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P57716 · NICA_MOUSE

  • Protein
    Nicastrin
  • Gene
    Ncstn
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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). 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.

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentcytoplasmic vesicle membrane
Cellular Componentearly endosome
Cellular Componentendoplasmic reticulum
Cellular Componentendoplasmic reticulum membrane
Cellular Componentgamma-secretase complex
Cellular ComponentGolgi apparatus
Cellular ComponentGolgi membrane
Cellular Componentlysosomal membrane
Cellular Componentlysosome
Cellular Componentmelanosome
Cellular Componentmembrane
Cellular Componentplasma membrane
Cellular Componentpresynaptic membrane
Cellular Componentprotein-containing complex
Cellular Componentsarcolemma
Cellular Componentsynaptic vesicle
Molecular FunctionATPase binding
Molecular Functiongrowth factor receptor binding
Molecular Functionpeptidase activity
Molecular Functionprotein-macromolecule adaptor activity
Biological Processadult behavior
Biological Processamyloid precursor protein biosynthetic process
Biological Processamyloid precursor protein catabolic process
Biological Processamyloid precursor protein metabolic process
Biological Processamyloid-beta formation
Biological Processamyloid-beta metabolic process
Biological Processcellular response to calcium ion
Biological Processcentral nervous system myelination
Biological Processcerebellum development
Biological Processepithelial cell proliferation
Biological ProcessG protein-coupled dopamine receptor signaling pathway
Biological Processglutamate receptor signaling pathway
Biological Processlearning or memory
Biological Processmembrane protein ectodomain proteolysis
Biological Processmembrane protein intracellular domain proteolysis
Biological Processmyeloid cell homeostasis
Biological Processneuron apoptotic process
Biological ProcessNotch receptor processing
Biological ProcessNotch signaling pathway
Biological Processpositive regulation of amyloid precursor protein biosynthetic process
Biological Processpositive regulation of endopeptidase activity
Biological Processprotein processing
Biological Processregulation of long-term synaptic potentiation
Biological Processshort-term synaptic potentiation
Biological ProcessT cell proliferation

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Nicastrin

Gene names

    • Name
      Ncstn

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    P57716
  • Secondary accessions
    • E9QLZ6
    • Q8VE20

Proteomes

Organism-specific databases

Subcellular Location

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.

Features

Showing features for topological domain, transmembrane.

Type
IDPosition(s)Description
Topological domain28-668Lumenal
Transmembrane669-689Helical
Topological domain690-708Cytoplasmic

Keywords

Phenotypes & Variants

Disruption phenotype

Full embryonic lethality. No embryos survive past 10.d dpc. At 9.5 dpc the embryos display a phenotype similar to that of Notch1-deficient mice, with defects in the development of the caudal part of the embryo and in somite segementation, defective vascular morphogenesis in the yolk sac, and patterning defects in the developing heart and neural tube. Assembly of the gamma-secretase complex and APP processing are disrupted.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 34 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for signal, chain, glycosylation, disulfide bond.

Type
IDPosition(s)Description
Signal1-27
ChainPRO_000001968228-708Nicastrin
Glycosylation44N-linked (GlcNAc...) asparagine
Disulfide bond49↔61
Glycosylation54N-linked (GlcNAc...) asparagine
Glycosylation128N-linked (GlcNAc...) asparagine
Disulfide bond139↔158
Glycosylation186N-linked (GlcNAc...) asparagine
Disulfide bond194↔212
Glycosylation203N-linked (GlcNAc...) asparagine
Disulfide bond229↔247
Glycosylation263N-linked (GlcNAc...) asparagine
Glycosylation386N-linked (GlcNAc...) asparagine
Glycosylation434N-linked (GlcNAc...) asparagine
Glycosylation463N-linked (GlcNAc...) asparagine
Glycosylation505N-linked (GlcNAc...) asparagine
Glycosylation529N-linked (GlcNAc...) asparagine
Glycosylation561N-linked (GlcNAc...) asparagine
Glycosylation572N-linked (GlcNAc...) asparagine
Glycosylation579N-linked (GlcNAc...) asparagine
Disulfide bond585↔619
Glycosylation593N-linked (GlcNAc...) asparagine
Glycosylation611N-linked (GlcNAc...) asparagine

Post-translational modification

N-glycosylated.

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

Component of the gamma-secretase complex. 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 PEN2 (PubMed:12716934).
Binds to proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP). Interacts with PSEN1 and PSEN2

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntAct
BINARY P57716Calr P142112EBI-998934, EBI-644340
BINARY P57716Syvn1 Q9DBY12EBI-998934, EBI-644384

Complex viewer

View interactors in UniProtKB
View CPX-4234 in Complex Portal

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Sequence similarities

Belongs to the nicastrin family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    708
  • Mass (Da)
    78,492
  • Last updated
    2011-07-27 v3
  • MD5 Checksum
    BAF82D04E52BBCDA8CAE4A8749378F06
MATTRGGSGPDPGSRGLLLLSFSVVLAGLCGGNSVERKIYIPLNKTAPCVRLLNATHQIGCQSSISGDTGVIHVVEKEEDLKWVLTDGPNPPYMVLLEGKLFTRDVMEKLKGTTSRIAGLAVTLAKPNSTSSFSPSVQCPNDGFGIYSNSYGPEFAHCKKTLWNELGNGLAYEDFSFPIFLLEDENETKVIKQCYQDHNLGQNGSAPSFPLCAMQLFSHMHAVISTATCMRRSFIQSTFSINPEIVCDPLSDYNVWSMLKPINTSVGLEPDVRVVVAATRLDSRSFFWNVAPGAESAVASFVTQLAAAEALHKAPDVTTLSRNVMFVFFQGETFDYIGSSRMVYDMENGKFPVRLENIDSFVELGQVALRTSLDLWMHTDPMSQKNESVKNQVEDLLATLEKSGAGVPEVVLRRLAQSQALPPSSLQRFLRARNISGVVLADHSGSFHNRYYQSIYDTAENINVTYPEWQSPEEDLNFVTDTAKALANVATVLARALYELAGGTNFSSSIQADPQTVTRLLYGFLVRANNSWFQSILKHDLRSYLDDRPLQHYIAVSSPTNTTYVVQYALANLTGKATNLTREQCQDPSKVPNESKDLYEYSWVQGPWNSNRTERLPQCVRSTVRLARALSPAFELSQWSSTEYSTWAESRWKDIQARIFLIASKELEFITLIVGFSTLVFSLIVTYCINAKADVLFVAPREPGAVSY

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
D6RCJ2D6RCJ2_MOUSENcstn62

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict527in Ref. 1; AAG11413 and 3; AAH19998
Sequence conflict666in Ref. 1; AAG11413
Sequence conflict678-680in Ref. 1; AAG11413 and 3; AAH19998

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF240469
EMBL· GenBank· DDBJ
AAG11413.1
EMBL· GenBank· DDBJ
mRNA
AC158930
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
BC019998
EMBL· GenBank· DDBJ
AAH19998.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
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