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Protein

Nicastrin

Gene

Ncstn

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • endopeptidase activity Source: MGI

GO - Biological processi

  • beta-amyloid metabolic process Source: MGI
  • epithelial cell proliferation Source: MGI
  • membrane protein ectodomain proteolysis Source: UniProtKB
  • myeloid cell homeostasis Source: MGI
  • Notch signaling pathway Source: UniProtKB-KW
  • positive regulation of catalytic activity Source: UniProtKB
  • protein processing Source: UniProtKB
  • T cell proliferation Source: MGI
Complete GO annotation...

Keywords - Biological processi

Notch signaling pathway

Enzyme and pathway databases

ReactomeiREACT_275864. Degradation of the extracellular matrix.
REACT_279153. Signaling by NOTCH3.
REACT_286692. Activated NOTCH1 Transmits Signal to the Nucleus.
REACT_312443. NOTCH2 Activation and Transmission of Signal to the Nucleus.
REACT_314615. EPH-ephrin mediated repulsion of cells.
REACT_315710. Regulated proteolysis of p75NTR.
REACT_342872. NRIF signals cell death from the nucleus.
REACT_345101. Signaling by NOTCH4.
REACT_345486. Nuclear signaling by ERBB4.

Protein family/group databases

TCDBi9.B.47.1.1. the -secretase (-secretase) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Nicastrin
Gene namesi
Name:Ncstn
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1891700. Ncstn.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 668641ExtracellularSequence AnalysisAdd
BLAST
Transmembranei669 – 68921HelicalSequence AnalysisAdd
BLAST
Topological domaini690 – 70819CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence AnalysisAdd
BLAST
Chaini28 – 708681NicastrinPRO_0000019682Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi44 – 441N-linked (GlcNAc...)Sequence Analysis
Glycosylationi54 – 541N-linked (GlcNAc...)Sequence Analysis
Glycosylationi128 – 1281N-linked (GlcNAc...)Sequence Analysis
Glycosylationi186 – 1861N-linked (GlcNAc...)1 Publication
Glycosylationi203 – 2031N-linked (GlcNAc...)Sequence Analysis
Glycosylationi263 – 2631N-linked (GlcNAc...)1 Publication
Glycosylationi386 – 3861N-linked (GlcNAc...)1 Publication
Glycosylationi434 – 4341N-linked (GlcNAc...)Sequence Analysis
Glycosylationi463 – 4631N-linked (GlcNAc...)Sequence Analysis
Glycosylationi505 – 5051N-linked (GlcNAc...)1 Publication
Glycosylationi529 – 5291N-linked (GlcNAc...)Sequence Analysis
Glycosylationi530 – 5301N-linked (GlcNAc...); atypical1 Publication
Glycosylationi561 – 5611N-linked (GlcNAc...)1 Publication
Glycosylationi572 – 5721N-linked (GlcNAc...)Sequence Analysis
Glycosylationi579 – 5791N-linked (GlcNAc...)Sequence Analysis
Glycosylationi593 – 5931N-linked (GlcNAc...)Sequence Analysis
Glycosylationi611 – 6111N-linked (GlcNAc...)1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiP57716.
PaxDbiP57716.
PRIDEiP57716.

PTM databases

PhosphoSiteiP57716.

Expressioni

Gene expression databases

BgeeiP57716.
CleanExiMM_NCSTN.
ExpressionAtlasiP57716. baseline and differential.
GenevestigatoriP57716.

Interactioni

Subunit structurei

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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CalrP142112EBI-998934,EBI-644340
Syvn1Q9DBY12EBI-998934,EBI-644384

Protein-protein interaction databases

BioGridi208543. 12 interactions.
DIPiDIP-36334N.
IntActiP57716. 7 interactions.
MINTiMINT-1177052.

Structurei

3D structure databases

ProteinModelPortaliP57716.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the nicastrin family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG253370.
GeneTreeiENSGT00390000014633.
HOVERGENiHBG006497.
InParanoidiP57716.
KOiK06171.
OMAiHMHAVIS.
OrthoDBiEOG77WWCF.
TreeFamiTF317086.

Family and domain databases

InterProiIPR008710. Nicastrin.
[Graphical view]
PANTHERiPTHR21092. PTHR21092. 1 hit.
PfamiPF05450. Nicastrin. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P57716-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATTRGGSGP DPGSRGLLLL SFSVVLAGLC GGNSVERKIY IPLNKTAPCV
60 70 80 90 100
RLLNATHQIG CQSSISGDTG VIHVVEKEED LKWVLTDGPN PPYMVLLEGK
110 120 130 140 150
LFTRDVMEKL KGTTSRIAGL AVTLAKPNST SSFSPSVQCP NDGFGIYSNS
160 170 180 190 200
YGPEFAHCKK TLWNELGNGL AYEDFSFPIF LLEDENETKV IKQCYQDHNL
210 220 230 240 250
GQNGSAPSFP LCAMQLFSHM HAVISTATCM RRSFIQSTFS INPEIVCDPL
260 270 280 290 300
SDYNVWSMLK PINTSVGLEP DVRVVVAATR LDSRSFFWNV APGAESAVAS
310 320 330 340 350
FVTQLAAAEA LHKAPDVTTL SRNVMFVFFQ GETFDYIGSS RMVYDMENGK
360 370 380 390 400
FPVRLENIDS FVELGQVALR TSLDLWMHTD PMSQKNESVK NQVEDLLATL
410 420 430 440 450
EKSGAGVPEV VLRRLAQSQA LPPSSLQRFL RARNISGVVL ADHSGSFHNR
460 470 480 490 500
YYQSIYDTAE NINVTYPEWQ SPEEDLNFVT DTAKALANVA TVLARALYEL
510 520 530 540 550
AGGTNFSSSI QADPQTVTRL LYGFLVRANN SWFQSILKHD LRSYLDDRPL
560 570 580 590 600
QHYIAVSSPT NTTYVVQYAL ANLTGKATNL TREQCQDPSK VPNESKDLYE
610 620 630 640 650
YSWVQGPWNS NRTERLPQCV RSTVRLARAL SPAFELSQWS STEYSTWAES
660 670 680 690 700
RWKDIQARIF LIASKELEFI TLIVGFSTLV FSLIVTYCIN AKADVLFVAP

REPGAVSY
Length:708
Mass (Da):78,492
Last modified:July 27, 2011 - v3
Checksum:i32B57BB478FEB0AC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti527 – 5271R → K in AAG11413 (PubMed:10993067).Curated
Sequence conflicti527 – 5271R → K in AAH19998 (PubMed:15489334).Curated
Sequence conflicti666 – 6661E → K in AAG11413 (PubMed:10993067).Curated
Sequence conflicti678 – 6803TLV → ILI in AAG11413 (PubMed:10993067).Curated
Sequence conflicti678 – 6803TLV → ILI in AAH19998 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF240469 mRNA. Translation: AAG11413.1.
AC158930 Genomic DNA. No translation available.
BC019998 mRNA. Translation: AAH19998.1.
CCDSiCCDS15507.1.
RefSeqiNP_067620.3. NM_021607.3.
UniGeneiMm.218203.

Genome annotation databases

EnsembliENSMUST00000003550; ENSMUSP00000003550; ENSMUSG00000003458.
GeneIDi59287.
KEGGimmu:59287.
UCSCiuc007dpk.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF240469 mRNA. Translation: AAG11413.1.
AC158930 Genomic DNA. No translation available.
BC019998 mRNA. Translation: AAH19998.1.
CCDSiCCDS15507.1.
RefSeqiNP_067620.3. NM_021607.3.
UniGeneiMm.218203.

3D structure databases

ProteinModelPortaliP57716.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi208543. 12 interactions.
DIPiDIP-36334N.
IntActiP57716. 7 interactions.
MINTiMINT-1177052.

Protein family/group databases

TCDBi9.B.47.1.1. the -secretase (-secretase) family.

PTM databases

PhosphoSiteiP57716.

Proteomic databases

MaxQBiP57716.
PaxDbiP57716.
PRIDEiP57716.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000003550; ENSMUSP00000003550; ENSMUSG00000003458.
GeneIDi59287.
KEGGimmu:59287.
UCSCiuc007dpk.2. mouse.

Organism-specific databases

CTDi23385.
MGIiMGI:1891700. Ncstn.

Phylogenomic databases

eggNOGiNOG253370.
GeneTreeiENSGT00390000014633.
HOVERGENiHBG006497.
InParanoidiP57716.
KOiK06171.
OMAiHMHAVIS.
OrthoDBiEOG77WWCF.
TreeFamiTF317086.

Enzyme and pathway databases

ReactomeiREACT_275864. Degradation of the extracellular matrix.
REACT_279153. Signaling by NOTCH3.
REACT_286692. Activated NOTCH1 Transmits Signal to the Nucleus.
REACT_312443. NOTCH2 Activation and Transmission of Signal to the Nucleus.
REACT_314615. EPH-ephrin mediated repulsion of cells.
REACT_315710. Regulated proteolysis of p75NTR.
REACT_342872. NRIF signals cell death from the nucleus.
REACT_345101. Signaling by NOTCH4.
REACT_345486. Nuclear signaling by ERBB4.

Miscellaneous databases

NextBioi314784.
PROiP57716.
SOURCEiSearch...

Gene expression databases

BgeeiP57716.
CleanExiMM_NCSTN.
ExpressionAtlasiP57716. baseline and differential.
GenevestigatoriP57716.

Family and domain databases

InterProiIPR008710. Nicastrin.
[Graphical view]
PANTHERiPTHR21092. PTHR21092. 1 hit.
PfamiPF05450. Nicastrin. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. 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.

Entry informationi

Entry nameiNICA_MOUSE
AccessioniPrimary (citable) accession number: P57716
Secondary accession number(s): E9QLZ6, Q8VE20
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: July 27, 2011
Last modified: May 27, 2015
This is version 111 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.