UniProtKB - Q6QI68 (PEN2_RAT)
Gamma-secretase subunit PEN-2
Psenen
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). 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. PSENEN modulates both endoproteolysis of presenilin and gamma-secretase activity.
By similarityCaution
GO - Molecular functioni
- endopeptidase activator activity Source: RGD
- enzyme binding Source: RGD
GO - Biological processi
- amyloid-beta formation Source: UniProtKB
- amyloid precursor protein catabolic process Source: RGD
- amyloid precursor protein metabolic process Source: UniProtKB
- membrane protein ectodomain proteolysis Source: RGD
- membrane protein intracellular domain proteolysis Source: RGD
- Notch receptor processing Source: RGD
- Notch signaling pathway Source: UniProtKB-KW
- positive regulation of catalytic activity Source: RGD
- positive regulation of endopeptidase activity Source: RGD
- protein processing Source: RGD
Keywordsi
Biological process | Notch signaling pathway |
Enzyme and pathway databases
Reactomei | R-RNO-1251985, Nuclear signaling by ERBB4 R-RNO-193692, Regulated proteolysis of p75NTR R-RNO-205043, NRIF signals cell death from the nucleus R-RNO-3928665, EPH-ephrin mediated repulsion of cells R-RNO-9013507, NOTCH3 Activation and Transmission of Signal to the Nucleus R-RNO-9017802, Noncanonical activation of NOTCH3 |
Names & Taxonomyi
Protein namesi | Recommended name: Gamma-secretase subunit PEN-2Alternative name(s): Liver regeneration-related protein LRRGT00140 Presenilin enhancer protein 2 |
Gene namesi | Name:Psenen |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 1312037, Psenen |
Subcellular locationi
Golgi apparatus
- Golgi stack membrane By similarity; Multi-pass membrane protein By similarity
Endoplasmic reticulum
- Endoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity
Plasma membrane
- Cell membrane By similarity; 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.By similarity
Endoplasmic reticulum
- endoplasmic reticulum Source: RGD
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Golgi apparatus
- Golgi apparatus Source: RGD
- Golgi cisterna membrane Source: UniProtKB-SubCell
Mitochondrion
- mitochondrion Source: RGD
Plasma Membrane
- gamma-secretase complex Source: UniProtKB
- integral component of plasma membrane Source: RGD
- integral component of presynaptic membrane Source: SynGO
- plasma membrane Source: RGD
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_0000327207 | 1 – 101 | Gamma-secretase subunit PEN-2Add BLAST | 101 |
Proteomic databases
PaxDbi | Q6QI68 |
PTM databases
PhosphoSitePlusi | Q6QI68 |
Expressioni
Gene expression databases
Bgeei | ENSRNOG00000020941, Expressed in liver and 21 other tissues |
Genevisiblei | Q6QI68, RN |
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.
By similarityGO - Molecular functioni
- enzyme binding Source: RGD
Protein-protein interaction databases
BioGRIDi | 253977, 1 interactor |
IntActi | Q6QI68, 1 interactor |
STRINGi | 10116.ENSRNOP00000028438 |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3402, Eukaryota |
GeneTreei | ENSGT00390000016319 |
HOGENOMi | CLU_124142_2_0_1 |
InParanoidi | Q6QI68 |
OMAi | WYFRAGF |
OrthoDBi | 1517974at2759 |
PhylomeDBi | Q6QI68 |
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 |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MNLERVSNEE KLNLCRKYYL GGFAFLPFLW LVNIFWFFKE AFFAPAYTEQ
60 70 80 90 100
SQIKGYVWRS AVGFLFWVIV LTTWITIFQI YRPRWGALGD YLSFTIPLGT
P
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY539891 mRNA Translation: AAS66231.1 BC100104 mRNA Translation: AAI00105.1 |
RefSeqi | NP_001008764.1, NM_001008764.2 XP_006228832.1, XM_006228770.3 |
Genome annotation databases
Ensembli | ENSRNOT00000028438; ENSRNOP00000028438; ENSRNOG00000020941 |
GeneIDi | 292788 |
KEGGi | rno:292788 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY539891 mRNA Translation: AAS66231.1 BC100104 mRNA Translation: AAI00105.1 |
RefSeqi | NP_001008764.1, NM_001008764.2 XP_006228832.1, XM_006228770.3 |
3D structure databases
AlphaFoldDBi | Q6QI68 |
SMRi | Q6QI68 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 253977, 1 interactor |
IntActi | Q6QI68, 1 interactor |
STRINGi | 10116.ENSRNOP00000028438 |
PTM databases
PhosphoSitePlusi | Q6QI68 |
Proteomic databases
PaxDbi | Q6QI68 |
Genome annotation databases
Ensembli | ENSRNOT00000028438; ENSRNOP00000028438; ENSRNOG00000020941 |
GeneIDi | 292788 |
KEGGi | rno:292788 |
Organism-specific databases
CTDi | 55851 |
RGDi | 1312037, Psenen |
Phylogenomic databases
eggNOGi | KOG3402, Eukaryota |
GeneTreei | ENSGT00390000016319 |
HOGENOMi | CLU_124142_2_0_1 |
InParanoidi | Q6QI68 |
OMAi | WYFRAGF |
OrthoDBi | 1517974at2759 |
PhylomeDBi | Q6QI68 |
TreeFami | TF313116 |
Enzyme and pathway databases
Reactomei | R-RNO-1251985, Nuclear signaling by ERBB4 R-RNO-193692, Regulated proteolysis of p75NTR R-RNO-205043, NRIF signals cell death from the nucleus R-RNO-3928665, EPH-ephrin mediated repulsion of cells R-RNO-9013507, NOTCH3 Activation and Transmission of Signal to the Nucleus R-RNO-9017802, Noncanonical activation of NOTCH3 |
Miscellaneous databases
PROi | PR:Q6QI68 |
Gene expression databases
Bgeei | ENSRNOG00000020941, Expressed in liver and 21 other tissues |
Genevisiblei | Q6QI68, RN |
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 |
MobiDBi | Search... |
Entry informationi
Entry namei | PEN2_RAT | |
Accessioni | Q6QI68Primary (citable) accession number: Q6QI68 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 8, 2008 |
Last sequence update: | July 5, 2004 | |
Last modified: | May 25, 2022 | |
This is version 101 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
- SIMILARITY comments
Index of protein domains and families