PSENEN

Protein identityUniProt · HPA

UniProt accession

Q9NZ42

Gene

PSENEN

Ensembl

ENSG00000205155

Chromosome

19

Canonical length

101 aa

Protein class

Disease related genes, Human disease related genes, Predicted membrane proteins

Quaternary structure

Homodimer

OverviewNCBI Gene

Presenilins, which are components of the gamma-secretase protein complex, are required for intramembranous processing of some type I transmembrane proteins, such as the Notch proteins and the beta-amyloid precursor protein. Signaling by Notch receptors mediates a wide range of developmental cell fates. Processing of the beta-amyloid precursor protein generates neurotoxic amyloid beta peptides, the major component of senile plaques associated with Alzheimer's disease. This gene encodes a protein that is required for Notch pathway signaling, and for the activity and accumulation of gamma-secretase. Mutations resulting in haploinsufficiency for this gene cause familial acne inversa-2 (ACNINV2). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Canonical amino-acid sequenceUniProt

101 residues, UniProt reviewed canonical sequence.

>Q9NZ42|PSENEN
     1  MNLERVSNEE KLNLCRKYYL GGFAFLPFLW LVNIFWFFRE AFLVPAYTEQ SQIKGYVWRS
    61  AVGFLFWVIV LTSWITIFQI YRPRWGALGD YLSFTIPLGT P

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PSENEN can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.37

Highest tissue expression

320 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PSENEN.

Disease | AllUniProt

Conditions PSENEN is implicated in, by any mechanism.

• Acne inversa, familial, 2, with or without Dowling-Degos disease (ACNINV2) MIM:613736

Disease | GeneticClinVar

7 pathogenic / likely-pathogenic of 68 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Acne inversa, familial, 2
• Squamous cell lung carcinoma

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.44

gnomAD pLI

0.88

gnomAD missense Z

0.64

DepMap mean gene effect

-0.19

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• amyloid precursor protein catabolic process
• amyloid precursor protein metabolic process
• amyloid-beta formation
• membrane protein ectodomain proteolysis
• membrane protein intracellular domain proteolysis
• Notch receptor processing
• Notch signaling pathway
• positive regulation of endopeptidase activity
• protein processing

Molecular functions

• endopeptidase activator activity
• enzyme binding

Cellular components

• endoplasmic reticulum
• endoplasmic reticulum membrane
• endosome membrane
• gamma-secretase complex
• Golgi apparatus
• Golgi cisterna membrane
• Golgi membrane
• membrane
• plasma membrane
• presynaptic membrane

Protein domainsUniProt · Pfam · InterPro

• Gamma-secretase aspartyl protease complex, presenilin enhancer-2 subunit
• Presenilin enhancer-2 subunit of gamma secretase

KeywordsUniProt

• Cell membrane
• Endoplasmic reticulum
• Golgi apparatus
• Membrane
• Notch signaling pathway
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of PSENEN in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• APH1A
• NCSTN
• PSEN1