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Protein

Nicastrin

Gene

Ncstn

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 (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.1 Publication

GO - Molecular functioni

  • endopeptidase activity Source: MGI

GO - Biological processi

  • amyloid-beta formation Source: UniProtKB
  • amyloid-beta metabolic process Source: MGI
  • amyloid precursor protein metabolic process Source: UniProtKB
  • epithelial cell proliferation Source: MGI
  • membrane protein ectodomain proteolysis Source: UniProtKB
  • myeloid cell homeostasis Source: MGI
  • Notch receptor processing Source: GO_Central
  • Notch signaling pathway Source: UniProtKB-KW
  • positive regulation of catalytic activity Source: UniProtKB
  • protein processing Source: UniProtKB
  • T cell proliferation Source: MGI

Keywordsi

Biological processNotch signaling pathway

Enzyme and pathway databases

ReactomeiR-MMU-1251985 Nuclear signaling by ERBB4
R-MMU-193692 Regulated proteolysis of p75NTR
R-MMU-1980150 Signaling by NOTCH4
R-MMU-205043 NRIF signals cell death from the nucleus
R-MMU-3928665 EPH-ephrin mediated repulsion of cells
R-MMU-6798695 Neutrophil degranulation
R-MMU-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus
R-MMU-9017802 Noncanonical activation of NOTCH3

Protein family/group databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Nicastrin
Gene namesi
Name:Ncstn
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1891700 Ncstn

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini28 – 668LumenalBy similarityAdd BLAST641
Transmembranei669 – 689HelicalBy similarityAdd BLAST21
Topological domaini690 – 708CytoplasmicBy similarityAdd BLAST19

Keywords - Cellular componenti

Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

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...) asparagineSequence analysis1
Disulfide bondi49 ↔ 61By similarity
Glycosylationi54N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi128N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi139 ↔ 158By similarity
Glycosylationi186N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi194 ↔ 212By similarity
Glycosylationi203N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi229 ↔ 247By similarity
Glycosylationi263N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi386N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi434N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi463N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi505N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi529N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi530N-linked (GlcNAc...) asparagine; atypical1 Publication1
Glycosylationi561N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi572N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi579N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi585 ↔ 619By similarity
Glycosylationi593N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi611N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP57716
MaxQBiP57716
PaxDbiP57716
PeptideAtlasiP57716
PRIDEiP57716

PTM databases

iPTMnetiP57716
PhosphoSitePlusiP57716
SwissPalmiP57716

Expressioni

Gene expression databases

BgeeiENSMUSG00000003458
CleanExiMM_NCSTN
ExpressionAtlasiP57716 baseline and differential
GenevisibleiP57716 MM

Interactioni

Subunit structurei

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.By similarity1 Publication

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi20854349 interactors.
CORUMiP57716
DIPiDIP-36334N
IntActiP57716 46 interactors.
MINTiP57716
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

InterProiView protein in InterPro
IPR008710 Nicastrin
PANTHERiPTHR21092 PTHR21092, 1 hit
PfamiView protein in Pfam
PF05450 Nicastrin, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiNICA_MOUSE
AccessioniPrimary (citable) accession number: P57716
Secondary accession number(s): E9QLZ6, Q8VE20
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: July 27, 2011
Last modified: March 28, 2018
This is version 136 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome