NPC1A_CAEEL
ID NPC1A_CAEEL Reviewed; 1383 AA.
AC Q19127;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=NPC intracellular cholesterol transporter 1 homolog 1 {ECO:0000305};
DE AltName: Full=Niemann-Pick C1 protein homolog 1 {ECO:0000305};
DE Flags: Precursor;
GN Name=ncr-1 {ECO:0000312|WormBase:F02E8.6}; Synonyms=npc-1;
GN ORFNames=F02E8.6;
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=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 [2] {ECO:0000305}
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).
RN [3] {ECO:0000305}
RP IDENTIFICATION.
RX PubMed=9211850; DOI=10.1126/science.277.5323.232;
RA Loftus S.K., Morris J.A., Carstea E.D., Gu J.Z., Cummings C., Brown A.,
RA Ellison J., Ohno K., Rosenfeld M.A., Tagle D.A., Pentchev P.G., Pavan W.J.;
RT "Murine model of Niemann-Pick C disease: mutation in a cholesterol
RT homeostasis gene.";
RL Science 277:232-235(1997).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-231, AND IDENTIFICATION BY MASS
RP 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: 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; Multi-pass membrane protein.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; FO081068; CCD83387.1; -; Genomic_DNA.
DR PIR; T15961; T15961.
DR RefSeq; NP_508771.1; NM_076370.3.
DR AlphaFoldDB; Q19127; -.
DR SMR; Q19127; -.
DR BioGRID; 45654; 3.
DR STRING; 6239.F02E8.6; -.
DR TCDB; 2.A.6.6.8; the resistance-nodulation-cell division (rnd) superfamily.
DR iPTMnet; Q19127; -.
DR PaxDb; Q19127; -.
DR EnsemblMetazoa; F02E8.6.1; F02E8.6.1; WBGene00003561.
DR EnsemblMetazoa; F02E8.6.2; F02E8.6.2; WBGene00003561.
DR GeneID; 180719; -.
DR KEGG; cel:CELE_F02E8.6; -.
DR UCSC; F02E8.6; c. elegans.
DR CTD; 180719; -.
DR WormBase; F02E8.6; CE29251; WBGene00003561; ncr-1.
DR eggNOG; KOG1933; Eukaryota.
DR HOGENOM; CLU_002359_0_0_1; -.
DR InParanoid; Q19127; -.
DR OMA; VSLHCQN; -.
DR OrthoDB; 731120at2759; -.
DR PhylomeDB; Q19127; -.
DR Reactome; R-CEL-8963678; Intestinal lipid absorption.
DR PRO; PR:Q19127; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00003561; Expressed in larva and 3 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005770; C:late endosome; ISS:WormBase.
DR GO; GO:0005764; C:lysosome; ISS:WormBase.
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; IMP:WormBase.
DR GO; GO:0030301; P:cholesterol transport; IMP: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:0040010; P:positive regulation of growth rate; IMP:WormBase.
DR GO; GO:0046662; P:regulation of oviposition; IMP:WormBase.
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; 1.
DR PROSITE; PS50156; SSD; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Disulfide bond; Glycoprotein; Lipid transport;
KW Membrane; Reference proteome; Signal; Transmembrane; Transmembrane helix;
KW Transport.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..1383
FT /note="NPC intracellular cholesterol transporter 1 homolog
FT 1"
FT /id="PRO_0000023264"
FT TRANSMEM 282..302
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 353..373
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 627..647
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 665..685
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 697..717
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 746..766
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 780..800
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 856..876
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1126..1146
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1157..1177
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1179..1199
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1226..1246
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1260..1280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 627..800
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199,
FT ECO:0000305"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 231
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17761667"
FT CARBOHYD 447
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 558
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 993
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1082
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 22..76
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 28..39
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 65..111
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 77..115
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 99..246
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 102..167
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 182..187
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 235..251
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 464..474
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 526..541
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 929..934
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 976..1046
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 977..1005
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 988..1002
FT /evidence="ECO:0000250|UniProtKB:O15118"
SQ SEQUENCE 1383 AA; 155457 MW; A1392ED28CF9D24C CRC64;
MKQLLIFCLL FGSIFHHGDA GCIMRGLCQK HTENAYGPCV TNDTNVEPTA FDKTHPAYEK
MVEFCPHLLT GDNKLCCTPS QAEGLTKQIA QARHILGRCP SCFDNFAKLW CEFTCSPNQQ
DFVSISEMKP IEKKEGFTPE YQPAEAYVNT VEYRLSTDFA EGMFSSCKDV TFGGQPALRV
MCTSTPCTLT NWLEFIGTQN LDLNIPIHTK FLLYDPIKTP PSDRSTYMNV NFTGCDKSAR
VGWPACSTSE CNKEEYANLI DLDDGKTSGQ TCNVHGIACL NIFVMLAFIG SLAVLLCVGF
VFTSYDEDYT NLRQTQSGEE SPKRNRIKRT GAWIHNFMEN NARDIGMMAG RNPKSHFFIG
CAVLIFCLPG MIYHKESTNV VDMWSSPRSR ARQEEMVFNA NFGRPQRYQQ IMLLSHRDFQ
SSGKLYGPVF HKDIFEELFD ILNAIKNIST QDSDGRTITL DDVCYRPMGP GYDCLIMSPT
NYFQGNKEHL DMKSNKEETV SEDDDAFDYF SSEATTDEWM NHMAACIDQP MSQKTKSGLS
CMGTYGGPSA PNMVFGKNST NHQAANSIMM TILVTQRTEP EIQKAELWEK EFLKFCKEYR
EKSPKVIFSF MAERSITDEI ENDAKDEIVT VVIALAFLIG YVTFSLGRYF VCENQLWSIL
VHSRICLGML SVIINLLSSF CSWGIFSMFG IHPVKNALVV QFFVVTLLGV CRTFMVVKYY
AQQRVSMPYM SPDQCPEIVG MVMAGTMPAM FSSSLGCAFS FFIGGFTDLP AIRTFCLYAG
LAVLIDVVLH CTIFLALFVW DTQRELNGKP EFFFPYQIKD LLGAYLIGRQ RATDTFMTQF
FHFQVAPFLM HRMTRIITGI IFIASFITTV ILSSKISVGF DQSMAFTEKS YISTHFRYLD
KFFDVGPPVF FTVDGELDWH RPDVQNKFCT FPGCSDTSFG NIMNYAVGHT EQTYLSGEMY
NWIDNYLEWI SRKSPCCKVY VHDPNTFCST NRNKSALDDK ACRTCMDFDY VANSYPKSSI
MYHRPSIEVF YRHLRHFLED TPNSECVFGG RASFKDAISF TSRGRIQASQ FMTFHKKLSI
SNSSDFIKAM DTARMVSRRL ERSIDDTAHV FAYSKIFPFY EQYSTIMPIL TTQLFITVVG
VFGIICVTLG IDVKGAACAV ICQVSNYFHI VAFMYIFNIP VNALSATNLV MSSGILIEFS
VNVLKGYACS LRQRAKDRAE STVGSIGPII LSGPVVTMAG STMFLSGAHL QIITVYFFKL
FLITIVSSAV HALIILPILL AFGGSRGHGS SETSTNDNDE QHDACVLSPT AESHISNVEE
GILNRPSLLD ASHILDPLLK AEGGIDKAID IITIDRSYPS TPSSLPCTSR MPRAHIEPDL
RSL
