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Reviewed, UniProtKB/Swiss-Prot P49769 (PSN1_MOUSE)

Last modified January 19, 2010. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Presenilin-1
      Short name=PS-1
    EC=3.4.23.-
Alternative name(s):
    Protein S182
Cleaved into the following 3 chains:
    1- Recommended name:
            Presenilin-1 NTF subunit
    2- Recommended name:
            Presenilin-1 CTF subunit
    3- Recommended name:
            Presenilin-1 CTF12
                Short name=PS1-CTF12
Gene names
Name: Psen1
Synonyms: Ad3h, Psnl1
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

Sequence length467 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Probable 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 (beta-amyloid precursor protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. Stimulates cell-cell adhesion though its association with the E-cadherin/catenin complex. Under conditions of apoptosis or calcium influx, cleaves E-cadherin promoting the disassembly of the E-cadherin/catenin complex and increasing the pool of cytoplasmic beta-catenin, thus negatively regulating Wnt signaling. May also play a role in hematopoiesis By similarity.

Subunit structure

Homodimer. Component of the gamma-secretase complex, a complex composed of 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, PHB and PSEN1 isoform 3. 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. Component of 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, HERPUD1, FLNA, FLNB, MTCH1, PKP4 and PARL. Interacts through its N-terminus with isoform 3 of GFAP. Interacts with DOCK3 By similarity. Ref.5

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Cell surface By similarity.

Domain

The PAL motif is required for normal active site conformation By similarity.

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 By similarity.

After endoproteolysis, the C-terminal fragment (CTF) is phosphorylated on serine residues by PKA and/or PKC. Phosphorylation on Ser-346 inhibits endoproteolysis By similarity. Ref.6 Ref.7 Ref.8

Sequence similarities

Belongs to the peptidase A22A family.

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Ontologies

Keywords
   Biological processApoptosis
Cell adhesion
Notch signaling pathway
   Cellular componentEndoplasmic reticulum
Golgi apparatus
Membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
   Molecular functionHydrolase
Protease
   PTMPhosphoprotein
Gene Ontology (GO)
   Biological processCajal-Retzius cell differentiation

Inferred from mutant phenotype. Source: MGI

L-glutamate transport

Inferred from mutant phenotype. Source: MGI

Notch receptor processing

Inferred from mutant phenotype. Source: MGI

T cell activation during immune response

Inferred from genetic interaction. Source: MGI

T cell receptor signaling pathway

Inferred from genetic interaction. Source: MGI

activation of MAPKK activity

Inferred from mutant phenotype. Source: MGI

amyloid precursor protein catabolic process

Inferred from mutant phenotype. Source: MGI

anagen

Inferred from genetic interaction. Source: MGI

autophagic vacuole assembly

Inferred from mutant phenotype. Source: MGI

beta-amyloid metabolic process

Inferred from mutant phenotype. Source: MGI

blood vessel development

Inferred from mutant phenotype. Source: MGI

brain morphogenesis

Inferred from genetic interaction. Source: MGI

cell fate specification

Inferred from genetic interaction. Source: MGI

cerebral cortex cell migration

Inferred from mutant phenotype. Source: MGI

choline transport

Inferred from mutant phenotype. Source: MGI

dorsal/ventral neural tube patterning

Inferred from genetic interaction. Source: MGI

embryonic limb morphogenesis

Inferred from genetic interaction. Source: MGI

epithelial cell proliferation

Inferred from genetic interaction. Source: MGI

heart looping

Inferred from genetic interaction. Source: MGI

hemopoietic progenitor cell differentiation

Inferred from genetic interaction. Source: MGI

membrane protein ectodomain proteolysis

Inferred from sequence or structural similarity. Source: UniProtKB

memory

Inferred from mutant phenotype. Source: MGI

mitochondrial transport

Inferred from mutant phenotype. Source: MGI

myeloid leukocyte differentiation

Inferred from genetic interaction. Source: MGI

negative regulation of axonogenesis

Inferred from mutant phenotype. Source: MGI

negative regulation of protein amino acid phosphorylation

Inferred from genetic interaction. Source: MGI

negative regulation of protein kinase activity

Inferred from mutant phenotype. Source: MGI

neuron apoptosis

Inferred from genetic interaction. Source: MGI

neuron development

Inferred from mutant phenotype. Source: MGI

neuron migration

Inferred from mutant phenotype. Source: MGI

positive regulation of MAP kinase activity

Inferred from mutant phenotype. Source: MGI

positive regulation of apoptosis

Inferred from genetic interaction. Source: MGI

positive regulation of coagulation

Inferred from mutant phenotype. Source: MGI

positive regulation of protein amino acid phosphorylation

Inferred from mutant phenotype. Source: MGI

post-embryonic development

Inferred from mutant phenotype. Source: MGI

protein amino acid glycosylation

Inferred from mutant phenotype. Source: MGI

protein transport

Inferred from genetic interaction. Source: MGI

regulation of epidermal growth factor receptor activity

Inferred from genetic interaction. Source: MGI

regulation of protein binding

Inferred from genetic interaction. Source: MGI

regulation of resting membrane potential

Inferred from mutant phenotype. Source: MGI

regulation of synaptic plasticity

Inferred from mutant phenotype. Source: MGI

regulation of synaptic transmission, glutamatergic

Inferred from mutant phenotype. Source: MGI

response to DNA damage stimulus

Inferred from mutant phenotype. Source: MGI

response to oxidative stress

Inferred from mutant phenotype. Source: MGI

skeletal system morphogenesis

Inferred from mutant phenotype. Source: MGI

smooth endoplasmic reticulum calcium ion homeostasis

Inferred from genetic interaction. Source: MGI

somitogenesis

Inferred from mutant phenotype. Source: MGI

synaptic vesicle targeting

Inferred from mutant phenotype. Source: MGI

thymus development

Inferred from genetic interaction. Source: MGI

   Cellular componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

axon

Inferred from direct assay. Source: MGI

cell soma

Inferred from direct assay. Source: MGI

cell surface

Inferred from electronic annotation. Source: UniProtKB-SubCell

ciliary rootlet

Inferred from direct assay. Source: MGI

cytoplasmic vesicle

Inferred from direct assay. Source: MGI

dendritic shaft

Inferred from direct assay. Source: MGI

endoplasmic reticulum Ref.5

Inferred from sequence or structural similarity. Source: UniProtKB

growth cone

Inferred from direct assay. Source: MGI

integral to plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular functioncadherin binding

Inferred from physical interaction. Source: MGI

endopeptidase activity

Inferred from mutant phenotype. Source: MGI

Complete GO annotation...

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

Ctnnb1Q022481EBI-990067,EBI-397872
JUPP149231EBI-990067,EBI-702484From a different organism.
Tmed2Q9R0Q31EBI-990067,EBI-998894

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P49769-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P49769-2)

The sequence of this isoform differs from the canonical sequence as follows:
     257-261: DLVAV → GKAQD
     262-467: Missing.
Note: Due to intron retention. No experimental confirmation available.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 298298Presenilin-1 NTF subunit By similarity
PRO_0000025597
Chain299 – 467169Presenilin-1 CTF subunit By similarity
PRO_0000025598
Chain346 – 467122Presenilin-1 CTF12 By similarity
PRO_0000236058

Regions

Topological domain1 – 8282Cytoplasmic Potential
Transmembrane83 – 10321 Potential
Topological domain104 – 13229Lumenal Potential
Transmembrane133 – 15321 Potential
Topological domain154 – 1607Cytoplasmic Potential
Transmembrane161 – 18121 Potential
Topological domain182 – 19413Lumenal Potential
Transmembrane195 – 21521 Potential
Topological domain216 – 2205Cytoplasmic Potential
Transmembrane221 – 24121 Potential
Topological domain242 – 2432Lumenal Potential
Transmembrane244 – 26421 Potential
Topological domain265 – 407143Cytoplasmic Potential
Transmembrane408 – 42821 Potential
Transmembrane433 – 45321 Potential
Region322 – 450129Required for interaction with CTNNB1 By similarity
Region372 – 39928Required for interaction with CTNND2 By similarity
Region464 – 4674Interaction with MTCH1 By similarity
Motif433 – 4353PAL

Sites

Active site2571 By similarity
Active site3851 By similarity
Site291 – 2922Cleavage; alternate By similarity
Site292 – 2932Cleavage; alternate By similarity
Site298 – 2992Cleavage By similarity
Site345 – 3462Cleavage; by caspase By similarity

Amino acid modifications

Modified residue3461Phosphoserine; by PKC By similarity
Modified residue3651Phosphoserine Ref.8
Modified residue3671Phosphoserine Ref.7 Ref.8
Modified residue3701Phosphothreonine Ref.6 Ref.7 Ref.8
Modified residue3711Phosphoserine Ref.7 Ref.8

Natural variations

Alternative sequence257 – 2615DLVAV → GKAQD in isoform 2.
VSP_008381
Alternative sequence262 – 467206Missing in isoform 2.
VSP_008382
Natural variant91S → T in strain: SAM P8.
Natural variant401D → E in strain: SAM P8.
Natural variant671E → CM in strain: SAM P8.
Natural variant1961V → L in strain: SAM P8.
Natural variant321 – 3222ER → RRD in strain: SAM P8.

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: D07215B4BAD2D549

FASTA46752,640
        10         20         30         40         50         60 
MTEIPAPLSY FQNAQMSEDS HSSSAIRSQN DSQERQQQHD RQRLDNPEPI SNGRPQSNSR 

        70         80         90        100        110        120 
QVVEQDEEED EELTLKYGAK HVIMLFVPVT LCMVVVVATI KSVSFYTRKD GQLIYTPFTE 

       130        140        150        160        170        180 
DTETVGQRAL HSILNAAIMI SVIVIMTILL VVLYKYRCYK VIHAWLIISS LLLLFFFSFI 

       190        200        210        220        230        240 
YLGEVFKTYN VAVDYVTVAL LIWNFGVVGM IAIHWKGPLR LQQAYLIMIS ALMALVFIKY 

       250        260        270        280        290        300 
LPEWTAWLIL AVISVYDLVA VLCPKGPLRM LVETAQERNE TLFPALIYSS TMVWLVNMAE 

       310        320        330        340        350        360 
GDPEAQRRVP KNPKYNTQRA ERETQDSGSG NDDGGFSEEW EAQRDSHLGP HRSTPESRAA 

       370        380        390        400        410        420 
VQELSGSILT SEDPEERGVK LGLGDFIFYS VLVGKASATA SGDWNTTIAC FVAILIGLCL 

       430        440        450        460 
TLLLLAIFKK ALPALPISIT FGLVFYFATD YLVQPFMDQL AFHQFYI

« Hide

Isoform 2.

Checksum: 16FB53FBE20EA4EB
Show »

FASTA26129,849

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References

« Hide 'large scale' references
[1]"Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease."
Sherrington R., Rogaev E.I., Liang Y., Rogaeva E.A., Levesque G., Ikeda M., Chi H., Lin C., Li G., Holman K., Tsuda T., Mar L., Foncin J.-F., Bruni A.C., Montesi M.P., Sorbi S., Rainero I., Pinessi L. expand/collapse author list , Nee L., Chumakov I., Pollen D., Brookes A., Sanseau P., Polinsky R.J., Wasco W., da Silva H.A.R., Haines J.L., Pericak-Vance M.A., Tanzi R.E., Roses A.D., Fraser P.E., Rommens J.M., St George-Hyslop P.H.
Nature 375:754-760(1995) [PubMed: 7596406] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"Transcriptional regulation of the mouse presenilin-1 gene."
Mitsuda N., Roses A.D., Vitek M.P.
J. Biol. Chem. 272:23489-23497(1997) [PubMed: 9295283] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
Strain: 129/SvJ.
[3]"Molecular cloning and tissue distribution of presenilin-1 in senenscence accelerated mice (SAM P8) mice."
Kumar V.B., Vyas K.C., Choudhary V., Franko M., Flood J.F., Morley J.E.
Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: SAM P8.
Tissue: Hippocampus.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Strain: FVB/N.
Tissue: Eye, Liver, Mammary gland and Retina.
[5]"Isolation and characterization of novel presenilin binding protein."
Kashiwa A., Yoshida H., Lee S., Paladino T., Liu Y., Chen Q., Dargusch R., Schubert D., Kimura H.
J. Neurochem. 75:109-116(2000) [PubMed: 10854253] [Abstract]
Cited for: INTERACTION WITH DOCK3.
Tissue: Brain.
[6]"Phosphoproteomic analysis of the developing mouse brain."
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.
Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed: 15345747] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-370, MASS SPECTROMETRY.
Tissue: Brain.
[7]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367; THR-370 AND SER-371, MASS SPECTROMETRY.
Tissue: Liver.
[8]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed: 19144319] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-365; SER-367; THR-370 AND SER-371, MASS SPECTROMETRY.
Tissue: Macrophage.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		L42177 mRNA. Translation: AAC42094.1.
AF007560 Genomic DNA. Translation: AAB72049.1.
AF149111 mRNA. Translation: AAF73153.1.
BC014744 mRNA. Translation: AAH14744.1.
BC030409 mRNA. Translation: AAH30409.1.
BC071233 mRNA. Translation: AAH71233.1.
IPIIPI00117124.
IPI00352799.
PIRI78388.
RefSeqNP_032969.1.
UniGeneMm.998

3D structure databases

ModBaseSearch...

Protein-protein interaction databases

IntActP49769. 6 interactions.
STRINGP49769.

Protein family/group databases

MEROPSA22.001.

PTM databases

PhosphoSiteP49769.

Proteomic databases

PRIDEP49769.

Genome annotation databases

EnsemblENSMUST00000041806; ENSMUSP00000048363; ENSMUSG00000019969; Mus musculus. [Genome view]
ENSMUST00000101225; ENSMUSP00000098786; ENSMUSG00000019969; Mus musculus. [Genome view]
GeneID19164.
KEGGmmu:19164.
UCSCuc007odo.1. mouse.
uc007odp.1. mouse.

Organism-specific databases

CTD19164.
MGIMGI:1202717. Psen1.

Phylogenomic databases

eggNOGroNOG12441.
HOGENOMHBG559840.
HOVERGENP49769.
InParanoidP49769.
OMAFYFATDN.
OrthoDBEOG9F20NN.
PhylomeDBP49769.

Gene expression databases

ArrayExpressP49769.
BgeeP49769.
CleanExMM_PSEN1.
GenevestigatorP49769.
GermOnlineENSMUSG00000019969. Mus musculus.

Family and domain databases

InterProIPR002031. Pept_A22A_PS1.
IPR006639. Peptidase_A22.
IPR001108. Peptidase_A22A.
[Graphical view]
PANTHERPTHR10202:SF7. Pept_A22A_PS1. 1 hit.
PTHR10202. Peptidase_A22A. 1 hit.
PfamPF01080. Presenilin. 1 hit.
[Graphical view]
PRINTSPR01072. PRESENILIN.
PR01073. PRESENILIN1.
SMARTSM00730. PSN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio295822.
SOURCESearch...

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Entry information

Entry namePSN1_MOUSE
AccessionPrimary (citable) accession number: P49769
Secondary accession number(s): Q91WK6, Q9JLP9
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: January 19, 2010
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents