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Protein

Nicastrin

Gene

Ncstn

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity

GO - Molecular functioni

  • endopeptidase activity Source: Ensembl
  • peptidase activity Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Notch signaling pathway

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Nicastrin
Gene namesi
Name:Ncstn
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 13

Organism-specific databases

RGDi631418. Ncstn.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini35 – 668ExtracellularSequence analysisAdd BLAST634
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 – 34Sequence analysisAdd BLAST34
ChainiPRO_000001968335 – 708NicastrinAdd BLAST674

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...)Sequence analysis1
Glycosylationi203N-linked (GlcNAc...)Sequence analysis1
Glycosylationi263N-linked (GlcNAc...)Sequence analysis1
Glycosylationi386N-linked (GlcNAc...)Sequence analysis1
Glycosylationi434N-linked (GlcNAc...)Sequence analysis1
Glycosylationi463N-linked (GlcNAc...)Sequence analysis1
Glycosylationi507N-linked (GlcNAc...)Sequence analysis1
Glycosylationi529N-linked (GlcNAc...)Sequence analysis1
Glycosylationi561N-linked (GlcNAc...)Sequence analysis1
Glycosylationi572N-linked (GlcNAc...)Sequence analysis1
Glycosylationi579N-linked (GlcNAc...)Sequence analysis1
Glycosylationi593N-linked (GlcNAc...)Sequence analysis1
Glycosylationi611N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8CGU6.
PRIDEiQ8CGU6.

PTM databases

PhosphoSitePlusiQ8CGU6.
UniCarbKBiQ8CGU6.

Expressioni

Gene expression databases

BgeeiENSRNOG00000005355.
ExpressionAtlasiQ8CGU6. baseline and differential.
GenevisibleiQ8CGU6. RN.

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

Protein-protein interaction databases

BioGridi252837. 1 interactor.
IntActiQ8CGU6. 4 interactors.
MINTiMINT-4575162.
STRINGi10116.ENSRNOP00000008150.

Structurei

3D structure databases

ProteinModelPortaliQ8CGU6.
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.
HOGENOMiHOG000044212.
HOVERGENiHBG006497.
InParanoidiQ8CGU6.
KOiK06171.
OMAiHMHAVIS.
OrthoDBiEOG091G03DV.
PhylomeDBiQ8CGU6.
TreeFamiTF317086.

Family and domain databases

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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8CGU6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MATARGGSGP DPGSRGLLLL SFSVVLAGLC GGNSVERKIY IPLNKTAPCV
60 70 80 90 100
RLLNATHQIG CQSSISGDTG VIHVVEKEDD LKWVLTDGPN PPYMVLLEGK
110 120 130 140 150
LFTRDIMEKL KGETSRIAGL AVTLAKPNST SSFSPSVQCP NDGFGIYSNS
160 170 180 190 200
YGPEFAHCKK TLWNELGNGL AYDDFSFPIF LLEDENETKV IKQCYQDHNL
210 220 230 240 250
GQNGSAPSFP LCAMQLFSHM HAVISTATCM RRSFIQSTFS INPEIVCDPL
260 270 280 290 300
SDYNVWSMLK PINTSGGLEP DVRVVVAATR LDSRSFFWNV APGAESAVAS
310 320 330 340 350
FVTQLAAAEA LHKAPDVTTL PRNVMFVFFQ GETFDYIGSS RMVYDMENGK
360 370 380 390 400
FPVRLENIDS FVELGQVALR TSLELWMHTD PMSQKNESVK NQVEDLLVTL
410 420 430 440 450
EQSGADTPQV VLSRLVQSQA LPPSSLQRFL RARNISGVVL ADHSGSFHNR
460 470 480 490 500
YYQSIYDTAE NINVTYPESQ SPEEDLNFVT DTAKALADVA TVLARALYKL
510 520 530 540 550
AGGTNFNNSI QADPQTVTRL LYGFLVRANN SWFQSILRHD LRSYLDDGPL
560 570 580 590 600
QHYIAVSSPT NTTYVVQYAL ANLTGKVTNL TQEQCQDPSK VPNESKDLYE
610 620 630 640 650
YSWVQGPWNS NKTERLPRCV RSTVRLARAL SPAFELSQWS STEYSTWAES
660 670 680 690 700
RWKDIQARIF LIASKELEFI TLIVGFSILV FSLIVTYCIN AKADVLFVAP

REPGAVSY
Length:708
Mass (Da):78,400
Last modified:March 1, 2003 - v1
Checksum:i023713E3526F393F
GO
Isoform 2 (identifier: Q8CGU6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     63-708: Missing.

Note: No experimental confirmation available.
Show »
Length:62
Mass (Da):6,380
Checksum:iD1E32A7E0B7A0421
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00838763 – 708Missing in isoform 2. 1 PublicationAdd BLAST646

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF510722 mRNA. Translation: AAO15915.1.
AY101378 mRNA. Translation: AAM44078.1.
RefSeqiNP_777353.1. NM_174864.3. [Q8CGU6-1]
XP_008767955.1. XM_008769733.1. [Q8CGU6-1]
UniGeneiRn.51975.

Genome annotation databases

EnsembliENSRNOT00000008150; ENSRNOP00000008150; ENSRNOG00000005355. [Q8CGU6-1]
GeneIDi289231.
KEGGirno:289231.
UCSCiRGD:631418. rat. [Q8CGU6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF510722 mRNA. Translation: AAO15915.1.
AY101378 mRNA. Translation: AAM44078.1.
RefSeqiNP_777353.1. NM_174864.3. [Q8CGU6-1]
XP_008767955.1. XM_008769733.1. [Q8CGU6-1]
UniGeneiRn.51975.

3D structure databases

ProteinModelPortaliQ8CGU6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi252837. 1 interactor.
IntActiQ8CGU6. 4 interactors.
MINTiMINT-4575162.
STRINGi10116.ENSRNOP00000008150.

PTM databases

PhosphoSitePlusiQ8CGU6.
UniCarbKBiQ8CGU6.

Proteomic databases

PaxDbiQ8CGU6.
PRIDEiQ8CGU6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000008150; ENSRNOP00000008150; ENSRNOG00000005355. [Q8CGU6-1]
GeneIDi289231.
KEGGirno:289231.
UCSCiRGD:631418. rat. [Q8CGU6-1]

Organism-specific databases

CTDi23385.
RGDi631418. Ncstn.

Phylogenomic databases

eggNOGiKOG2657. Eukaryota.
ENOG410XT6X. LUCA.
GeneTreeiENSGT00390000014633.
HOGENOMiHOG000044212.
HOVERGENiHBG006497.
InParanoidiQ8CGU6.
KOiK06171.
OMAiHMHAVIS.
OrthoDBiEOG091G03DV.
PhylomeDBiQ8CGU6.
TreeFamiTF317086.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ8CGU6.

Gene expression databases

BgeeiENSRNOG00000005355.
ExpressionAtlasiQ8CGU6. baseline and differential.
GenevisibleiQ8CGU6. RN.

Family and domain databases

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

Entry informationi

Entry nameiNICA_RAT
AccessioniPrimary (citable) accession number: Q8CGU6
Secondary accession number(s): Q8CH12
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: March 1, 2003
Last modified: November 30, 2016
This is version 101 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. 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.