ABCG8_HUMAN
ID ABCG8_HUMAN Reviewed; 673 AA.
AC Q9H221; Q53QN8;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=ATP-binding cassette sub-family G member 8 {ECO:0000305};
DE EC=7.6.2.- {ECO:0000250|UniProtKB:Q9DBM0};
DE AltName: Full=Sterolin-2 {ECO:0000303|PubMed:11452359};
GN Name=ABCG8 {ECO:0000312|HGNC:HGNC:13887};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, VARIANTS STSL1 THR-231;
RP GLN-263; ARG-574 AND ARG-596, AND VARIANT CYS-54.
RX PubMed=11099417; DOI=10.1126/science.290.5497.1771;
RA Berge K.E., Tian H., Graf G.A., Yu L., Grishin N.V., Schultz J.,
RA Kwiterovich P., Shan B., Barnes R., Hobbs H.H.;
RT "Accumulation of dietary cholesterol in sitosterolemia caused by mutations
RT in adjacent ABC transporters.";
RL Science 290:1771-1775(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), FUNCTION,
RP TISSUE SPECIFICITY, VARIANTS STSL1 HIS-184; THR-231; LYS-238; GLN-263;
RP HIS-405; PRO-501; SER-543; PHE-570 DEL; PRO-572; ARG-574; GLU-574 AND
RP ARG-596, AND VARIANTS HIS-19; CYS-54; VAL-259; LYS-400; ARG-575 AND
RP ALA-632.
RC TISSUE=Liver;
RX PubMed=11452359; DOI=10.1086/321294;
RA Lu K., Lee M.-H., Hazard S., Brooks-Wilson A., Hidaka H., Kojima H.,
RA Ose L., Stalenhoef A.F.H., Mietinnen T., Bjorkhem I., Bruckert E.,
RA Pandya A., Brewer H.B. Jr., Salen G., Dean M., Srivastava A.K., Patel S.B.;
RT "Two genes that map to the STSL locus cause sitosterolemia: genomic
RT structure and spectrum of mutations involving sterolin-1 and sterolin-2,
RT encoded by ABCG5 and ABCG8, respectively.";
RL Am. J. Hum. Genet. 69:278-290(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP REVIEW.
RX PubMed=11590207;
RA Schmitz G., Langmann T., Heimerl S.;
RT "Role of ABCG1 and other ABCG family members in lipid metabolism.";
RL J. Lipid Res. 42:1513-1520(2001).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=14504269; DOI=10.1074/jbc.m310223200;
RA Graf G.A., Yu L., Li W.P., Gerard R., Tuma P.L., Cohen J.C., Hobbs H.H.;
RT "ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and
RT biliary cholesterol excretion.";
RL J. Biol. Chem. 278:48275-48282(2003).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND GLYCOSYLATION.
RX PubMed=16893193; DOI=10.1021/bi0608055;
RA Wang Z., Stalcup L.D., Harvey B.J., Weber J., Chloupkova M., Dumont M.E.,
RA Dean M., Urbatsch I.L.;
RT "Purification and ATP hydrolysis of the putative cholesterol transporters
RT ABCG5 and ABCG8.";
RL Biochemistry 45:9929-9939(2006).
RN [7]
RP FUNCTION, ACTIVITY REGULATION, SUBUNIT, AND GLYCOSYLATION.
RX PubMed=20210363; DOI=10.1021/bi902064g;
RA Johnson B.J., Lee J.Y., Pickert A., Urbatsch I.L.;
RT "Bile acids stimulate ATP hydrolysis in the purified cholesterol
RT transporter ABCG5/G8.";
RL Biochemistry 49:3403-3411(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9] {ECO:0007744|PDB:5DO7}
RP X-RAY CRYSTALLOGRAPHY (3.93 ANGSTROMS) IN COMPLEX WITH ABCG5, FUNCTION,
RP ACTIVITY REGULATION, MUTAGENESIS OF GLY-216, SUBUNIT, AND TOPOLOGY.
RX PubMed=27144356; DOI=10.1038/nature17666;
RA Lee J.Y., Kinch L.N., Borek D.M., Wang J., Wang J., Urbatsch I.L.,
RA Xie X.S., Grishin N.V., Cohen J.C., Otwinowski Z., Hobbs H.H.,
RA Rosenbaum D.M.;
RT "Crystal structure of the human sterol transporter ABCG5/ABCG8.";
RL Nature 533:561-564(2016).
RN [10]
RP VARIANTS HIS-19; CYS-54; LYS-400; ALA-632 AND PHE-641.
RX PubMed=11668628; DOI=10.1002/humu.1206;
RA Hubacek J.A., Berge K.E., Cohen J.C., Hobbs H.H.;
RT "Mutations in ATP-cassette binding proteins G5 (ABCG5) and G8 (ABCG8)
RT causing sitosterolemia.";
RL Hum. Mutat. 18:359-360(2001).
RN [11]
RP VARIANTS CYS-54 AND LYS-400.
RX PubMed=12111378; DOI=10.1007/s100380200041;
RA Iida A., Saito S., Sekine A., Mishima C., Kitamura Y., Kondo K.,
RA Harigae S., Osawa S., Nakamura Y.;
RT "Catalog of 605 single-nucleotide polymorphisms (SNPs) among 13 genes
RT encoding human ATP-binding cassette transporters: ABCA4, ABCA7, ABCA8,
RT ABCD1, ABCD3, ABCD4, ABCE1, ABCF1, ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8.";
RL J. Hum. Genet. 47:285-310(2002).
RN [12]
RP CHARACTERIZATION OF VARIANTS STSL1 HIS-184; THR-231; GLN-263; PRO-501;
RP SER-543; GLU-574 AND ARG-596, AND FUNCTION.
RX PubMed=15054092; DOI=10.1074/jbc.m402634200;
RA Graf G.A., Cohen J.C., Hobbs H.H.;
RT "Missense mutations in ABCG5 and ABCG8 disrupt heterodimerization and
RT trafficking.";
RL J. Biol. Chem. 279:24881-24888(2004).
RN [13]
RP VARIANT HIS-19, AND INVOLVEMENT IN GBD4.
RX PubMed=17632509; DOI=10.1038/ng2101;
RA Buch S., Schafmayer C., Voelzke H., Becker C., Franke A.,
RA von Eller-Eberstein H., Kluck C., Baessmann I., Brosch M., Lammert F.,
RA Miquel J.F., Nervi F., Wittig M., Rosskopf D., Timm B., Hoell C.,
RA Seeger M., ElSharawy A., Lu T., Egberts J., Faendrich F., Foelsch U.R.,
RA Krawczak M., Schreiber S., Nuernberg P., Tepel J., Hampe J.;
RT "A genome-wide association scan identifies the hepatic cholesterol
RT transporter ABCG8 as a susceptibility factor for human gallstone disease.";
RL Nat. Genet. 39:995-999(2007).
CC -!- FUNCTION: ABCG5 and ABCG8 form an obligate heterodimer that mediates
CC Mg(2+)- and ATP-dependent sterol transport across the cell membrane.
CC Plays an essential role in the selective transport of the dietary
CC cholesterol in and out of the enterocytes and in the selective sterol
CC excretion by the liver into bile (PubMed:11099417, PubMed:11452359,
CC PubMed:27144356, PubMed:15054092). Required for normal sterol
CC homeostasis (PubMed:11099417, PubMed:11452359, PubMed:15054092). The
CC heterodimer with ABCG5 has ATPase activity (PubMed:16893193,
CC PubMed:20210363, PubMed:27144356). {ECO:0000269|PubMed:11099417,
CC ECO:0000269|PubMed:11452359, ECO:0000269|PubMed:15054092,
CC ECO:0000269|PubMed:16893193, ECO:0000269|PubMed:27144356}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + cholesterol(in) + H2O = ADP + cholesterol(out) + H(+) +
CC phosphate; Xref=Rhea:RHEA:39051, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16113, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q9DBM0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39052;
CC Evidence={ECO:0000250|UniProtKB:Q9DBM0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + sitosterol(in) = ADP + H(+) + phosphate +
CC sitosterol(out); Xref=Rhea:RHEA:39103, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:27693, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q9DBM0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39104;
CC Evidence={ECO:0000250|UniProtKB:Q9DBM0};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9DBM0};
CC -!- ACTIVITY REGULATION: The ATPase activity of the heterodimer is
CC stimulated by cholate. Taurocholate, glycocholate,
CC taurochenodeoxycholate, glycochenodeoxycholate and taurodeoxycholate
CC also stimulate ATPase activity, but to a lower degree.
CC Glycodeoxycholate has no significant effect on ATPase activity. ATPase
CC activity is inhibited by vanadate and by berillium fluoride.
CC {ECO:0000269|PubMed:20210363, ECO:0000269|PubMed:27144356}.
CC -!- SUBUNIT: Heterodimer with ABCG8. {ECO:0000269|PubMed:16893193,
CC ECO:0000269|PubMed:20210363, ECO:0000269|PubMed:27144356}.
CC -!- INTERACTION:
CC Q9H221; Q9H222: ABCG5; NbExp=2; IntAct=EBI-3908684, EBI-1761423;
CC Q9H221; Q14696: MESD; NbExp=3; IntAct=EBI-3908684, EBI-6165891;
CC Q9H221-1; Q9H222-1: ABCG5; NbExp=5; IntAct=EBI-16205990, EBI-16205983;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:16893193};
CC Multi-pass membrane protein {ECO:0000269|PubMed:27144356}. Apical cell
CC membrane {ECO:0000269|PubMed:14504269}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:27144356}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H221-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H221-2; Sequence=VSP_000052;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the liver
CC (PubMed:11099417, PubMed:11452359). Low expression levels in the small
CC intestine and colon (PubMed:11099417). Very low levels in other
CC tissues, including brain, heart and spleen (PubMed:11452359).
CC {ECO:0000269|PubMed:11099417, ECO:0000269|PubMed:11452359}.
CC -!- DOMAIN: A functional Walker motif (consensus sequence G-X-X-G-X-G-K-
CC [ST]-T) is expected to bind ATP. The essential Lys in this region is
CC not conserved in ABCG8 (G-S-S-G-C-R-A-S) and is not required for
CC transport activity mediated by the heterodimer with ABCG5.
CC {ECO:0000250|UniProtKB:Q9DBM0}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16893193,
CC ECO:0000269|PubMed:20210363}.
CC -!- DISEASE: Gallbladder disease 4 (GBD4) [MIM:611465]: One of the major
CC digestive diseases. Gallstones composed of cholesterol (cholelithiasis)
CC are the common manifestations in western countries. Most people with
CC gallstones, however, remain asymptomatic through their lifetimes.
CC {ECO:0000269|PubMed:17632509}. Note=Disease susceptibility may be
CC associated with variants affecting the gene represented in this entry.
CC -!- DISEASE: Sitosterolemia 1 (STSL1) [MIM:210250]: A form of
CC sitosterolemia, an autosomal recessive metabolic disorder characterized
CC by unregulated intestinal absorption of cholesterol, phytosterols and
CC shellfish sterols, and decreased biliary excretion of dietary sterols
CC into bile. Patients have hypercholesterolemia, very high levels of
CC plant sterols in the plasma, and frequently develop tendon and tuberous
CC xanthomas, accelerated atherosclerosis and premature coronary artery
CC disease. {ECO:0000269|PubMed:11099417, ECO:0000269|PubMed:11452359,
CC ECO:0000269|PubMed:15054092}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Minor form detected in approximately 10% of
CC the cDNA clones. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCG family.
CC Eye pigment precursor importer (TC 3.A.1.204) subfamily. {ECO:0000305}.
CC -!- CAUTION: Seems to have a defective ATP-binding region. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins;
CC URL="http://abcm2.hegelab.org/search";
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DR EMBL; AF320294; AAG40004.1; -; mRNA.
DR EMBL; AF324494; AAK84078.1; -; mRNA.
DR EMBL; AF351824; AAK84663.1; -; Genomic_DNA.
DR EMBL; AF351812; AAK84663.1; JOINED; Genomic_DNA.
DR EMBL; AF351813; AAK84663.1; JOINED; Genomic_DNA.
DR EMBL; AF351814; AAK84663.1; JOINED; Genomic_DNA.
DR EMBL; AF351815; AAK84663.1; JOINED; Genomic_DNA.
DR EMBL; AF351816; AAK84663.1; JOINED; Genomic_DNA.
DR EMBL; AF351817; AAK84663.1; JOINED; Genomic_DNA.
DR EMBL; AF351818; AAK84663.1; JOINED; Genomic_DNA.
DR EMBL; AF351819; AAK84663.1; JOINED; Genomic_DNA.
DR EMBL; AF351820; AAK84663.1; JOINED; Genomic_DNA.
DR EMBL; AF351821; AAK84663.1; JOINED; Genomic_DNA.
DR EMBL; AF351822; AAK84663.1; JOINED; Genomic_DNA.
DR EMBL; AF351823; AAK84663.1; JOINED; Genomic_DNA.
DR EMBL; AC108476; AAY24011.1; -; Genomic_DNA.
DR CCDS; CCDS1815.1; -. [Q9H221-1]
DR RefSeq; NP_071882.1; NM_022437.2. [Q9H221-1]
DR RefSeq; XP_005264540.1; XM_005264483.3.
DR PDB; 5DO7; X-ray; 3.93 A; B/D=2-673.
DR PDB; 7JR7; EM; 3.30 A; B=1-673.
DR PDB; 7R87; EM; 3.40 A; B=1-673.
DR PDB; 7R88; EM; 3.50 A; B=1-673.
DR PDB; 7R89; EM; 2.60 A; B=1-673.
DR PDB; 7R8A; EM; 2.90 A; B=1-673.
DR PDB; 7R8B; EM; 3.10 A; B=1-673.
DR PDBsum; 5DO7; -.
DR PDBsum; 7JR7; -.
DR PDBsum; 7R87; -.
DR PDBsum; 7R88; -.
DR PDBsum; 7R89; -.
DR PDBsum; 7R8A; -.
DR PDBsum; 7R8B; -.
DR AlphaFoldDB; Q9H221; -.
DR SMR; Q9H221; -.
DR BioGRID; 122125; 16.
DR CORUM; Q9H221; -.
DR DIP; DIP-42631N; -.
DR IntAct; Q9H221; 14.
DR MINT; Q9H221; -.
DR STRING; 9606.ENSP00000272286; -.
DR DrugBank; DB11635; Tocofersolan.
DR TCDB; 3.A.1.204.5; the atp-binding cassette (abc) superfamily.
DR GlyGen; Q9H221; 1 site.
DR iPTMnet; Q9H221; -.
DR PhosphoSitePlus; Q9H221; -.
DR BioMuta; ABCG8; -.
DR DMDM; 17432916; -.
DR MassIVE; Q9H221; -.
DR PaxDb; Q9H221; -.
DR PeptideAtlas; Q9H221; -.
DR PRIDE; Q9H221; -.
DR ProteomicsDB; 80473; -. [Q9H221-1]
DR ProteomicsDB; 80474; -. [Q9H221-2]
DR Antibodypedia; 14910; 323 antibodies from 26 providers.
DR DNASU; 64241; -.
DR Ensembl; ENST00000272286.4; ENSP00000272286.2; ENSG00000143921.9. [Q9H221-1]
DR GeneID; 64241; -.
DR KEGG; hsa:64241; -.
DR MANE-Select; ENST00000272286.4; ENSP00000272286.2; NM_022437.3; NP_071882.1.
DR UCSC; uc002rtq.3; human. [Q9H221-1]
DR CTD; 64241; -.
DR DisGeNET; 64241; -.
DR GeneCards; ABCG8; -.
DR GeneReviews; ABCG8; -.
DR HGNC; HGNC:13887; ABCG8.
DR HPA; ENSG00000143921; Group enriched (intestine, liver).
DR MalaCards; ABCG8; -.
DR MIM; 210250; phenotype.
DR MIM; 605460; gene.
DR MIM; 611465; phenotype.
DR neXtProt; NX_Q9H221; -.
DR OpenTargets; ENSG00000143921; -.
DR Orphanet; 391665; Homozygous familial hypercholesterolemia.
DR Orphanet; 2882; Sitosterolemia.
DR PharmGKB; PA24412; -.
DR VEuPathDB; HostDB:ENSG00000143921; -.
DR eggNOG; KOG0061; Eukaryota.
DR GeneTree; ENSGT00940000159739; -.
DR HOGENOM; CLU_000604_57_9_1; -.
DR InParanoid; Q9H221; -.
DR OMA; RDTDDHM; -.
DR OrthoDB; 1022017at2759; -.
DR PhylomeDB; Q9H221; -.
DR TreeFam; TF105212; -.
DR PathwayCommons; Q9H221; -.
DR Reactome; R-HSA-1369062; ABC transporters in lipid homeostasis.
DR Reactome; R-HSA-5679090; Defective ABCG8 causes GBD4 and sitosterolemia.
DR Reactome; R-HSA-5679096; Defective ABCG5 causes sitosterolemia.
DR Reactome; R-HSA-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR SignaLink; Q9H221; -.
DR SIGNOR; Q9H221; -.
DR BioGRID-ORCS; 64241; 12 hits in 1059 CRISPR screens.
DR GeneWiki; ABCG8; -.
DR GenomeRNAi; 64241; -.
DR Pharos; Q9H221; Tbio.
DR PRO; PR:Q9H221; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9H221; protein.
DR Bgee; ENSG00000143921; Expressed in right lobe of liver and 49 other tissues.
DR ExpressionAtlas; Q9H221; baseline and differential.
DR Genevisible; Q9H221; HS.
DR GO; GO:0016324; C:apical plasma membrane; IMP:BHF-UCL.
DR GO; GO:0043190; C:ATP-binding cassette (ABC) transporter complex; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; IDA:BHF-UCL.
DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0120020; F:cholesterol transfer activity; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL.
DR GO; GO:0038183; P:bile acid signaling pathway; IEA:Ensembl.
DR GO; GO:0033344; P:cholesterol efflux; IMP:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB.
DR GO; GO:0030299; P:intestinal cholesterol absorption; IC:BHF-UCL.
DR GO; GO:0045796; P:negative regulation of intestinal cholesterol absorption; IMP:BHF-UCL.
DR GO; GO:0010949; P:negative regulation of intestinal phytosterol absorption; IMP:BHF-UCL.
DR GO; GO:0015914; P:phospholipid transport; IEA:Ensembl.
DR GO; GO:0014850; P:response to muscle activity; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0015918; P:sterol transport; ISS:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:0070328; P:triglyceride homeostasis; IEA:Ensembl.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR013525; ABC_2_trans.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR043926; ABCG_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF01061; ABC2_membrane; 1.
DR Pfam; PF19055; ABC2_membrane_7; 1.
DR Pfam; PF00005; ABC_tran; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disease variant;
KW Glycoprotein; Lipid transport; Magnesium; Membrane; Metal-binding;
KW Reference proteome; Translocase; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..673
FT /note="ATP-binding cassette sub-family G member 8"
FT /id="PRO_0000093396"
FT TOPO_DOM 1..416
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27144356"
FT TRANSMEM 417..437
FT /note="Helical; Name=1"
FT /evidence="ECO:0000269|PubMed:27144356"
FT TOPO_DOM 438..447
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27144356"
FT TRANSMEM 448..468
FT /note="Helical; Name=2"
FT /evidence="ECO:0000269|PubMed:27144356"
FT TOPO_DOM 469..497
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27144356"
FT TRANSMEM 498..518
FT /note="Helical; Name=3"
FT /evidence="ECO:0000269|PubMed:27144356"
FT TOPO_DOM 519..527
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27144356"
FT TRANSMEM 528..548
FT /note="Helical; Name=4"
FT /evidence="ECO:0000269|PubMed:27144356"
FT TOPO_DOM 549..555
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27144356"
FT TRANSMEM 556..576
FT /note="Helical; Name=5"
FT /evidence="ECO:0000269|PubMed:27144356"
FT TOPO_DOM 577..639
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27144356"
FT TRANSMEM 640..660
FT /note="Helical; Name=6"
FT /evidence="ECO:0000269|PubMed:27144356"
FT TOPO_DOM 661..673
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27144356"
FT DOMAIN 47..313
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 411..665
FT /note="ABC transmembrane type-2"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 619
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 376
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11452359"
FT /id="VSP_000052"
FT VARIANT 19
FT /note="D -> H (associated significantly with GBD4;
FT dbSNP:rs11887534)"
FT /evidence="ECO:0000269|PubMed:11452359,
FT ECO:0000269|PubMed:11668628, ECO:0000269|PubMed:17632509"
FT /id="VAR_012250"
FT VARIANT 54
FT /note="Y -> C (in dbSNP:rs4148211)"
FT /evidence="ECO:0000269|PubMed:11099417,
FT ECO:0000269|PubMed:11452359, ECO:0000269|PubMed:11668628,
FT ECO:0000269|PubMed:12111378"
FT /id="VAR_012251"
FT VARIANT 184
FT /note="R -> H (in STSL1; strongly decreased maturation of
FT glycan chains; dbSNP:rs766212636)"
FT /evidence="ECO:0000269|PubMed:11452359,
FT ECO:0000269|PubMed:15054092"
FT /id="VAR_012252"
FT VARIANT 210
FT /note="V -> M (in dbSNP:rs9282574)"
FT /id="VAR_022074"
FT VARIANT 231
FT /note="P -> T (in STSL1; strongly decreased maturation of
FT glycan chains; dbSNP:rs137852993)"
FT /evidence="ECO:0000269|PubMed:11099417,
FT ECO:0000269|PubMed:11452359, ECO:0000269|PubMed:15054092"
FT /id="VAR_012253"
FT VARIANT 238
FT /note="E -> K (in STSL1; unknown pathological significance;
FT dbSNP:rs34754243)"
FT /evidence="ECO:0000269|PubMed:11452359"
FT /id="VAR_012254"
FT VARIANT 259
FT /note="A -> V (in dbSNP:rs35518570)"
FT /evidence="ECO:0000269|PubMed:11452359"
FT /id="VAR_012255"
FT VARIANT 263
FT /note="R -> Q (in STSL1; strongly decreased maturation of
FT glycan chains; dbSNP:rs137852990)"
FT /evidence="ECO:0000269|PubMed:11099417,
FT ECO:0000269|PubMed:11452359, ECO:0000269|PubMed:15054092"
FT /id="VAR_012256"
FT VARIANT 400
FT /note="T -> K (in dbSNP:rs4148217)"
FT /evidence="ECO:0000269|PubMed:11452359,
FT ECO:0000269|PubMed:11668628, ECO:0000269|PubMed:12111378"
FT /id="VAR_012257"
FT VARIANT 405
FT /note="R -> H (in STSL1; dbSNP:rs1177309800)"
FT /evidence="ECO:0000269|PubMed:11452359"
FT /id="VAR_012258"
FT VARIANT 501
FT /note="L -> P (in STSL1; strongly decreased maturation of
FT glycan chains; dbSNP:rs1233989408)"
FT /evidence="ECO:0000269|PubMed:11452359,
FT ECO:0000269|PubMed:15054092"
FT /id="VAR_012259"
FT VARIANT 543
FT /note="R -> S (in STSL1; decreased maturation of glycan
FT chains; dbSNP:rs201690654)"
FT /evidence="ECO:0000269|PubMed:11452359,
FT ECO:0000269|PubMed:15054092"
FT /id="VAR_012260"
FT VARIANT 570
FT /note="Missing (in STSL1)"
FT /evidence="ECO:0000269|PubMed:11452359"
FT /id="VAR_012261"
FT VARIANT 572
FT /note="L -> P (in STSL1; dbSNP:rs769576789)"
FT /evidence="ECO:0000269|PubMed:11452359"
FT /id="VAR_012262"
FT VARIANT 574
FT /note="G -> E (in STSL1; strongly decreased maturation of
FT glycan chains; dbSNP:rs1325979386)"
FT /evidence="ECO:0000269|PubMed:11452359,
FT ECO:0000269|PubMed:15054092"
FT /id="VAR_012263"
FT VARIANT 574
FT /note="G -> R (in STSL1; decreased maturation of glycan
FT chains; dbSNP:rs137852988)"
FT /evidence="ECO:0000269|PubMed:11099417,
FT ECO:0000269|PubMed:11452359, ECO:0000269|PubMed:15054092"
FT /id="VAR_012264"
FT VARIANT 575
FT /note="G -> R"
FT /evidence="ECO:0000269|PubMed:11452359"
FT /id="VAR_012265"
FT VARIANT 596
FT /note="L -> R (in STSL1; strongly decreased maturation of
FT glycan chains; dbSNP:rs137852992)"
FT /evidence="ECO:0000269|PubMed:11099417,
FT ECO:0000269|PubMed:11452359, ECO:0000269|PubMed:15054092"
FT /id="VAR_012266"
FT VARIANT 632
FT /note="V -> A (in dbSNP:rs6544718)"
FT /evidence="ECO:0000269|PubMed:11452359,
FT ECO:0000269|PubMed:11668628"
FT /id="VAR_012267"
FT VARIANT 641
FT /note="Y -> F (in dbSNP:rs145125968)"
FT /evidence="ECO:0000269|PubMed:11668628"
FT /id="VAR_020785"
FT VARIANT 655
FT /note="M -> V (in dbSNP:rs9282573)"
FT /id="VAR_022075"
FT MUTAGEN 216
FT /note="G->D: Loss of ATPase activity."
FT /evidence="ECO:0000269|PubMed:27144356"
FT STRAND 46..55
FT /evidence="ECO:0007829|PDB:7R89"
FT STRAND 88..96
FT /evidence="ECO:0007829|PDB:7R89"
FT STRAND 100..106
FT /evidence="ECO:0007829|PDB:7R89"
FT STRAND 110..112
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 114..119
FT /evidence="ECO:0007829|PDB:7R89"
FT STRAND 130..134
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 141..147
FT /evidence="ECO:0007829|PDB:7R89"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 163..174
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 181..194
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 198..200
FT /evidence="ECO:0007829|PDB:7R8B"
FT STRAND 201..204
FT /evidence="ECO:0007829|PDB:7R87"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:7JR7"
FT HELIX 215..227
FT /evidence="ECO:0007829|PDB:7R89"
FT STRAND 232..238
FT /evidence="ECO:0007829|PDB:7R89"
FT TURN 239..242
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 245..259
FT /evidence="ECO:0007829|PDB:7R89"
FT STRAND 264..268
FT /evidence="ECO:0007829|PDB:7R89"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:7R89"
FT STRAND 281..287
FT /evidence="ECO:0007829|PDB:7R89"
FT STRAND 290..297
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 300..305
FT /evidence="ECO:0007829|PDB:7R89"
FT TURN 306..308
FT /evidence="ECO:0007829|PDB:7R89"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:7R8B"
FT HELIX 317..323
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 333..352
FT /evidence="ECO:0007829|PDB:7R8B"
FT TURN 353..355
FT /evidence="ECO:0007829|PDB:7JR7"
FT HELIX 357..359
FT /evidence="ECO:0007829|PDB:7JR7"
FT HELIX 395..410
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 414..434
FT /evidence="ECO:0007829|PDB:7R89"
FT STRAND 438..441
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 445..458
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 460..472
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 475..484
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 491..516
FT /evidence="ECO:0007829|PDB:7R89"
FT TURN 517..520
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 526..552
FT /evidence="ECO:0007829|PDB:7R89"
FT STRAND 553..555
FT /evidence="ECO:0007829|PDB:7R8B"
FT HELIX 556..572
FT /evidence="ECO:0007829|PDB:7R89"
FT TURN 575..577
FT /evidence="ECO:0007829|PDB:7R89"
FT TURN 579..581
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 586..592
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 595..608
FT /evidence="ECO:0007829|PDB:7R89"
FT HELIX 628..632
FT /evidence="ECO:0007829|PDB:7R89"
FT STRAND 636..638
FT /evidence="ECO:0007829|PDB:7JR7"
FT HELIX 640..664
FT /evidence="ECO:0007829|PDB:7R89"
SQ SEQUENCE 673 AA; 75679 MW; 594AFD1D6C1BB50F CRC64;
MAGKAAEERG LPKGATPQDT SGLQDRLFSS ESDNSLYFTY SGQPNTLEVR DLNYQVDLAS
QVPWFEQLAQ FKMPWTSPSC QNSCELGIQN LSFKVRSGQM LAIIGSSGCG RASLLDVITG
RGHGGKIKSG QIWINGQPSS PQLVRKCVAH VRQHNQLLPN LTVRETLAFI AQMRLPRTFS
QAQRDKRVED VIAELRLRQC ADTRVGNMYV RGLSGGERRR VSIGVQLLWN PGILILDEPT
SGLDSFTAHN LVKTLSRLAK GNRLVLISLH QPRSDIFRLF DLVLLMTSGT PIYLGAAQHM
VQYFTAIGYP CPRYSNPADF YVDLTSIDRR SREQELATRE KAQSLAALFL EKVRDLDDFL
WKAETKDLDE DTCVESSVTP LDTNCLPSPT KMPGAVQQFT TLIRRQISND FRDLPTLLIH
GAEACLMSMT IGFLYFGHGS IQLSFMDTAA LLFMIGALIP FNVILDVISK CYSERAMLYY
ELEDGLYTTG PYFFAKILGE LPEHCAYIII YGMPTYWLAN LRPGLQPFLL HFLLVWLVVF
CCRIMALAAA ALLPTFHMAS FFSNALYNSF YLAGGFMINL SSLWTVPAWI SKVSFLRWCF
EGLMKIQFSR RTYKMPLGNL TIAVSGDKIL SVMELDSYPL YAIYLIVIGL SGGFMVLYYV
SLRFIKQKPS QDW
