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; AllianceGenome:HGNC:30100
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
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Genomic context

Location:: 19q13.12

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (35745651..35747519)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (38290961..38292828)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (36236552..36238420)

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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Converging roles of PSENEN/PEN2 and CLN3 in the autophagy-lysosome system.
Title: Converging roles of PSENEN/PEN2 and CLN3 in the autophagy-lysosome system.
Human Papillomavirus L2 Capsid Protein Stabilizes gamma-Secretase during Viral Infection.
Title: Human Papillomavirus L2 Capsid Protein Stabilizes γ-Secretase during Viral Infection.
Mutations in gamma-secretase subunit-encoding PSENEN gene alone may not be sufficient for the development of acne inversa.
Title: Mutations in γ-secretase subunit-encoding PSENEN gene alone may not be sufficient for the development of acne inversa.
SERP1 is an assembly regulator of gamma-secretase in metabolic stress conditions.
Title: SERP1 is an assembly regulator of γ-secretase in metabolic stress conditions.
Super-resolution microscopy reveals majorly mono- and dimeric presenilin1/gamma-secretase at the cell surface.
Title: Super-resolution microscopy reveals majorly mono- and dimeric presenilin1/γ-secretase at the cell surface.
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.

Submit: New GeneRIF Correction See all GeneRIFs (63)

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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables endopeptidase activator activity	IGI Inferred from Genetic Interaction more info	PubMed
enables endopeptidase activator activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in Notch receptor processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in Notch receptor processing	NAS Non-traceable Author Statement more info	PubMed
involved_in Notch receptor processing	TAS Traceable Author Statement more info	PubMed
involved_in Notch signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in amyloid precursor protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in amyloid precursor protein catabolic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in amyloid precursor protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in amyloid precursor protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in amyloid precursor protein catabolic process	TAS Traceable Author Statement more info	PubMed
involved_in amyloid precursor protein metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in amyloid-beta formation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in amyloid-beta formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in membrane protein ectodomain proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in membrane protein intracellular domain proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in membrane protein intracellular domain proteolysis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of endopeptidase activity	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein processing	IDA Inferred from Direct Assay more info	PubMed
involved_in protein processing	IGI Inferred from Genetic Interaction more info	PubMed
involved_in protein processing	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi cisterna membrane	IEA Inferred from Electronic Annotation more info
located_in Golgi membrane	NAS Non-traceable Author Statement more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	NAS Non-traceable Author Statement more info	PubMed
located_in endosome membrane	TAS Traceable Author Statement more info
part_of gamma-secretase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of gamma-secretase complex	IDA Inferred from Direct Assay more info	PubMed
part_of gamma-secretase complex	IGI Inferred from Genetic Interaction more info	PubMed
part_of gamma-secretase complex	IPI Inferred from Physical Interaction more info	PubMed
part_of gamma-secretase complex	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in presynaptic membrane	IEA Inferred from Electronic Annotation 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

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GenBank, FASTA, Sequence Viewer (Graphics), LRG_222

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

B2R5L9, 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

B2R5L9, Q9NZ42

Related

ENSP00000468411.1, ENST00000587708.7

Conserved Domains (1) summary

pfam10251
Location:7 → 99

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

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

35745651..35747519

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060943.1 Alternate T2T-CHM13v2.0

Range

38290961..38292828

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_018468.4: Suppressed sequence

Description

NM_018468.4: This RefSeq record was removed by NCBI staff. Contact [email protected] for further information.