UniProt:P97887 Psen1

chain
  • chain:1-298
  • chain:299-468
  • chain:347-468
checksum 17CB791E88A16FC0
comment
  • 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 (By similarity). It acts through the control of SYT7 presynaptic expression (PubMed:30429473).SUBUNIT Homodimer. The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A/APH1B) and PEN2. Such minimal complex is sufficient for secretase activity. Other components which are associated with the complex include SLC25A64, SLC5A7, PHB and PSEN1 isoform 3. As part of the gamma-secretase complex, interacts with CRB2 (via transmembrane domain). 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) (via transmembrane domain). Associates with NOTCH1 (via transmembrane domain). 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 (isoform 2). Interacts with DOCK3; this interaction mediates the membrane association of DOCK3. Interacts with isoform 1 and isoform 3 of UBQLN1.INTERACTION 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. Also highly enriched in mitochondria-associated endoplasmic reticulum membrane contact site (By similarity).TISSUE SPECIFICITY Detected in embryonic and adult brain.DOMAIN The PAL motif is required for normal active site conformation.DOMAIN 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.PTM 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.PTM After endoproteolysis, the C-terminal fragment (CTF) is phosphorylated on serine residues by PKA and/or PKC. Phosphorylation on Ser-347 inhibits endoproteolysis.SIMILARITY Belongs to the peptidase A22A family.
crossReference
databaseName UniProt
dbId 99157
description
  • recommendedName: fullName evidence="7 8"Presenilin-1 shortName evidence="1"PS-1 ecNumber evidence="1"3.4.23.- alternativeName: Protein S182 component recommendedName: fullName evidence="1"Presenilin-1 NTF subunit /component component recommendedName: fullName evidence="1"Presenilin-1 CTF subunit /component component recommendedName: fullName evidence="1"Presenilin-1 CTF12 shortName: PS1-CTF12 /component
displayName UniProt:P97887 Psen1
geneName
  • Psen1
  • Psnl1
identifier P97887
isSequenceChanged false
keyword
  • Apoptosis
  • Cell adhesion
  • Cell membrane
  • Cell projection
  • Endoplasmic reticulum
  • Endosome
  • Golgi apparatus
  • Hydrolase
  • Membrane
  • Notch signaling pathway
  • Phosphoprotein
  • Protease
  • Reference proteome
  • Synapse
  • Transmembrane
  • Transmembrane helix
modified [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType Protein
name
  • Psen1
otherIdentifier
  • 10885808
  • 1368792_at
  • 1376075_at
  • 1379528_at
  • 17817254
  • 29192
  • 5645080
  • 5765351
  • 5846203
  • 5849395
  • 5883632
  • 6017845
  • 6032021
  • 6131995
  • 6166980
  • 6211266
  • 6288956
  • 6331329
  • 6418343
  • 6425635
  • 6449276
  • 6558176
  • 6634407
  • 6664176
  • 6736699
  • A_44_P142016
  • A_44_P776995
  • A_64_P044315
  • D82363_s_at
  • GE1104073
  • GE1230198
  • GE1237309
  • GE1293562
  • GE20560
  • GO:0000045
  • GO:0000122
  • GO:0000776
  • GO:0001568
  • GO:0001708
  • GO:0001756
  • GO:0001764
  • GO:0001921
  • GO:0001947
  • GO:0002038
  • GO:0002244
  • GO:0002265
  • GO:0002286
  • GO:0002376
  • GO:0002573
  • GO:0004175
  • GO:0004190
  • GO:0005262
  • GO:0005634
  • GO:0005640
  • GO:0005654
  • GO:0005737
  • GO:0005739
  • GO:0005783
  • GO:0005790
  • GO:0005791
  • GO:0005794
  • GO:0005813
  • GO:0005815
  • GO:0005886
  • GO:0005938
  • GO:0006355
  • GO:0006486
  • GO:0006509
  • GO:0006839
  • GO:0006874
  • GO:0006914
  • GO:0006974
  • GO:0006979
  • GO:0007219
  • GO:0007220
  • GO:0007420
  • GO:0007507
  • GO:0007611
  • GO:0007613
  • GO:0008013
  • GO:0009791
  • GO:0010467
  • GO:0010468
  • GO:0010628
  • GO:0010629
  • GO:0010975
  • GO:0015031
  • GO:0015871
  • GO:0016020
  • GO:0016080
  • GO:0016235
  • GO:0016485
  • GO:0021795
  • GO:0021870
  • GO:0021904
  • GO:0021987
  • GO:0022008
  • GO:0030054
  • GO:0030154
  • GO:0030165
  • GO:0030182
  • GO:0030326
  • GO:0030424
  • GO:0030425
  • GO:0030426
  • GO:0030900
  • GO:0031410
  • GO:0031965
  • GO:0032436
  • GO:0032469
  • GO:0032760
  • GO:0032991
  • GO:0034205
  • GO:0034330
  • GO:0035253
  • GO:0035282
  • GO:0035556
  • GO:0040011
  • GO:0042059
  • GO:0042307
  • GO:0042500
  • GO:0042982
  • GO:0042987
  • GO:0043005
  • GO:0043011
  • GO:0043025
  • GO:0043065
  • GO:0043066
  • GO:0043198
  • GO:0043226
  • GO:0043589
  • GO:0045121
  • GO:0045296
  • GO:0045821
  • GO:0045893
  • GO:0048143
  • GO:0048167
  • GO:0048538
  • GO:0048666
  • GO:0048705
  • GO:0048854
  • GO:0048856
  • GO:0048870
  • GO:0050435
  • GO:0050673
  • GO:0050771
  • GO:0050808
  • GO:0050820
  • GO:0050852
  • GO:0050877
  • GO:0051117
  • GO:0051208
  • GO:0051402
  • GO:0051563
  • GO:0051604
  • GO:0051966
  • GO:0055085
  • GO:0060075
  • GO:0060828
  • GO:0060999
  • GO:0070050
  • GO:0070765
  • GO:0070851
  • GO:0097190
  • GO:0098609
  • GO:0098693
  • GO:0098712
  • GO:0098978
  • GO:0099175
  • GO:0140249
  • GO:1904646
  • GO:1905908
  • GO:1990535
  • GO:2000059
  • GO:2001234
  • ILMN_1351184
  • PH_rn_0011513
  • rc_AI009495_at
  • rc_AI169563_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • PSN1_RAT
  • P97529
sequenceLength 468
species [Species:48895] Rattus norvegicus
stId uniprot:P97887
url http://purl.uniprot.org/uniprot/P97887
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