NCSTN Gene (Protein Coding)

Nicastrin

GC01P160343
GIFtS:
47
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 ... See more...

Aliases for NCSTN Gene

Aliases for NCSTN Gene

  • Nicastrin 2 3 4 5
  • Anterior Pharynx-Defective 2 3
  • ATAG1874 3
  • KIAA0253 4

External Ids for NCSTN Gene

Previous GeneCards Identifiers for NCSTN Gene

  • GC01P158105
  • GC01P156045
  • GC01P157090
  • GC01P157529
  • GC01P157126
  • GC01P158579
  • GC01P160313
  • GC01P131669

Summaries for NCSTN Gene

Entrez Gene Summary for NCSTN Gene

  • 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]

GeneCards Summary for NCSTN Gene

NCSTN (Nicastrin) is a Protein Coding gene. Diseases associated with NCSTN include Acne Inversa, Familial, 1 and Hidradenitis Suppurativa. Among its related pathways are Innate Immune System and ERK Signaling. Gene Ontology (GO) annotations related to this gene include peptidase activity and endopeptidase activity.

UniProtKB/Swiss-Prot Summary for NCSTN Gene

  • Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:10993067, PubMed:12679784, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels.

Gene Wiki entry for NCSTN Gene

Additional gene information for NCSTN Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NCSTN Gene

Genomics for NCSTN Gene

GeneHancer (GH) Regulatory Elements for NCSTN Gene

Promoters and enhancers for NCSTN Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NCSTN on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NCSTN

Top Transcription factor binding sites by QIAGEN in the NCSTN gene promoter:
  • Brachyury
  • Evi-1
  • LCR-F1
  • Pax-4a
  • POU2F1
  • POU2F1a
  • RSRFC4
  • TGIF

Genomic Locations for NCSTN Gene

Genomic Locations for NCSTN Gene
chr1:160,343,273-160,358,952
(GRCh38/hg38)
Size:
15,680 bases
Orientation:
Plus strand
chr1:160,313,062-160,328,742
(GRCh37/hg19)
Size:
15,681 bases
Orientation:
Plus strand

Genomic View for NCSTN Gene

Genes around NCSTN on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NCSTN Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NCSTN Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for NCSTN Gene

Proteins for NCSTN Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for NCSTN Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q92542-NICA_HUMAN
    Recommended name:
    Nicastrin
    Protein Accession:
    Q92542
    Secondary Accessions:
    • Q5T207
    • Q5T208
    • Q86VV5

    Protein attributes for NCSTN Gene

    Size:
    709 amino acids
    Molecular mass:
    78411 Da
    Quaternary structure:
    • Component of the gamma-secretase complex (PubMed:10993067, PubMed:30598546, PubMed:30630874). The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PSENEN/PEN2 (PubMed:12740439, PubMed:25043039, PubMed:26623517, PubMed:26280335, PubMed:25918421, PubMed:30598546, PubMed:30630874). Binds to proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP) (PubMed:10993067, PubMed:30630874). Interacts with PSEN1 and PSEN2 (PubMed:10993067).

    Three dimensional structures from OCA and Proteopedia for NCSTN Gene

    Alternative splice isoforms for NCSTN Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NCSTN Gene

Protein Expression for NCSTN Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for NCSTN Gene

  • N-glycosylated.
  • Glycosylation at Asn45, Asn55, Asn187, Asn200, Asn204, Asn264, Asn387, Asn417, Asn435, Asn464, Asn506, Asn530, Asn562, Asn573, Asn580, and Asn612
  • Ubiquitination at Lys351 and Lys403
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

Other Protein References for NCSTN Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Boster Bio Antibodies for NCSTN

No data available for DME Specific Peptides for NCSTN Gene

Domains & Families for NCSTN Gene

Gene Families for NCSTN Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for NCSTN Gene

Blocks:
  • Nicastrin
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for NCSTN Gene

GenScript: Design optimal peptide antigens:
  • Nicastrin (NICA_HUMAN)
  • Nicastrin (Q5T204_HUMAN)
  • Nicastrin (Q5T205_HUMAN)
  • Nicastrin (Q5T206_HUMAN)
  • cDNA, FLJ95633, Homo sapiens nicastrin (NCSTN), mRNA (Q5T208_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q92542

UniProtKB/Swiss-Prot:

NICA_HUMAN :
  • Belongs to the nicastrin family.
Family:
  • Belongs to the nicastrin family.
genes like me logo Genes that share domains with NCSTN: view

Function for NCSTN Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for NCSTN Gene

UniProtKB/Swiss-Prot Function:
Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:10993067, PubMed:12679784, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels.
UniProtKB/Swiss-Prot Induction:
Constitutively expressed in neural cells.

Phenotypes From GWAS Catalog for NCSTN Gene

Gene Ontology (GO) - Molecular Function for NCSTN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004175 endopeptidase activity IEA --
GO:0005515 protein binding IPI 12297508
GO:0008233 peptidase activity IEA --
genes like me logo Genes that share ontologies with NCSTN: view
genes like me logo Genes that share phenotypes with NCSTN: view

Human Phenotype Ontology for NCSTN Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for NCSTN Gene

MGI Knock Outs for NCSTN:

Animal Model Products

  • Taconic Biosciences Mouse Models for NCSTN

CRISPR Products

Clone Products

  • Addgene plasmids for NCSTN

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for NCSTN Gene

Localization for NCSTN Gene

Subcellular locations from UniProtKB/Swiss-Prot for NCSTN Gene

Membrane; Single-pass type I membrane protein. Cytoplasmic vesicle membrane; Single-pass type I membrane protein. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NCSTN gene
Compartment Confidence
plasma membrane 5
endoplasmic reticulum 4
endosome 4
lysosome 4
golgi apparatus 4
extracellular 3
cytoskeleton 3
mitochondrion 3
nucleus 2
cytosol 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NCSTN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005739 mitochondrion IEA --
GO:0005764 lysosome IEA --
GO:0005765 lysosomal membrane IEA,HDA 17897319
GO:0005769 early endosome IEA --
genes like me logo Genes that share ontologies with NCSTN: view

Pathways & Interactions for NCSTN Gene

genes like me logo Genes that share pathways with NCSTN: view

Pathways by source for NCSTN Gene

2 KEGG pathways for NCSTN Gene
3 GeneGo (Thomson Reuters) pathways for NCSTN Gene
  • Development MAG-dependent inhibition of neurite outgrowth
  • Development Notch Signaling Pathway
  • Development NOTCH1-mediated pathway for NF-KB activity modulation
4 Qiagen pathways for NCSTN Gene
  • ErbB4 Pathway
  • Molecular Mechanisms of Cancer
  • Notch Signaling
  • Presenilin-Mediated Signaling
2 Cell Signaling Technology pathways for NCSTN Gene

SIGNOR curated interactions for NCSTN Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for NCSTN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002262 myeloid cell homeostasis IEA --
GO:0006508 proteolysis NAS 10993067
GO:0006509 membrane protein ectodomain proteolysis IDA 15274632
GO:0007212 dopamine receptor signaling pathway IEA --
GO:0007215 glutamate receptor signaling pathway IEA --
genes like me logo Genes that share ontologies with NCSTN: view

Drugs & Compounds for NCSTN Gene

Products:

  1. Drug

(5) Drugs for NCSTN Gene - From: DGIdb and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
GSI-136 Investigational Pharma 0
BMS-299897 Pharma 0
BMS-708163 Pharma 0
MK0752 Pharma inhibitor, other Notch signaling pathway inhibitor, Other 0

(1) Additional Compounds for NCSTN Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with NCSTN: view

Transcripts for NCSTN Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for NCSTN Gene

4 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
14 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for NCSTN

Alternative Splicing Database (ASD) splice patterns (SP) for NCSTN Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7a · 7b · 7c ^ 8 ^ 9a · 9b · 9c ^ 10 ^ 11 ^ 12a · 12b ^ 13 ^ 14 ^ 15a · 15b ^ 16a · 16b ^
SP1: - - - - - -
SP2: - - - - - - -
SP3: - - - -
SP4: -
SP5: - - - - -
SP6: - - - - - - - - - - -
SP7: - - -
SP8: - - -
SP9:
SP10:
SP11: - - -
SP12: - -
SP13: - - -
SP14:
SP15:
SP16:

ExUns: 17a · 17b · 17c ^ 18a · 18b ^ 19 ^ 20a · 20b · 20c ^ 21a · 21b · 21c ^ 22a · 22b · 22c
SP1: - - - -
SP2: - - - -
SP3: - -
SP4: -
SP5:
SP6:
SP7:
SP8:
SP9: - - - - -
SP10: - -
SP11:
SP12:
SP13:
SP14: -
SP15:
SP16:

Relevant External Links for NCSTN Gene

GeneLoc Exon Structure for
NCSTN

Expression for NCSTN Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NCSTN Gene

mRNA expression in normal human tissues for NCSTN Gene
mRNA expression by GTEx for NCSTN GenemRNA expression by BioGPS for NCSTN Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for NCSTN Gene

This gene is overexpressed in Nasal epithelium (40.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NCSTN Gene



Protein tissue co-expression partners for NCSTN Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NCSTN

SOURCE GeneReport for Unigene cluster for NCSTN Gene:

Hs.517249

mRNA Expression by UniProt/SwissProt for NCSTN Gene:

Q92542-NICA_HUMAN
Tissue specificity: Detected in brain (at protein level) (PubMed:10993067). Widely expressed (PubMed:11396676).

Evidence on tissue expression from TISSUES for NCSTN Gene

  • Nervous system(4.6)
  • Bone marrow(4.3)
  • Liver(4.3)
  • Lung(3.4)
  • Skin(2.2)
  • Kidney(2)
  • Pancreas(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for NCSTN Gene

Germ Layers:
  • ectoderm
Systems:
  • integumentary
Regions:
General:
  • skin
genes like me logo Genes that share expression patterns with NCSTN: view

No data available for mRNA differential expression in normal tissues for NCSTN Gene

Orthologs for NCSTN Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for NCSTN Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia NCSTN 31 30
  • 99.58 (n)
 OneToOne
cow
(Bos Taurus)
 Mammalia NCSTN 31 30
  • 87.49 (n)
 OneToOne
mouse
(Mus musculus)
 Mammalia Ncstn 17 31 30
  • 86.82 (n)
rat
(Rattus norvegicus)
 Mammalia Ncstn 30
  • 86.72 (n)
dog
(Canis familiaris)
 Mammalia NCSTN 31 30
  • 86.42 (n)
 OneToOne
oppossum
(Monodelphis domestica)
 Mammalia NCSTN 31
  • 75 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia NCSTN 31
  • 64 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves NCSTN 31 30
  • 68.84 (n)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia NCSTN 31
  • 60 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia ncstn 30
  • 63.48 (n)
African clawed frog
(Xenopus laevis)
 Amphibia Xl.19808 30
zebrafish
(Danio rerio)
 Actinopterygii ncstn 30
  • 59.97 (n)
CABZ01052486.1 31
  • 56 (a)
 OneToOne
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP001734 30
  • 44.25 (n)
fruit fly
(Drosophila melanogaster)
 Insecta nct 31 32 30
  • 44.08 (n)
 OneToOne
worm
(Caenorhabditis elegans)
 Secernentea aph-2 31 30
  • 41.82 (n)
 OneToOne
thale cress
(Arabidopsis thaliana)
 eudicotyledons AT3G52640 30
  • 40.39 (n)
rice
(Oryza sativa)
 Liliopsida Os02g0736500 30
  • 42.72 (n)
sea squirt
(Ciona savignyi)
 Ascidiacea -- 31
  • 36 (a)
 OneToOne
Species where no ortholog for NCSTN was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for NCSTN Gene

ENSEMBL:
Gene Tree for NCSTN (if available)
TreeFam:
Gene Tree for NCSTN (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NCSTN: view image

Paralogs for NCSTN Gene

No data available for Paralogs for NCSTN Gene

Variants for NCSTN Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NCSTN Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
rs1085307081 Pathogenic: Familial acne inversa 1 160,354,238(+) C/T