NPC1B_CAEEL
ID NPC1B_CAEEL Reviewed; 1274 AA.
AC P34389; Q8MYQ6;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 24-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=NPC intracellular cholesterol transporter 1 homolog 2 {ECO:0000305};
DE AltName: Full=Niemann-Pick C1 protein homolog 2 {ECO:0000305};
DE Flags: Precursor;
GN Name=ncr-2 {ECO:0000312|WormBase:F09G8.4}; Synonyms=npc-2;
GN ORFNames=F09G8.4;
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=7906398; DOI=10.1038/368032a0;
RA Wilson R., Ainscough R., Anderson K., Baynes C., Berks M., Bonfield J.,
RA Burton J., Connell M., Copsey T., Cooper J., Coulson A., Craxton M.,
RA Dear S., Du Z., Durbin R., Favello A., Fraser A., Fulton L., Gardner A.,
RA Green P., Hawkins T., Hillier L., Jier M., Johnston L., Jones M.,
RA Kershaw J., Kirsten J., Laisster N., Latreille P., Lightning J., Lloyd C.,
RA Mortimore B., O'Callaghan M., Parsons J., Percy C., Rifken L., Roopra A.,
RA Saunders D., Shownkeen R., Sims M., Smaldon N., Smith A., Smith M.,
RA Sonnhammer E., Staden R., Sulston J., Thierry-Mieg J., Thomas K.,
RA Vaudin M., Vaughan K., Waterston R., Watson A., Weinstock L.,
RA Wilkinson-Sproat J., Wohldman P.;
RT "2.2 Mb of contiguous nucleotide sequence from chromosome III of C.
RT elegans.";
RL Nature 368:32-38(1994).
RN [2]
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 [3]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=10801441; DOI=10.1016/s0960-9822(00)00468-1;
RA Sym M., Basson M., Johnson C.;
RT "A model for Niemann-Pick type C disease in the nematode Caenorhabditis
RT elegans.";
RL Curr. Biol. 10:527-530(2000).
CC -!- FUNCTION: Involved in the uptake or utilization of cholesterol (By
CC similarity). Ncr-1 and ncr-2 act redundantly to prevent dauer larva
CC formation under favorable growth conditions, and are required for the
CC normal functioning of ADF, ASI and ASG neurons (PubMed:10801441).
CC {ECO:0000250|UniProtKB:O15118, ECO:0000269|PubMed:10801441}.
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: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Both ncr-1 single mutant and ncr-1 and ncr-2
CC double mutants exhibit slow embryonic and larval development, and
CC hyperactive egg-laying behavior (egg-laying constitutive (egl-c)
CC phenotype). Ncr-1 and ncr-2 double mutants inappropriately and
CC transiently form dauer larvae under favorable conditions (dauer-
CC constitutive (daf-c) phenotype). {ECO:0000269|PubMed:10801441}.
CC -!- SIMILARITY: Belongs to the patched family. {ECO:0000305}.
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DR EMBL; FO080289; CCD62644.1; -; Genomic_DNA.
DR PIR; S44797; S44797.
DR RefSeq; NP_498813.1; NM_066412.3.
DR AlphaFoldDB; P34389; -.
DR SMR; P34389; -.
DR BioGRID; 41369; 1.
DR STRING; 6239.F09G8.4; -.
DR TCDB; 2.A.6.6.9; the resistance-nodulation-cell division (rnd) superfamily.
DR PaxDb; P34389; -.
DR EnsemblMetazoa; F09G8.4.1; F09G8.4.1; WBGene00003562.
DR GeneID; 176165; -.
DR KEGG; cel:CELE_F09G8.4; -.
DR UCSC; F09G8.4; c. elegans.
DR CTD; 176165; -.
DR WormBase; F09G8.4; CE24891; WBGene00003562; ncr-2.
DR eggNOG; KOG1933; Eukaryota.
DR GeneTree; ENSGT00940000156182; -.
DR HOGENOM; CLU_002359_0_0_1; -.
DR InParanoid; P34389; -.
DR OMA; NIFIMVH; -.
DR OrthoDB; 731120at2759; -.
DR PhylomeDB; P34389; -.
DR Reactome; R-CEL-8963678; Intestinal lipid absorption.
DR Reactome; R-CEL-8964038; LDL clearance.
DR PRO; PR:P34389; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00003562; Expressed in adult organism and 1 other tissue.
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:0042632; P:cholesterol homeostasis; IGI:WormBase.
DR GO; GO:0030301; P:cholesterol transport; IGI:WormBase.
DR GO; GO:0040024; P:dauer larval development; IGI:WormBase.
DR GO; GO:0030299; P:intestinal cholesterol absorption; IBA:GO_Central.
DR GO; GO:0015918; P:sterol transport; IBA:GO_Central.
DR GO; GO:0040025; P:vulval development; IGI:WormBase.
DR InterPro; IPR032190; NPC1_N.
DR InterPro; IPR003392; Ptc/Disp.
DR InterPro; IPR000731; SSD.
DR Pfam; PF16414; NPC1_N; 1.
DR Pfam; PF02460; Patched; 1.
DR PROSITE; PS50156; SSD; 1.
PE 3: Inferred from homology;
KW Developmental protein; Disulfide bond; Glycoprotein; Lipid transport;
KW Membrane; Reference proteome; Signal; Transmembrane; Transmembrane helix;
KW Transport.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..1274
FT /note="NPC intracellular cholesterol transporter 1 homolog
FT 2"
FT /id="PRO_0000023265"
FT TRANSMEM 268..288
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 327..347
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 588..608
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 630..650
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 656..676
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 722..742
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 745..765
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 824..844
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1079..1101
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1106..1128
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1138..1160
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1172..1194
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1204..1226
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 586..767
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REGION 1245..1274
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1255..1274
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 419
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 426
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 518
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 566
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 690
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 787
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 959
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1010
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1030
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..86
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 34..45
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 73..121
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 87..125
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 109..235
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 112..164
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 224..240
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 435..445
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 485..500
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 897..902
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 946..997
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 947..966
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 955..963
FT /evidence="ECO:0000250|UniProtKB:O15118"
SQ SEQUENCE 1274 AA; 142634 MW; 798A9A3C36D3A9BD CRC64;
MRQGGGGGER MVSVLFLLLI HLALCQAKCV MTECDGEEDS NHPPCKTNKS TYLPITVTRS
LNPTYMARFE KYCSYLVQEE DKAQVCCTEL QLKGMTDRIS NAATILGSCP SCFDNFAKLW
CQFTCSPDQS KFMKVMETTG PKNVVVKMEF KVNRDFVEGL YESCRHTWFA NGLALRLMSL
GGKVSFENFY GFMGTKNLAQ SIPINTEFQF SRMKNAMNIP TTPCHKSAGP KVPACGAIDC
PTNAHQLVDI SKVEHLGTKV FHPHFPDFEW LLKICGCLAL TVLLVFILKY SCHRRSAPNG
EDGCYVDLGK GNLEVQFEGL CARYANAVIK HPLIFVSLGL IVAAACCSGN FKFHSLTHSV
DQVSAADGET RRNEKKFIHS FGPNHRIEQI FINLPPTTKS MFNMPLFEEM FQLVGNIQNL
TACYGNSSVK LDDICYKPIG KNHGCAIMSP TNYFQNKWTN FENAGPPTID DEIFDDQHWE
HLKYCIRNPL TVSTYSEMSC FGEFSGPIDP ILVFGGSNES IKGAEMYYTA RTIMITVLIR
GPEDQAIAWE TAFLNMMSRY EMKHANFTFM TETSVAEEIH TAVETDKIVS VIACAAVLIW
VITMLGINHW PESSILSALV HHKLLISISA VMISVISVWC SIGMFSLFGV HATDNAIVVL
FFVITCLGIN RIFVIIRTFQ ANGHCYGLPN ISYREMNHRI SNVMRRSIPI VLTNSLICST
CLFLAGGVLP YVSVSMPAVE VFARHAGLAI LMDTAFYLLV MLPLFQYDAR REMSGKCEIW
PWYELSNESK INLCMEAVDG NLRSPVDWFK LAIAPLLLKK ICRIWIATFF FVSLIIACYC
TLCLEFGFNQ VMAFSETSYL TKHFQNMNEN LNIGPPLWFV VEGDVKWHDP KMQNKFCTLA
GCDDNSMGNK IRSLAYAENY KGNYLHGDVN IWLDSYLQFM HPRGSCCKMD GKQFCDPSNA
THCSSCSSSS VASLTTTEYE FYRNLHHFLE TPPSIQCAHG GMALAKPAIN LTRNGKIQSA
YFSTFFKKLN LSDSIQLYDA WRFAKYLADD IERELEIPGV KVYVYSTFFP YYEQYLTLST
TVYTLVVLVL FVAFVTISLF LRVNLAGSLV TVFVLLSSYL HLMEWMYLLG ITVNVVSVIN
MAMSLGIAVE FFGQMLHGFY NSKKPKREER AFAALVSNGS TTLSGIFPAI MITAGCLSFA
DSRVLITYFC NQLVGIGLVC AVHGVVYMPT LLAIFGSDFY QNVSSEEEST DEAELQDTPP
STTSSTSSTS ETSV
