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NCSTN nicastrin [ Homo sapiens (human) ]

Gene ID: 23385, updated on 15-Jun-2019

Summary

Official Symbol
NCSTNprovided by HGNC
Official Full Name
nicastrinprovided by HGNC
Primary source
HGNC:HGNC:17091
See related
Ensembl:ENSG00000162736 MIM:605254
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
ATAG1874
Summary
This gene encodes a type I transmembrane glycoprotein that is an integral component of the multimeric gamma-secretase complex. The encoded protein cleaves integral membrane proteins, including Notch receptors and beta-amyloid precursor protein, and may be a stabilizing cofactor required for gamma-secretase complex assembly. The cleavage of beta-amyloid precursor protein yields amyloid beta peptide, the main component of the neuritic plaque and the hallmark lesion in the brains of patients with Alzheimer's disease; however, the nature of the encoded protein's role in Alzheimer's disease is not known for certain. Mutations in this gene are associated with familial acne inversa. A pseudogene of this gene is present on chromosome 21. Alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Feb 2014]
Expression
Ubiquitous expression in placenta (RPKM 38.1), duodenum (RPKM 30.4) and 25 other tissues See more
Orthologs

Genomic context

See NCSTN in Genome Data Viewer
Location:
1q23.2
Exon count:
19
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 1 NC_000001.11 (160343273..160358952)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (160313063..160328742)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107985219 Neighboring gene peroxisomal biogenesis factor 19 Neighboring gene coatomer protein complex subunit alpha Neighboring gene SUMO1 pseudogene 3 Neighboring gene uncharacterized LOC105371466 Neighboring gene nescient helix-loop-helix 1 Neighboring gene RNA, U4 small nuclear 42, pseudogene

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Pathways from BioSystems

  • Activated NOTCH1 Transmits Signal to the Nucleus, organism-specific biosystem (from REACTOME)
    Activated NOTCH1 Transmits Signal to the Nucleus, organism-specific biosystemMature NOTCH1 heterodimer on the cell surface is activated by one of its ligands: DLL1 (Cordle et al. 2008, Jarriault et al. 1998), DLL4 (Benedito et al. 2009), JAG1 (Li et al. 1998, Benedito et al. ...
  • Alzheimer's disease, organism-specific biosystem (from KEGG)
    Alzheimer's disease, organism-specific biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
  • Alzheimer's disease, conserved biosystem (from KEGG)
    Alzheimer's disease, conserved biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
  • Alzheimers Disease, organism-specific biosystem (from WikiPathways)
    Alzheimers Disease, organism-specific biosystemThis pathway displays current genes, proteolytic events and other processes associated with the progression of Alzheimer's disease. This pathway was adapted from KEGG on 10/7/2011. Note: mitochondria...
  • Axon guidance, organism-specific biosystem (from REACTOME)
    Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
  • Cell death signalling via NRAGE, NRIF and NADE, organism-specific biosystem (from REACTOME)
    Cell death signalling via NRAGE, NRIF and NADE, organism-specific biosystemp75NTR is a key regulator of neuronal apoptosis, both during development and after injury. Apoptosis is triggered by binding of either mature neurotrophin or proneurotrophin (proNGF, proBDNF). ProNG...
  • Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants, organism-specific biosystem (from REACTOME)
    Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants, organism-specific biosystemWhen found in cis, HD and PEST domain mutations act synergistically, increasing NOTCH1 transcriptional activity up to ~40-fold, compared with up to ~10-fold and up to ~2-fold increase with HD mutatio...
  • Constitutive Signaling by NOTCH1 PEST Domain Mutants, organism-specific biosystem (from REACTOME)
    Constitutive Signaling by NOTCH1 PEST Domain Mutants, organism-specific biosystemAs NOTCH1 PEST domain is intracellular, NOTCH1 PEST domain mutants are expected to behave as the wild-type NOTCH1 with respect to ligand binding and proteolytic cleavage mediated activation of signal...
  • Degradation of the extracellular matrix, organism-specific biosystem (from REACTOME)
    Degradation of the extracellular matrix, organism-specific biosystemMatrix metalloproteinases (MMPs), previously referred to as matrixins because of their role in degradation of the extracellular matrix (ECM), are zinc and calcium dependent proteases belonging to the...
  • Developmental Biology, organism-specific biosystem (from REACTOME)
    Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Diseases of signal transduction, organism-specific biosystem (from REACTOME)
    Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...
  • EPH-Ephrin signaling, organism-specific biosystem (from REACTOME)
    EPH-Ephrin signaling, organism-specific biosystemDuring the development process cell migration and adhesion are the main forces involved in morphing the cells into critical anatomical structures. The ability of a cell to migrate to its correct dest...
  • EPH-ephrin mediated repulsion of cells, organism-specific biosystem (from REACTOME)
    EPH-ephrin mediated repulsion of cells, organism-specific biosystemDespite high-affinity multimeric interaction between EPHs and ephrins (EFNs), the cellular response to EPH-EFN engagement is usually repulsion between the two cells and signal termination. These repu...
  • Extracellular matrix organization, organism-specific biosystem (from REACTOME)
    Extracellular matrix organization, organism-specific biosystemThe extracellular matrix is a component of all mammalian tissues, a network consisting largely of the fibrous proteins collagen, elastin and associated-microfibrils, fibronectin and laminins embedded...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • NOTCH2 Activation and Transmission of Signal to the Nucleus, organism-specific biosystem (from REACTOME)
    NOTCH2 Activation and Transmission of Signal to the Nucleus, organism-specific biosystemSimilar to NOTCH1, NOTCH2 is activated by Delta-like and Jagged ligands (DLL/JAG) expressed in trans on a neighboring cell (Shimizu et al. 1999, Shimizu et al. 2000, Hicks et al. 2000, Ji et al. 2004...
  • NRIF signals cell death from the nucleus, organism-specific biosystem (from REACTOME)
    NRIF signals cell death from the nucleus, organism-specific biosystemNRIF (nuclear receptor-interacting factor) is a DNA binding protein that is essential for p75-mediated apoptosis in retina and sympathetic neurons. Neurotrophin or proneurotrophin binding to p75TR in...
  • Neutrophil degranulation, organism-specific biosystem (from REACTOME)
    Neutrophil degranulation, organism-specific biosystemNeutrophils are the most abundant leukocytes (white blood cells), indispensable in defending the body against invading microorganisms. In response to infection, neutrophils leave the circulation and ...
  • Notch Signaling Pathway, organism-specific biosystem (from WikiPathways)
    Notch Signaling Pathway, organism-specific biosystemThe Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch pro...
  • Notch Signaling Pathway, organism-specific biosystem (from WikiPathways)
    Notch Signaling Pathway, organism-specific biosystemThe Notch pathway is an evolutionally conserved signaling pathway which plays an important role in diverse developmental and physiological processes. These include cell-fate determination, tissue pat...
  • Notch signaling, organism-specific biosystem (from KEGG)
    Notch signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
  • Notch signaling, conserved biosystem (from KEGG)
    Notch signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
  • Notch signaling pathway, organism-specific biosystem (from KEGG)
    Notch signaling pathway, organism-specific biosystemThe Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch pro...
  • Notch signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    Notch signaling pathway, organism-specific biosystem
    Notch signaling pathway
  • Notch signaling pathway, conserved biosystem (from KEGG)
    Notch signaling pathway, conserved biosystemThe Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch pro...
  • Nuclear signaling by ERBB4, organism-specific biosystem (from REACTOME)
    Nuclear signaling by ERBB4, organism-specific biosystemBesides signaling as a transmembrane receptor, ligand activated homodimers of ERBB4 JM-A isoforms (ERBB4 JM-A CYT1 and ERBB4 JM-A CYT2) undergo proteolytic cleavage by ADAM17 (TACE) in the juxtamembr...
  • Presenilin action in Notch and Wnt signaling, organism-specific biosystem (from Pathway Interaction Database)
    Presenilin action in Notch and Wnt signaling, organism-specific biosystem
    Presenilin action in Notch and Wnt signaling
  • Regulated proteolysis of p75NTR, organism-specific biosystem (from REACTOME)
    Regulated proteolysis of p75NTR, organism-specific biosystemp75NTR undergoes a process of regulated intramembrane proteolysis (RIP) similar to other transmembrane proteins such as NOTCH, beta-amyloid precursor protein (APP), and ERBB4. Each of these proteins ...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by ERBB4, organism-specific biosystem (from REACTOME)
    Signaling by ERBB4, organism-specific biosystemERBB4, also known as HER4, belongs to the ERBB family of receptors, which also includes ERBB1 (EGFR i.e. HER1), ERBB2 (HER2 i.e. NEU) and ERBB3 (HER3). Similar to EGFR, ERBB4 has an extracellular lig...
  • Signaling by NOTCH, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH, organism-specific biosystemThe Notch Signaling Pathway (NSP) is a highly conserved pathway for cell-cell communication. NSP is involved in the regulation of cellular differentiation, proliferation, and specification. For exam...
  • Signaling by NOTCH1, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH1, organism-specific biosystemNOTCH1 functions as both a transmembrane receptor presented on the cell surface and as a transcriptional regulator in the nucleus.NOTCH1 receptor presented on the plasma membrane is activated by a me...
  • Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer, organism-specific biosystemMutations in the heterodimerization domain (HD) and PEST domain of NOTCH1 are frequently found in cis in T-cell acute lymphoblastic leukemia. While HD mutations alone result in up to ~10-fold increas...
  • Signaling by NOTCH1 PEST Domain Mutants in Cancer, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH1 PEST Domain Mutants in Cancer, organism-specific biosystemNOTCH1 PEST domain mutations are frequently found in T-cell acute lymphoblastic leukemia (T-ALL). PEST domain mutations interfere with ubiquitination-mediated NOTCH1 downregulation and result in prol...
  • Signaling by NOTCH1 in Cancer, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH1 in Cancer, organism-specific biosystemHuman NOTCH1 was cloned as a chromosome 9 gene, translocated to the T-cell beta receptor (TCBR) promoter on chromosome 7 in T-cell acute lymphoblastic leukemia (T-ALL) (Ellisen et al. 1991). This tra...
  • Signaling by NOTCH2, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH2, organism-specific biosystemNOTCH2 is activated by binding Delta-like and Jagged ligands (DLL/JAG) expressed in trans on neighboring cells (Shimizu et al. 1999, Shimizu et al. 2000, Hicks et al. 2000, Ji et al. 2004). In trans ...
  • Signaling by NOTCH3, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH3, organism-specific biosystemSimilar to NOTCH1, NOTCH3 is activated by delta-like and jagged ligands (DLL/JAG) expressed in trans on a neighboring cell. The activation triggers cleavage of NOTCH3, first by ADAM10 at the S2 cleav...
  • Signaling by NOTCH4, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH4, organism-specific biosystemSimilar to NOTCH1, NOTCH4 is activated by delta-like and jagged ligands (DLL/JAG) expressed in trans on a neighboring cell. The activation triggers cleavage of NOTCH4, first by ADAM10 at the S2 cleav...
  • Signalling by NGF, organism-specific biosystem (from REACTOME)
    Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
  • Syndecan-3-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    Syndecan-3-mediated signaling events, organism-specific biosystem
    Syndecan-3-mediated signaling events
  • p75 NTR receptor-mediated signalling, organism-specific biosystem (from REACTOME)
    p75 NTR receptor-mediated signalling, organism-specific biosystemBesides signalling through the tyrosine kinase receptors TRK A, B, and C, the mature neurotrophins NGF, BDNF, and NT3/4 signal through their common receptor p75NTR. NGF binding to p75NTR activates a ...
  • p75(NTR)-mediated signaling, organism-specific biosystem (from Pathway Interaction Database)
    p75(NTR)-mediated signaling, organism-specific biosystem
    p75(NTR)-mediated signaling

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • KIAA0253, RP11-517F10.1

Gene Ontology Provided by GOA

Function Evidence Code Pubs
endopeptidase activity IEA
Inferred from Electronic Annotation
more info
 
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
 
T cell proliferation IEA
Inferred from Electronic Annotation
more info
 
adult behavior IEA
Inferred from Electronic Annotation
more info
 
amyloid precursor protein biosynthetic process IEA
Inferred from Electronic Annotation
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
 
cellular response to calcium ion IEA
Inferred from Electronic Annotation
more info
 
central nervous system myelination IEA
Inferred from Electronic Annotation
more info
 
cerebellum development IEA
Inferred from Electronic Annotation
more info
 
dopamine receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
ephrin receptor signaling pathway TAS
Traceable Author Statement
more info
 
epithelial cell proliferation IEA
Inferred from Electronic Annotation
more info
 
glutamate receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
learning or memory IEA
Inferred from Electronic Annotation
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
 
myeloid cell homeostasis IEA
Inferred from Electronic Annotation
more info
 
neuron apoptotic process IEA
Inferred from Electronic Annotation
more info
 
neutrophil degranulation TAS
Traceable Author Statement
more info
 
positive regulation of amyloid precursor protein biosynthetic process IEA
Inferred from Electronic Annotation
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 
protein processing IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein processing IDA
Inferred from Direct Assay
more info
PubMed 
proteolysis NAS
Non-traceable Author Statement
more info
PubMed 
regulation of long-term synaptic potentiation IEA
Inferred from Electronic Annotation
more info
 
short-term synaptic potentiation IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
Golgi apparatus IDA
Inferred from Direct Assay
more info
PubMed 
azurophil granule membrane TAS
Traceable Author Statement
more info
 
early endosome IEA
Inferred from Electronic Annotation
more info
 
endoplasmic reticulum IDA
Inferred from Direct Assay
more info
PubMed 
endosome membrane TAS
Traceable Author Statement
more info
 
extracellular exosome HDA PubMed 
focal adhesion HDA 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 membrane NAS
Non-traceable Author Statement
more info
PubMed 
integral component of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
integral component of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
integral component of presynaptic membrane IEA
Inferred from Electronic Annotation
more info
 
lysosomal membrane HDA PubMed 
melanosome IEA
Inferred from Electronic Annotation
more info
 
membrane HDA PubMed 
mitochondrion IEA
Inferred from Electronic Annotation
more info
 
plasma membrane TAS
Traceable Author Statement
more info
 
sarcolemma IEA
Inferred from Electronic Annotation
more info
 
synaptic vesicle IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
nicastrin
Names
anterior pharynx-defective 2

NCBI Reference Sequences (RefSeq)

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_027935.1 RefSeqGene

    Range
    5001..20680
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001290184.2NP_001277113.1  nicastrin isoform 2

    See identical proteins and their annotated locations for NP_001277113.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) has a different 5' structure resulting in translation initiation at an alternate AUG compared to variant 1; the 5'-most AUG, as used in variant 1, is associated with a truncated ORF that would render the transcript a candidate for nonsense-mediated decay (NMD). Leaky scanning may allow translation initiation at the alternate AUG resulting in a shorter isoform (2) with a distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AL445230, BC047621, CN429672
    UniProtKB/Swiss-Prot
    Q92542
    Conserved Domains (1) summary
    cd03881
    Location:155462
    M28_Nicastrin; M28 Zn-Peptidase Nicastrin, a main component of gamma-secretase complex
  2. NM_001290186.2NP_001277115.1  nicastrin isoform 3 precursor

    See identical proteins and their annotated locations for NP_001277115.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks three alternate in-frame exons in the coding region compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
    Source sequence(s)
    AF240468, AK299142, AL445230, CN429672
    UniProtKB/Swiss-Prot
    Q92542
    UniProtKB/TrEMBL
    B4DR82
    Conserved Domains (1) summary
    cl14876
    Location:195361
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42
  3. NM_001349729.2NP_001336658.1  nicastrin isoform 4 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks an alternate in-frame exon in the 3' coding region, compared to variant 1. It encodes isoform 5, which is shorter than isoform 1.
    Source sequence(s)
    AL445230, H15133
    Conserved Domains (1) summary
    cd03881
    Location:175482
    M28_Nicastrin; M28 Zn-Peptidase Nicastrin, a main component of gamma-secretase complex
  4. NM_015331.3NP_056146.1  nicastrin isoform 1 precursor

    See identical proteins and their annotated locations for NP_056146.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AF240468, BC047621, CN429672
    Consensus CDS
    CCDS1203.1
    UniProtKB/Swiss-Prot
    Q92542
    Related
    ENSP00000294785.5, ENST00000294785.10
    Conserved Domains (1) summary
    cd03881
    Location:175482
    M28_Nicastrin; M28 Zn-Peptidase Nicastrin, a main component of gamma-secretase complex

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p13 Primary Assembly

    Range
    160343328..160358949
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005245053.5XP_005245110.1  nicastrin isoform X1

    Conserved Domains (1) summary
    cd03881
    Location:175395
    M28_Nicastrin; M28 Zn-Peptidase Nicastrin, a main component of gamma-secretase complex
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