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FLASH GENE

Symbol

NCSTN

contributors: mct - updated : 27-01-2015

HGNC name	nicastrin
HGNC id	17091

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	AIF acne inversa, familial
Location	1q23.2      Physical location : 160.313.062 - 160.328.741
Synonym name	anterior pharynx-defective 2
Synonym symbol(s)	KIAA0253, APH2, NCT

DNA

TYPE	functioning gene
STRUCTURE	15.68 kb     17 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_015331 17 - 2944 - 709 - 2006 16938437

EXPRESSION

Type	ubiquitous

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth tongue     highly Reproductive female system uterus cervix   highly   female system breast mammary gland   highly   female system placenta     highly   male system prostate     highly   male system testis     highly Respiratory lung       highly   respiratory tract larynx     highly Skin/Tegument skin       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Connective bone       Muscular

cell lineage
cell lines
fluid/secretion	blood

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES		Hydrophilic
STRUCTURE

motifs/domains	a N terminal signal peptide, a region with four conserved cysteine residues, followed by the DYIGS
	two highly conserved domains
	a transmembrane segment (TM1)
	a short hydrophilic cytoplasmic tail of 20 AA with 16 extracellular potential glycosylation sites
	one aminopeptidase I transferrin receptor superfamily domain (binding domain for beta-amyloid precursor protein)

conjugated

GlycoP

HOMOLOGY

interspecies	ortholog to rattus Ncstn
	ortholog to murine Ncstn

Homologene

FAMILY	gamma secretase family
	nicastrin family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,lysosome
text	colocalizing with presenilin

basic FUNCTION	modulating presenilin mediated notch/glp-1 signal transduction in C elegans
	potential modulator of APP beta cleavage by secretase gamma
	involved in the degradation of amyloid precursor protein to produce beta-amyloid peptides
	member of the gamma-secretase complex, playing a role, with PSEN1, APH1A, PSENEN, necessary and sufficient to reconstitute gamma-secretase activity
	essential component of the gamma secretase (GS) enzyme complex, required for its synthesis and recognition of substrates for proteolytic cleavage
	can function to maintain epithelial to mesenchymal transition during breast cancer progression
	part of the gamma-secretase complex and potentially involved in substrate recognition and selection
	regulates EMT and breast cancer stem cells through NOTCH and AKT1 pathways

CELLULAR PROCESS

protein, degradation

PHYSIOLOGICAL PROCESS

text	amyloid precursor protein catabolism
	membrane protein ectodomain proteolysis

PATHWAY

metabolism

signaling

signal transduction

a component	component of PSEN1 and PSEN2 complexes
	may be part of a complex involved in the intramembrane processing of transmembrane protein
	part of gamma-secretase complex, composed of four non-covalently bound transmembrane proteins Presenilin, Nicastrin APH1A, APH1B, PSENEN, that is responsible for the intramembranous cleavage of amyloid precursor protein (APP) and NOTCH
	PSEN1 or PSEN2, nicastrin (NCSTN), anterior pharynx-defective 1 (APH1A), and PSENEN have been considered the minimal essential subunits required to form an active gamma-secretase complex

INTERACTION

DNA

RNA

small molecule

protein	PSEN1
	PSEN2
	interacted with LMAN1 prior to its association with the active gamma-secretase complex
	SYVN1 interacts with NCSTN (SYVN1-mediated ubiquitination is involved in the degradation of immature nicastrin, and probably regulates amyloid beta-protein generation)
	HERPUD1 is likely involved in degradation of immature nicastrin by facilitating VCP-dependent nicastrin retranslocation and ubiquitination)
	may have an important mechanistic role underlying the increased risk of dissemination of Breast cancer cells through regulation of vimentin, SNAI1, and MMPs
	extracellular domain of NCSTN directly binds PSENEN at the thin end

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

AIF

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in breast cancer (

Susceptibility

to Alzheimer disease

Variant & Polymorphism SNP	HAPB increased the risk of early-onset Alzheimer disease
	rare SNP (N417Y) with a statistically higher frequency in Alzheimer disease compared to controls

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive breast nicastrin blocking antibody could be used to limit metastatic dissemination in invasive breast cancer

ANIMAL & CELL MODELS