ABCG8_MOUSE
ID ABCG8_MOUSE Reviewed; 673 AA.
AC Q9DBM0; Q8R543;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=ATP-binding cassette sub-family G member 8 {ECO:0000305};
DE EC=7.6.2.- {ECO:0000269|PubMed:16867993};
DE AltName: Full=Sterolin-2 {ECO:0000303|PubMed:11452359, ECO:0000303|PubMed:11907139};
GN Name=Abcg8 {ECO:0000312|MGI:MGI:1914720};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; 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 [2] {ECO:0000312|EMBL:AAL82898.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING,
RP AND TISSUE SPECIFICITY.
RC STRAIN=129/Sv {ECO:0000312|EMBL:AAL82898.1};
RX PubMed=11907139;
RA Lu K., Lee M.H., Yu H., Zhou Y., Sandell S.A., Salen G., Patel S.B.;
RT "Molecular cloning, genomic organization, genetic variations, and
RT characterization of murine sterolin genes Abcg5 and Abcg8.";
RL J. Lipid Res. 43:565-578(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP TISSUE SPECIFICITY, AND INDUCTION.
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 [5]
RP SUBUNIT, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=12208867; DOI=10.1172/jci16000;
RA Graf G.A., Li W.P., Gerard R.D., Gelissen I., White A., Cohen J.C.,
RA Hobbs H.H.;
RT "Coexpression of ATP-binding cassette proteins ABCG5 and ABCG8 permits
RT their transport to the apical surface.";
RL J. Clin. Invest. 110:659-669(2002).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX PubMed=12444248; DOI=10.1073/pnas.252582399;
RA Yu L., Hammer R.E., Li-Hawkins J., Von Bergmann K., Lutjohann D.,
RA Cohen J.C., Hobbs H.H.;
RT "Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in
RT biliary cholesterol secretion.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16237-16242(2002).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
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 [8]
RP DOWN-REGULATION BY ENDOTOXIN.
RX PubMed=12777468; DOI=10.1194/jlr.m300100-jlr200;
RA Khovidhunkit W., Moser A.H., Shigenaga J.K., Grunfeld C., Feingold K.R.;
RT "Endotoxin down-regulates ABCG5 and ABCG8 in mouse liver and ABCA1 and
RT ABCG1 in J774 murine macrophages: differential role of LXR.";
RL J. Lipid Res. 44:1728-1736(2003).
RN [9]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=15040800; DOI=10.1186/1741-7015-2-5;
RA Klett E.L., Lu K., Kosters A., Vink E., Lee M.H., Altenburg M., Shefer S.,
RA Batta A.K., Yu H., Chen J., Klein R., Looije N., Oude-Elferink R.,
RA Groen A.K., Maeda N., Salen G., Patel S.B.;
RT "A mouse model of sitosterolemia: absence of Abcg8/sterolin-2 results in
RT failure to secrete biliary cholesterol.";
RL BMC Med. 2:5-5(2004).
RN [10]
RP SUBUNIT, GLYCOSYLATION AT ASN-619, AND MUTAGENESIS OF ASN-619.
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 [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14657202; DOI=10.1194/jlr.m300377-jlr200;
RA Yu L., von Bergmann K., Lutjohann D., Hobbs H.H., Cohen J.C.;
RT "Selective sterol accumulation in ABCG5/ABCG8-deficient mice.";
RL J. Lipid Res. 45:301-307(2004).
RN [12]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-112; VAL-214;
RP GLY-216; GLY-217 AND GLU-239, AND DOMAIN.
RX PubMed=16352607; DOI=10.1074/jbc.m512277200;
RA Zhang D.W., Graf G.A., Gerard R.D., Cohen J.C., Hobbs H.H.;
RT "Functional asymmetry of nucleotide-binding domains in ABCG5 and ABCG8.";
RL J. Biol. Chem. 281:4507-4516(2006).
RN [13]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF
RP ARG-112 AND GLY-217, ACTIVITY REGULATION, COFACTOR, AND CATALYTIC ACTIVITY.
RX PubMed=16867993; DOI=10.1074/jbc.m605603200;
RA Wang J., Sun F., Zhang D.W., Ma Y., Xu F., Belani J.D., Cohen J.C.,
RA Hobbs H.H., Xie X.S.;
RT "Sterol transfer by ABCG5 and ABCG8: in vitro assay and reconstitution.";
RL J. Biol. Chem. 281:27894-27904(2006).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, TISSUE SPECIFICITY, GLYCOSYLATION,
RP AND MUTAGENESIS OF 664-LEU--TRP-673.
RX PubMed=18402465; DOI=10.1021/bi800292v;
RA Wang J., Zhang D.W., Lei Y., Xu F., Cohen J.C., Hobbs H.H., Xie X.S.;
RT "Purification and reconstitution of sterol transfer by native mouse ABCG5
RT and ABCG8.";
RL Biochemistry 47:5194-5204(2008).
RN [15]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=25378657; DOI=10.1194/jlr.m054544;
RA Wang J., Mitsche M.A., Luetjohann D., Cohen J.C., Xie X.S., Hobbs H.H.;
RT "Relative roles of ABCG5/ABCG8 in liver and intestine.";
RL J. Lipid Res. 56:319-330(2015).
CC -!- FUNCTION: ABCG5 and ABCG8 form an obligate heterodimer that mediates
CC Mg(2+)- and ATP-dependent sterol transport across the cell membrane
CC (PubMed:16352607, PubMed:16867993, PubMed:18402465). Plays an essential
CC role in the selective transport of the dietary cholesterol in and out
CC of the enterocytes and in the selective sterol excretion by the liver
CC into bile (PubMed:12444248, PubMed:14504269, PubMed:14657202,
CC PubMed:25378657). Plays an important role in preventing the
CC accumulation of dietary plant sterols in the body (PubMed:12444248,
CC PubMed:14657202). Required for normal sterol homeostasis
CC (PubMed:12444248, PubMed:14657202). The heterodimer with ABCG5 has
CC ATPase activity (PubMed:16352607, PubMed:16867993).
CC {ECO:0000269|PubMed:12444248, ECO:0000269|PubMed:14504269,
CC ECO:0000269|PubMed:14657202, ECO:0000269|PubMed:16352607,
CC ECO:0000269|PubMed:16867993, ECO:0000269|PubMed:18402465,
CC ECO:0000269|PubMed:25378657}.
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:0000269|PubMed:16867993};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39052;
CC Evidence={ECO:0000269|PubMed:16867993};
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:0000269|PubMed:16867993};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39104;
CC Evidence={ECO:0000269|PubMed:16867993};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:16867993};
CC -!- ACTIVITY REGULATION: Cholesterol transport is inhibited by vanadate and
CC by beryllium fluoride. {ECO:0000269|PubMed:16867993}.
CC -!- SUBUNIT: Heterodimer with ABCG5. {ECO:0000269|PubMed:12208867,
CC ECO:0000269|PubMed:14504269, ECO:0000269|PubMed:15054092,
CC ECO:0000269|PubMed:16352607, ECO:0000269|PubMed:16867993,
CC ECO:0000269|PubMed:18402465}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12208867,
CC ECO:0000269|PubMed:18402465, ECO:0000305|PubMed:16352607}; Multi-pass
CC membrane protein {ECO:0000305}. Apical cell membrane
CC {ECO:0000269|PubMed:12208867, ECO:0000269|PubMed:14504269,
CC ECO:0000269|PubMed:16867993, ECO:0000269|PubMed:18402465}; Multi-pass
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9DBM0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9DBM0-2; Sequence=VSP_000053;
CC -!- TISSUE SPECIFICITY: Detected in liver and jejunum (at protein level)
CC (PubMed:12444248, PubMed:18402465, PubMed:25378657). Expressed in
CC jejunum and ileum and, at lower level, in the liver (PubMed:11907139,
CC PubMed:11099417, PubMed:12444248, PubMed:15040800, PubMed:25378657).
CC {ECO:0000269|PubMed:11099417, ECO:0000269|PubMed:11907139,
CC ECO:0000269|PubMed:12444248, ECO:0000269|PubMed:15040800,
CC ECO:0000269|PubMed:18402465, ECO:0000269|PubMed:25378657}.
CC -!- INDUCTION: Up-regulated in liver and small intestine by cholesterol
CC feeding (PubMed:11099417). Possibly mediated by the liver X
CC receptor/retinoic X receptor (LXR/RXR) pathway. Endotoxin (LPS)
CC significantly decreased mRNA levels in the liver but not in the small
CC intestine (PubMed:12777468). {ECO:0000269|PubMed:11099417,
CC ECO:0000269|PubMed:12777468}.
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:0000269|PubMed:16352607}.
CC -!- PTM: N-glycosylated (PubMed:12208867, PubMed:12444248, PubMed:16867993,
CC PubMed:15054092, PubMed:18402465). N-glycosylation is important for
CC efficient export out of the endoplasmic reticulum (PubMed:15054092).
CC {ECO:0000269|PubMed:12208867, ECO:0000269|PubMed:12444248,
CC ECO:0000269|PubMed:15054092, ECO:0000269|PubMed:16867993,
CC ECO:0000269|PubMed:18402465}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate.
CC They display decreased cholesterol levels, but strongly increased
CC levels of the food-derived plant sterols campesterol and beta-
CC sitosterol in blood plasma, liver and spleen (PubMed:25378657).
CC Besides, mutant mice may have slightly increased total plasma
CC triglyceride levels. Expression of Abcg5 is not affected. Mutant mice
CC display decreased biliary sterol secretion (PubMed:15040800). Mice
CC deficient for both Abcg5 and Abcg8 appear healthy and are fertile, but
CC display strongly increased levels of the food-derived plant sterols
CC sitosterol and campesterol in liver and blood plasma (PubMed:12444248,
CC PubMed:14657202, PubMed:25378657). When mice are fed chow containing
CC 0.02% cholesterol, cholesterol levels in blood plasma and in liver are
CC considerably lower than in wild-type (PubMed:12444248,
CC PubMed:14657202). In spite of the increased plasma and liver levels of
CC plant sterols, and the decreased cholesterol levels, the total sterol
CC levels in plasma and liver are closely similar in wild-type and mutant
CC mice (PubMed:14657202). When mice are fed chow containing 2%
CC cholesterol, plasma cholesterol levels remain stable in wild-type, but
CC increase 2.4-fold in mutant mice. In the liver of mice kept on chow
CC containing 2% cholesterol, cholesterol levels increase 3-fold for wild-
CC type mice and 18-fold for mutant mice, resulting in much higher
CC cholesterol levels than in wild-type livers (PubMed:12444248). Dietary
CC cholesterol absorption appears normal in mutant mice, but the
CC absorption of dietary cholestanol, campesterol and sitosterol is
CC increased (PubMed:12444248). At the same time, mutant mice have very
CC low cholesterol levels in bile, suggesting that the increased hepatic
CC cholesterol levels are due to impaired cholesterol secretion into bile
CC (PubMed:12444248). Likewise, the levels of the food-derived plant
CC sterols stigmasterol, sitosterol, campesterol and brassicasterol are
CC strongly decreased in bile from mutant mice (PubMed:14657202). In
CC contrast, biliary phospholipid and bile acid levels appear unchanged
CC relative to wild-type (PubMed:12444248). The blood plasma of mice with
CC liver-specific or intestine-specific disruption of Abcg5 and Abcg8 has
CC nearly normal levels of cholesterol, and mildly increased levels of
CC sitosterol and campesterol (PubMed:25378657). Mice with intestine-
CC specific disruption of Abcg5 and Abcg8 have strongly increased levels
CC of sitosterol and campesterol in enterocytes, similar to that observed
CC for mice with complete gene disruption (PubMed:25378657). In addition,
CC they display strongly increased levels of sitosterol and campesterol in
CC bile (PubMed:25378657). Mice with liver-specific disruption of Abcg5
CC and Abcg8 have slightly increased levels of campesterol and sitosterol
CC in the liver, and normal, low levels of sitosterol and campesterol in
CC bile (PubMed:25378657). Enterocytes and liver from mice with liver-
CC specific or intestine-specific disruption of Abcg5 and Abcg8 have
CC normal cholesterol levels (PubMed:25378657).
CC {ECO:0000269|PubMed:12444248, ECO:0000269|PubMed:14657202,
CC ECO:0000269|PubMed:15040800, ECO:0000269|PubMed:25378657}.
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}.
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DR EMBL; AH011518; AAL82898.1; -; Genomic_DNA.
DR EMBL; AF351799; AAL82898.1; JOINED; Genomic_DNA.
DR EMBL; AF351800; AAL82898.1; JOINED; Genomic_DNA.
DR EMBL; AF351801; AAL82898.1; JOINED; Genomic_DNA.
DR EMBL; AF351802; AAL82898.1; JOINED; Genomic_DNA.
DR EMBL; AF351803; AAL82898.1; JOINED; Genomic_DNA.
DR EMBL; AF351804; AAL82898.1; JOINED; Genomic_DNA.
DR EMBL; AF351807; AAL82898.1; JOINED; Genomic_DNA.
DR EMBL; AF351808; AAL82898.1; JOINED; Genomic_DNA.
DR EMBL; AF351809; AAL82898.1; JOINED; Genomic_DNA.
DR EMBL; AF351810; AAL82898.1; JOINED; Genomic_DNA.
DR EMBL; AF324495; AAK84079.1; -; mRNA.
DR EMBL; AK004871; BAB23630.1; -; mRNA.
DR CCDS; CCDS29002.1; -. [Q9DBM0-1]
DR RefSeq; NP_001272934.1; NM_001286005.1.
DR RefSeq; NP_001334347.1; NM_001347418.1.
DR RefSeq; NP_080456.1; NM_026180.3. [Q9DBM0-1]
DR AlphaFoldDB; Q9DBM0; -.
DR SMR; Q9DBM0; -.
DR CORUM; Q9DBM0; -.
DR STRING; 10090.ENSMUSP00000035246; -.
DR GlyGen; Q9DBM0; 1 site.
DR iPTMnet; Q9DBM0; -.
DR PhosphoSitePlus; Q9DBM0; -.
DR SwissPalm; Q9DBM0; -.
DR jPOST; Q9DBM0; -.
DR MaxQB; Q9DBM0; -.
DR PaxDb; Q9DBM0; -.
DR PRIDE; Q9DBM0; -.
DR ProteomicsDB; 285821; -. [Q9DBM0-1]
DR ProteomicsDB; 285822; -. [Q9DBM0-2]
DR Antibodypedia; 14910; 323 antibodies from 26 providers.
DR DNASU; 67470; -.
DR Ensembl; ENSMUST00000045714; ENSMUSP00000035246; ENSMUSG00000024254. [Q9DBM0-1]
DR GeneID; 67470; -.
DR KEGG; mmu:67470; -.
DR UCSC; uc008dta.2; mouse. [Q9DBM0-1]
DR CTD; 64241; -.
DR MGI; MGI:1914720; Abcg8.
DR VEuPathDB; HostDB:ENSMUSG00000024254; -.
DR eggNOG; KOG0061; Eukaryota.
DR GeneTree; ENSGT00940000159739; -.
DR InParanoid; Q9DBM0; -.
DR OMA; RDTDDHM; -.
DR OrthoDB; 1022017at2759; -.
DR PhylomeDB; Q9DBM0; -.
DR TreeFam; TF105212; -.
DR Reactome; R-MMU-1369062; ABC transporters in lipid homeostasis.
DR BioGRID-ORCS; 67470; 3 hits in 72 CRISPR screens.
DR PRO; PR:Q9DBM0; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9DBM0; protein.
DR Bgee; ENSMUSG00000024254; Expressed in small intestine Peyer's patch and 21 other tissues.
DR ExpressionAtlas; Q9DBM0; baseline and differential.
DR Genevisible; Q9DBM0; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0043190; C:ATP-binding cassette (ABC) transporter complex; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA: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; ISO:MGI.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISO:MGI.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; ISO:MGI.
DR GO; GO:0120020; F:cholesterol transfer activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0038183; P:bile acid signaling pathway; IEA:Ensembl.
DR GO; GO:0033344; P:cholesterol efflux; IMP:BHF-UCL.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:MGI.
DR GO; GO:0030299; P:intestinal cholesterol absorption; IC:BHF-UCL.
DR GO; GO:0045796; P:negative regulation of intestinal cholesterol absorption; ISO:MGI.
DR GO; GO:0010949; P:negative regulation of intestinal phytosterol absorption; ISO:MGI.
DR GO; GO:0015914; P:phospholipid transport; IMP:MGI.
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:0055092; P:sterol homeostasis; IMP:MGI.
DR GO; GO:0015918; P:sterol transport; IDA: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 Alternative splicing; Cell membrane; Glycoprotein; Lipid transport;
KW Magnesium; Membrane; Metal-binding; Reference proteome; Translocase;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..673
FT /note="ATP-binding cassette sub-family G member 8"
FT /id="PRO_0000093397"
FT TOPO_DOM 1..416
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TRANSMEM 417..437
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TOPO_DOM 438..447
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TRANSMEM 448..468
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TOPO_DOM 469..497
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TRANSMEM 498..518
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TOPO_DOM 519..527
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TRANSMEM 528..548
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TOPO_DOM 549..555
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TRANSMEM 556..576
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TOPO_DOM 577..639
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TRANSMEM 640..660
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TOPO_DOM 661..673
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT DOMAIN 48..314
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 411..665
FT /note="ABC transmembrane type-2"
FT CARBOHYD 619
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15054092"
FT VAR_SEQ 377
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11452359,
FT ECO:0000303|PubMed:11907139"
FT /id="VSP_000053"
FT MUTAGEN 112
FT /note="R->K,M: No effect on ATP-binding and on expression
FT of both ABCG5 and ABCG8. No effect on sterol transport."
FT /evidence="ECO:0000269|PubMed:16352607"
FT MUTAGEN 214
FT /note="V->I: No effect on sterol transport; when associated
FT with S-216."
FT /evidence="ECO:0000269|PubMed:16352607"
FT MUTAGEN 216
FT /note="G->S: No effect on sterol transport; when associated
FT with I-214."
FT /evidence="ECO:0000269|PubMed:16352607"
FT MUTAGEN 217
FT /note="G->D: Abolishes cholesterol transport activity, and
FT nearly abolishes plant sterol transport."
FT /evidence="ECO:0000269|PubMed:16352607,
FT ECO:0000269|PubMed:16867993"
FT MUTAGEN 239
FT /note="E->D: No effect on sterol transport."
FT /evidence="ECO:0000269|PubMed:16352607"
FT MUTAGEN 239
FT /note="E->Q: Mildly decreases cholesterol transport. No
FT effect on plant sterol transport."
FT /evidence="ECO:0000269|PubMed:16352607"
FT MUTAGEN 619
FT /note="N->A,Q: Abolishes N-glycosylation."
FT /evidence="ECO:0000269|PubMed:15054092"
FT MUTAGEN 664..673
FT /note="Missing: Abolishes expression at the apical cell
FT membrane. Strongly decreases cholesterol secretion into
FT bile."
FT /evidence="ECO:0000269|PubMed:18402465"
FT CONFLICT 544
FT /note="T -> N (in Ref. 2; AAL82898)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 673 AA; 75996 MW; 78012611A5DF2589 CRC64;
MAEKTKEETQ LWNGTVLQDA SQGLQDSLFS SESDNSLYFT YSGQSNTLEV RDLTYQVDIA
SQVPWFEQLA QFKIPWRSHS SQDSCELGIR NLSFKVRSGQ MLAIIGSSGC GRASLLDVIT
GRGHGGKMKS GQIWINGQPS TPQLVRKCVA HVRQHDQLLP NLTVRETLAF IAQMRLPRTF
SQAQRDKRVE DVIAELRLRQ CANTRVGNTY VRGVSGGERR RVSIGVQLLW NPGILILDEP
TSGLDSFTAH NLVTTLSRLA KGNRLVLISL HQPRSDIFRL FDLVLLMTSG TPIYLGAAQQ
MVQYFTSIGH PCPRYSNPAD FYVDLTSIDR RSKEREVATV EKAQSLAALF LEKVQGFDDF
LWKAEAKELN TSTHTVSLTL TQDTDCGTAV ELPGMIEQFS TLIRRQISND FRDLPTLLIH
GSEACLMSLI IGFLYYGHGA KQLSFMDTAA LLFMIGALIP FNVILDVVSK CHSERSMLYY
ELEDGLYTAG PYFFAKILGE LPEHCAYVII YAMPIYWLTN LRPVPELFLL HFLLVWLVVF
CCRTMALAAS AMLPTFHMSS FFCNALYNSF YLTAGFMINL DNLWIVPAWI SKLSFLRWCF
SGLMQIQFNG HLYTTQIGNF TFSILGDTMI SAMDLNSHPL YAIYLIVIGI SYGFLFLYYL
SLKLIKQKSI QDW
