NPC1B_DROME
ID NPC1B_DROME Reviewed; 1254 AA.
AC Q9VRC9;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=NPC intracellular cholesterol transporter 1 homolog 1b {ECO:0000305};
DE AltName: Full=Niemann-Pick type protein homolog 1b {ECO:0000305};
DE Flags: Precursor;
GN Name=Npc1b {ECO:0000312|FlyBase:FBgn0261675};
GN ORFNames=CG12092 {ECO:0000312|FlyBase:FBgn0261675};
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 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=17339027; DOI=10.1016/j.cmet.2007.01.011;
RA Voght S.P., Fluegel M.L., Andrews L.A., Pallanck L.J.;
RT "Drosophila NPC1b promotes an early step in sterol absorption from the
RT midgut epithelium.";
RL Cell Metab. 5:195-205(2007).
CC -!- FUNCTION: Important for cholesterol absorption at the midgut
CC epithelium. Acts only in the early steps of sterol absorption, prior to
CC Npc1a-dependent intracellular sterol trafficking.
CC {ECO:0000269|PubMed:17339027}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol(in) = cholesterol(out); Xref=Rhea:RHEA:39747,
CC ChEBI:CHEBI:16113; Evidence={ECO:0000250|UniProtKB:O15118};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:17339027};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in the midgut.
CC {ECO:0000269|PubMed:17339027}.
CC -!- DEVELOPMENTAL STAGE: Expressed specifically in the midgut epithelium.
CC In third-instar larvae, expressed in the epithelium of two distinct
CC areas of the midgut; the m2 and m10-m12 compartments. Levels decrease
CC during pupation, and then increase in the adult midgut 2 days after
CC eclosion. {ECO:0000269|PubMed:17339027}.
CC -!- DISRUPTION PHENOTYPE: Larval lethal at the second instar stage. In
CC larvae dietary cholesterol absorption is impaired. In the larval midgut
CC there is a severe reduction in cholesterol and failure to accumulate
CC cholesterol-rich trafficking organelles. No effect on total cholesterol
CC content, possibly due to maternal contributions. Glucose absorption in
CC the midgut is not affected. {ECO:0000269|PubMed:17339027}.
CC -!- SIMILARITY: Belongs to the patched family. {ECO:0000305}.
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DR EMBL; AE014298; AAF50873.2; -; Genomic_DNA.
DR RefSeq; NP_608417.2; NM_134573.3.
DR AlphaFoldDB; Q9VRC9; -.
DR SMR; Q9VRC9; -.
DR IntAct; Q9VRC9; 1.
DR STRING; 7227.FBpp0076932; -.
DR GlyGen; Q9VRC9; 6 sites.
DR PaxDb; Q9VRC9; -.
DR PRIDE; Q9VRC9; -.
DR EnsemblMetazoa; FBtr0077239; FBpp0076932; FBgn0261675.
DR GeneID; 33072; -.
DR KEGG; dme:Dmel_CG12092; -.
DR UCSC; CG12092-RA; d. melanogaster.
DR CTD; 33072; -.
DR FlyBase; FBgn0261675; Npc1b.
DR VEuPathDB; VectorBase:FBgn0261675; -.
DR eggNOG; KOG1933; Eukaryota.
DR HOGENOM; CLU_002359_0_0_1; -.
DR InParanoid; Q9VRC9; -.
DR OMA; NIFIMVH; -.
DR OrthoDB; 731120at2759; -.
DR PhylomeDB; Q9VRC9; -.
DR Reactome; R-DME-8963678; Intestinal lipid absorption.
DR BioGRID-ORCS; 33072; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 33072; -.
DR PRO; PR:Q9VRC9; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0261675; Expressed in midgut and 12 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0015485; F:cholesterol binding; IBA:GO_Central.
DR GO; GO:0032934; F:sterol binding; IBA:GO_Central.
DR GO; GO:0007417; P:central nervous system development; IMP:FlyBase.
DR GO; GO:0042632; P:cholesterol homeostasis; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0007391; P:dorsal closure; IMP:FlyBase.
DR GO; GO:0030299; P:intestinal cholesterol absorption; IMP:FlyBase.
DR GO; GO:0007422; P:peripheral nervous system development; IMP:FlyBase.
DR GO; GO:0015918; P:sterol transport; IBA:GO_Central.
DR InterPro; IPR032190; NPC1_N.
DR InterPro; IPR003392; Ptc/Disp.
DR InterPro; IPR000731; SSD.
DR Pfam; PF16414; NPC1_N; 1.
DR Pfam; PF02460; Patched; 2.
DR PROSITE; PS50156; SSD; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cholesterol metabolism; Disulfide bond; Glycoprotein;
KW Lipid metabolism; Lipid transport; Membrane; Reference proteome; Signal;
KW Steroid metabolism; Sterol metabolism; Transmembrane; Transmembrane helix;
KW Transport.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..1254
FT /note="NPC intracellular cholesterol transporter 1 homolog
FT 1b"
FT /id="PRO_5004338412"
FT TOPO_DOM 17..272
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 273..293
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 294..325
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 326..346
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 347..593
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 594..614
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 615..625
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 626..646
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 647..657
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 658..678
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 679..736
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 737..757
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 758..815
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 816..836
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 837..857
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 858..878
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 879..1079
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1080..1100
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1101..1105
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1106..1126
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1127..1132
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1133..1153
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1154..1174
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1175..1195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1196..1207
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1208..1228
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1229..1254
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 592..757
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 132
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 479
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 896
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 939
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 24..81
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 62..116
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 82..120
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 104..241
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 107..161
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 178..186
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 231..246
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 243..250
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 438..454
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 491..500
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 889..894
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 935..990
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 936..958
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 946..955
FT /evidence="ECO:0000250|UniProtKB:O15118"
SQ SEQUENCE 1254 AA; 139556 MW; 01A76C1B1184F249 CRC64;
MKVIFATIWL IAGAWSQSAE QLGCIWYGQS HMIGAHWVNK GDTNPARPLN SPTSEAIFAK
RCPMLYKEYK GESGEDELSL CCDAAQIETM ESGLSQADGV FSRCPTCTRN MALTVCAMTC
AKNHTLFLTA YNDTNDAGVD YVKYIDYRLT DDTVSKIYNS CIGIQHTQTG RPAMDLGCGS
YNAKTCNYRR WYEFMGDVSG DYVPFQINYK WSEDAEEGSN EIYLDLSPLK CGESYEDSYA
CACIDCEESC PLTDAPTGPD ELWKIAGLYG VTFILALIIA CALSFFIFWG AFGKTSAPSV
CMPTLFGEFF YHGFRIWGTF CAKHPVIVLA LCSWAIAGLS FGIRYMTITT DPVELWAGEE
SQTRIEKDYF DQHFGPFYRT NQMFVKAVNQ TYFTHETSNG VLNFGPAFEY NFLKEVFELQ
DSIMKLGMAD NEGLDKICYA PVLMAGETPT VDRCAIQSVY GYFQHDMDRF ENSYVDSNNY
TINYLNQLED CLRVPMMEDC FGTFGGPIEP GIAVGGMPKV AVGEDPDYML ATGLVLTFLG
RNYNDESKLE PNMKWEKLFV DFLRDYKSDR LDIAYMAERS IQDAIVELSE GEVSTVVISY
VVMFVYVAIA LGHIRSCRGF LRESRIMLAI GGIVIVLASV VCSLGFWGYL DVTTTMLAIE
VIPFLVLAVG VDNIFIMVHT YQRLDHSKFK TTHEAIGEAI GQVGPSILQT AGSEMACFAI
GCISDMPAVK TFAMYAAIAI LLDFLLQITA FVALMAIDEK RYLDGRLDML CCVKSGGKKI
NDEDGDGVDR PKEVGLLETL FKNFYSPFLL SKPVKVSVLL IFTVITCLSL MVTPSIEKGL
DQEMSMPKNS HVVKYFRYMV DLLAMGAPVY WVLKPGLNYS EPLQQNLICG GVECNNNSLS
VQLYTQAQYP EITSLARPAS SWLDDYIDWL AISDCCKYNV TTGGFCSSNS KSEDCLPCER
GFTENGLRPD AETFNKYIPY FLFDLPDAEC AKAGRASYAD AVIYTIDDVG MSTVQDSYFM
QYSTTSTTSE EFYSQLREVR RISGEINAMF KENNVDAEIF AYCVFYIYYE QYLTIWGDAM
FSLGMSLVAI FLVTLLITGL DITSTFIVLF MVICILINML GMMWAWSINL NAISLVNLVV
CVGIGVEFVA HIVRSFKRAE GTAQERARHS LNVTGSSVLS GITLTKFAGI VVLGFSNSQI
FQVFYFRMYL GIVLIGAAHG LILLPVLLSL LGPPQKLARS SGAEPTASIT ITTN
