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Protein

Presenilin-1

Gene

Psen1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei257 – 2571By similarity
Active sitei386 – 3861By similarity

GO - Molecular functioni

  • aspartic-type endopeptidase activity Source: InterPro
  • beta-catenin binding Source: GO_Central
  • cadherin binding Source: GO_Central
  • calcium channel activity Source: Ensembl
  • endopeptidase activity Source: RGD
  • peptidase activity Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease

Keywords - Biological processi

Apoptosis, Cell adhesion, Notch signaling pathway

Protein family/group databases

MEROPSiA22.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Presenilin-1 (EC:3.4.23.-)
Short name:
PS-1
Alternative name(s):
Protein S182
Cleaved into the following 3 chains:
Gene namesi
Name:Psen1
Synonyms:Psnl1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 6

Organism-specific databases

RGDi3425. Psen1.

Subcellular locationi

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

  • Note: Bound to NOTCH1 also at 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.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 8181CytoplasmicSequence analysisAdd
BLAST
Transmembranei82 – 10221HelicalSequence analysisAdd
BLAST
Topological domaini103 – 13230LumenalSequence analysisAdd
BLAST
Transmembranei133 – 15321HelicalSequence analysisAdd
BLAST
Topological domaini154 – 1607CytoplasmicSequence analysis
Transmembranei161 – 18121HelicalSequence analysisAdd
BLAST
Topological domaini182 – 19413LumenalSequence analysisAdd
BLAST
Transmembranei195 – 21521HelicalSequence analysisAdd
BLAST
Topological domaini216 – 2205CytoplasmicSequence analysis
Transmembranei221 – 24121HelicalSequence analysisAdd
BLAST
Topological domaini242 – 2432LumenalSequence analysis
Transmembranei244 – 26421HelicalSequence analysisAdd
BLAST
Topological domaini265 – 381117CytoplasmicSequence analysisAdd
BLAST
Transmembranei382 – 40221HelicalSequence analysisAdd
BLAST
Topological domaini403 – 4086LumenalSequence analysis
Transmembranei409 – 42921HelicalSequence analysisAdd
BLAST
Topological domaini430 – 4334CytoplasmicSequence analysis
Intramembranei434 – 45421HelicalSequence analysisAdd
BLAST
Topological domaini455 – 46814CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • aggresome Source: UniProtKB
  • axon Source: Ensembl
  • cell junction Source: Ensembl
  • cell surface Source: RGD
  • centrosome Source: Ensembl
  • ciliary rootlet Source: Ensembl
  • cytoplasmic vesicle Source: Ensembl
  • dendritic shaft Source: Ensembl
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • gamma-secretase complex Source: Ensembl
  • Golgi apparatus Source: UniProtKB
  • Golgi membrane Source: UniProtKB-SubCell
  • growth cone Source: Ensembl
  • integral component of plasma membrane Source: UniProtKB
  • kinetochore Source: Ensembl
  • lysosomal membrane Source: RGD
  • membrane raft Source: RGD
  • mitochondrial inner membrane Source: RGD
  • mitochondrion Source: UniProtKB
  • neuromuscular junction Source: RGD
  • neuronal cell body Source: Ensembl
  • neuron projection Source: RGD
  • nuclear outer membrane Source: Ensembl
  • nucleus Source: GO_Central
  • plasma membrane Source: UniProtKB
  • presynapse Source: GOC
  • protein complex Source: RGD
  • rough endoplasmic reticulum Source: Ensembl
  • smooth endoplasmic reticulum Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 298298Presenilin-1 NTF subunitBy similarityPRO_0000025599Add
BLAST
Chaini299 – 468170Presenilin-1 CTF subunitBy similarityPRO_0000025600Add
BLAST
Chaini347 – 468122Presenilin-1 CTF12By similarityPRO_0000236062Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei50 – 501PhosphoserineCombined sources
Modified residuei330 – 3301PhosphothreonineCombined sources
Modified residuei332 – 3321PhosphoserineCombined sources
Modified residuei347 – 3471Phosphoserine; by PKCBy similarity
Modified residuei368 – 3681PhosphoserineCombined sources
Modified residuei371 – 3711PhosphothreonineCombined sources
Modified residuei372 – 3721PhosphoserineCombined sources

Post-translational modificationi

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).By similarity
After endoproteolysis, the C-terminal fragment (CTF) is phosphorylated on serine residues by PKA and/or PKC. Phosphorylation on Ser-347 inhibits endoproteolysis (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei291 – 2922Cleavage; alternateBy similarity
Sitei292 – 2932Cleavage; alternateBy similarity
Sitei298 – 2992CleavageBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP97887.
PRIDEiP97887.

PTM databases

iPTMnetiP97887.
PhosphoSiteiP97887.
SwissPalmiP97887.

Expressioni

Gene expression databases

BgeeiENSRNOG00000009110.
GenevisibleiP97887. RN.

Interactioni

Subunit structurei

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. 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, HERPUD1, FLNA, FLNB, MTCH1, PKP4 and PARL. Interacts through its N-terminus with isoform 3 of GFAP. Interacts with DOCK3. Interacts with UBQLN1.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Aph1aQ5PQQ32EBI-2606447,EBI-2606456

GO - Molecular functioni

Protein-protein interaction databases

BioGridi247872. 3 interactions.
DIPiDIP-48909N.
IntActiP97887. 10 interactions.
MINTiMINT-4567301.
STRINGi10116.ENSRNOP00000012495.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni323 – 451129Required for interaction with CTNNB1By similarityAdd
BLAST
Regioni373 – 40028Required for interaction with CTNND2By similarityAdd
BLAST
Regioni465 – 4684Interaction with MTCH1By similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi434 – 4363PAL

Domaini

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

Sequence similaritiesi

Belongs to the peptidase A22A family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2736. Eukaryota.
ENOG410XPZD. LUCA.
GeneTreeiENSGT00390000016593.
HOGENOMiHOG000240228.
HOVERGENiHBG011375.
InParanoidiP97887.
KOiK04505.
OMAiNTNDNRE.
OrthoDBiEOG091G0C72.
PhylomeDBiP97887.
TreeFamiTF315040.

Family and domain databases

InterProiIPR002031. Pept_A22A_PS1.
IPR001108. Peptidase_A22A.
IPR006639. Preselin/SPP.
[Graphical view]
PANTHERiPTHR10202. PTHR10202. 1 hit.
PTHR10202:SF18. PTHR10202:SF18. 1 hit.
PfamiPF01080. Presenilin. 1 hit.
[Graphical view]
PRINTSiPR01072. PRESENILIN.
PR01073. PRESENILIN1.
SMARTiSM00730. PSN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P97887-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTEIPAPLSY FQNAQMSEDS HSSSVRSQND NQERQQHHDR QRLDNPESIS
60 70 80 90 100
NGRPQSNFTR QVIEQDEEED EELTLKYGAK HVIMLFVPVT LCMVVVVATI
110 120 130 140 150
KSVSFYTRKD GQLIYTPFTE DTETVGQRAL HSILNAAIMI SVIVVMTILL
160 170 180 190 200
VVLYKYRCYK VIHAWLIVSS LLLLFFFSFI YLGEVFKTYN VAVDYITVAL
210 220 230 240 250
LIWNFGVVGM IAIHWKGPLR LQQAYLIMIS ALMALVFIKY LPEWTAWLIL
260 270 280 290 300
AVISVYDLVA VLCPKGPLRM LVETAQERNE TLFPALIYSS TMVWLVNMAE
310 320 330 340 350
GDPEAQRRVP KNPKYSTQGT EREETQDTGT GSDDGGFSEE WEAQRDSHLG
360 370 380 390 400
PHRSTPESRA AVQELSGSIL TSEDPEERGV KLGLGDFIFY SVLVGKASAT
410 420 430 440 450
ASGDWNTTIA CFVAILIGLC LTLLLLAIFK KALPALPISI TFGLIFYFAT
460
DYLVQPFMDQ LAFHQFYI
Length:468
Mass (Da):52,790
Last modified:May 1, 1997 - v1
Checksum:i17CB791E88A16FC0
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti234 – 2341A → S in BAA11564 (PubMed:9047347).Curated
Sequence conflicti381 – 3811K → R in BAA11564 (PubMed:9047347).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D82363 mRNA. Translation: BAA11564.1.
D82578 mRNA. Translation: BAA11575.1.
BC070887 mRNA. Translation: AAH70887.1.
RefSeqiNP_062036.2. NM_019163.3.
XP_006240383.1. XM_006240321.2.
XP_006240384.1. XM_006240322.2.
UniGeneiRn.44440.

Genome annotation databases

EnsembliENSRNOT00000012495; ENSRNOP00000012495; ENSRNOG00000009110.
GeneIDi29192.
KEGGirno:29192.
UCSCiRGD:3425. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D82363 mRNA. Translation: BAA11564.1.
D82578 mRNA. Translation: BAA11575.1.
BC070887 mRNA. Translation: AAH70887.1.
RefSeqiNP_062036.2. NM_019163.3.
XP_006240383.1. XM_006240321.2.
XP_006240384.1. XM_006240322.2.
UniGeneiRn.44440.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247872. 3 interactions.
DIPiDIP-48909N.
IntActiP97887. 10 interactions.
MINTiMINT-4567301.
STRINGi10116.ENSRNOP00000012495.

Protein family/group databases

MEROPSiA22.001.

PTM databases

iPTMnetiP97887.
PhosphoSiteiP97887.
SwissPalmiP97887.

Proteomic databases

PaxDbiP97887.
PRIDEiP97887.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000012495; ENSRNOP00000012495; ENSRNOG00000009110.
GeneIDi29192.
KEGGirno:29192.
UCSCiRGD:3425. rat.

Organism-specific databases

CTDi5663.
RGDi3425. Psen1.

Phylogenomic databases

eggNOGiKOG2736. Eukaryota.
ENOG410XPZD. LUCA.
GeneTreeiENSGT00390000016593.
HOGENOMiHOG000240228.
HOVERGENiHBG011375.
InParanoidiP97887.
KOiK04505.
OMAiNTNDNRE.
OrthoDBiEOG091G0C72.
PhylomeDBiP97887.
TreeFamiTF315040.

Miscellaneous databases

PROiP97887.

Gene expression databases

BgeeiENSRNOG00000009110.
GenevisibleiP97887. RN.

Family and domain databases

InterProiIPR002031. Pept_A22A_PS1.
IPR001108. Peptidase_A22A.
IPR006639. Preselin/SPP.
[Graphical view]
PANTHERiPTHR10202. PTHR10202. 1 hit.
PTHR10202:SF18. PTHR10202:SF18. 1 hit.
PfamiPF01080. Presenilin. 1 hit.
[Graphical view]
PRINTSiPR01072. PRESENILIN.
PR01073. PRESENILIN1.
SMARTiSM00730. PSN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPSN1_RAT
AccessioniPrimary (citable) accession number: P97887
Secondary accession number(s): P97529
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: May 1, 1997
Last modified: September 7, 2016
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.