Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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 receptor processing Source: Reactome
  • Notch signaling pathway Source: Reactome
  • 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

ReactomeiR-MMU-1251985. Nuclear signaling by ERBB4.
R-MMU-193692. Regulated proteolysis of p75NTR.
R-MMU-1980148. Signaling by NOTCH3.
R-MMU-1980150. Signaling by NOTCH4.
R-MMU-205043. NRIF signals cell death from the nucleus.
R-MMU-2122948. Activated NOTCH1 Transmits Signal to the Nucleus.
R-MMU-3928665. EPH-ephrin mediated repulsion of cells.
R-MMU-6798695. Neutrophil degranulation.

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
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1891700. Ncstn.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini28 – 668ExtracellularSequence analysisAdd BLAST641
Transmembranei669 – 689HelicalSequence analysisAdd BLAST21
Topological domaini690 – 708CytoplasmicSequence analysisAdd BLAST19

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000001968228 – 708NicastrinAdd BLAST681

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi44N-linked (GlcNAc...)Sequence analysis1
Glycosylationi54N-linked (GlcNAc...)Sequence analysis1
Glycosylationi128N-linked (GlcNAc...)Sequence analysis1
Glycosylationi186N-linked (GlcNAc...)1 Publication1
Glycosylationi203N-linked (GlcNAc...)Sequence analysis1
Glycosylationi263N-linked (GlcNAc...)1 Publication1
Glycosylationi386N-linked (GlcNAc...)1 Publication1
Glycosylationi434N-linked (GlcNAc...)Sequence analysis1
Glycosylationi463N-linked (GlcNAc...)Sequence analysis1
Glycosylationi505N-linked (GlcNAc...)1 Publication1
Glycosylationi529N-linked (GlcNAc...)Sequence analysis1
Glycosylationi530N-linked (GlcNAc...); atypical1 Publication1
Glycosylationi561N-linked (GlcNAc...)1 Publication1
Glycosylationi572N-linked (GlcNAc...)Sequence analysis1
Glycosylationi579N-linked (GlcNAc...)Sequence analysis1
Glycosylationi593N-linked (GlcNAc...)Sequence analysis1
Glycosylationi611N-linked (GlcNAc...)1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiP57716.
MaxQBiP57716.
PaxDbiP57716.
PeptideAtlasiP57716.
PRIDEiP57716.

PTM databases

PhosphoSitePlusiP57716.
SwissPalmiP57716.

Expressioni

Gene expression databases

BgeeiENSMUSG00000003458.
CleanExiMM_NCSTN.
ExpressionAtlasiP57716. baseline and differential.
GenevisibleiP57716. MM.

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. 48 interactors.
DIPiDIP-36334N.
IntActiP57716. 43 interactors.
MINTiMINT-1177052.
STRINGi10090.ENSMUSP00000003550.

Structurei

3D structure databases

ProteinModelPortaliP57716.
SMRiP57716.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the nicastrin family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2657. Eukaryota.
ENOG410XT6X. LUCA.
GeneTreeiENSGT00390000014633.
HOVERGENiHBG006497.
InParanoidiP57716.
KOiK06171.
OMAiHMHAVIS.
OrthoDBiEOG091G03DV.
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)DescriptionActionsGraphical viewLength
Sequence conflicti527R → K in AAG11413 (PubMed:10993067).Curated1
Sequence conflicti527R → K in AAH19998 (PubMed:15489334).Curated1
Sequence conflicti666E → K in AAG11413 (PubMed:10993067).Curated1
Sequence conflicti678 – 680TLV → ILI in AAG11413 (PubMed:10993067).Curated3
Sequence conflicti678 – 680TLV → ILI in AAH19998 (PubMed:15489334).Curated3

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.
SMRiP57716.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi208543. 48 interactors.
DIPiDIP-36334N.
IntActiP57716. 43 interactors.
MINTiMINT-1177052.
STRINGi10090.ENSMUSP00000003550.

Protein family/group databases

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

PTM databases

PhosphoSitePlusiP57716.
SwissPalmiP57716.

Proteomic databases

EPDiP57716.
MaxQBiP57716.
PaxDbiP57716.
PeptideAtlasiP57716.
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

eggNOGiKOG2657. Eukaryota.
ENOG410XT6X. LUCA.
GeneTreeiENSGT00390000014633.
HOVERGENiHBG006497.
InParanoidiP57716.
KOiK06171.
OMAiHMHAVIS.
OrthoDBiEOG091G03DV.
TreeFamiTF317086.

Enzyme and pathway databases

ReactomeiR-MMU-1251985. Nuclear signaling by ERBB4.
R-MMU-193692. Regulated proteolysis of p75NTR.
R-MMU-1980148. Signaling by NOTCH3.
R-MMU-1980150. Signaling by NOTCH4.
R-MMU-205043. NRIF signals cell death from the nucleus.
R-MMU-2122948. Activated NOTCH1 Transmits Signal to the Nucleus.
R-MMU-3928665. EPH-ephrin mediated repulsion of cells.
R-MMU-6798695. Neutrophil degranulation.

Miscellaneous databases

PROiP57716.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000003458.
CleanExiMM_NCSTN.
ExpressionAtlasiP57716. baseline and differential.
GenevisibleiP57716. MM.

Family and domain databases

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

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: November 30, 2016
This is version 125 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

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 one 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.