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P57716

- NICA_MOUSE

UniProt

P57716 - NICA_MOUSE

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Protein

Nicastrin

Gene

Ncstn

Organism
Mus musculus (Mouse)
Status
Reviewed - 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

  1. endopeptidase activity Source: MGI

GO - Biological processi

  1. beta-amyloid metabolic process Source: MGI
  2. epithelial cell proliferation Source: MGI
  3. membrane protein ectodomain proteolysis Source: UniProtKB
  4. myeloid cell homeostasis Source: MGI
  5. Notch signaling pathway Source: UniProtKB-KW
  6. positive regulation of catalytic activity Source: UniProtKB
  7. protein processing Source: UniProtKB
  8. T cell proliferation Source: MGI
Complete GO annotation...

Keywords - Biological processi

Notch signaling pathway

Enzyme and pathway databases

ReactomeiREACT_196589. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
REACT_196591. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
REACT_198574. Nuclear signaling by ERBB4.
REACT_199052. Degradation of the extracellular matrix.
REACT_199384. Activated NOTCH1 Transmits Signal to the Nucleus.
REACT_199404. Signaling by NOTCH4.
REACT_199411. NOTCH2 Activation and Transmission of Signal to the Nucleus.
REACT_199413. Signaling by NOTCH3.
REACT_202271. NRIF signals cell death from the nucleus.
REACT_218614. Regulated proteolysis of p75NTR.

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: Chromosome 1

Organism-specific databases

MGIiMGI:1891700. Ncstn.

Subcellular locationi

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

GO - Cellular componenti

  1. endoplasmic reticulum Source: UniProtKB
  2. extracellular vesicular exosome Source: Ensembl
  3. Golgi apparatus Source: UniProtKB
  4. integral component of plasma membrane Source: UniProtKB
  5. lysosomal membrane Source: Ensembl
  6. membrane Source: MGI
  7. plasma membrane Source: MGI
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.
SMRiP57716. Positions 52-661.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

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

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei669 – 68921HelicalSequence AnalysisAdd
BLAST

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:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
AF240469 mRNA. Translation: AAG11413.1 .
AC158930 Genomic DNA. No translation available.
BC019998 mRNA. Translation: AAH19998.1 .
CCDSi CCDS15507.1.
RefSeqi NP_067620.3. NM_021607.3.
UniGenei Mm.218203.

3D structure databases

ProteinModelPortali P57716.
SMRi P57716. Positions 52-661.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 208543. 12 interactions.
DIPi DIP-36334N.
IntActi P57716. 7 interactions.
MINTi MINT-1177052.

Chemistry

BindingDBi P57716.

Protein family/group databases

TCDBi 9.B.47.1.1. the -secretase (-secretase) family.

PTM databases

PhosphoSitei P57716.

Proteomic databases

MaxQBi P57716.
PaxDbi P57716.
PRIDEi P57716.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000003550 ; ENSMUSP00000003550 ; ENSMUSG00000003458 .
GeneIDi 59287.
KEGGi mmu:59287.
UCSCi uc007dpk.2. mouse.

Organism-specific databases

CTDi 23385.
MGIi MGI:1891700. Ncstn.

Phylogenomic databases

eggNOGi NOG253370.
GeneTreei ENSGT00390000014633.
HOVERGENi HBG006497.
InParanoidi P57716.
KOi K06171.
OMAi HMHAVIS.
OrthoDBi EOG77WWCF.
TreeFami TF317086.

Enzyme and pathway databases

Reactomei REACT_196589. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
REACT_196591. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
REACT_198574. Nuclear signaling by ERBB4.
REACT_199052. Degradation of the extracellular matrix.
REACT_199384. Activated NOTCH1 Transmits Signal to the Nucleus.
REACT_199404. Signaling by NOTCH4.
REACT_199411. NOTCH2 Activation and Transmission of Signal to the Nucleus.
REACT_199413. Signaling by NOTCH3.
REACT_202271. NRIF signals cell death from the nucleus.
REACT_218614. Regulated proteolysis of p75NTR.

Miscellaneous databases

NextBioi 314784.
PROi P57716.
SOURCEi Search...

Gene expression databases

Bgeei P57716.
CleanExi MM_NCSTN.
ExpressionAtlasi P57716. baseline and differential.
Genevestigatori P57716.

Family and domain databases

InterProi IPR008710. Nicastrin.
[Graphical view ]
PANTHERi PTHR21092. PTHR21092. 1 hit.
Pfami PF05450. Nicastrin. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: October 29, 2014
This is version 106 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