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    NCSTN nicastrin [ Homo sapiens (human) ]

    Gene ID: 23385, updated on 26-Jul-2021

    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See NCSTN in Genome Data Viewer
    Location:
    1q23.2
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 1 NC_000001.11 (160343328..160358949)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (160313173..160328739)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107985219 Neighboring gene peroxisomal biogenesis factor 19 Neighboring gene COPI coat 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 Functions

    What's a GeneRIF?

    Pathways from PubChem

    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
    enables ATPase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables aspartic endopeptidase activity, intramembrane cleaving IEA
    Inferred from Electronic Annotation
    more info
     
    enables growth factor receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein-macromolecule adaptor activity IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    enables protein-macromolecule adaptor activity IMP
    Inferred from Mutant Phenotype
    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 IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in Notch receptor processing IMP
    Inferred from Mutant Phenotype
    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 T cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in adult behavior IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in amyloid precursor protein biosynthetic process 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 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 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 cellular response to calcium ion IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in central nervous system myelination IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cerebellum development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in dopamine receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in epithelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in glutamate receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in learning or memory IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in membrane protein ectodomain proteolysis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in myeloid cell homeostasis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in neuron apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of amyloid precursor protein biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
     
    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 IBA
    Inferred from Biological aspect of Ancestor
    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 
    involved_in proteolysis NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in regulation of long-term synaptic potentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in short-term synaptic potentiation IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in azurophil granule membrane TAS
    Traceable Author Statement
    more info
     
    located_in early endosome IEA
    Inferred from Electronic Annotation
    more info
     
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in endosome membrane TAS
    Traceable Author Statement
    more info
     
    located_in extracellular exosome HDA PubMed 
    located_in focal adhesion HDA PubMed 
    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 NAS
    Non-traceable Author Statement
    more info
    PubMed 
    located_in integral component of membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in integral component of membrane NAS
    Non-traceable Author Statement
    more info
    PubMed 
    is_active_in integral component of plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in integral component of plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in integral component of presynaptic membrane IEA
    Inferred from Electronic Annotation
    more info
     
    located_in lysosomal membrane HDA PubMed 
    located_in melanosome IEA
    Inferred from Electronic Annotation
    more info
     
    located_in membrane HDA PubMed 
    located_in mitochondrion IEA
    Inferred from Electronic Annotation
    more info
     
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     
    located_in sarcolemma IEA
    Inferred from Electronic Annotation
    more info
     
    located_in synaptic vesicle IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    nicastrin
    Names
    anterior pharynx-defective 2

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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
      5111..20677
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_223

    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:52654
      M28_Nicastrin; M28 Zn-peptidase nicastrin, a main component of gamma-secretase complex

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

    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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