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

Gene ID: 55851, updated on 22-Sep-2022

Summary

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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
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Genomic context

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See PSENEN in Genome Data Viewer
Location:
19q13.12
Exon count:
4
Annotation release Status Assembly Chr Location
110 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (35745651..35747519)
110 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (38290961..38292828)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (36236552..36238420)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene lysine methyltransferase 2B Neighboring gene IGF like family receptor 1 Neighboring gene U2 small nuclear RNA auxiliary factor 1 like 4 Neighboring gene lin-37 DREAM MuvB core complex component Neighboring gene heat shock protein family B (small) member 6

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Mutations in γ-secretase subunit-encoding PSENEN gene alone may not be sufficient for the development of acne inversa. Zhou P, et al. J Dermatol Sci, 2021 Aug. PMID 34330582
  2. A phenotype combining hidradenitis suppurativa with Dowling-Degos disease caused by a founder mutation in PSENEN. Pavlovsky M, et al. Br J Dermatol, 2018 Feb. PMID 28922471
  3. Qualitative changes in human γ-secretase underlie familial Alzheimer's disease. Szaruga M, et al. J Exp Med, 2015 Nov 16. PMID 26481686, Free PMC Article
  4. The topology of pen-2, a γ-secretase subunit, revisited: evidence for a reentrant loop and a single pass transmembrane domain. Zhang X, et al. Mol Neurodegener, 2015 Aug 22. PMID 26296997, Free PMC Article
  5. A Frameshift Mutation in PEN-2 Causes Familial Comedones Syndrome. Panmontha W, et al. Dermatology, 2015. PMID 26044244

See all (96) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. Human Papillomavirus L2 Capsid Protein Stabilizes gamma-Secretase during Viral Infection.
    Title: Human Papillomavirus L2 Capsid Protein Stabilizes γ-Secretase during Viral Infection.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Potential readthrough

Included gene: LIN37

Homology

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
 PubMed 
involved_in Notch receptor processing IC
Inferred by Curator
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 IC
Inferred by Curator
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 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 IC
Inferred by Curator
more info
  
involved_in membrane protein intracellular domain proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of catalytic activity IDA
Inferred from Direct Assay
more info
 PubMed 
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 endoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum membrane IEA
Inferred from Electronic Annotation
more info
  
located_in endosome membrane TAS
Traceable Author Statement
more info
  
part_of gamma-secretase complex IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
part_of gamma-secretase complex IC
Inferred by Curator
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 
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrion IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
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

  1. NG_027934.1 RefSeqGene

    Range
    5059..6927
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_222

mRNA and Protein(s)

  1. 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

  2. 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: Homo sapiens Annotation Release 110 details...Open this link in a new tab

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    35745651..35747519
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. 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

  1. NM_018468.4: Suppressed sequence

    Description
    NM_018468.4: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NZ42.1 GenPept UniProtKB/Swiss-Prot:Q9NZ42

Gene LinkOut

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