGAGCTGCT
GTCCAGGAACTTTCCAGCAGTATCCTCGCTGGTGAAGACCCAGAGGAAAGGGGAGTAAAA
CTTGGATTGGGAGATTTCATTTTCTACAGTGTTCTGGTTGGTAAAGCCTCAGCAACAGCC
AGTGGAGACTGGAACACAACCATAGCCTGTTTCGTAGCCATATTAATTGGTTTGTGCCTT
ACATTATTACTCCTTGCCATTTTCAAGAAAGCATTGCCAGCTCTTCCAATCTCCATCACC
TTTGGGCTTGTTTTCTACTTTGCCACAGATTATCTTGTACAGCCTTTTATGGACCAATTA
GCATTCCATCAATTTTATATCTAG
Chromosome Location
14
Locus
14q24.2
External Identifiers
ResourceLink
UniProtKB IDP49768
UniProtKB Entry NamePSN1_HUMAN
HGNC IDHGNC:9508
General References
Not Available

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12005Nirogacestatapproved, investigationalyesinhibitorDetails