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NCSTN nicastrin [ Homo sapiens (human) ]

Gene ID: 23385, updated on 25-Nov-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
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Genomic context

See NCSTN in Genome Data Viewer
Location:
1q23.2
Exon count:
19
Annotation release Status Assembly Chr Location
109.20211119 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 membrane protein intracellular domain 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 IPI
Inferred from Physical 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 IDA
Inferred from Direct Assay
more info
PubMed 
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)

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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_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 109.20211119

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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