Ncstn nicastrin [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Ncstnprovided by RGD
Official Full Name: nicastrinprovided by RGD
Primary source: RGD:631418
See related: Ensembl:ENSRNOG00000005355 AllianceGenome:RGD:631418
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Summary: Enables peptidase activity. Involved in cerebellum development and protein processing. Located in several cellular components, including cytoplasmic vesicle; lysosomal membrane; and sarcolemma. Part of protein-containing complex. Is integral component of presynaptic membrane. 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, Apr 2022]
Expression: Biased expression in Lung (RPKM 283.7), Kidney (RPKM 279.9) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 13q24

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	13	NC_086031.1 (87062827..87078839, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	13	NC_051348.1 (84530442..84546454, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	13	NC_005112.4 (90451046..90467256, complement)

Chromosome 13 - NC_086031.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

These results demonstrated the localization of VDR on the neuronal plasma membrane and the co-localization of VDR and APP or ADAM10 or Nicastrin and limited co-localization of VDR and PS1.
Title: Vitamin D receptor is present on the neuronal plasma membrane and is co-localized with amyloid precursor protein, ADAM10 or Nicastrin.
Down-regulation of the ATP-binding cassette transporter 2 (Abca2) reduces amyloid-beta production by altering Nicastrin maturation and intracellular localization.
Title: Down-regulation of the ATP-binding cassette transporter 2 (Abca2) reduces amyloid-β production by altering Nicastrin maturation and intracellular localization.
At the cellular level, nicastrin is localized predominantly in neuronal cell bodies at early postnatal stages, but is apparent both in cell bodies and dendrites/neuropil in all brain regions at the later stages.
Title: Cellular distribution of gamma-secretase subunit nicastrin in the developing and adult rat brains.
Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria
Title: Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria.
experiments establish amyloid precursor protein, nicastrin, and presenilin-1 as resident lysosomal membrane proteins and indicate that gamma-secretase is a lysosomal protease
Title: Presenilin-1, nicastrin, amyloid precursor protein, and gamma-secretase activity are co-localized in the lysosomal membrane.
The amount of presenilin-1 in the nucleus and membrane fraction was more abundantly expressed in the denervated muscle fibers. In contrast, no significant difference in the nicastrin protein level was observed between normal and denervated muscle fibers.
Title: Normal distribution of presenilin-1 and nicastrin in skeletal muscle and the differential responses of these proteins after denervation.
a novel skipped isoform of nicastrin which may suggest a new possible control mechanism based on the alternative splicing and nonsense-mediated mRNA decay to regulate brain protein expression.
Title: Rat nicastrin gene: cDNA isolation, mRNA variants and expression pattern analysis.

Submit: New GeneRIF Correction

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH127477 (e-PCR)
- UniSTS:210787

RH127998 (e-PCR)
- UniSTS:210787

RH140256 (e-PCR)
- UniSTS:222335

Gene Ontology Provided by RGD

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

Process	Evidence Code	Pubs
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 signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within T cell proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within adult behavior	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within amyloid precursor protein biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in amyloid precursor protein catabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within amyloid precursor protein metabolic process	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cellular response to calcium ion	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within central nervous system myelination	ISO Inferred from Sequence Orthology more info
involved_in cerebellum development	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within dopamine receptor signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within epithelial cell proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within glutamate receptor signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within learning or memory	ISO Inferred from Sequence Orthology more info
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
acts_upstream_of_or_within myeloid cell homeostasis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neuron apoptotic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of amyloid precursor protein biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in protein processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein processing	IEA Inferred from Electronic Annotation more info
involved_in protein processing	IEP Inferred from Expression Pattern more info	PubMed
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	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within short-term synaptic potentiation	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
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 cytoplasmic vesicle membrane	IEA Inferred from Electronic Annotation more info
located_in early endosome	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
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	IDA Inferred from Direct Assay more info	PubMed
located_in lysosome	ISO Inferred from Sequence Orthology more info
located_in melanosome	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
is_active_in presynaptic membrane	IDA Inferred from Direct Assay more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
located_in synaptic membrane	IDA Inferred from Direct Assay more info	PubMed
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_174864.3 → NP_777353.1 nicastrin precursor

See identical proteins and their annotated locations for NP_777353.1

Status: VALIDATED

Source sequence(s)

AY101378, BC074006

UniProtKB/Swiss-Prot

Q8CGU6, Q8CH12

UniProtKB/TrEMBL

A6JG19

Related

ENSRNOP00000008150.3, ENSRNOT00000008150.6

Conserved Domains (1) summary

cd03881
Location:51 → 653

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

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086031.1 Reference GRCr8

Range

87062827..87078839 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_063272133.1 → XP_063128203.1 nicastrin isoform X3

UniProtKB/TrEMBL

A0A0G2K9X9, A6JG20, B3DM90
XM_063272131.1 → XP_063128201.1 nicastrin isoform X1
XM_063272132.1 → XP_063128202.1 nicastrin isoform X2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001034026.1: Suppressed sequence

Description

NM_001034026.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
NM_001034027.1: Suppressed sequence

Description

NM_001034027.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.