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P57716

- NICA_MOUSE

UniProt

P57716 - NICA_MOUSE

Protein

Nicastrin

Gene

Ncstn

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 105 (01 Oct 2014)
      Sequence version 3 (27 Jul 2011)
      Previous versions | rss
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    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
    2. protein binding Source: IntAct

    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

    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. Golgi apparatus Source: UniProtKB
    3. integral component of plasma membrane Source: UniProtKB
    4. lysosomal membrane Source: Ensembl
    5. melanosome Source: UniProtKB-SubCell
    6. membrane Source: MGI
    7. plasma membrane Source: MGI

    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

    ArrayExpressiP57716.
    BgeeiP57716.
    CleanExiMM_NCSTN.
    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...

    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

    MATTRGGSGP DPGSRGLLLL SFSVVLAGLC GGNSVERKIY IPLNKTAPCV    50
    RLLNATHQIG CQSSISGDTG VIHVVEKEED LKWVLTDGPN PPYMVLLEGK 100
    LFTRDVMEKL KGTTSRIAGL AVTLAKPNST SSFSPSVQCP NDGFGIYSNS 150
    YGPEFAHCKK TLWNELGNGL AYEDFSFPIF LLEDENETKV IKQCYQDHNL 200
    GQNGSAPSFP LCAMQLFSHM HAVISTATCM RRSFIQSTFS INPEIVCDPL 250
    SDYNVWSMLK PINTSVGLEP DVRVVVAATR LDSRSFFWNV APGAESAVAS 300
    FVTQLAAAEA LHKAPDVTTL SRNVMFVFFQ GETFDYIGSS RMVYDMENGK 350
    FPVRLENIDS FVELGQVALR TSLDLWMHTD PMSQKNESVK NQVEDLLATL 400
    EKSGAGVPEV VLRRLAQSQA LPPSSLQRFL RARNISGVVL ADHSGSFHNR 450
    YYQSIYDTAE NINVTYPEWQ SPEEDLNFVT DTAKALANVA TVLARALYEL 500
    AGGTNFSSSI QADPQTVTRL LYGFLVRANN SWFQSILKHD LRSYLDDRPL 550
    QHYIAVSSPT NTTYVVQYAL ANLTGKATNL TREQCQDPSK VPNESKDLYE 600
    YSWVQGPWNS NRTERLPQCV RSTVRLARAL SPAFELSQWS STEYSTWAES 650
    RWKDIQARIF LIASKELEFI TLIVGFSTLV FSLIVTYCIN AKADVLFVAP 700
    REPGAVSY 708
    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.
    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

    ArrayExpressi P57716.
    Bgeei P57716.
    CleanExi MM_NCSTN.
    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

    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 1, 2014
    This is version 105 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