CHUP1_CAEEL
ID CHUP1_CAEEL Reviewed; 756 AA.
AC Q9GYF0; A7YH04; A7YH06;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Cholesterol uptake protein 1 {ECO:0000303|PubMed:22479487};
DE Flags: Precursor;
GN Name=chup-1 {ECO:0000312|WormBase:ZK721.1};
GN Synonyms=cup-1 {ECO:0000303|PubMed:22479487},
GN tag-130 {ECO:0000312|WormBase:ZK721.1};
GN ORFNames=ZK721.1 {ECO:0000312|WormBase:ZK721.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
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:0000312|EMBL:ABU75284.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 304-504, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18201385; DOI=10.1186/gb-2008-9-1-r10;
RA Tomoyasu Y., Miller S.C., Tomita S., Schoppmeier M., Grossmann D.,
RA Bucher G.;
RT "Exploring systemic RNA interference in insects: a genome-wide survey for
RT RNAi genes in Tribolium.";
RL Genome Biol. 9:R10.1-R10.22(2008).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF TYR-576.
RX PubMed=22479487; DOI=10.1371/journal.pone.0033962;
RA Valdes V.J., Athie A., Salinas L.S., Navarro R.E., Vaca L.;
RT "CUP-1 is a novel protein involved in dietary cholesterol uptake in
RT Caenorhabditis elegans.";
RL PLoS ONE 7:E33962-E33962(2012).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=29025917; DOI=10.1534/g3.117.300308;
RA Whangbo J.S., Weisman A.S., Chae J., Hunter C.P.;
RT "SID-1 Domains Important for dsRNA Import in Caenorhabditis elegans.";
RL G3 (Bethesda) 7:3887-3899(2017).
CC -!- FUNCTION: Cholesterol-binding protein which is involved in dietary
CC cholesterol uptake from the environment (PubMed:22479487). Does not
CC play a role in double-stranded RNA transport in contrast to other SID1
CC family members (PubMed:29025917, PubMed:18201385).
CC {ECO:0000269|PubMed:18201385, ECO:0000269|PubMed:22479487,
CC ECO:0000269|PubMed:29025917}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol(in) = cholesterol(out); Xref=Rhea:RHEA:39747,
CC ChEBI:CHEBI:16113; Evidence={ECO:0000269|PubMed:22479487};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:39749;
CC Evidence={ECO:0000269|PubMed:22479487};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22479487};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed along the intestine with
CC expression also detected in the pharynx, especially at the terminal
CC bulb, and in the excretory gland cells. {ECO:0000269|PubMed:22479487}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the embryo, larva and adult with no
CC difference in expression level across larval stages and adult.
CC {ECO:0000269|PubMed:22479487}.
CC -!- DISRUPTION PHENOTYPE: Hypersensitivity to cholesterol availability and
CC decreased cholesterol uptake (PubMed:22479487). When grown in low
CC cholesterol conditions, 72% reduction in offspring number compared to
CC 25% reduction in wild-type worms, 60% reduction in oocyte number,
CC altered oocyte distribution in 47% of mutants, and 5-fold increase in
CC embryonic lethality (PubMed:22479487). In addition, in low cholesterol
CC conditions, growth of mutants ceases by day 3, resulting in a 63%
CC reduction in adult size at day 5, there is a 22% reduction in the
CC number of L1 larvae that reach adulthood and a 4-5 hour delay in the
CC L4-to-adult transition (PubMed:22479487). 78% reduction in dauer
CC formation, increased sensitivity of adult hermaphrodites to heat
CC exposure and reduced speed of movement independent of cholesterol
CC availability (PubMed:22479487). Mutants show a twitching phenotype upon
CC administration of unc-22 feeding RNAi, indicating a lack of involvement
CC in the systemic RNAi response (PubMed:18201385). RNAi-mediated
CC knockdown results in decreased cholesterol uptake and, when grown in
CC low-cholesterol conditions, altered oocyte distribution in 42% of
CC mutants, reduced oocyte numbers and reduced speed (PubMed:22479487).
CC {ECO:0000269|PubMed:18201385, ECO:0000269|PubMed:22479487}.
CC -!- SIMILARITY: Belongs to the SID1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABU75285.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={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; BX284606; CCD73100.1; -; Genomic_DNA.
DR EMBL; EF695397; ABU75284.1; -; mRNA.
DR EMBL; EF695398; ABU75285.1; ALT_SEQ; mRNA.
DR PIR; T28870; T28870.
DR RefSeq; NP_509489.1; NM_077088.4.
DR AlphaFoldDB; Q9GYF0; -.
DR STRING; 6239.ZK721.1a; -.
DR TCDB; 1.A.79.1.5; the cholesterol uptake protein (chup) or double stranded rna uptake family.
DR EPD; Q9GYF0; -.
DR PaxDb; Q9GYF0; -.
DR EnsemblMetazoa; ZK721.1.1; ZK721.1.1; WBGene00006477.
DR GeneID; 181125; -.
DR KEGG; cel:CELE_ZK721.1; -.
DR CTD; 181125; -.
DR WormBase; ZK721.1; CE26397; WBGene00006477; chup-1.
DR eggNOG; ENOG502QUXZ; Eukaryota.
DR GeneTree; ENSGT00390000010091; -.
DR HOGENOM; CLU_357018_0_0_1; -.
DR InParanoid; Q9GYF0; -.
DR OMA; GLHQTMT; -.
DR OrthoDB; 139174at2759; -.
DR PhylomeDB; Q9GYF0; -.
DR PRO; PR:Q9GYF0; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00006477; Expressed in embryo and 3 other tissues.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:WormBase.
DR GO; GO:0005768; C:endosome; IDA:WormBase.
DR GO; GO:0005794; C:Golgi apparatus; IDA:WormBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005764; C:lysosome; IDA:WormBase.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0015485; F:cholesterol binding; IDA:WormBase.
DR GO; GO:0003725; F:double-stranded RNA binding; IBA:GO_Central.
DR GO; GO:0051033; F:RNA transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0070508; P:cholesterol import; IMP:WormBase.
DR GO; GO:0050658; P:RNA transport; IBA:GO_Central.
DR InterPro; IPR025958; SID1_TM_fam.
DR PANTHER; PTHR12185; PTHR12185; 1.
DR Pfam; PF13965; SID-1_RNA_chan; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Lipid-binding; Membrane; Reference proteome;
KW Signal; Steroid-binding; Transmembrane; Transmembrane helix.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..756
FT /note="Cholesterol uptake protein 1"
FT /evidence="ECO:0000255"
FT /id="PRO_5004326670"
FT TOPO_DOM 19..268
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 269..289
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 290..373
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 374..394
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 395..421
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 422..442
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 443..473
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 474..494
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 495..498
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 499..517
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 518..530
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 531..551
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 552..554
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 555..575
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 576..612
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 613..633
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 634..637
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 638..658
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 659..671
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 672..692
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 693..728
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 729..749
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 750..756
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT MOTIF 124..129
FT /note="Cholesterol-binding sequence motif"
FT /evidence="ECO:0000269|PubMed:22479487"
FT MOTIF 570..578
FT /note="Cholesterol-binding sequence motif"
FT /evidence="ECO:0000269|PubMed:22479487"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 63
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 174
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 257
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 576
FT /note="Y->G: Reduced interaction with cholesterol."
FT /evidence="ECO:0000269|PubMed:22479487"
FT CONFLICT 504
FT /note="D -> G (in Ref. 2; ABU75284)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 756 AA; 87092 MW; 52E9D7BEA145F0CD CRC64;
MRTSQAIFIL IFLDSVRNQS PQVIPAKWDV VYEKETGHNM SLTVFRFQVK EQYSVARIIM
SCNESTEHNP LLAVFREKLA ILSLQVPLIV DNYEYSQVAR TLCPFTEYKE GEAFTVEVTS
SRPVHYNFRA ELVQNFYLYN NSQRLVTASA SEPVYLRYDI PGDVDSVAVH LDSNSTICMT
VSVQKIGCPV FDLPDNVNSM GLHQTMTTSA TIPVEKSRMS SFYVVFVVNT NDDLCSEILS
IKPNKPTKFP LRMKSFNVTI ESSMKIFDYT IPIVFWACIL LLVTIVVFVY HYFDGIWERR
FVSRAYTHLE DNAQEQRIRD FYDFQRMSED DDLKDYDLLT DCQDMMVVRA KASLTVADLS
MTPYEERELK YDVYKIALAI IGIFYNITVL QLIISKAGSL RQSGDLDECT FNFQCARPLW
YFVAFNNVVS NGGYVYFGTL IIVMNYCRER SFRRLFAVQP TLAERYGLPQ HSGLMTAIGL
AVIMEGISSA TYHVCPNNIN YQFDTALMYV IGMLGKLKIW SLRHPDMVVS AYHAFGFLGV
FLMAAIAGVY VHNMIFWALF SIIYIASMLL VSLEFYFKGI WTLNLRELRN SIRLSWVSSR
HLSCVVPAYK ARFFVILLLN IANTAVVVYG LEAHPKDFLS FLLIPFIGNL FIYIIYYILM
KMIYREKIPK RAIALLFAAV ISWTCAGILF NQRVSDWSKM PAISRELNKP CIFLNFYDNH
DLWHLSSAFA IFFSFTAINV IDDDLMFVMR NTIRVF
