PSENEN presenilin enhancer, gamma-secretase subunit [Homo sapiens (human)] - Gene

Summary

Official Symbol: PSENENprovided by HGNC
Official Full Name: presenilin enhancer, gamma-secretase subunitprovided by HGNC
Primary source: HGNC:HGNC:30100
See related: Ensembl:ENSG00000205155 MIM:607632
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PEN2; PEN-2; MDS033; ACNINV2; MSTP064
Summary: 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]
Expression: Ubiquitous expression in testis (RPKM 43.8), lung (RPKM 19.9) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 19q13.12

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
109.20200228	current	GRCh38.p13 (GCF_000001405.39)	19	NC_000019.10 (35745651..35747519)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (36236478..36238056)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Modulation of the PSENEN trafficking pathway might be a potential target for the development of Abeta42-lowering Alzheimer disease therapeutics
Title: Retrograde transport of γ-secretase from endosomes to the trans-Golgi network regulates Aβ42 production.
No mutation that was likely to be pathogenic for acne inversa was found in PSEN1 or PSENEN in any participant.
Title: Mutations in the γ-secretase genes PSEN1, PSENEN, and NCSTN in a family with acne inversa.
The present study further expands the spectrum of PSENEN mutations associated with HS-DDD and suggests a role for Notch signalling in the pathogenesis of this intriguing combined disorder.
Title: A phenotype combining hidradenitis suppurativa with Dowling-Degos disease caused by a founder mutation in PSENEN.
High gamma-secretase expression is associated with head and neck squamous cell carcinoma.
Title: γ-Secretase inhibitor reduces immunosuppressive cells and enhances tumour immunity in head and neck squamous cell carcinoma.
APP substrate occupancy of these three pockets of gamma-secretase occurs after initial substrate binding but precedes catalysis, suggesting a conformational change in substrate may be required for cleavage.
Title: The amyloid-beta forming tripeptide cleavage mechanism of γ-secretase.
PSENEN mutations can indeed cause a comanifestation of Dowling-Degos disease and acne inversa (AI) that is likely triggered by predisposing factors for AI.
Title: Mutations in γ-secretase subunit-encoding PSENEN underlie Dowling-Degos disease associated with acne inversa.
zinc, copper inhibited Abeta production by directly targeting the subunits presenilin and nicastrin in the gamma-secretase complex
Title: Zinc and Copper Differentially Modulate Amyloid Precursor Protein Processing by γ-Secretase and Amyloid-β Peptide Production.
PSENEN may play a crucial role in the progression of atopic dermatitis by participating in the Notch signaling pathway.
Title: Identification of candidate genes in atopic dermatitis based on bioinformatic methods.
Remarkably, PEN-2 was identified besides nicastrin as additional substrate-binding subunit.
Title: Substrate recruitment of γ-secretase and mechanism of clinical presenilin mutations revealed by photoaffinity mapping.
Results suggest deltaOR-Phe27Cys variation modulates beta- and gamma-secretase activity in late-stage Alzheimer's disease likely via post-translational mechanisms
Title: Genetic Variation in δ-Opioid Receptor Associates with Increased β- and γ-Secretase Activity in the Late Stages of Alzheimer's Disease.

Submit: New GeneRIF Correction See all GeneRIFs (58)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Acne inversa, familial, 2 MedGen: C3151037 OMIM: 613736 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH99245 (e-PCR)
- UniSTS:88326

RH91910 (e-PCR)
- UniSTS:86476

Homology

Homologs of the PSENEN gene: The PSENEN gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, zebrafish, fruit fly, mosquito, C.elegans, and frog.
Orthologs from Annotation Pipeline: 239 organisms have orthologs with human gene PSENEN
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
Notch receptor processing	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Notch receptor processing	TAS Traceable Author Statement more info	PubMed
Notch receptor processing, ligand-dependent	TAS Traceable Author Statement more info
amyloid precursor protein catabolic process	TAS Traceable Author Statement more info	PubMed
amyloid precursor protein metabolic process	IDA Inferred from Direct Assay more info	PubMed
amyloid-beta formation	IMP Inferred from Mutant Phenotype more info	PubMed
cellular protein metabolic process	TAS Traceable Author Statement more info
ephrin receptor signaling pathway	TAS Traceable Author Statement more info
membrane protein ectodomain proteolysis	IDA Inferred from Direct Assay more info	PubMed
membrane protein intracellular domain proteolysis	TAS Traceable Author Statement more info
positive regulation of apoptotic process	TAS Traceable Author Statement more info
positive regulation of catalytic activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
protein processing	IDA Inferred from Direct Assay more info	PubMed
protein processing	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
Golgi cisterna membrane	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
endosome membrane	TAS Traceable Author Statement more info
gamma-secretase complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
gamma-secretase complex	IDA Inferred from Direct Assay more info	PubMed
integral component of membrane	IDA Inferred from Direct Assay more info	PubMed
integral component of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: gamma-secretase subunit PEN-2

Names: hematopoietic stem/progenitor cells protein MDS033; presenilin enhancer 2 homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_027934.1 RefSeqGene

Range

5059..6927

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001281532.3 → NP_001268461.1 gamma-secretase subunit PEN-2

See identical proteins and their annotated locations for NP_001268461.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same protein.

Source sequence(s)

AA252937, AF220053, AI215167, BC009575, BE563017

Consensus CDS

CCDS12474.1

UniProtKB/Swiss-Prot

Q9NZ42

Related

ENSP00000222266.1, ENST00000222266.2

Conserved Domains (1) summary

pfam10251
Location:7 → 99

PEN-2; Presenilin enhancer-2 subunit of gamma secretase
NM_172341.4 → NP_758844.1 gamma-secretase subunit PEN-2

See identical proteins and their annotated locations for NP_758844.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript. Variants 1 and 2 encode the same protein.

Source sequence(s)

AA252937, AF220053, AI215167, BE563017

Consensus CDS

CCDS12474.1

UniProtKB/Swiss-Prot

Q9NZ42

Related

ENSP00000468411.1, ENST00000587708.7

Conserved Domains (1) summary

pfam10251
Location:7 → 99

PEN-2; Presenilin enhancer-2 subunit of gamma secretase