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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

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 (amyloid-beta 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 sitei385By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease
Biological processApoptosis, 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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 – 380CytoplasmicBy similarityAdd BLAST108
Transmembranei381 – 401HelicalBy similarityAdd BLAST21
Topological domaini402 – 407LumenalBy similarity6
Transmembranei408 – 428HelicalBy similarityAdd BLAST21
Topological domaini429 – 432CytoplasmicBy similarity4
Transmembranei433 – 453HelicalBy similarityAdd BLAST21
Topological domaini454 – 467LumenalBy similarityAdd BLAST14

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000255931 – 298Presenilin-1 NTF subunitBy similarityAdd BLAST298
ChainiPRO_0000025594299 – 467Presenilin-1 CTF subunitBy similarityAdd BLAST169
ChainiPRO_0000236057346 – 467Presenilin-1 CTF12By similarityAdd BLAST122

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei51PhosphoserineBy similarity1
Modified residuei310Phosphoserine; by PKABy similarity1
Modified residuei346Phosphoserine; by PKCBy similarity1
Modified residuei367PhosphoserineBy similarity1
Modified residuei371PhosphoserineBy similarity1

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-346 inhibits endoproteolysis.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei291 – 292Cleavage; alternateBy similarity2
Sitei292 – 293Cleavage; alternateBy similarity2
Sitei298 – 299CleavageBy similarity2
Sitei345 – 346Cleavage; by caspaseBy similarity2

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. 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

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni322 – 450Required for interaction with CTNNB1By similarityAdd BLAST129
Regioni372 – 399Required for interaction with CTNND2By similarityAdd BLAST28
Regioni464 – 467Interaction with MTCH1By similarity4

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi433 – 435PALCurated3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi94 – 97Poly-Val4

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

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

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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00519326 – 29Missing in isoform I-463. 1 Publication4

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]

Genome annotation databases

GeneIDi105858213.

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPSN1_MICMU
AccessioniPrimary (citable) accession number: P79802
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: May 1, 1997
Last modified: October 25, 2017
This is version 101 of the entry and version 1 of the sequence. See 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