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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

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 presence of the other members of the gamma-secretase complex for protease activity. Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. Stimulates cell-cell adhesion via its interaction with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin). Under conditions of apoptosis or calcium influx, cleaves CDH1. This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling (By similarity). Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei257By similarity1
Active sitei386By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease
Biological processApoptosis, Cell adhesion, Notch signaling pathway

Enzyme and pathway databases

ReactomeiR-RNO-6798695. Neutrophil degranulation.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 6

Organism-specific databases

RGDi3425. Psen1.

Subcellular locationi

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

  • Note: Translocates with bound NOTCH1 from the endoplasmic reticulum and/or Golgi to the cell surface. Colocalizes with CDH1/2 at sites of cell-cell contact. Colocalizes with CTNNB1 in the endoplasmic reticulum and the proximity of the plasma membrane. Also present in azurophil granules of neutrophils. Colocalizes with UBQLN1 in the cell membrane and in cytoplasmic juxtanuclear structures called aggresomes.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 82CytoplasmicBy similarityAdd BLAST82
Transmembranei83 – 103HelicalBy similarityAdd BLAST21
Topological domaini104 – 132LumenalBy similarityAdd BLAST29
Transmembranei133 – 153HelicalBy similarityAdd BLAST21
Topological domaini154 – 166CytoplasmicBy similarityAdd BLAST13
Transmembranei167 – 189HelicalBy similarityAdd BLAST23
Topological domaini190 – 194LumenalBy similarity5
Transmembranei195 – 216HelicalBy similarityAdd BLAST22
Topological domaini217 – 220CytoplasmicBy similarity4
Transmembranei221 – 241HelicalBy similarityAdd BLAST21
Topological domaini242 – 248LumenalBy similarity7
Transmembranei249 – 272HelicalBy similarityAdd BLAST24
Topological domaini273 – 381CytoplasmicBy similarityAdd BLAST109
Transmembranei382 – 402HelicalBy similarityAdd BLAST21
Topological domaini403 – 408LumenalBy similarity6
Transmembranei409 – 429HelicalBy similarityAdd BLAST21
Topological domaini430 – 433CytoplasmicBy similarity4
Transmembranei434 – 454HelicalBy similarityAdd BLAST21
Topological domaini455 – 468LumenalBy similarityAdd BLAST14

GO - Cellular componenti

  • aggresome Source: UniProtKB
  • axon Source: GO_Central
  • cell cortex Source: GO_Central
  • cell junction Source: Ensembl
  • cell surface Source: RGD
  • centrosome Source: Ensembl
  • ciliary rootlet Source: GO_Central
  • cytoplasmic vesicle Source: Ensembl
  • dendritic shaft Source: GO_Central
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • gamma-secretase complex Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • Golgi membrane Source: UniProtKB-SubCell
  • growth cone Source: GO_Central
  • integral component of membrane Source: UniProtKB
  • 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: RGD
  • neuromuscular junction Source: RGD
  • neuronal cell body Source: GO_Central
  • neuron projection Source: RGD
  • nuclear outer membrane Source: Ensembl
  • nucleus Source: GO_Central
  • perinuclear region of cytoplasm Source: GO_Central
  • plasma membrane Source: UniProtKB
  • presynapse Source: GOC
  • protein complex Source: RGD
  • rough endoplasmic reticulum Source: Ensembl
  • smooth endoplasmic reticulum Source: Ensembl
  • Z disc Source: GO_Central

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000255991 – 298Presenilin-1 NTF subunitBy similarityAdd BLAST298
ChainiPRO_0000025600299 – 468Presenilin-1 CTF subunitBy similarityAdd BLAST170
ChainiPRO_0000236062347 – 468Presenilin-1 CTF12By similarityAdd BLAST122

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei50PhosphoserineCombined sources1
Modified residuei330PhosphothreonineCombined sources1
Modified residuei332PhosphoserineCombined sources1
Modified residuei347Phosphoserine; by PKCBy similarity1
Modified residuei368PhosphoserineCombined sources1
Modified residuei371PhosphothreonineCombined sources1
Modified residuei372PhosphoserineCombined sources1

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
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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei291 – 292Cleavage; alternateBy similarity2
Sitei292 – 293Cleavage; alternateBy similarity2
Sitei298 – 299CleavageBy similarity2
Sitei346 – 347Cleavage; by caspaseBy similarity2

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP97887.
PRIDEiP97887.

PTM databases

iPTMnetiP97887.
PhosphoSitePlusiP97887.
SwissPalmiP97887.

Expressioni

Tissue specificityi

Detected in embryonic and adult brain.1 Publication

Gene expression databases

BgeeiENSRNOG00000009110.
GenevisibleiP97887. RN.

Interactioni

Subunit structurei

Homodimer. The functional gamma-secretase complex is composed of at least four polypeptides: 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, CTNND1, JUP, HERPUD1, FLNA, FLNB, MTCH1, PKP4 and PARL. Interacts through its N-terminus with isoform 3 of GFAP (By similarity). Interacts with DOCK3 (By similarity). Interacts with isoform 1 and isoform 3 of UBQLN1 (By similarity).By similarity

Binary interactionsi

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

GO - Molecular functioni

Protein-protein interaction databases

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

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni322 – 451Required for interaction with CTNNB1By similarityAdd BLAST130
Regioni373 – 400Required for interaction with CTNND2By similarityAdd BLAST28
Regioni465 – 468Interaction with MTCH1By similarity4

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi434 – 436PALCurated3

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.
OMAiIAIHWKG.
OrthoDBiEOG091G0C72.
PhylomeDBiP97887.
TreeFamiTF315040.

Family and domain databases

InterProiView protein in InterPro
IPR002031. Pept_A22A_PS1.
IPR001108. Peptidase_A22A.
IPR006639. Preselin/SPP.
PANTHERiPTHR10202. PTHR10202. 1 hit.
PTHR10202:SF27. PTHR10202:SF27. 1 hit.
PfamiView protein in Pfam
PF01080. Presenilin. 1 hit.
PRINTSiPR01072. PRESENILIN.
PR01073. PRESENILIN1.
SMARTiView protein in SMART
SM00730. PSN. 1 hit.

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)DescriptionActionsGraphical viewLength
Sequence conflicti234A → S in BAA11564 (PubMed:9047347).Curated1
Sequence conflicti381K → R in BAA11564 (PubMed:9047347).Curated1

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_006240321.3.
XP_006240384.1. XM_006240322.3.
UniGeneiRn.44440.

Genome annotation databases

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

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.

Entry informationi

Entry nameiPSN1_RAT
AccessioniPrimary (citable) accession number: P97887
Secondary accession number(s): P97529
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: May 1, 1997
Last modified: July 5, 2017
This is version 150 of the entry and version 1 of the sequence. See 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