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P57716 (NICA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nicastrin
Gene names
Name:Ncstn
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length708 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 (beta-amyloid precursor protein). It probably represents a stabilizing cofactor required for the assembly of the gamma-secretase complex.

Subunit structure

Component of the gamma-secretase complex, a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity, although other components may exist. Binds to proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP) By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein By similarity. Melanosome By similarity.

Sequence similarities

Belongs to the nicastrin family.

Ontologies

Keywords
   Biological processNotch signaling pathway
   Cellular componentMembrane
   DomainSignal
Transmembrane
Transmembrane helix
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNotch signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

T cell proliferation

Inferred from mutant phenotype PubMed 17913918. Source: MGI

beta-amyloid metabolic process

Inferred from mutant phenotype PubMed 17913918. Source: MGI

epithelial cell proliferation

Inferred from mutant phenotype PubMed 17913918. Source: MGI

membrane protein ectodomain proteolysis

Inferred from sequence or structural similarity. Source: UniProtKB

myeloid cell homeostasis

Inferred from mutant phenotype PubMed 17913918. Source: MGI

positive regulation of catalytic activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein processing

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

endoplasmic reticulum

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

lysosomal membrane

Inferred from electronic annotation. Source: Ensembl

melanosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Inferred from direct assay PubMed 11943765PubMed 15634781PubMed 15886206. Source: MGI

plasma membrane

Inferred from direct assay PubMed 12646573PubMed 21187406. Source: MGI

   Molecular_functionendopeptidase activity

Inferred from mutant phenotype PubMed 17913918. Source: MGI

protein binding

Inferred from physical interaction PubMed 19725872PubMed 23585889. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CalrP142112EBI-998934,EBI-644340
Syvn1Q9DBY12EBI-998934,EBI-644384

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Chain28 – 708681Nicastrin
PRO_0000019682

Regions

Topological domain28 – 668641Extracellular Potential
Transmembrane669 – 68921Helical; Potential
Topological domain690 – 70819Cytoplasmic Potential

Amino acid modifications

Glycosylation441N-linked (GlcNAc...) Potential
Glycosylation541N-linked (GlcNAc...) Potential
Glycosylation1281N-linked (GlcNAc...) Potential
Glycosylation1861N-linked (GlcNAc...) Ref.4
Glycosylation2031N-linked (GlcNAc...) Potential
Glycosylation2631N-linked (GlcNAc...) Ref.4
Glycosylation3861N-linked (GlcNAc...) Ref.4
Glycosylation4341N-linked (GlcNAc...) Potential
Glycosylation4631N-linked (GlcNAc...) Potential
Glycosylation5051N-linked (GlcNAc...) Ref.4
Glycosylation5291N-linked (GlcNAc...) Potential
Glycosylation5301N-linked (GlcNAc...); atypical Ref.4
Glycosylation5611N-linked (GlcNAc...) Ref.4
Glycosylation5721N-linked (GlcNAc...) Potential
Glycosylation5791N-linked (GlcNAc...) Potential
Glycosylation5931N-linked (GlcNAc...) Potential
Glycosylation6111N-linked (GlcNAc...) Ref.4

Experimental info

Sequence conflict5271R → K in AAG11413. Ref.1
Sequence conflict5271R → K in AAH19998. Ref.3
Sequence conflict6661E → K in AAG11413. Ref.1
Sequence conflict678 – 6803TLV → ILI in AAG11413. Ref.1
Sequence conflict678 – 6803TLV → ILI in AAH19998. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P57716 [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: 32B57BB478FEB0AC

FASTA70878,492
        10         20         30         40         50         60 
MATTRGGSGP DPGSRGLLLL SFSVVLAGLC GGNSVERKIY IPLNKTAPCV RLLNATHQIG 

        70         80         90        100        110        120 
CQSSISGDTG VIHVVEKEED LKWVLTDGPN PPYMVLLEGK LFTRDVMEKL KGTTSRIAGL 

       130        140        150        160        170        180 
AVTLAKPNST SSFSPSVQCP NDGFGIYSNS YGPEFAHCKK TLWNELGNGL AYEDFSFPIF 

       190        200        210        220        230        240 
LLEDENETKV IKQCYQDHNL GQNGSAPSFP LCAMQLFSHM HAVISTATCM RRSFIQSTFS 

       250        260        270        280        290        300 
INPEIVCDPL SDYNVWSMLK PINTSVGLEP DVRVVVAATR LDSRSFFWNV APGAESAVAS 

       310        320        330        340        350        360 
FVTQLAAAEA LHKAPDVTTL SRNVMFVFFQ GETFDYIGSS RMVYDMENGK FPVRLENIDS 

       370        380        390        400        410        420 
FVELGQVALR TSLDLWMHTD PMSQKNESVK NQVEDLLATL EKSGAGVPEV VLRRLAQSQA 

       430        440        450        460        470        480 
LPPSSLQRFL RARNISGVVL ADHSGSFHNR YYQSIYDTAE NINVTYPEWQ SPEEDLNFVT 

       490        500        510        520        530        540 
DTAKALANVA TVLARALYEL AGGTNFSSSI QADPQTVTRL LYGFLVRANN SWFQSILKHD 

       550        560        570        580        590        600 
LRSYLDDRPL QHYIAVSSPT NTTYVVQYAL ANLTGKATNL TREQCQDPSK VPNESKDLYE 

       610        620        630        640        650        660 
YSWVQGPWNS NRTERLPQCV RSTVRLARAL SPAFELSQWS STEYSTWAES RWKDIQARIF 

       670        680        690        700 
LIASKELEFI TLIVGFSTLV FSLIVTYCIN AKADVLFVAP REPGAVSY 

« Hide

References

« Hide 'large scale' references
[1]"Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing."
Yu G., Nishimura M., Arawaka S., Levitan D., Zhang L., Tandon A., Song Y.-Q., Rogaeva E., Chen F., Kawarai T., Supala A., Levesque L., Yu H., Yang D.-S., Holmes E., Milman P., Liang Y., Zhang D.M. expand/collapse author list , Xu D.H., Sato C., Rogaev E., Smith M., Janus C., Zhang Y., Aebersold R., Farrer L.S., Sorbi S., Bruni A., Fraser P.E., St George-Hyslop P.H.
Nature 407:48-54(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-186; ASN-263; ASN-386; ASN-505; ASN-530; ASN-561 AND ASN-611.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF240469 mRNA. Translation: AAG11413.1.
AC158930 Genomic DNA. No translation available.
BC019998 mRNA. Translation: AAH19998.1.
CCDSCCDS15507.1.
RefSeqNP_067620.3. NM_021607.3.
UniGeneMm.218203.

3D structure databases

ProteinModelPortalP57716.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid208543. 12 interactions.
DIPDIP-36334N.
IntActP57716. 7 interactions.
MINTMINT-1177052.

Chemistry

BindingDBP57716.

Protein family/group databases

TCDB9.B.47.1.1. the -secretase (-secretase) family.

PTM databases

PhosphoSiteP57716.

Proteomic databases

MaxQBP57716.
PaxDbP57716.
PRIDEP57716.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000003550; ENSMUSP00000003550; ENSMUSG00000003458.
GeneID59287.
KEGGmmu:59287.
UCSCuc007dpk.2. mouse.

Organism-specific databases

CTD23385.
MGIMGI:1891700. Ncstn.

Phylogenomic databases

eggNOGNOG253370.
GeneTreeENSGT00390000014633.
HOVERGENHBG006497.
InParanoidP57716.
KOK06171.
OMAHMHAVIS.
OrthoDBEOG77WWCF.
TreeFamTF317086.

Enzyme and pathway databases

ReactomeREACT_188257. Signal Transduction.
REACT_189085. Disease.

Gene expression databases

ArrayExpressP57716.
BgeeP57716.
CleanExMM_NCSTN.
GenevestigatorP57716.

Family and domain databases

InterProIPR008710. Nicastrin.
[Graphical view]
PANTHERPTHR21092. PTHR21092. 1 hit.
PfamPF05450. Nicastrin. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio314784.
PROP57716.
SOURCESearch...

Entry information

Entry nameNICA_MOUSE
AccessionPrimary (citable) accession number: P57716
Secondary accession number(s): E9QLZ6, Q8VE20
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 103 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot