NICA_RAT
ID NICA_RAT Reviewed; 708 AA.
AC Q8CGU6; Q8CH12;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Nicastrin;
DE Flags: Precursor;
GN Name=Ncstn;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=Sprague-Dawley;
RA Crestini A., Piscopo P., Tartaglia M., Confaloni A.;
RT "Rat nicastrin cDNA.";
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 83-100; 314-322; 355-385; 391-428; 485-495; 520-527;
RP 622-651 AND 659-665, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Lubec G., Kang S.U., Lubec S.;
RL Submitted (SEP-2007) to UniProtKB.
RN [3]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-434, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24090084; DOI=10.1021/pr400783j;
RA Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R.,
RA Graham M.E., Packer N.H., Cordwell S.J.;
RT "Site-specific glycan-peptide analysis for determination of N-glycoproteome
RT heterogeneity.";
RL J. Proteome Res. 12:5791-5800(2013).
CC -!- FUNCTION: Essential subunit of the gamma-secretase complex, an
CC endoprotease complex that catalyzes the intramembrane cleavage of
CC integral membrane proteins such as Notch receptors and APP (amyloid-
CC beta precursor protein). The gamma-secretase complex plays a role in
CC Notch and Wnt signaling cascades and regulation of downstream processes
CC via its role in processing key regulatory proteins, and by regulating
CC cytosolic CTNNB1 levels. {ECO:0000250|UniProtKB:Q92542}.
CC -!- SUBUNIT: Component of the gamma-secretase complex. The functional
CC gamma-secretase complex is composed of at least four polypeptides: a
CC presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A
CC or APH1B) and PEN2. Binds to proteolytic processed C-terminal fragments
CC C83 and C99 of the amyloid precursor protein (APP). Interacts with
CC PSEN1 and PSEN2. {ECO:0000250|UniProtKB:Q92542}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q92542}; Single-
CC pass type I membrane protein {ECO:0000250|UniProtKB:Q92542}.
CC Cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:Q92542}; Single-
CC pass type I membrane protein {ECO:0000250|UniProtKB:Q92542}. Melanosome
CC {ECO:0000250|UniProtKB:Q92542}. Note=Identified by mass spectrometry in
CC melanosome fractions from stage I to stage IV.
CC {ECO:0000250|UniProtKB:Q92542}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8CGU6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8CGU6-2; Sequence=VSP_008387;
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q92542}.
CC -!- SIMILARITY: Belongs to the nicastrin family. {ECO:0000305}.
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DR EMBL; AF510722; AAO15915.1; -; mRNA.
DR EMBL; AY101378; AAM44078.1; -; mRNA.
DR RefSeq; NP_777353.1; NM_174864.3. [Q8CGU6-1]
DR RefSeq; XP_008767955.1; XM_008769733.1. [Q8CGU6-1]
DR AlphaFoldDB; Q8CGU6; -.
DR SMR; Q8CGU6; -.
DR BioGRID; 252837; 1.
DR CORUM; Q8CGU6; -.
DR IntAct; Q8CGU6; 4.
DR STRING; 10116.ENSRNOP00000008150; -.
DR GlyGen; Q8CGU6; 16 sites, 7 N-linked glycans (1 site).
DR iPTMnet; Q8CGU6; -.
DR PhosphoSitePlus; Q8CGU6; -.
DR jPOST; Q8CGU6; -.
DR PaxDb; Q8CGU6; -.
DR PRIDE; Q8CGU6; -.
DR Ensembl; ENSRNOT00000008150; ENSRNOP00000008150; ENSRNOG00000005355. [Q8CGU6-1]
DR Ensembl; ENSRNOT00000081534; ENSRNOP00000075174; ENSRNOG00000005355. [Q8CGU6-2]
DR GeneID; 289231; -.
DR KEGG; rno:289231; -.
DR UCSC; RGD:631418; rat. [Q8CGU6-1]
DR CTD; 23385; -.
DR RGD; 631418; Ncstn.
DR eggNOG; KOG2657; Eukaryota.
DR GeneTree; ENSGT00390000014633; -.
DR HOGENOM; CLU_024257_0_0_1; -.
DR InParanoid; Q8CGU6; -.
DR OMA; CMRRNSI; -.
DR OrthoDB; 777987at2759; -.
DR PhylomeDB; Q8CGU6; -.
DR TreeFam; TF317086; -.
DR Reactome; R-RNO-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-RNO-193692; Regulated proteolysis of p75NTR.
DR Reactome; R-RNO-205043; NRIF signals cell death from the nucleus.
DR Reactome; R-RNO-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
DR Reactome; R-RNO-9017802; Noncanonical activation of NOTCH3.
DR PRO; PR:Q8CGU6; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000005355; Expressed in jejunum and 19 other tissues.
DR ExpressionAtlas; Q8CGU6; baseline and differential.
DR Genevisible; Q8CGU6; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0070765; C:gamma-secretase complex; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0005765; C:lysosomal membrane; IDA:RGD.
DR GO; GO:0005764; C:lysosome; ISO:RGD.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0042383; C:sarcolemma; IDA:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0097060; C:synaptic membrane; IDA:RGD.
DR GO; GO:0008021; C:synaptic vesicle; IDA:RGD.
DR GO; GO:0042500; F:aspartic endopeptidase activity, intramembrane cleaving; IEA:Ensembl.
DR GO; GO:0051117; F:ATPase binding; ISO:RGD.
DR GO; GO:0070851; F:growth factor receptor binding; ISO:RGD.
DR GO; GO:0008233; F:peptidase activity; IDA:RGD.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:RGD.
DR GO; GO:0030534; P:adult behavior; ISO:RGD.
DR GO; GO:0042983; P:amyloid precursor protein biosynthetic process; ISO:RGD.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; ISO:RGD.
DR GO; GO:0042982; P:amyloid precursor protein metabolic process; ISS:UniProtKB.
DR GO; GO:0034205; P:amyloid-beta formation; ISS:UniProtKB.
DR GO; GO:0050435; P:amyloid-beta metabolic process; ISO:RGD.
DR GO; GO:0071277; P:cellular response to calcium ion; ISO:RGD.
DR GO; GO:0022010; P:central nervous system myelination; ISO:RGD.
DR GO; GO:0021549; P:cerebellum development; IEP:RGD.
DR GO; GO:0007212; P:dopamine receptor signaling pathway; ISO:RGD.
DR GO; GO:0050673; P:epithelial cell proliferation; ISO:RGD.
DR GO; GO:0007215; P:glutamate receptor signaling pathway; ISO:RGD.
DR GO; GO:0007611; P:learning or memory; ISO:RGD.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; ISS:UniProtKB.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; ISO:RGD.
DR GO; GO:0002262; P:myeloid cell homeostasis; ISO:RGD.
DR GO; GO:0051402; P:neuron apoptotic process; ISO:RGD.
DR GO; GO:0070997; P:neuron death; ISO:RGD.
DR GO; GO:0007220; P:Notch receptor processing; ISO:RGD.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0042986; P:positive regulation of amyloid precursor protein biosynthetic process; ISO:RGD.
DR GO; GO:0043085; P:positive regulation of catalytic activity; ISS:UniProtKB.
DR GO; GO:0010950; P:positive regulation of endopeptidase activity; ISO:RGD.
DR GO; GO:0016485; P:protein processing; IEP:RGD.
DR GO; GO:1900271; P:regulation of long-term synaptic potentiation; ISO:RGD.
DR GO; GO:1990926; P:short-term synaptic potentiation; ISO:RGD.
DR GO; GO:0042098; P:T cell proliferation; ISO:RGD.
DR InterPro; IPR041084; Ncstrn_small.
DR InterPro; IPR008710; Nicastrin.
DR PANTHER; PTHR21092; PTHR21092; 1.
DR Pfam; PF18266; Ncstrn_small; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasmic vesicle; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Membrane; Notch signaling pathway;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..34
FT /evidence="ECO:0000255"
FT CHAIN 35..708
FT /note="Nicastrin"
FT /id="PRO_0000019683"
FT TOPO_DOM 35..668
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q92542"
FT TRANSMEM 669..689
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q92542"
FT TOPO_DOM 690..708
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q92542"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 54
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 186
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 203
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 263
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 386
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 434
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PubMed:24090084"
FT CARBOHYD 463
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 507
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 529
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 561
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 572
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 579
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 593
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 611
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 49..61
FT /evidence="ECO:0000250|UniProtKB:Q92542"
FT DISULFID 139..158
FT /evidence="ECO:0000250|UniProtKB:Q92542"
FT DISULFID 194..212
FT /evidence="ECO:0000250|UniProtKB:Q92542"
FT DISULFID 229..247
FT /evidence="ECO:0000250|UniProtKB:Q92542"
FT DISULFID 585..619
FT /evidence="ECO:0000250|UniProtKB:Q92542"
FT VAR_SEQ 63..708
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_008387"
SQ SEQUENCE 708 AA; 78400 MW; 023713E3526F393F CRC64;
MATARGGSGP DPGSRGLLLL SFSVVLAGLC GGNSVERKIY IPLNKTAPCV RLLNATHQIG
CQSSISGDTG VIHVVEKEDD LKWVLTDGPN PPYMVLLEGK LFTRDIMEKL KGETSRIAGL
AVTLAKPNST SSFSPSVQCP NDGFGIYSNS YGPEFAHCKK TLWNELGNGL AYDDFSFPIF
LLEDENETKV IKQCYQDHNL GQNGSAPSFP LCAMQLFSHM HAVISTATCM RRSFIQSTFS
INPEIVCDPL SDYNVWSMLK PINTSGGLEP DVRVVVAATR LDSRSFFWNV APGAESAVAS
FVTQLAAAEA LHKAPDVTTL PRNVMFVFFQ GETFDYIGSS RMVYDMENGK FPVRLENIDS
FVELGQVALR TSLELWMHTD PMSQKNESVK NQVEDLLVTL EQSGADTPQV VLSRLVQSQA
LPPSSLQRFL RARNISGVVL ADHSGSFHNR YYQSIYDTAE NINVTYPESQ SPEEDLNFVT
DTAKALADVA TVLARALYKL AGGTNFNNSI QADPQTVTRL LYGFLVRANN SWFQSILRHD
LRSYLDDGPL QHYIAVSSPT NTTYVVQYAL ANLTGKVTNL TQEQCQDPSK VPNESKDLYE
YSWVQGPWNS NKTERLPRCV RSTVRLARAL SPAFELSQWS STEYSTWAES RWKDIQARIF
LIASKELEFI TLIVGFSILV FSLIVTYCIN AKADVLFVAP REPGAVSY
