NICA_DROME
ID NICA_DROME Reviewed; 695 AA.
AC Q9VC27;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-APR-2001, sequence version 3.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Nicastrin {ECO:0000303|PubMed:10993067};
DE Flags: Precursor;
GN Name=Nct {ECO:0000312|FlyBase:FBgn0039234}; Synonyms=NCSTN;
GN ORFNames=CG7012 {ECO:0000312|FlyBase:FBgn0039234};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION IN NOTCH SIGNALING.
RX PubMed=11781576; DOI=10.1038/ncb1201-1129;
RA Chung H.-M., Struhl G.;
RT "Nicastrin is required for Presenilin-mediated transmembrane cleavage in
RT Drosophila.";
RL Nat. Cell Biol. 3:1129-1132(2001).
RN [6]
RP FUNCTION IN THE GAMMA-SECRETASE COMPLEX.
RX PubMed=11782315; DOI=10.1016/s1534-5807(01)00105-8;
RA Hu Y., Ye Y., Fortini M.E.;
RT "Nicastrin is required for gamma-secretase cleavage of the Drosophila Notch
RT receptor.";
RL Dev. Cell 2:69-78(2002).
RN [7]
RP FUNCTION IN NOTCH SIGNALING.
RX PubMed=11782316; DOI=10.1016/s1534-5807(01)00109-5;
RA Lopez-Schier H., St Johnston D.;
RT "Drosophila nicastrin is essential for the intramembranous cleavage of
RT notch.";
RL Dev. Cell 2:79-89(2002).
RN [8]
RP FUNCTION IN THE GAMMA-SECRETASE COMPLEX, AND INTERACTION WITH PSN; PEN-2
RP AND APH-1.
RX PubMed=12660785; DOI=10.1038/nature01506;
RA Takasugi N., Tomita T., Hayashi I., Tsuruoka M., Niimura M., Takahashi Y.,
RA Thinakaran G., Iwatsubo T.;
RT "The role of presenilin cofactors in the gamma-secretase complex.";
RL Nature 422:438-441(2003).
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. It probably represents a
CC stabilizing cofactor required for the assembly of the gamma-secretase
CC complex. {ECO:0000269|PubMed:11781576, ECO:0000269|PubMed:11782315,
CC ECO:0000269|PubMed:11782316, ECO:0000269|PubMed:12660785}.
CC -!- SUBUNIT: Component of the gamma-secretase complex, a complex composed
CC of a presenilin (Psn) homodimer, nicastrin (Nct), Aph-1 and Pen-2.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the nicastrin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO25002.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF240470; AAG11414.1; -; mRNA.
DR EMBL; AE014297; AAF56349.2; -; Genomic_DNA.
DR EMBL; BT003245; AAO25002.1; ALT_INIT; mRNA.
DR RefSeq; NP_001163713.1; NM_001170242.2.
DR RefSeq; NP_651297.2; NM_143040.5.
DR AlphaFoldDB; Q9VC27; -.
DR SMR; Q9VC27; -.
DR BioGRID; 67889; 9.
DR DIP; DIP-23689N; -.
DR STRING; 7227.FBpp0291079; -.
DR GlyGen; Q9VC27; 9 sites.
DR PaxDb; Q9VC27; -.
DR PRIDE; Q9VC27; -.
DR DNASU; 42964; -.
DR EnsemblMetazoa; FBtr0084705; FBpp0084083; FBgn0039234.
DR EnsemblMetazoa; FBtr0301865; FBpp0291079; FBgn0039234.
DR GeneID; 42964; -.
DR KEGG; dme:Dmel_CG7012; -.
DR UCSC; CG7012-RA; d. melanogaster.
DR CTD; 42964; -.
DR FlyBase; FBgn0039234; Nct.
DR VEuPathDB; VectorBase:FBgn0039234; -.
DR eggNOG; KOG2657; Eukaryota.
DR GeneTree; ENSGT00390000014633; -.
DR InParanoid; Q9VC27; -.
DR OMA; CMRRNSI; -.
DR OrthoDB; 777987at2759; -.
DR PhylomeDB; Q9VC27; -.
DR Reactome; R-DME-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-DME-6798695; Neutrophil degranulation.
DR SignaLink; Q9VC27; -.
DR BioGRID-ORCS; 42964; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 42964; -.
DR PRO; PR:Q9VC27; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0039234; Expressed in wing disc and 30 other tissues.
DR ExpressionAtlas; Q9VC27; baseline and differential.
DR Genevisible; Q9VC27; DM.
DR GO; GO:0070765; C:gamma-secretase complex; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005770; C:late endosome; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; HDA:FlyBase.
DR GO; GO:0055037; C:recycling endosome; IDA:FlyBase.
DR GO; GO:0034205; P:amyloid-beta formation; IDA:FlyBase.
DR GO; GO:0046331; P:lateral inhibition; IMP:FlyBase.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:FlyBase.
DR GO; GO:0007220; P:Notch receptor processing; IMP:FlyBase.
DR GO; GO:0035333; P:Notch receptor processing, ligand-dependent; IGI:FlyBase.
DR GO; GO:0007219; P:Notch signaling pathway; IMP:FlyBase.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR GO; GO:0045314; P:regulation of compound eye photoreceptor development; IMP:FlyBase.
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 Glycoprotein; Membrane; Notch signaling pathway; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..695
FT /note="Nicastrin"
FT /id="PRO_0000019685"
FT TOPO_DOM 23..654
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 655..675
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 676..695
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 45
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 381
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 461
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 489
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 585
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 609
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 244..257
FT /note="YATLYPRKPAIENN -> SPPCTPESQQSETT (in Ref. 1;
FT AAG11414)"
FT /evidence="ECO:0000305"
FT CONFLICT 448
FT /note="I -> T (in Ref. 1; AAG11414)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 695 AA; 77993 MW; C9D9D0C05CDC772B CRC64;
MEMRLNAASI WLLILSYGAT IAQGERTRDK MYEPIGGASC FRRLNGTHQT GCSSTYSGSV
GVLHLINVEA DLEFLLSSPP SPPYAPMIPP HLFTRNNLMR LKEAGPKNIS VVLLINRTNQ
MKQFSHELNC PNQYSGLNST SETCDASNPA KNWNPWGTGL LHEDFPFPIY YIADLDQVTK
LEKCFQDFNN HNYETHALRS LCAVEVKSFM SAAVNTEVCM RRTNFINNLG GSKYCDPLEG
RNVYATLYPR KPAIENNLET VHTNEKFILV TCRLDTTTMF DGVGLGAMDS LMGFAVFTHV
AYLLKQLLPP QSKDLHNVLF VTFNGESYDY IGSQRFVYDM EKLQFPTEST GTPPIAFDNI
DFMLDIGTLD DISNIKLHAL NGTTLAQQIL ERLNNYAKSP RYGFNLNIQS EMSAHLPPTS
AQSFLRRDPN FNALILNARP TNKYYHSIYD DADNVDFTYA NTSKDFTQLT EVNDFKSLNP
DSLQMKVRNV SSIVAMALYQ TITGKEYTGT KVANPLMADE FLYCFLQSAD CPLFKAASYP
GSQLTNLPPM RYISVLGGSQ ESSGYTYRLL GYLLSQLQPD IHRDNCTDLP LHYFAGFNNI
GECRLTTQNY SHALSPAFLI DGYDWSSGMY STWTESTWSQ FSARIFLRPS NVHQVTTLSV
GIVVLIISFC LVYIISSRSE VLFEDLPASN AALFG
