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Database: UniProt
Entry: NICA_CAEEL
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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   23-MAY-2018, entry version 122.
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   Rhabditoidea; Rhabditidae; Peloderinae; 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
RT   investigating 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.,
RA   Yu H., Yang D.-S., Holmes E., Milman P., Liang Y., Zhang D.M.,
RA   Xu D.H., Sato C., Rogaev E., Smith M., Janus C., Zhang Y.,
RA   Aebersold R., Farrer L.S., Sorbi S., Bruni A., Fraser P.E.,
RA   St George-Hyslop P.H.;
RT   "Nicastrin modulates presenilin-mediated notch/glp-1 signal
RT   transduction and betaAPP processing.";
RL   Nature 407:48-54(2000).
RN   [3]
RP   FUNCTION.
RX   PubMed=10804188;
RA   Goutte C., Hepler W., Mickey K.M., Priess J.R.;
RT   "aph-2 encodes a novel extracellular protein required for GLP-1-
RT   mediated signaling.";
RL   Development 127:2481-2492(2000).
RN   [4]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-181, AND IDENTIFICATION BY
RP   MASS 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
CC       probably composed of the presenilin homodimer (sel-12, hop-1 or
CC       spe-4), 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}.
DR   EMBL; Z75714; CAB00063.2; -; Genomic_DNA.
DR   PIR; T27570; T27570.
DR   RefSeq; NP_492712.2; NM_060311.3.
DR   UniGene; Cel.5001; -.
DR   ProteinModelPortal; Q23316; -.
DR   BioGrid; 38322; 1.
DR   STRING; 6239.ZC434.6b; -.
DR   iPTMnet; Q23316; -.
DR   EPD; Q23316; -.
DR   PaxDb; Q23316; -.
DR   PRIDE; Q23316; -.
DR   EnsemblMetazoa; ZC434.6b; ZC434.6b; WBGene00000148.
DR   GeneID; 172905; -.
DR   KEGG; cel:CELE_ZC434.6; -.
DR   UCSC; ZC434.6b; c. elegans.
DR   CTD; 172905; -.
DR   WormBase; ZC434.6b; CE34446; WBGene00000148; aph-2.
DR   eggNOG; KOG2657; Eukaryota.
DR   eggNOG; ENOG410XT6X; LUCA.
DR   GeneTree; ENSGT00390000014633; -.
DR   HOGENOM; HOG000290224; -.
DR   InParanoid; Q23316; -.
DR   KO; K06171; -.
DR   OMA; DNIFAFP; -.
DR   OrthoDB; EOG091G03DV; -.
DR   PhylomeDB; Q23316; -.
DR   Reactome; R-CEL-1251985; Nuclear signaling by ERBB4.
DR   Reactome; R-CEL-6798695; Neutrophil degranulation.
DR   SignaLink; Q23316; -.
DR   PRO; PR:Q23316; -.
DR   Proteomes; UP000001940; Chromosome I.
DR   Bgee; WBGene00000148; -.
DR   ExpressionAtlas; Q23316; baseline and differential.
DR   GO; GO:0070765; C:gamma-secretase complex; ISS:WormBase.
DR   GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR   GO; GO:0004175; F:endopeptidase activity; IBA:GO_Central.
DR   GO; GO:0060581; P:cell fate commitment involved in pattern specification; 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:0018991; P:oviposition; IMP:WormBase.
DR   GO; GO:0060465; P:pharynx development; IMP:WormBase.
DR   GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR   InterPro; IPR008710; Nicastrin.
DR   PANTHER; PTHR21092; PTHR21092; 1.
DR   Pfam; PF05450; Nicastrin; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Glycoprotein; Membrane; Notch signaling pathway;
KW   Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL        1     16       {ECO:0000255}.
FT   CHAIN        17    723       Nicastrin.
FT                                /FTId=PRO_0000019684.
FT   TOPO_DOM     17    678       Extracellular. {ECO:0000255}.
FT   TRANSMEM    679    699       Helical. {ECO:0000255}.
FT   TOPO_DOM    700    723       Cytoplasmic. {ECO:0000255}.
FT   CARBOHYD     40     40       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    181    181       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:17761667}.
FT   CARBOHYD    271    271       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    328    328       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    409    409       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    627    627       N-linked (GlcNAc...) asparagine.
FT                                {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
//
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