ID NICA_CAEEL Reviewed; 723 AA.
AC Q23316;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2003, sequence version 3.
DT 27-MAR-2024, entry version 149.
DE RecName: Full=Nicastrin;
DE AltName: Full=Anterior-pharynx-defective protein 2;
DE Flags: Precursor;
GN Name=aph-2; ORFNames=ZC434.6;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP FUNCTION, AND GENE NAME.
RX PubMed=10993067; DOI=10.1038/35024009;
RA Yu G., Nishimura M., Arawaka S., Levitan D., Zhang L., Tandon A.,
RA Song Y.-Q., Rogaeva E., Chen F., Kawarai T., Supala A., Levesque L., Yu H.,
RA Yang D.-S., Holmes E., Milman P., Liang Y., Zhang D.M., Xu D.H., Sato C.,
RA Rogaev E., Smith M., Janus C., Zhang Y., Aebersold R., Farrer L.S.,
RA Sorbi S., Bruni A., Fraser P.E., St George-Hyslop P.H.;
RT "Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction
RT and betaAPP processing.";
RL Nature 407:48-54(2000).
RN [3]
RP FUNCTION.
RX PubMed=10804188; DOI=10.1242/dev.127.11.2481;
RA Goutte C., Hepler W., Mickey K.M., Priess J.R.;
RT "aph-2 encodes a novel extracellular protein required for GLP-1-mediated
RT signaling.";
RL Development 127:2481-2492(2000).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-181, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Bristol N2;
RX PubMed=17761667; DOI=10.1074/mcp.m600392-mcp200;
RA Kaji H., Kamiie J., Kawakami H., Kido K., Yamauchi Y., Shinkawa T.,
RA Taoka M., Takahashi N., Isobe T.;
RT "Proteomics reveals N-linked glycoprotein diversity in Caenorhabditis
RT elegans and suggests an atypical translocation mechanism for integral
RT membrane proteins.";
RL Mol. Cell. Proteomics 6:2100-2109(2007).
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 (glp-1 or lin-12). It may
CC represents a stabilizing cofactor required for the assembly of the
CC gamma-secretase complex. {ECO:0000269|PubMed:10804188,
CC ECO:0000269|PubMed:10993067}.
CC -!- SUBUNIT: Component of the gamma-secretase complex, a complex probably
CC composed of the presenilin homodimer (sel-12, hop-1 or spe-4),
CC nicastrin (aph-2), aph-1 and pen-2. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the nicastrin family. {ECO:0000305}.
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DR EMBL; Z75714; CAB00063.2; -; Genomic_DNA.
DR PIR; T27570; T27570.
DR RefSeq; NP_492712.2; NM_060311.3.
DR AlphaFoldDB; Q23316; -.
DR SMR; Q23316; -.
DR BioGRID; 38322; 2.
DR STRING; 6239.ZC434.6b.1; -.
DR GlyCosmos; Q23316; 6 sites, No reported glycans.
DR iPTMnet; Q23316; -.
DR EPD; Q23316; -.
DR PaxDb; 6239-ZC434-6b; -.
DR EnsemblMetazoa; ZC434.6b.1; ZC434.6b.1; WBGene00000148.
DR GeneID; 172905; -.
DR KEGG; cel:CELE_ZC434.6; -.
DR UCSC; ZC434.6b; c. elegans.
DR AGR; WB:WBGene00000148; -.
DR WormBase; ZC434.6b; CE34446; WBGene00000148; aph-2.
DR eggNOG; KOG2657; Eukaryota.
DR GeneTree; ENSGT00390000014633; -.
DR InParanoid; Q23316; -.
DR OMA; DNIFAFP; -.
DR OrthoDB; 1330770at2759; -.
DR PhylomeDB; Q23316; -.
DR Reactome; R-CEL-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-CEL-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-CEL-6798695; Neutrophil degranulation.
DR SignaLink; Q23316; -.
DR PRO; PR:Q23316; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00000148; Expressed in embryo and 4 other cell types or tissues.
DR ExpressionAtlas; Q23316; baseline and differential.
DR GO; GO:0070765; C:gamma-secretase complex; ISS:WormBase.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0060581; P:cell fate commitment involved in pattern specification; IMP:WormBase.
DR GO; GO:0018991; P:egg-laying behavior; IMP:WormBase.
DR GO; GO:0048598; P:embryonic morphogenesis; IMP:WormBase.
DR GO; GO:0007220; P:Notch receptor processing; IBA:GO_Central.
DR GO; GO:0007219; P:Notch signaling pathway; IMP:WormBase.
DR GO; GO:0060465; P:pharynx development; IMP:WormBase.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR CDD; cd03881; M28_Nicastrin; 1.
DR Gene3D; 3.40.630.10; Zn peptidases; 1.
DR InterPro; IPR041084; Ncstrn_small.
DR InterPro; IPR008710; Nicastrin.
DR PANTHER; PTHR21092; NICASTRIN; 1.
DR PANTHER; PTHR21092:SF0; NICASTRIN; 1.
DR Pfam; PF18266; Ncstrn_small; 1.
DR Pfam; PF05450; Nicastrin; 1.
DR SUPFAM; SSF53187; Zn-dependent exopeptidases; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Membrane; Notch signaling pathway; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..723
FT /note="Nicastrin"
FT /id="PRO_0000019684"
FT TOPO_DOM 17..678
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 679..699
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 700..723
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 40
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17761667"
FT CARBOHYD 271
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 409
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 627
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 723 AA; 81659 MW; C7DF2D12ADBF8D9D CRC64;
MKKWLVIVLI IAGIRCDGFS DQVFRTLFIG EGNACYRTFN KTHEFGCQAN RENENGLIVR
IDKQEDFKNL DSCWNSFYPK YSGKYWALLP VNLIRRDTIS QLKSSKCLSG IVLYNSGESI
HPGDESTAAS HDAECPNAAS DYYLQDKNEE YCERKINSRG AITRDGLMKI DWRIQMVFID
NSTDLEIIEK CYSMFNKPKE DGSSGYPYCG MSFRLANMAA GNSEICYRRG KNDAKLFQMN
IDSGDAPQLC GAMHSDNIFA FPTPIPTSPT NETIITSKYM MVTARMDSFG MIPEISVGEV
SVLTSIISVL AAARSMGTQI EKWQKASNTS NRNVFFAFFN GESLDYIGSG AAAYQMENGK
FPQMIRSDRT HIHPIRPNEL DYILEVQQIG VAKGRKYYVH VDGERYQQNK TQTDRVIDRI
ERGLRSHAFD LEKPSGSGDR VPPASWHSFA KADAHVQSVL LAPYGKEYEY QRVNSILDKN
EWTEDEREKA IQEIEAVSTA ILAAAADYVG VETDEVVAKV DKKLITTIFD CLITSNFWFD
CDFMQKLDGG RYHKLFNSYG FNQKSTYISM ESHTAFPTVL HWLTIFALGS DKETLNVKSE
KSCSHLGQFQ AFQMYTYTWQ PNPYTGNFSC LKSAIVKKVM VSPAVDSQTP EEEMNTRYST
WMESVYIIES VNLYLMEDAS FEYTMILIAV ISALLSIFAV GRCSETTFIV DEGEPAAEGG
EPL
//
