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Protein

Presenilin-1

Gene

PSEN1

Organism
Microcebus murinus (Lesser mouse lemur) (Gray Mouse Lemur)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 sitei385 – 3851By similarity

GO - Molecular functioni

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
Cleaved into the following 3 chains:
Gene namesi
Name:PSEN1
Synonyms:PS1, PSNL1
OrganismiMicrocebus murinus (Lesser mouse lemur) (Gray Mouse Lemur)
Taxonomic identifieri30608 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesStrepsirrhiniLemuriformesCheirogaleidaeMicrocebus

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 – 1909LumenalSequence analysis
Transmembranei191 – 21121HelicalSequence analysisAdd
BLAST
Topological domaini212 – 2209CytoplasmicSequence analysis
Transmembranei221 – 24121HelicalSequence analysisAdd
BLAST
Topological domaini242 – 2432LumenalSequence analysis
Transmembranei244 – 26421HelicalSequence analysisAdd
BLAST
Topological domaini265 – 380116CytoplasmicSequence analysisAdd
BLAST
Transmembranei381 – 40121HelicalSequence analysisAdd
BLAST
Topological domaini402 – 4076LumenalSequence analysis
Transmembranei408 – 42821HelicalSequence analysisAdd
BLAST
Topological domaini429 – 4324CytoplasmicSequence analysis
Intramembranei433 – 45321HelicalSequence analysisAdd
BLAST
Topological domaini454 – 46714CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

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_0000025593Add
BLAST
Chaini299 – 467169Presenilin-1 CTF subunitBy similarityPRO_0000025594Add
BLAST
Chaini346 – 467122Presenilin-1 CTF12By similarityPRO_0000236057Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei51 – 511PhosphoserineBy similarity
Modified residuei310 – 3101Phosphoserine; by PKABy similarity
Modified residuei346 – 3461Phosphoserine; by PKCBy similarity
Modified residuei367 – 3671PhosphoserineBy similarity
Modified residuei371 – 3711PhosphoserineBy similarity

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-346 inhibits endoproteolysis (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei291 – 2922Cleavage; alternateBy similarity
Sitei292 – 2932Cleavage; alternateBy similarity
Sitei298 – 2992CleavageBy similarity
Sitei345 – 3462Cleavage; by caspaseBy similarity

Keywords - PTMi

Phosphoprotein

Expressioni

Tissue specificityi

Found predominantly in neurons of the different cortical layers and hippocampus but also in subcortical structures.1 Publication

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

Protein-protein interaction databases

STRINGi30608.ENSMICP00000016318.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni322 – 450129Required for interaction with CTNNB1By similarityAdd
BLAST
Regioni372 – 39928Required for interaction with CTNND2By similarityAdd
BLAST
Regioni464 – 4674Interaction with MTCH1By similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi433 – 4353PAL

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi94 – 974Poly-Val

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.
HOVERGENiHBG011375.

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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform I-467 (identifier: P79802-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MTELPAPLSY FQNAQMSEDN HLSNTVRSQN DNREQQDHGD RRRLGNPEPL
60 70 80 90 100
SNGRPQGNSG PVVERDEEED EELTLKYGAK HVIMLFVPVT LCMVVVVATI
110 120 130 140 150
KSVSFYTRKD GQLIYTPFTE DTETVGQRAL HSVLNAAIMI SVIVVMTILL
160 170 180 190 200
VVLYKYRCYK VIHAWLIISS LLLLFFFSFI YLGEVFKTYN VAVDYITVAL
210 220 230 240 250
LIWNFGVVGM ISIHWKGPLR LQQAYLIMIS ALMALVFIKY LPEWTAWLIL
260 270 280 290 300
AVISVYDLVA VLCPKGPLRM LVETAQERNE TLFPALIYSS TMVWLVNMAE
310 320 330 340 350
GDPEAQRRVS KNTKYNAQGT EREAQASVPE NDDGGFSEEW EAQRDSQLGP
360 370 380 390 400
HRSTSVSRAA VQEISSSIPA SEDPEERGVK LGLGDFVFYS VLVGKASATA
410 420 430 440 450
SGDWNTTIAC FVAILIGLCL TLLLLAIFKK ALPALPISIT FGLVFYFATD
460
YLVQPFMDQL AFHQFYI
Length:467
Mass (Da):52,385
Last modified:May 1, 1997 - v1
Checksum:iD986FF2CA7F2975C
GO
Isoform I-463 (identifier: P79802-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     26-29: Missing.

Show »
Length:463
Mass (Da):51,914
Checksum:i12DA9F4B45581F73
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei26 – 294Missing in isoform I-463. 1 PublicationVSP_005193

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z71333 mRNA. Translation: CAA95930.1.
PIRiJC5080.
JC5081.
RefSeqiNP_001296874.1. NM_001309945.1. [P79802-1]
XP_012596667.1. XM_012741213.1. [P79802-1]

Genome annotation databases

GeneIDi105858213.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z71333 mRNA. Translation: CAA95930.1.
PIRiJC5080.
JC5081.
RefSeqiNP_001296874.1. NM_001309945.1. [P79802-1]
XP_012596667.1. XM_012741213.1. [P79802-1]

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi30608.ENSMICP00000016318.

Protein family/group databases

MEROPSiA22.001.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi105858213.

Organism-specific databases

CTDi5663.

Phylogenomic databases

eggNOGiKOG2736. Eukaryota.
ENOG410XPZD. LUCA.
HOVERGENiHBG011375.

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_MICMU
AccessioniPrimary (citable) accession number: P79802
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: May 1, 1997
Last modified: May 11, 2016
This is version 94 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.