PSN1_MOUSE
ID PSN1_MOUSE Reviewed; 467 AA.
AC P49769; Q91WK6; Q9JLP9;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 216.
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=Ad3h, Psnl1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=7596406; DOI=10.1038/375754a0;
RA Sherrington R., Rogaev E.I., Liang Y., Rogaeva E.A., Levesque G., Ikeda M.,
RA Chi H., Lin C., Li G., Holman K., Tsuda T., Mar L., Foncin J.-F.,
RA Bruni A.C., Montesi M.P., Sorbi S., Rainero I., Pinessi L., Nee L.,
RA Chumakov I., Pollen D., Brookes A., Sanseau P., Polinsky R.J., Wasco W.,
RA da Silva H.A.R., Haines J.L., Pericak-Vance M.A., Tanzi R.E., Roses A.D.,
RA Fraser P.E., Rommens J.M., St George-Hyslop P.H.;
RT "Cloning of a gene bearing missense mutations in early-onset familial
RT Alzheimer's disease.";
RL Nature 375:754-760(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC STRAIN=129/SvJ;
RX PubMed=9295283; DOI=10.1074/jbc.272.38.23489;
RA Mitsuda N., Roses A.D., Vitek M.P.;
RT "Transcriptional regulation of the mouse presenilin-1 gene.";
RL J. Biol. Chem. 272:23489-23497(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=SAM P8; TISSUE=Hippocampus;
RA Kumar V.B., Vyas K.C., Choudhary V., Franko M., Flood J.F., Morley J.E.;
RT "Molecular cloning and tissue distribution of presenilin-1 in senenscence
RT accelerated mice (SAM P8) mice.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=FVB/N; TISSUE=Eye, Liver, Mammary gland, and Retina;
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 [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=9160754; DOI=10.1016/s0092-8674(00)80244-5;
RA Shen J., Bronson R.T., Chen D.F., Xia W., Selkoe D.J., Tonegawa S.;
RT "Skeletal and CNS defects in Presenilin-1-deficient mice.";
RL Cell 89:629-639(1997).
RN [6]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=10421573; DOI=10.1016/s0960-9822(99)80331-5;
RA Hartmann D., De Strooper B., Saftig P.;
RT "Presenilin-1 deficiency leads to loss of Cajal-Retzius neurons and
RT cortical dysplasia similar to human type 2 lissencephaly.";
RL Curr. Biol. 9:719-727(1999).
RN [7]
RP INTERACTION WITH DOCK3.
RC TISSUE=Brain;
RX PubMed=10854253; DOI=10.1046/j.1471-4159.2000.0750109.x;
RA Kashiwa A., Yoshida H., Lee S., Paladino T., Liu Y., Chen Q., Dargusch R.,
RA Schubert D., Kimura H.;
RT "Isolation and characterization of novel presenilin binding protein.";
RL J. Neurochem. 75:109-116(2000).
RN [8]
RP FUNCTION, AND IDENTIFICATION IN COMPLEX WITH CDH1; CTNNB1; CTNND1 AND JUP.
RX PubMed=11226248; DOI=10.1073/pnas.041603398;
RA Baki L., Marambaud P., Efthimiopoulos S., Georgakopoulos A., Wen P.,
RA Cui W., Shioi J., Koo E., Ozawa M., Friedrich V.L., Robakis N.K.;
RT "Presenilin-1 binds cytoplasmic epithelial cadherin, inhibits cadherin/p120
RT association, and regulates stability and function of the cadherin/catenin
RT adhesion complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:2381-2386(2001).
RN [9]
RP DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=11517342; DOI=10.1073/pnas.191284198;
RA Xia X., Qian S., Soriano S., Wu Y., Fletcher A.M., Wang X.J., Koo E.H.,
RA Wu X., Zheng H.;
RT "Loss of presenilin 1 is associated with enhanced beta-catenin signaling
RT and skin tumorigenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:10863-10868(2001).
RN [10]
RP FUNCTION.
RX PubMed=11953314; DOI=10.1093/emboj/21.8.1948;
RA Marambaud P., Shioi J., Serban G., Georgakopoulos A., Sarner S., Nagy V.,
RA Baki L., Wen P., Efthimiopoulos S., Shao Z., Wisniewski T., Robakis N.K.;
RT "A presenilin-1/gamma-secretase cleavage releases the E-cadherin
RT intracellular domain and regulates disassembly of adherens junctions.";
RL EMBO J. 21:1948-1956(2002).
RN [11]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=12834865; DOI=10.1016/s0925-4773(03)00064-9;
RA Nakajima M., Yuasa S., Ueno M., Takakura N., Koseki H., Shirasawa T.;
RT "Abnormal blood vessel development in mice lacking presenilin-1.";
RL Mech. Dev. 120:657-667(2003).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [13]
RP FUNCTION.
RX PubMed=16959576; DOI=10.1016/j.cell.2006.06.059;
RA Tu H., Nelson O., Bezprozvanny A., Wang Z., Lee S.F., Hao Y.H.,
RA Serneels L., De Strooper B., Yu G., Bezprozvanny I.;
RT "Presenilins form ER Ca2+ leak channels, a function disrupted by familial
RT Alzheimer's disease-linked mutations.";
RL Cell 126:981-993(2006).
RN [14]
RP FUNCTION.
RX PubMed=17428795; DOI=10.1074/jbc.m611449200;
RA Litterst C., Georgakopoulos A., Shioi J., Ghersi E., Wisniewski T.,
RA Wang R., Ludwig A., Robakis N.K.;
RT "Ligand binding and calcium influx induce distinct ectodomain/gamma-
RT secretase-processing pathways of EphB2 receptor.";
RL J. Biol. Chem. 282:16155-16163(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367; THR-370 AND SER-371, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-329, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-329; SER-367; THR-370 AND
RP SER-371, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [18]
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 (By similarity).
CC Plays a role in Notch and Wnt signaling cascades and regulation of
CC downstream processes via its role in processing key regulatory
CC proteins, and by regulating cytosolic CTNNB1 levels (PubMed:10421573,
CC PubMed:11517342). Stimulates cell-cell adhesion via its interaction
CC with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and
CC its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-
CC catenin) (PubMed:11226248). Under conditions of apoptosis or calcium
CC influx, cleaves CDH1 (PubMed:11953314). This promotes the disassembly
CC of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the
CC pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt
CC signaling (PubMed:11226248). Required for normal embryonic brain and
CC skeleton development, and for normal angiogenesis (PubMed:9160754,
CC PubMed:10421573, PubMed:12834865). Mediates the proteolytic cleavage of
CC EphB2/CTF1 into EphB2/CTF2 (PubMed:17428795). The holoprotein functions
CC as a calcium-leak channel that allows the passive movement of calcium
CC from endoplasmic reticulum to cytosol and is involved in calcium
CC homeostasis (PubMed:16959576). Involved in the regulation of neurite
CC outgrowth (By similarity). Is a regulator of presynaptic facilitation,
CC spike transmission and synaptic vesicles replenishment in a process
CC that depends on gamma-secretase activity. It acts through the control
CC of SYT7 presynaptic expression (PubMed:30429473).
CC {ECO:0000250|UniProtKB:P49768, ECO:0000269|PubMed:10421573,
CC ECO:0000269|PubMed:11226248, ECO:0000269|PubMed:11517342,
CC ECO:0000269|PubMed:11953314, ECO:0000269|PubMed:12834865,
CC ECO:0000269|PubMed:16959576, ECO:0000269|PubMed:17428795,
CC ECO:0000269|PubMed:30429473, ECO:0000269|PubMed:9160754}.
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 (PubMed:11226248). Interaction with CDH1 stabilizes the complex
CC and stimulates cell-cell aggregation. Interaction with CDH2 is
CC essential for trafficking of CDH2 from the endoplasmic reticulum to the
CC plasma membrane. Interacts with CTNND2, CTNNB1, CTNND1, JUP, HERPUD1,
CC FLNA, FLNB, MTCH1, PKP4 and PARL. Interacts through its N-terminus with
CC GFAP (isoform 2) (By similarity). Interacts with DOCK3
CC (PubMed:10854253). Interacts with UBQLN1 (By similarity).
CC {ECO:0000250|UniProtKB:P49768, ECO:0000269|PubMed:10854253,
CC ECO:0000269|PubMed:11226248}.
CC -!- INTERACTION:
CC P49769; Q9Z1G4: Atp6v0a1; NbExp=2; IntAct=EBI-990067, EBI-771149;
CC P49769; P14211: Calr; NbExp=3; IntAct=EBI-990067, EBI-644340;
CC P49769; P52795: Efnb1; NbExp=2; IntAct=EBI-990067, EBI-8107507;
CC P49769; P35438: Grin1; NbExp=3; IntAct=EBI-990067, EBI-400084;
CC P49769; Q9Z280: Pld1; NbExp=2; IntAct=EBI-990067, EBI-15566315;
CC P49769; P46096: Syt1; NbExp=6; IntAct=EBI-990067, EBI-445340;
CC PRO_0000025597; Q9WV31: Arc; NbExp=2; IntAct=EBI-5260983, EBI-397779;
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:0000269|PubMed:10421573, ECO:0000269|PubMed:11517342}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P49768}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:10421573, ECO:0000305|PubMed:11517342}. Cell
CC projection, growth cone {ECO:0000250|UniProtKB:P49768}. Cell
CC projection, neuron projection {ECO:0000250|UniProtKB:P49768}. Early
CC endosome {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 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P49769-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P49769-2; Sequence=VSP_008381, VSP_008382;
CC -!- TISSUE SPECIFICITY: Detected in embryonic brain (PubMed:10421573).
CC Detected in adult skin epidermis (at protein level) (PubMed:11517342).
CC {ECO:0000269|PubMed:10421573, ECO:0000269|PubMed:11517342}.
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-346 inhibits endoproteolysis. {ECO:0000250|UniProtKB:P49768}.
CC -!- DISRUPTION PHENOTYPE: Perinatal lethality; all of the homozygous
CC mutants die within 30 minutes after birth (PubMed:9160754).
CC Heterozygotes have no visible phenotype (PubMed:9160754). Mutant mice
CC display important skeletal malformations (PubMed:9160754,
CC PubMed:10421573). After 12.5 dpc, they exhibit important defects in
CC embryonic brain development, with a decrease in the number of neural
CC progenitor cells in specific brain regions (PubMed:9160754,
CC PubMed:10421573). The cell density in the marginal zone is normal at 13
CC dpc, but then becomes much reduced, including a strong reduction in the
CC number of Cajal-Retzius cells (PubMed:10421573). At the same time,
CC Notch1 expression is reduced in the developing brain cortex
CC (PubMed:10421573). At 17.5 dpc, all layers of the ventricular zone in
CC the ventrolateral region at the posterior portion of the lateral
CC ventricles have disappeared, giving rise to symmetric cavitation in the
CC posterior part of the brain (PubMed:9160754). They also display cranial
CC hemorrhages that are first observed at 12.5 dpc (PubMed:9160754,
CC PubMed:10421573, PubMed:12834865). This is due to defects in
CC angiogenesis, with increased blood vessel diameter and abnormal
CC morphology and increased proliferation of capillary endothelial cells
CC that lead to stenosis of the capillary lumen (PubMed:12834865). Psen1-
CC deficient mice can be rescued by neuronal expression of human PSEN1;
CC these mice lack any detectable PSEN1 in their skin and display
CC increased levels of cytosolic and nuclear CTNNB1 in skin, which leads
CC to aberrant Wnt signaling (PubMed:11517342). Mutant mice display
CC epidermal hyperplasia and hyperkeratosis that gives rise to skin tumors
CC (PubMed:11517342). {ECO:0000269|PubMed:10421573,
CC ECO:0000269|PubMed:11517342, ECO:0000269|PubMed:12834865,
CC ECO:0000269|PubMed:9160754}.
CC -!- MISCELLANEOUS: [Isoform 2]: Due to intron retention. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the peptidase A22A family. {ECO:0000305}.
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DR EMBL; L42177; AAC42094.1; -; mRNA.
DR EMBL; AF007560; AAB72049.1; -; Genomic_DNA.
DR EMBL; AF149111; AAF73153.1; -; mRNA.
DR EMBL; BC014744; AAH14744.1; -; mRNA.
DR EMBL; BC030409; AAH30409.1; -; mRNA.
DR EMBL; BC071233; AAH71233.1; -; mRNA.
DR CCDS; CCDS26030.1; -. [P49769-1]
DR PIR; I78388; I78388.
DR RefSeq; NP_032969.1; NM_008943.2.
DR RefSeq; XP_006515668.1; XM_006515605.3.
DR AlphaFoldDB; P49769; -.
DR SMR; P49769; -.
DR BioGRID; 202414; 24.
DR ComplexPortal; CPX-4234; Gamma-secretase complex, Aph1a-Psen1 variant.
DR ComplexPortal; CPX-4235; Gamma-secretase complex, Aph1b-Psen1 variant.
DR CORUM; P49769; -.
DR DIP; DIP-36237N; -.
DR IntAct; P49769; 27.
DR MINT; P49769; -.
DR STRING; 10090.ENSMUSP00000098786; -.
DR MEROPS; A22.001; -.
DR iPTMnet; P49769; -.
DR PhosphoSitePlus; P49769; -.
DR SwissPalm; P49769; -.
DR EPD; P49769; -.
DR jPOST; P49769; -.
DR MaxQB; P49769; -.
DR PaxDb; P49769; -.
DR PeptideAtlas; P49769; -.
DR PRIDE; P49769; -.
DR ProteomicsDB; 301995; -. [P49769-1]
DR ProteomicsDB; 301996; -. [P49769-2]
DR Antibodypedia; 3480; 1003 antibodies from 44 providers.
DR Ensembl; ENSMUST00000041806; ENSMUSP00000048363; ENSMUSG00000019969. [P49769-1]
DR Ensembl; ENSMUST00000101225; ENSMUSP00000098786; ENSMUSG00000019969. [P49769-1]
DR UCSC; uc007odo.1; mouse. [P49769-2]
DR UCSC; uc007odp.1; mouse. [P49769-1]
DR MGI; MGI:1202717; Psen1.
DR VEuPathDB; HostDB:ENSMUSG00000019969; -.
DR eggNOG; KOG2736; Eukaryota.
DR GeneTree; ENSGT00940000158751; -.
DR HOGENOM; CLU_022975_3_0_1; -.
DR InParanoid; P49769; -.
DR OMA; MQPVADP; -.
DR PhylomeDB; P49769; -.
DR TreeFam; TF315040; -.
DR Reactome; R-MMU-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-MMU-193692; Regulated proteolysis of p75NTR.
DR Reactome; R-MMU-205043; NRIF signals cell death from the nucleus.
DR Reactome; R-MMU-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
DR Reactome; R-MMU-9017802; Noncanonical activation of NOTCH3.
DR BioGRID-ORCS; 19164; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Psen1; mouse.
DR PRO; PR:P49769; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P49769; protein.
DR Bgee; ENSMUSG00000019969; Expressed in urinary bladder urothelium and 278 other tissues.
DR ExpressionAtlas; P49769; baseline and differential.
DR Genevisible; P49769; MM.
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; IDA:MGI.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0035253; C:ciliary rootlet; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0030425; C:dendrite; IDA:MGI.
DR GO; GO:0043198; C:dendritic shaft; IDA:MGI.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IC:ComplexPortal.
DR GO; GO:0070765; C:gamma-secretase complex; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0000139; C:Golgi membrane; IC:ComplexPortal.
DR GO; GO:0030426; C:growth cone; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0000776; C:kinetochore; ISO:MGI.
DR GO; GO:0005765; C:lysosomal membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0043227; C:membrane-bounded organelle; IDA:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0031594; C:neuromuscular junction; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005640; C:nuclear outer membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0005791; C:rough endoplasmic reticulum; ISO:MGI.
DR GO; GO:0042383; C:sarcolemma; ISO:MGI.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0097060; C:synaptic membrane; ISO:MGI.
DR GO; GO:0008021; C:synaptic vesicle; ISO:MGI.
DR GO; GO:0030018; C:Z disc; IBA:GO_Central.
DR GO; GO:0042500; F:aspartic endopeptidase activity, intramembrane cleaving; IMP:MGI.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IMP:MGI.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI.
DR GO; GO:0045296; F:cadherin binding; IPI:MGI.
DR GO; GO:0005262; F:calcium channel activity; ISO:MGI.
DR GO; GO:0004175; F:endopeptidase activity; IMP:MGI.
DR GO; GO:0070851; F:growth factor receptor binding; ISO:MGI.
DR GO; GO:0030165; F:PDZ domain binding; ISO:MGI.
DR GO; GO:0008233; F:peptidase activity; ISO:MGI.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; IMP:MGI.
DR GO; GO:0042982; P:amyloid precursor protein metabolic process; ISS:UniProtKB.
DR GO; GO:0034205; P:amyloid-beta formation; IMP:MGI.
DR GO; GO:0050435; P:amyloid-beta metabolic process; IMP:MGI.
DR GO; GO:0097190; P:apoptotic signaling pathway; IGI:MGI.
DR GO; GO:0048143; P:astrocyte activation; ISO:MGI.
DR GO; GO:0002265; P:astrocyte activation involved in immune response; ISO:MGI.
DR GO; GO:0000045; P:autophagosome assembly; IMP:MGI.
DR GO; GO:0006914; P:autophagy; IMP:MGI.
DR GO; GO:0001568; P:blood vessel development; IMP:MGI.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0048854; P:brain morphogenesis; IGI:MGI.
DR GO; GO:0021870; P:Cajal-Retzius cell differentiation; IMP:MGI.
DR GO; GO:0006816; P:calcium ion transport; IBA:GO_Central.
DR GO; GO:0001708; P:cell fate specification; IGI:MGI.
DR GO; GO:0098609; P:cell-cell adhesion; ISO:MGI.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:MGI.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:MGI.
DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl.
DR GO; GO:0021795; P:cerebral cortex cell migration; IMP:MGI.
DR GO; GO:0021987; P:cerebral cortex development; IMP:MGI.
DR GO; GO:0015871; P:choline transport; IMP:MGI.
DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; IGI:MGI.
DR GO; GO:0030326; P:embryonic limb morphogenesis; IGI:MGI.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IMP:MGI.
DR GO; GO:0050673; P:epithelial cell proliferation; IGI:MGI.
DR GO; GO:0030900; P:forebrain development; IGI:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0001947; P:heart looping; IGI:MGI.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IGI:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0098712; P:L-glutamate import across plasma membrane; IMP:MGI.
DR GO; GO:0007611; P:learning or memory; IGI:MGI.
DR GO; GO:0040011; P:locomotion; IGI:MGI.
DR GO; GO:0060291; P:long-term synaptic potentiation; TAS:ARUK-UCL.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; ISS:UniProtKB.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; ISO:MGI.
DR GO; GO:0007613; P:memory; IMP:MGI.
DR GO; GO:0006839; P:mitochondrial transport; IMP:MGI.
DR GO; GO:0043011; P:myeloid dendritic cell differentiation; IMP:MGI.
DR GO; GO:0002573; P:myeloid leukocyte differentiation; IGI:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:MGI.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IGI:MGI.
DR GO; GO:0050771; P:negative regulation of axonogenesis; IMP:MGI.
DR GO; GO:1904797; P:negative regulation of core promoter binding; ISO:MGI.
DR GO; GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; IMP:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IMP:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IGI:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; IMP:BHF-UCL.
DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; IMP:BHF-UCL.
DR GO; GO:0003407; P:neural retina development; IEA:Ensembl.
DR GO; GO:0022008; P:neurogenesis; IMP:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IGI:MGI.
DR GO; GO:0070050; P:neuron cellular homeostasis; IMP:MGI.
DR GO; GO:0048666; P:neuron development; IMP:MGI.
DR GO; GO:0030182; P:neuron differentiation; IMP:MGI.
DR GO; GO:0001764; P:neuron migration; IMP:MGI.
DR GO; GO:1990535; P:neuron projection maintenance; ISO:MGI.
DR GO; GO:0007220; P:Notch receptor processing; IMP:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; IMP:MGI.
DR GO; GO:1905908; P:positive regulation of amyloid fibril formation; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IGI:MGI.
DR GO; GO:0043085; P:positive regulation of catalytic activity; ISS:UniProtKB.
DR GO; GO:0050820; P:positive regulation of coagulation; IMP:MGI.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0045821; P:positive regulation of glycolytic process; ISO:MGI.
DR GO; GO:0002038; P:positive regulation of L-glutamate import across plasma membrane; IMP:MGI.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IMP:MGI.
DR GO; GO:0042327; P:positive regulation of phosphorylation; ISO:MGI.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:BHF-UCL.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:MGI.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISO:MGI.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:0001921; P:positive regulation of receptor recycling; IMP:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0006486; P:protein glycosylation; IMP:MGI.
DR GO; GO:0051604; P:protein maturation; IGI:MGI.
DR GO; GO:0019538; P:protein metabolic process; IDA:MGI.
DR GO; GO:0016485; P:protein processing; IMP:MGI.
DR GO; GO:0015031; P:protein transport; IGI:MGI.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0007176; P:regulation of epidermal growth factor-activated receptor activity; IGI:MGI.
DR GO; GO:0010468; P:regulation of gene expression; ISO:MGI.
DR GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0042325; P:regulation of phosphorylation; ISO:MGI.
DR GO; GO:0043393; P:regulation of protein binding; IGI:MGI.
DR GO; GO:0060075; P:regulation of resting membrane potential; IMP:MGI.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IMP:MGI.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IMP:MGI.
DR GO; GO:0006979; P:response to oxidative stress; IMP:MGI.
DR GO; GO:0035282; P:segmentation; IMP:MGI.
DR GO; GO:0051208; P:sequestering of calcium ion; IMP:MGI.
DR GO; GO:0048705; P:skeletal system morphogenesis; IMP:MGI.
DR GO; GO:0043589; P:skin morphogenesis; IMP:BHF-UCL.
DR GO; GO:0051563; P:smooth endoplasmic reticulum calcium ion homeostasis; IGI:MGI.
DR GO; GO:0001756; P:somitogenesis; IMP:MGI.
DR GO; GO:0050808; P:synapse organization; ISO:MGI.
DR GO; GO:0016080; P:synaptic vesicle targeting; IMP:MGI.
DR GO; GO:0002286; P:T cell activation involved in immune response; IGI:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IGI:MGI.
DR GO; GO:0048538; P:thymus development; IMP:MGI.
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 Alternative splicing; Apoptosis; Cell adhesion; Cell membrane;
KW Cell projection; Cytoplasmic vesicle; Endoplasmic reticulum; Endosome;
KW Golgi apparatus; Hydrolase; Membrane; Notch signaling pathway;
KW Phosphoprotein; Protease; Reference proteome; Synapse; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..298
FT /note="Presenilin-1 NTF subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000025597"
FT CHAIN 299..467
FT /note="Presenilin-1 CTF subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000025598"
FT CHAIN 346..467
FT /note="Presenilin-1 CTF12"
FT /evidence="ECO:0000250"
FT /id="PRO_0000236058"
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..380
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 381..401
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 402..407
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 408..428
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 429..432
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TRANSMEM 433..453
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT TOPO_DOM 454..467
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 1..68
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..357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 322..450
FT /note="Required for interaction with CTNNB1"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 372..399
FT /note="Required for interaction with CTNND2"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 377..381
FT /note="Important for cleavage of target proteins"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 432..434
FT /note="Important for cleavage of target proteins"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT REGION 464..467
FT /note="Interaction with MTCH1"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT MOTIF 433..435
FT /note="PAL"
FT COMPBIAS 1..32
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..47
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 304..328
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 337..352
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 385
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 345..346
FT /note="Cleavage; by caspase"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT MOD_RES 51
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97887"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 346
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P49768"
FT MOD_RES 367
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 370
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT VAR_SEQ 257..261
FT /note="DLVAV -> GKAQD (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008381"
FT VAR_SEQ 262..467
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008382"
FT VARIANT 9
FT /note="S -> T (in strain: SAM P8)"
FT VARIANT 40
FT /note="D -> E (in strain: SAM P8)"
FT VARIANT 67
FT /note="E -> CM (in strain: SAM P8)"
FT VARIANT 196
FT /note="V -> L (in strain: SAM P8)"
FT VARIANT 321..322
FT /note="ER -> RRD (in strain: SAM P8)"
SQ SEQUENCE 467 AA; 52640 MW; D07215B4BAD2D549 CRC64;
MTEIPAPLSY FQNAQMSEDS HSSSAIRSQN DSQERQQQHD RQRLDNPEPI SNGRPQSNSR
QVVEQDEEED EELTLKYGAK HVIMLFVPVT LCMVVVVATI KSVSFYTRKD GQLIYTPFTE
DTETVGQRAL HSILNAAIMI SVIVIMTILL VVLYKYRCYK VIHAWLIISS LLLLFFFSFI
YLGEVFKTYN VAVDYVTVAL LIWNFGVVGM IAIHWKGPLR LQQAYLIMIS ALMALVFIKY
LPEWTAWLIL AVISVYDLVA VLCPKGPLRM LVETAQERNE TLFPALIYSS TMVWLVNMAE
GDPEAQRRVP KNPKYNTQRA ERETQDSGSG NDDGGFSEEW EAQRDSHLGP HRSTPESRAA
VQELSGSILT SEDPEERGVK LGLGDFIFYS VLVGKASATA SGDWNTTIAC FVAILIGLCL
TLLLLAIFKK ALPALPISIT FGLVFYFATD YLVQPFMDQL AFHQFYI
