Ncstn nicastrin [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Ncstnprovided by MGI
Official Full Name: nicastrinprovided by MGI
Primary source: MGI:MGI:1891700
See related: Ensembl:ENSMUSG00000003458 AllianceGenome:MGI:1891700
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Nct; Aph2; D1Dau13e; Kiaa0253; mKIAA0253; 9430068N19Rik
Summary: Contributes to aspartic endopeptidase activity, intramembrane cleaving. Acts upstream of or within several processes, including amyloid precursor protein biosynthetic process; amyloid-beta formation; and regulation of synaptic plasticity. Located in several cellular components, including Golgi apparatus; lysosome; and synaptic vesicle. Part of gamma-secretase complex. Is expressed in several structures, including brain and genitourinary system. Used to study chronic myeloid leukemia; schizophrenia; and urinary bladder cancer. Human ortholog(s) of this gene implicated in Alzheimer's disease; hidradenitis suppurativa; and schizophrenia. Orthologous to human NCSTN (nicastrin). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in genital fat pad adult (RPKM 56.1), large intestine adult (RPKM 48.9) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 1 H3; 1 79.54 cM

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (171893580..171910356, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (172066013..172082789, complement)

Chromosome 1 - NC_000067.7 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: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Effects of NCSTN Mutation on Hair Follicle Components in Mice.
Title: Effects of NCSTN Mutation on Hair Follicle Components in Mice.
A pig model carrying heterozygous point mutation of NCSTN simulates familial acne inversa and reveals dysregulated cholesterol biosynthesis via the Notch-pAMPK-HMGCR pathway.
Title: A pig model carrying heterozygous point mutation of NCSTN simulates familial acne inversa and reveals dysregulated cholesterol biosynthesis via the Notch-pAMPK-HMGCR pathway.
Keratin 5-Cre-driven deletion of Ncstn in an acne inversa-like mouse model leads to a markedly increased IL-36a and Sprr2 expression.
Title: Keratin 5-Cre-driven deletion of Ncstn in an acne inversa-like mouse model leads to a markedly increased IL-36a and Sprr2 expression.
The missense mutation severely limits the glycosylation of NCSTN to its mature form and impairs the integrity of the gamma-secretase complex as well as its catalytic activity toward its substrate Notch, a critical regulator of B cell and T cell development. Essential requirement for nicastrin in marginal zone and B-1 B cell development.
Title: Essential requirement for nicastrin in marginal zone and B-1 B cell development.
mice defective of the nicastrin subunit of gamma-secretase in oligodendrocytes have hypomyelination in the central nervous system.
Title: Loss of Nicastrin from Oligodendrocytes Results in Hypomyelination and Schizophrenia with Compulsive Behavior.
The results of this study showed that elevated p-tau levels in NCT cKO mice and have demonstrated that changes on p-tau were likely caused by enhanced activity of CDK5 but not GSK3beta.
Title: Astroglial Activation and Tau Hyperphosphorylation Precede to Neuron Loss in a Neurodegenerative Mouse Model.
PS1(exon8) interacts with nicastrin, participating in the gamma-secretase complex formation.
Title: Physiologically generated presenilin 1 lacking exon 8 fails to rescue brain PS1-/- phenotype and forms complexes with wildtype PS1 and nicastrin.
nicastrin plays essential roles in the regulation of short- and long-term synaptic plasticity, highlighting the importance of gamma-secretase in the function of mature synapses
Title: Synaptic function of nicastrin in hippocampal neurons.
These results reveal a key role for ncstn in modulating amyloid beta production and amyloid plaque formation.
Title: Conditional inactivation of nicastrin restricts amyloid deposition in an Alzheimer's disease mouse model.
Upregulation of PS1/gamma-secretase activity may be a risk factor for late onset sporadic Alzheimer's disease.
Title: Increased expression of PS1 is sufficient to elevate the level and activity of γ-secretase in vivo.

Submit: New GeneRIF Correction See all GeneRIFs (35)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (1)
Targeted (8) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH11634 (e-PCR)
- UniSTS:22843

G42046 (e-PCR)
- UniSTS:105071

RH140256 (e-PCR)
- UniSTS:222335

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATPase binding	IEA Inferred from Electronic Annotation more info
enables ATPase binding	ISO Inferred from Sequence Orthology more info
contributes_to aspartic endopeptidase activity, intramembrane cleaving	IGI Inferred from Genetic Interaction more info	PubMed
contributes_to endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
contributes_to endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables growth factor receptor binding	IEA Inferred from Electronic Annotation more info
enables growth factor receptor binding	ISO Inferred from Sequence Orthology more info
enables peptidase activity	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-macromolecule adaptor activity	IEA Inferred from Electronic Annotation more info
enables protein-macromolecule adaptor activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within G protein-coupled dopamine receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in Notch receptor processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in Notch receptor processing	ISO Inferred from Sequence Orthology more info
involved_in Notch receptor processing	NAS Non-traceable Author Statement more info	PubMed
involved_in Notch signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within T cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within adult behavior	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within amyloid precursor protein biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in amyloid precursor protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in amyloid precursor protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within amyloid precursor protein metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in amyloid precursor protein metabolic process	ISO Inferred from Sequence Orthology more info
involved_in amyloid precursor protein metabolic process	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within amyloid-beta formation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in amyloid-beta formation	ISO Inferred from Sequence Orthology more info
involved_in amyloid-beta formation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within amyloid-beta metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to calcium ion	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within central nervous system myelination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cerebellum development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within epithelial cell proliferation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within glutamate receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within learning or memory	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in membrane protein ectodomain proteolysis	ISO Inferred from Sequence Orthology more info
involved_in membrane protein ectodomain proteolysis	ISS Inferred from Sequence or Structural Similarity more info
involved_in membrane protein intracellular domain proteolysis	ISO Inferred from Sequence Orthology more info
involved_in membrane protein intracellular domain proteolysis	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within myeloid cell homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of amyloid precursor protein biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of endopeptidase activity	ISO Inferred from Sequence Orthology more info
involved_in protein processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein processing	ISO Inferred from Sequence Orthology more info
involved_in protein processing	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within regulation of long-term synaptic potentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within short-term synaptic potentiation	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 apparatus	ISO Inferred from Sequence Orthology more info
located_in Golgi apparatus	ISS Inferred from Sequence or Structural Similarity more info
located_in Golgi membrane	NAS Non-traceable Author Statement more info	PubMed
located_in cytoplasmic vesicle membrane	IEA Inferred from Electronic Annotation more info
located_in early endosome	IEA Inferred from Electronic Annotation more info
located_in early endosome	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum	NAS Non-traceable Author Statement more info	PubMed
located_in endoplasmic reticulum membrane	NAS Non-traceable Author Statement more info	PubMed
part_of gamma-secretase complex	IDA Inferred from Direct Assay more info	PubMed
part_of gamma-secretase complex	ISO Inferred from Sequence Orthology more info
part_of gamma-secretase complex	ISS Inferred from Sequence or Structural Similarity more info
located_in lysosomal membrane	IEA Inferred from Electronic Annotation more info
located_in lysosomal membrane	ISO Inferred from Sequence Orthology more info
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed
located_in melanosome	IEA Inferred from Electronic Annotation more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	ISO Inferred from Sequence Orthology more info
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
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
is_active_in presynaptic membrane	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info
located_in sarcolemma	IEA Inferred from Electronic Annotation more info
located_in sarcolemma	ISO Inferred from Sequence Orthology more info
located_in synaptic membrane	ISO Inferred from Sequence Orthology more info
located_in synaptic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in synaptic vesicle	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: nicastrin

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.

mRNA and Protein(s)

NM_021607.3 → NP_067620.3 nicastrin precursor

See identical proteins and their annotated locations for NP_067620.3

Status: VALIDATED

Source sequence(s)

AK033314, BF714603, CD549803

Consensus CDS

CCDS15507.1

UniProtKB/Swiss-Prot

E9QLZ6, P57716, Q8VE20

UniProtKB/TrEMBL

Q3T9E5, Q3TD54

Related

ENSMUSP00000003550.5, ENSMUST00000003550.11

Conserved Domains (1) summary

cd03881
Location:174 → 481

M28_Nicastrin; M28 Zn-Peptidase Nicastrin, a main component of gamma-secretase complex

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000067.7 Reference GRCm39 C57BL/6J

Range

171893580..171910356 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006496952.4 → XP_006497015.1 nicastrin isoform X1

UniProtKB/TrEMBL

Q3T9E5

Conserved Domains (1) summary

cd03881
Location:42 → 644

M28_Nicastrin; M28 Zn-peptidase nicastrin, a main component of gamma-secretase complex
XM_017321872.3 → XP_017177361.1 nicastrin isoform X2

Conserved Domains (1) summary

cl14876
Location:1 → 440

Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42