NPC2_DROME
ID NPC2_DROME Reviewed; 148 AA.
AC Q9VQ62;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=NPC intracellular cholesterol transporter 2 homolog a {ECO:0000305};
DE AltName: Full=Niemann Pick type C2 protein homolog;
DE Flags: Precursor;
GN Name=Npc2a {ECO:0000312|FlyBase:FBgn0031381}; Synonyms=NPC2;
GN ORFNames=CG7291;
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 [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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=17804599; DOI=10.1242/dev.004572;
RA Huang X., Warren J.T., Buchanan J., Gilbert L.I., Scott M.P.;
RT "Drosophila Niemann-Pick type C-2 genes control sterol homeostasis and
RT steroid biosynthesis: a model of human neurodegenerative disease.";
RL Development 134:3733-3742(2007).
CC -!- FUNCTION: Functions redundantly with Npc2b in regulating sterol
CC homeostasis and ecdysteroid biosynthesis, probably by controlling the
CC availability of sterol substrate. {ECO:0000269|PubMed:17804599}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Broadly expressed with a higher level of expression
CC in many tissues, including midgut, salivary gland and ventral nerve
CC cord. {ECO:0000269|PubMed:17804599}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC {ECO:0000269|PubMed:17804599}.
CC -!- DISRUPTION PHENOTYPE: Abnormal sterol distribution in many cells, also
CC lower than normal ecdysteroid levels. Npc2a and Npc2b double mutants
CC undergo apoptotic neurodegeneration. {ECO:0000269|PubMed:17804599}.
CC -!- SIMILARITY: Belongs to the NPC2 family. {ECO:0000305}.
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DR EMBL; AE014134; AAF51319.1; -; Genomic_DNA.
DR EMBL; AY118810; AAM50670.1; -; mRNA.
DR EMBL; BT001844; AAN71605.1; -; mRNA.
DR RefSeq; NP_608637.1; NM_134793.5.
DR AlphaFoldDB; Q9VQ62; -.
DR SMR; Q9VQ62; -.
DR BioGRID; 59609; 3.
DR DIP; DIP-23438N; -.
DR IntAct; Q9VQ62; 1.
DR STRING; 7227.FBpp0077492; -.
DR GlyGen; Q9VQ62; 1 site.
DR PaxDb; Q9VQ62; -.
DR PRIDE; Q9VQ62; -.
DR DNASU; 33374; -.
DR EnsemblMetazoa; FBtr0077816; FBpp0077492; FBgn0031381.
DR GeneID; 33374; -.
DR KEGG; dme:Dmel_CG7291; -.
DR CTD; 33374; -.
DR FlyBase; FBgn0031381; Npc2a.
DR VEuPathDB; VectorBase:FBgn0031381; -.
DR eggNOG; KOG4063; Eukaryota.
DR GeneTree; ENSGT00390000006223; -.
DR HOGENOM; CLU_109192_1_0_1; -.
DR InParanoid; Q9VQ62; -.
DR OMA; NLFCWEI; -.
DR OrthoDB; 1612792at2759; -.
DR PhylomeDB; Q9VQ62; -.
DR Reactome; R-DME-6798695; Neutrophil degranulation.
DR Reactome; R-DME-8964038; LDL clearance.
DR BioGRID-ORCS; 33374; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 33374; -.
DR PRO; PR:Q9VQ62; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0031381; Expressed in embryonic/larval hemocyte (Drosophila) and 31 other tissues.
DR Genevisible; Q9VQ62; DM.
DR GO; GO:0005615; C:extracellular space; IDA:FlyBase.
DR GO; GO:0015485; F:cholesterol binding; ISS:FlyBase.
DR GO; GO:0120020; F:cholesterol transfer activity; ISS:FlyBase.
DR GO; GO:0030882; F:lipid antigen binding; IDA:FlyBase.
DR GO; GO:0001530; F:lipopolysaccharide binding; IDA:FlyBase.
DR GO; GO:0070891; F:lipoteichoic acid binding; IDA:FlyBase.
DR GO; GO:0042834; F:peptidoglycan binding; IDA:FlyBase.
DR GO; GO:0032934; F:sterol binding; ISS:FlyBase.
DR GO; GO:0045456; P:ecdysteroid biosynthetic process; IGI:FlyBase.
DR GO; GO:0032367; P:intracellular cholesterol transport; ISS:FlyBase.
DR GO; GO:1900426; P:positive regulation of defense response to bacterium; IEP:FlyBase.
DR GO; GO:0055092; P:sterol homeostasis; IMP:FlyBase.
DR GO; GO:0015918; P:sterol transport; IMP:FlyBase.
DR GO; GO:0008039; P:synaptic target recognition; IMP:FlyBase.
DR CDD; cd00916; Npc2_like; 1.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR003172; ML_dom.
DR InterPro; IPR033916; ML_Npc2-like.
DR InterPro; IPR039670; NPC2-like.
DR PANTHER; PTHR11306; PTHR11306; 1.
DR Pfam; PF02221; E1_DerP2_DerF2; 1.
DR SMART; SM00737; ML; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
PE 2: Evidence at transcript level;
KW Disulfide bond; Glycoprotein; Lipid biosynthesis; Lipid metabolism;
KW Reference proteome; Secreted; Signal; Steroid biosynthesis.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..148
FT /note="NPC intracellular cholesterol transporter 2 homolog
FT a"
FT /id="PRO_0000019866"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 24..140
FT /evidence="ECO:0000250"
FT DISULFID 39..46
FT /evidence="ECO:0000250"
FT DISULFID 92..99
FT /evidence="ECO:0000250"
SQ SEQUENCE 148 AA; 16021 MW; 5AE2D4BC2AE03D49 CRC64;
MLRYAVIACA ALVVFAGALE FSDCGSKTGK FTRVAIEGCD TTKAECILKR NTTVSFSIDF
ALAEEATAVK TVVHGKVLGI EMPFPLANPD ACVDSGLKCP LEKDESYRYT ATLPVLRSYP
KVSVLVKWEL QDQDGADIIC VEIPAKIQ
