UniProtKB - Q9CQR7 (PEN2_MOUSE)
Protein
Gamma-secretase subunit PEN-2
Gene
Psenen
Organism
Mus musculus (Mouse)
Status
Functioni
Essential 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) (PubMed:12522139, PubMed:24941111). The gamma-secretase complex 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 (Probable). PSENEN modulates both endoproteolysis of presenilin and gamma-secretase activity (PubMed:12522139, PubMed:24941111).Curated2 Publications
Caution
3D-structure analysis of the human homolog indicates that the membrane topology differs from the predictions. Contrary to predictions, the N-terminus contains two short helices that dip into the membrane, but do not cross it. The C-terminus contains the single transmembrane helix. This gives rise to a topology where the N-terminus is cytoplasmic and the C-terminus is lumenal.Curated
GO - Molecular functioni
- endopeptidase activator activity Source: ARUK-UCL
- enzyme binding Source: MGI
GO - Biological processi
- amyloid-beta formation Source: UniProtKB
- amyloid precursor protein catabolic process Source: MGI
- amyloid precursor protein metabolic process Source: UniProtKB
- membrane protein ectodomain proteolysis Source: HGNC-UCL
- Notch receptor processing Source: MGI
- Notch signaling pathway Source: UniProtKB-KW
- positive regulation of catalytic activity Source: HGNC-UCL
- positive regulation of endopeptidase activity Source: UniProtKB
- protein processing Source: UniProtKB
Keywordsi
Biological process | Notch signaling pathway |
Enzyme and pathway databases
Reactomei | R-MMU-1251985, Nuclear signaling by ERBB4 R-MMU-193692, Regulated proteolysis of p75NTR R-MMU-205043, NRIF signals cell death from the nucleus R-MMU-3928665, EPH-ephrin mediated repulsion of cells R-MMU-9013507, NOTCH3 Activation and Transmission of Signal to the Nucleus R-MMU-9017802, Noncanonical activation of NOTCH3 |
Protein family/group databases
TCDBi | 4.G.1.1.1, the Gama-secretase (Gama-secretase) family |
Names & Taxonomyi
Protein namesi | Recommended name: Gamma-secretase subunit PEN-2Alternative name(s): Presenilin enhancer protein 2 |
Gene namesi | Name:Psenen Synonyms:Pen2 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1913590, Psenen |
Subcellular locationi
Golgi apparatus
- Golgi stack membrane 1 Publication; Multi-pass membrane protein By similarity
Plasma membrane
- Cell membrane By similarity; Multi-pass membrane protein By similarity
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein By similarity
Other locations
- Membrane By similarity; Multi-pass membrane protein By similarity
Note: Predominantly located in the endoplasmic reticulum and in the cis-Golgi.1 Publication
Endoplasmic reticulum
- endoplasmic reticulum Source: HGNC-UCL
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Golgi apparatus
- Golgi apparatus Source: HGNC-UCL
- Golgi cisterna membrane Source: UniProtKB-SubCell
Mitochondrion
- mitochondrion Source: MGI
Plasma Membrane
- gamma-secretase complex Source: MGI
- integral component of plasma membrane Source: HGNC-UCL
- integral component of presynaptic membrane Source: MGI
- plasma membrane Source: Reactome
Other locations
- integral component of membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 17 | CytoplasmicBy similarityAdd BLAST | 17 | |
Intramembranei | 18 – 36 | HelicalBy similarityAdd BLAST | 19 | |
Topological domaini | 37 – 57 | CytoplasmicBy similarityAdd BLAST | 21 | |
Transmembranei | 58 – 78 | HelicalBy similarityAdd BLAST | 21 | |
Topological domaini | 79 – 101 | LumenalBy similarityAdd BLAST | 23 |
Keywords - Cellular componenti
Cell membrane, Endoplasmic reticulum, Golgi apparatus, MembranePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000190901 | 1 – 101 | Gamma-secretase subunit PEN-2Add BLAST | 101 |
Proteomic databases
MaxQBi | Q9CQR7 |
PaxDbi | Q9CQR7 |
PeptideAtlasi | Q9CQR7 |
PRIDEi | Q9CQR7 |
ProteomicsDBi | 287913 |
TopDownProteomicsi | Q9CQR7 |
PTM databases
iPTMneti | Q9CQR7 |
PhosphoSitePlusi | Q9CQR7 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000036835, Expressed in primary oocyte and 57 other tissues |
Genevisiblei | Q9CQR7, MM |
Interactioni
Subunit structurei
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 PSENEN.
2 PublicationsGO - Molecular functioni
- enzyme binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 211397, 2 interactors |
ComplexPortali | CPX-4234, Gamma-secretase complex, Aph1a-Psen1 variant CPX-4235, Gamma-secretase complex, Aph1b-Psen1 variant CPX-4236, Gamma-secretase complex, Aph1a-Psen2 variant CPX-4237, Gamma-secretase complex, Aph1b-Psen2 variant |
CORUMi | Q9CQR7 |
DIPi | DIP-36333N |
IntActi | Q9CQR7, 5 interactors |
STRINGi | 10090.ENSMUSP00000044682 |
Miscellaneous databases
RNActi | Q9CQR7, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the PEN-2 family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3402, Eukaryota |
GeneTreei | ENSGT00390000016319 |
HOGENOMi | CLU_124142_2_0_1 |
InParanoidi | Q9CQR7 |
OMAi | WFFQEAF |
OrthoDBi | 1517974at2759 |
PhylomeDBi | Q9CQR7 |
TreeFami | TF313116 |
Family and domain databases
InterProi | View protein in InterPro IPR019379, Gamma_Secretase_Asp_P_PEN2 |
PANTHERi | PTHR16318, PTHR16318, 1 hit |
Pfami | View protein in Pfam PF10251, PEN-2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
Q9CQR7-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MNLERVSNEE KLNLCRKYYL GGFAFLPFLW LVNIFWFFRE AFLAPAYTEQ
60 70 80 90 100
SQIKGYVWRS AVGFLFWVII LATWITIFQI YRPRWGALGD YLSFTIPLGT
P
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A140LHM2 | A0A140LHM2_MOUSE | Gamma-secretase subunit PEN-2 | Psenen | 95 | Annotation score: | ||
A0A140LJC5 | A0A140LJC5_MOUSE | Gamma-secretase subunit PEN-2 | Psenen | 41 | Annotation score: | ||
A0A140LHQ1 | A0A140LHQ1_MOUSE | Gamma-secretase subunit PEN-2 | Psenen | 66 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK002440 mRNA Translation: BAB22102.1 AK006284 mRNA Translation: BAB24503.1 AK007621 mRNA Translation: BAB25141.1 BC024347 mRNA Translation: AAH24347.1 BC081443 mRNA Translation: AAH81443.1 |
CCDSi | CCDS21099.1 |
RefSeqi | NP_079774.1, NM_025498.2 |
Genome annotation databases
Ensembli | ENSMUST00000043898; ENSMUSP00000044682; ENSMUSG00000036835 ENSMUST00000207747; ENSMUSP00000146675; ENSMUSG00000036835 |
GeneIDi | 66340 |
KEGGi | mmu:66340 |
UCSCi | uc009gez.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK002440 mRNA Translation: BAB22102.1 AK006284 mRNA Translation: BAB24503.1 AK007621 mRNA Translation: BAB25141.1 BC024347 mRNA Translation: AAH24347.1 BC081443 mRNA Translation: AAH81443.1 |
CCDSi | CCDS21099.1 |
RefSeqi | NP_079774.1, NM_025498.2 |
3D structure databases
SMRi | Q9CQR7 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 211397, 2 interactors |
ComplexPortali | CPX-4234, Gamma-secretase complex, Aph1a-Psen1 variant CPX-4235, Gamma-secretase complex, Aph1b-Psen1 variant CPX-4236, Gamma-secretase complex, Aph1a-Psen2 variant CPX-4237, Gamma-secretase complex, Aph1b-Psen2 variant |
CORUMi | Q9CQR7 |
DIPi | DIP-36333N |
IntActi | Q9CQR7, 5 interactors |
STRINGi | 10090.ENSMUSP00000044682 |
Protein family/group databases
TCDBi | 4.G.1.1.1, the Gama-secretase (Gama-secretase) family |
PTM databases
iPTMneti | Q9CQR7 |
PhosphoSitePlusi | Q9CQR7 |
Proteomic databases
MaxQBi | Q9CQR7 |
PaxDbi | Q9CQR7 |
PeptideAtlasi | Q9CQR7 |
PRIDEi | Q9CQR7 |
ProteomicsDBi | 287913 |
TopDownProteomicsi | Q9CQR7 |
Genome annotation databases
Ensembli | ENSMUST00000043898; ENSMUSP00000044682; ENSMUSG00000036835 ENSMUST00000207747; ENSMUSP00000146675; ENSMUSG00000036835 |
GeneIDi | 66340 |
KEGGi | mmu:66340 |
UCSCi | uc009gez.1, mouse |
Organism-specific databases
CTDi | 55851 |
MGIi | MGI:1913590, Psenen |
Phylogenomic databases
eggNOGi | KOG3402, Eukaryota |
GeneTreei | ENSGT00390000016319 |
HOGENOMi | CLU_124142_2_0_1 |
InParanoidi | Q9CQR7 |
OMAi | WFFQEAF |
OrthoDBi | 1517974at2759 |
PhylomeDBi | Q9CQR7 |
TreeFami | TF313116 |
Enzyme and pathway databases
Reactomei | R-MMU-1251985, Nuclear signaling by ERBB4 R-MMU-193692, Regulated proteolysis of p75NTR R-MMU-205043, NRIF signals cell death from the nucleus R-MMU-3928665, EPH-ephrin mediated repulsion of cells R-MMU-9013507, NOTCH3 Activation and Transmission of Signal to the Nucleus R-MMU-9017802, Noncanonical activation of NOTCH3 |
Miscellaneous databases
BioGRID-ORCSi | 66340, 7 hits in 52 CRISPR screens |
ChiTaRSi | Psenen, mouse |
PROi | PR:Q9CQR7 |
RNActi | Q9CQR7, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000036835, Expressed in primary oocyte and 57 other tissues |
Genevisiblei | Q9CQR7, MM |
Family and domain databases
InterProi | View protein in InterPro IPR019379, Gamma_Secretase_Asp_P_PEN2 |
PANTHERi | PTHR16318, PTHR16318, 1 hit |
Pfami | View protein in Pfam PF10251, PEN-2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PEN2_MOUSE | |
Accessioni | Q9CQR7Primary (citable) accession number: Q9CQR7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 26, 2003 |
Last sequence update: | June 1, 2001 | |
Last modified: | April 7, 2021 | |
This is version 152 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families