PSN1_RAT
ID PSN1_RAT Reviewed; 468 AA.
AC P97887; P97529;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Presenilin-1;
DE Short=PS-1;
DE EC=3.4.23.-;
DE AltName: Full=Protein S182;
DE Contains:
DE RecName: Full=Presenilin-1 NTF subunit;
DE Contains:
DE RecName: Full=Presenilin-1 CTF subunit;
DE Contains:
DE RecName: Full=Presenilin-1 CTF12;
DE Short=PS1-CTF12;
GN Name=Psen1; Synonyms=Psnl1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=8710164; DOI=10.1016/s0304-3940(96)12449-6;
RA Takahashi H., Murayama M., Takashima A., Mercken M., Nakazato Y.,
RA Noguchi K., Imahori K.;
RT "Molecular cloning and expression of the rat homologue of presenilin-1.";
RL Neurosci. Lett. 206:113-116(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=9047347; DOI=10.1016/s0378-1119(96)00683-x;
RA Taniguchi T., Hashimoto T., Taniguchi R., Shimada K., Kawamata T.,
RA Yasuda M., Nakai M., Terashima A., Koizumi T., Maeda K., Tanaka C.;
RT "Cloning of the cDNA encoding rat presenilin-1.";
RL Gene 186:73-75(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50; THR-330; SER-332;
RP SER-368; THR-371 AND SER-372, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [5]
RP FUNCTION.
RX PubMed=30429473; DOI=10.1038/s41467-018-06813-x;
RA Barthet G., Jorda-Siquier T., Rumi-Masante J., Bernadou F., Mueller U.,
RA Mulle C.;
RT "Presenilin-mediated cleavage of APP regulates synaptotagmin-7 and
RT presynaptic plasticity.";
RL Nat. Commun. 9:4780-4780(2018).
CC -!- FUNCTION: Catalytic subunit of the gamma-secretase complex, an
CC endoprotease complex that catalyzes the intramembrane cleavage of
CC integral membrane proteins such as Notch receptors and APP (amyloid-
CC beta precursor protein). Requires the presence of the other members of
CC the gamma-secretase complex for protease activity. Plays a role in
CC Notch and Wnt signaling cascades and regulation of downstream processes
CC via its role in processing key regulatory proteins, and by regulating
CC cytosolic CTNNB1 levels. Stimulates cell-cell adhesion via its
CC interaction with CDH1; this stabilizes the complexes between CDH1 (E-
CC cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1
CC and JUP (gamma-catenin). Under conditions of apoptosis or calcium
CC influx, cleaves CDH1. This promotes the disassembly of the complexes
CC between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of
CC cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling (By
CC similarity). Required for normal embryonic brain and skeleton
CC development, and for normal angiogenesis (By similarity). Mediates the
CC proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2 (By similarity). The
CC holoprotein functions as a calcium-leak channel that allows the passive
CC movement of calcium from endoplasmic reticulum to cytosol and is
CC therefore involved in calcium homeostasis. Involved in the regulation
CC of neurite outgrowth (By similarity). Is a regulator of presynaptic
CC facilitation, spike transmission and synaptic vesicles replenishment in
CC a process that depends on gamma-secretase activity. It acts through the
CC control of SYT7 presynaptic expression (PubMed:30429473).
CC {ECO:0000250|UniProtKB:P49768, ECO:0000250|UniProtKB:P49769,
CC ECO:0000269|PubMed:30429473}.
CC -!- SUBUNIT: Homodimer. The functional gamma-secretase complex is composed
CC of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2),
CC nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex
CC is sufficient for secretase activity. Other components which are
CC associated with the complex include SLC25A64, SLC5A7 and PHB. As part
CC of the gamma-secretase complex, interacts with CRB2 (via transmembrane
CC domain) (By similarity). Predominantly heterodimer of a N-terminal
CC (NTF) and a C-terminal (CTF) endoproteolytical fragment. Associates
CC with proteolytic processed C-terminal fragments C83 and C99 of the
CC amyloid precursor protein (APP). Associates with NOTCH1. Associates
CC with cadherin/catenin adhesion complexes through direct binding to CDH1
CC or CDH2. Interaction with CDH1 stabilizes the complex and stimulates
CC cell-cell aggregation. Interaction with CDH2 is essential for
CC trafficking of CDH2 from the endoplasmic reticulum to the plasma
CC membrane. Interacts with CTNND2, CTNNB1, CTNND1, JUP, HERPUD1, FLNA,
CC FLNB, MTCH1, PKP4 and PARL. Interacts through its N-terminus with GFAP
CC (isoform 2) (By similarity). Interacts with DOCK3 (By similarity).
CC Interacts with UBQLN1 (By similarity). {ECO:0000250|UniProtKB:P49768,
CC ECO:0000250|UniProtKB:P49769}.
CC -!- INTERACTION:
CC PRO_0000025600; Q5PQQ3: Aph1a; NbExp=2; IntAct=EBI-2606447, EBI-2606456;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P49768}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P49768}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P49768}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:P49768}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P49768}. Cytoplasmic granule
CC {ECO:0000250|UniProtKB:P49768}. Cell membrane
CC {ECO:0000250|UniProtKB:P49768}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P49768}. Cell projection, growth cone
CC {ECO:0000250|UniProtKB:P49768}. Early endosome
CC {ECO:0000250|UniProtKB:P49768}. Early endosome membrane
CC {ECO:0000250|UniProtKB:P49768}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P49768}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q4JIM4}. Synapse {ECO:0000250|UniProtKB:Q4JIM4}.
CC Cell projection, neuron projection {ECO:0000250|UniProtKB:P49768}.
CC Note=Translocates with bound NOTCH1 from the endoplasmic reticulum
CC and/or Golgi to the cell surface. Colocalizes with CDH1/2 at sites of
CC cell-cell contact. Colocalizes with CTNNB1 in the endoplasmic reticulum
CC and the proximity of the plasma membrane. Also present in azurophil
CC granules of neutrophils. Colocalizes with UBQLN1 in the cell membrane
CC and in cytoplasmic juxtanuclear structures called aggresomes.
CC {ECO:0000250|UniProtKB:P49768}.
CC -!- TISSUE SPECIFICITY: Detected in embryonic and adult brain.
CC {ECO:0000269|PubMed:8710164}.
CC -!- DOMAIN: The PAL motif is required for normal active site conformation.
CC {ECO:0000250|UniProtKB:P49768}.
CC -!- DOMAIN: Substrates, such as NOTCH1 and APP peptides, are bound between
CC PSEN1 transmembrane domains and via the first lumenal loop and the
CC cytoplasmic loop between the sixth and seventh transmembrane domains.
CC Substrate binding causes a conformation change and formation of an
CC intermolecular antiparallel beta-sheet between PSEN1 and its
CC substrates. {ECO:0000250|UniProtKB:P49768}.
CC -!- PTM: Heterogeneous proteolytic processing generates N-terminal (NTF)
CC and C-terminal (CTF) fragments of approximately 35 and 20 kDa,
CC respectively. During apoptosis, the C-terminal fragment (CTF) is
CC further cleaved by caspase-3 to produce the fragment, PS1-CTF12.
CC {ECO:0000250|UniProtKB:P49768}.
CC -!- PTM: After endoproteolysis, the C-terminal fragment (CTF) is
CC phosphorylated on serine residues by PKA and/or PKC. Phosphorylation on
CC Ser-347 inhibits endoproteolysis. {ECO:0000250|UniProtKB:P49768}.
CC -!- SIMILARITY: Belongs to the peptidase A22A family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D82363; BAA11564.1; -; mRNA.
DR EMBL; D82578; BAA11575.1; -; mRNA.
DR EMBL; BC070887; AAH70887.1; -; mRNA.
DR RefSeq; NP_062036.2; NM_019163.3.
DR RefSeq; XP_006240383.1; XM_006240321.3.
DR RefSeq; XP_006240384.1; XM_006240322.3.
DR AlphaFoldDB; P97887; -.
DR SMR; P97887; -.
DR BioGRID; 247872; 3.
DR CORUM; P97887; -.
DR DIP; DIP-48909N; -.
DR IntAct; P97887; 11.
DR STRING; 10116.ENSRNOP00000012495; -.
DR MEROPS; A22.001; -.
DR iPTMnet; P97887; -.
DR PhosphoSitePlus; P97887; -.
DR SwissPalm; P97887; -.
DR PaxDb; P97887; -.
DR Ensembl; ENSRNOT00000012495; ENSRNOP00000012495; ENSRNOG00000009110.
DR GeneID; 29192; -.
DR KEGG; rno:29192; -.
DR UCSC; RGD:3425; rat.
DR CTD; 5663; -.
DR RGD; 3425; Psen1.
DR eggNOG; KOG2736; Eukaryota.
DR GeneTree; ENSGT00940000158751; -.
DR HOGENOM; CLU_022975_3_0_1; -.
DR InParanoid; P97887; -.
DR OMA; MQPVADP; -.
DR OrthoDB; 797738at2759; -.
DR PhylomeDB; P97887; -.
DR TreeFam; TF315040; -.
DR Reactome; R-RNO-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-RNO-193692; Regulated proteolysis of p75NTR.
DR Reactome; R-RNO-205043; NRIF signals cell death from the nucleus.
DR Reactome; R-RNO-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
DR Reactome; R-RNO-9017802; Noncanonical activation of NOTCH3.
DR PRO; PR:P97887; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000009110; Expressed in jejunum and 18 other tissues.
DR Genevisible; P97887; RN.
DR GO; GO:0016235; C:aggresome; ISS:UniProtKB.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; IBA:GO_Central.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0005938; C:cell cortex; ISO:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005813; C:centrosome; ISO:RGD.
DR GO; GO:0035253; C:ciliary rootlet; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0030425; C:dendrite; ISO:RGD.
DR GO; GO:0043198; C:dendritic shaft; ISO:RGD.
DR GO; GO:0005769; C:early endosome; IDA:RGD.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070765; C:gamma-secretase complex; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030426; C:growth cone; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0000776; C:kinetochore; ISO:RGD.
DR GO; GO:0005765; C:lysosomal membrane; IDA:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0043227; C:membrane-bounded organelle; ISO:RGD.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0031594; C:neuromuscular junction; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR GO; GO:0031965; C:nuclear membrane; ISO:RGD.
DR GO; GO:0005640; C:nuclear outer membrane; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0005791; C:rough endoplasmic reticulum; ISO:RGD.
DR GO; GO:0042383; C:sarcolemma; IDA:RGD.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; ISO:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0097060; C:synaptic membrane; IDA:RGD.
DR GO; GO:0008021; C:synaptic vesicle; IDA:RGD.
DR GO; GO:0030018; C:Z disc; IBA:GO_Central.
DR GO; GO:0042500; F:aspartic endopeptidase activity, intramembrane cleaving; ISS:UniProtKB.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; ISO:RGD.
DR GO; GO:0051117; F:ATPase binding; ISO:RGD.
DR GO; GO:0008013; F:beta-catenin binding; ISO:RGD.
DR GO; GO:0045296; F:cadherin binding; ISO:RGD.
DR GO; GO:0005262; F:calcium channel activity; ISO:RGD.
DR GO; GO:0004175; F:endopeptidase activity; IDA:RGD.
DR GO; GO:0070851; F:growth factor receptor binding; ISO:RGD.
DR GO; GO:0030165; F:PDZ domain binding; ISO:RGD.
DR GO; GO:0008233; F:peptidase activity; IDA:RGD.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; ISO:RGD.
DR GO; GO:0042982; P:amyloid precursor protein metabolic process; ISS:UniProtKB.
DR GO; GO:0034205; P:amyloid-beta formation; ISS:UniProtKB.
DR GO; GO:0050435; P:amyloid-beta metabolic process; ISO:RGD.
DR GO; GO:0097190; P:apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0048143; P:astrocyte activation; ISO:RGD.
DR GO; GO:0002265; P:astrocyte activation involved in immune response; ISO:RGD.
DR GO; GO:0000045; P:autophagosome assembly; ISO:RGD.
DR GO; GO:0006914; P:autophagy; ISO:RGD.
DR GO; GO:0001568; P:blood vessel development; ISO:RGD.
DR GO; GO:0007420; P:brain development; ISO:RGD.
DR GO; GO:0048854; P:brain morphogenesis; ISO:RGD.
DR GO; GO:0021870; P:Cajal-Retzius cell differentiation; ISO:RGD.
DR GO; GO:0006816; P:calcium ion transport; IBA:GO_Central.
DR GO; GO:0001708; P:cell fate specification; ISO:RGD.
DR GO; GO:0098609; P:cell-cell adhesion; ISO:RGD.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:RGD.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:RGD.
DR GO; GO:0021549; P:cerebellum development; IEP:RGD.
DR GO; GO:0021795; P:cerebral cortex cell migration; ISO:RGD.
DR GO; GO:0021987; P:cerebral cortex development; ISO:RGD.
DR GO; GO:0015871; P:choline transport; ISO:RGD.
DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; ISO:RGD.
DR GO; GO:0030326; P:embryonic limb morphogenesis; ISO:RGD.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; ISS:UniProtKB.
DR GO; GO:0050673; P:epithelial cell proliferation; ISO:RGD.
DR GO; GO:0042462; P:eye photoreceptor cell development; NAS:RGD.
DR GO; GO:0030900; P:forebrain development; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0001947; P:heart looping; ISO:RGD.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0098712; P:L-glutamate import across plasma membrane; ISO:RGD.
DR GO; GO:0007611; P:learning or memory; ISO:RGD.
DR GO; GO:0040011; P:locomotion; ISO:RGD.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IMP:RGD.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; ISO:RGD.
DR GO; GO:0007613; P:memory; ISO:RGD.
DR GO; GO:0006839; P:mitochondrial transport; ISO:RGD.
DR GO; GO:0043011; P:myeloid dendritic cell differentiation; ISO:RGD.
DR GO; GO:0002573; P:myeloid leukocyte differentiation; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:RGD.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0050771; P:negative regulation of axonogenesis; ISO:RGD.
DR GO; GO:1904797; P:negative regulation of core promoter binding; ISO:RGD.
DR GO; GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISO:RGD.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; ISO:RGD.
DR GO; GO:0003407; P:neural retina development; IEP:RGD.
DR GO; GO:0022008; P:neurogenesis; ISO:RGD.
DR GO; GO:0051402; P:neuron apoptotic process; ISO:RGD.
DR GO; GO:0070050; P:neuron cellular homeostasis; IEA:Ensembl.
DR GO; GO:0048666; P:neuron development; ISO:RGD.
DR GO; GO:0030182; P:neuron differentiation; ISO:RGD.
DR GO; GO:0001764; P:neuron migration; ISO:RGD.
DR GO; GO:1990535; P:neuron projection maintenance; ISO:RGD.
DR GO; GO:0007220; P:Notch receptor processing; ISO:RGD.
DR GO; GO:0007219; P:Notch signaling pathway; ISO:RGD.
DR GO; GO:1905908; P:positive regulation of amyloid fibril formation; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0043085; P:positive regulation of catalytic activity; ISS:UniProtKB.
DR GO; GO:0050820; P:positive regulation of coagulation; ISO:RGD.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0045821; P:positive regulation of glycolytic process; ISO:RGD.
DR GO; GO:0002038; P:positive regulation of L-glutamate import across plasma membrane; ISO:RGD.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0042327; P:positive regulation of phosphorylation; ISO:RGD.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:RGD.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISO:RGD.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0001921; P:positive regulation of receptor recycling; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0009791; P:post-embryonic development; ISO:RGD.
DR GO; GO:0006486; P:protein glycosylation; ISO:RGD.
DR GO; GO:0051604; P:protein maturation; ISO:RGD.
DR GO; GO:0016485; P:protein processing; IDA:RGD.
DR GO; GO:0015031; P:protein transport; ISO:RGD.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0007176; P:regulation of epidermal growth factor-activated receptor activity; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0042325; P:regulation of phosphorylation; ISO:RGD.
DR GO; GO:0043393; P:regulation of protein binding; ISO:RGD.
DR GO; GO:0060075; P:regulation of resting membrane potential; ISO:RGD.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISO:RGD.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; ISO:RGD.
DR GO; GO:0006979; P:response to oxidative stress; ISO:RGD.
DR GO; GO:0035282; P:segmentation; ISO:RGD.
DR GO; GO:0051208; P:sequestering of calcium ion; ISO:RGD.
DR GO; GO:0048705; P:skeletal system morphogenesis; ISO:RGD.
DR GO; GO:0043589; P:skin morphogenesis; ISO:RGD.
DR GO; GO:0051563; P:smooth endoplasmic reticulum calcium ion homeostasis; ISO:RGD.
DR GO; GO:0001756; P:somitogenesis; ISO:RGD.
DR GO; GO:0050808; P:synapse organization; ISO:RGD.
DR GO; GO:0016080; P:synaptic vesicle targeting; ISO:RGD.
DR GO; GO:0002286; P:T cell activation involved in immune response; ISO:RGD.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:RGD.
DR GO; GO:0048538; P:thymus development; ISO:RGD.
DR Gene3D; 1.10.472.100; -; 1.
DR InterPro; IPR002031; Pept_A22A_PS1.
DR InterPro; IPR001108; Peptidase_A22A.
DR InterPro; IPR006639; Preselin/SPP.
DR InterPro; IPR042524; Presenilin_C.
DR PANTHER; PTHR10202; PTHR10202; 1.
DR Pfam; PF01080; Presenilin; 1.
DR PRINTS; PR01072; PRESENILIN.
DR PRINTS; PR01073; PRESENILIN1.
DR SMART; SM00730; PSN; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cell adhesion; Cell membrane; Cell projection;
KW Endoplasmic reticulum; Endosome; Golgi apparatus; Hydrolase; Membrane;
KW Notch signaling pathway; Phosphoprotein; Protease; Reference proteome;
KW Synapse; Transmembrane; Transmembrane helix.
FT CHAIN 1..298
FT /note="Presenilin-1 NTF subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000025599"
FT CHAIN 299..468
FT /note="Presenilin-1 CTF subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000025600"
FT CHAIN 347..468
FT /note="Presenilin-1 CTF12"
FT /evidence="ECO:0000250"
FT /id="PRO_0000236062"
FT TOPO_DOM 1..82
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 83..103
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 104..132
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 133..153
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 154..166
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 167..189
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 190..194
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 195..216
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 217..220
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 221..241
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 242..248
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 249..272
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 273..381
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 382..402
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 403..408
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 409..429
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 430..433
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 434..454
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 455..468
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 1..58
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 288..290
FT /note="Important for cleavage of target proteins"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 304..338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 322..451
FT /note="Required for interaction with CTNNB1"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 373..400
FT /note="Required for interaction with CTNND2"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 378..382
FT /note="Important for cleavage of target proteins"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 433..435
FT /note="Important for cleavage of target proteins"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 465..468
FT /note="Interaction with MTCH1"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT MOTIF 434..436
FT /note="PAL"
FT /evidence="ECO:0000305"
FT COMPBIAS 1..30
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 31..46
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 257
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT ACT_SITE 386
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT SITE 291..292
FT /note="Cleavage; alternate"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT SITE 292..293
FT /note="Cleavage; alternate"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT SITE 298..299
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT SITE 346..347
FT /note="Cleavage; by caspase"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 330
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 332
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 347
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT MOD_RES 368
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 371
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CONFLICT 234
FT /note="A -> S (in Ref. 2; BAA11564)"
FT /evidence="ECO:0000305"
FT CONFLICT 381
FT /note="K -> R (in Ref. 2; BAA11564)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 468 AA; 52790 MW; 17CB791E88A16FC0 CRC64;
MTEIPAPLSY FQNAQMSEDS HSSSVRSQND NQERQQHHDR QRLDNPESIS NGRPQSNFTR
QVIEQDEEED EELTLKYGAK HVIMLFVPVT LCMVVVVATI KSVSFYTRKD GQLIYTPFTE
DTETVGQRAL HSILNAAIMI SVIVVMTILL VVLYKYRCYK VIHAWLIVSS LLLLFFFSFI
YLGEVFKTYN VAVDYITVAL LIWNFGVVGM IAIHWKGPLR LQQAYLIMIS ALMALVFIKY
LPEWTAWLIL AVISVYDLVA VLCPKGPLRM LVETAQERNE TLFPALIYSS TMVWLVNMAE
GDPEAQRRVP KNPKYSTQGT EREETQDTGT GSDDGGFSEE WEAQRDSHLG PHRSTPESRA
AVQELSGSIL TSEDPEERGV KLGLGDFIFY SVLVGKASAT ASGDWNTTIA CFVAILIGLC
LTLLLLAIFK KALPALPISI TFGLIFYFAT DYLVQPFMDQ LAFHQFYI
