ID ABCG5_HUMAN Reviewed; 651 AA. AC Q9H222; Q2T9G2; Q96QZ2; Q96QZ3; DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 24-JAN-2024, entry version 197. DE RecName: Full=ATP-binding cassette sub-family G member 5 {ECO:0000305}; DE EC=7.6.2.- {ECO:0000250|UniProtKB:Q99PE8}; DE AltName: Full=Sterolin-1 {ECO:0000303|PubMed:11452359}; GN Name=ABCG5 {ECO:0000312|HGNC:HGNC:13886}; 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), VARIANT GLU-604, FUNCTION, AND RP TISSUE SPECIFICITY. RC TISSUE=Liver; 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 [MRNA] (ISOFORM 1), VARIANTS STSL2 HIS-389; HIS-419 AND RP PRO-419, VARIANT GLU-604, FUNCTION, AND TISSUE SPECIFICITY. RC TISSUE=Liver; RX PubMed=11138003; DOI=10.1038/83799; RA Lee M.-H., Lu K., Hazard S., Yu H., Shulenin S., Hidaka H., Kojima H., RA Allikmets R., Sakuma N., Pegoraro R., Srivastava A.K., Salen G., Dean M., RA Patel S.B.; RT "Identification of a gene, ABCG5, important in the regulation of dietary RT cholesterol absorption."; RL Nat. Genet. 27:79-83(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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-88 (ISOFORM 1), VARIANTS STSL2 GLN-146; RP HIS-389; PRO-419; HIS-419 AND SER-550, AND VARIANT GLU-604. 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 [7] 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 [8] 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 [9] RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION. 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 [10] RP FUNCTION, SUBUNIT, GLYCOSYLATION, ACTIVITY REGULATION, AND MUTAGENESIS OF RP 92-LYS-THR-93. 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 [11] {ECO:0007744|PDB:5DO7} RP X-RAY CRYSTALLOGRAPHY (3.93 ANGSTROMS) IN COMPLEX WITH ABCG8, FUNCTION, RP ACTIVITY REGULATION, MUTAGENESIS OF TYR-432 AND ALA-540, SUBUNIT, AND RP 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 [12] RP VARIANT STSL2 LYS-437, AND VARIANTS VAL-523; TYR-600; GLU-604 AND VAL-622. 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 [13] RP CHARACTERIZATION OF VARIANTS STSL2 GLN-146; HIS-389; PRO-419; HIS-419 AND RP LYS-437, 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 [14] RP VARIANT STSL2 ARG-99. RX PubMed=35557526; DOI=10.3389/fcvm.2022.887618; RA Shen M.F., Hu Y.N., Chen W.X., Liao L.S., Wu M., Wu Q.Y., Zhang J.H., RA Zhang Y.P., Luo J.W., Lin X.F.; RT "Clinical and genetic analysis of a family with sitosterolemia caused by a RT novel ATP-binding cassette subfamily G member 5 compound heterozygous RT mutation."; RL Front. Cardiovasc. Med. 9:887618-887618(2022). 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:27144356). Plays an essential role in the selective transport CC of dietary plant sterols and cholesterol in and out of the enterocytes CC and in the selective sterol excretion by the liver into bile CC (PubMed:11099417, PubMed:11138003, PubMed:27144356, PubMed:15054092). CC Required for normal sterol homeostasis (PubMed:11099417, CC PubMed:11138003, PubMed:15054092). The heterodimer with ABCG8 has CC ATPase activity (PubMed:16893193, PubMed:20210363, PubMed:27144356). CC {ECO:0000269|PubMed:11138003, ECO:0000269|PubMed:15054092, CC ECO:0000269|PubMed:16893193, ECO:0000269|PubMed:20210363, CC ECO:0000269|PubMed:27144356, ECO:0000303|PubMed:11590207, CC ECO:0000305|PubMed:11099417}. 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:Q99PE8}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39052; CC Evidence={ECO:0000250|UniProtKB:Q99PE8}; 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:Q99PE8}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39104; CC Evidence={ECO:0000250|UniProtKB:Q99PE8}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:Q99PE8}; 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 Q9H222; Q9H221: ABCG8; NbExp=2; IntAct=EBI-1761423, EBI-3908684; CC Q9H222; P16333: NCK1; NbExp=2; IntAct=EBI-1761423, EBI-389883; CC Q9H222-1; Q9H221-1: ABCG8; NbExp=5; IntAct=EBI-16205983, EBI-16205990; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:16893193, CC ECO:0000305|PubMed:27144356}; Multi-pass membrane protein CC {ECO:0000269|PubMed:27144356}. Apical cell membrane CC {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=Q9H222-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9H222-2; Sequence=VSP_055770; CC -!- TISSUE SPECIFICITY: Strongly expressed in the liver, lower levels in CC the small intestine and colon. {ECO:0000269|PubMed:11099417, CC ECO:0000269|PubMed:11138003}. CC -!- DOMAIN: The Walker motif (consensus sequence G-X-X-G-X-G-K-[ST]-T) is CC expected to bind ATP. Within this motif, the conserved Lys is essential CC for transport activity mediated by the heterodimer with ABCG8. CC {ECO:0000250|UniProtKB:Q99PE8}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16893193, CC ECO:0000269|PubMed:20210363}. CC -!- DISEASE: Sitosterolemia 2 (STSL2) [MIM:618666]: 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:11138003, ECO:0000269|PubMed:11452359, CC ECO:0000269|PubMed:11668628, ECO:0000269|PubMed:15054092, CC ECO:0000269|PubMed:35557526}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCG family. CC Eye pigment precursor importer (TC 3.A.1.204) subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins; CC URL="http://abcm2.hegelab.org/search"; 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; AF320293; AAG40003.1; -; mRNA. DR EMBL; AF312715; AAG53099.1; -; mRNA. DR EMBL; AC011242; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC108476; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471053; EAX00286.1; -; Genomic_DNA. DR EMBL; BC111541; AAI11542.1; -; mRNA. DR EMBL; AF404106; AAK85387.1; -; Genomic_DNA. DR EMBL; AF404107; AAK85388.1; -; Genomic_DNA. DR CCDS; CCDS1814.1; -. [Q9H222-1] DR RefSeq; NP_071881.1; NM_022436.2. [Q9H222-1] DR PDB; 5DO7; X-ray; 3.93 A; A/C=1-651. DR PDB; 7JR7; EM; 3.30 A; A=1-651. DR PDB; 7R87; EM; 3.40 A; A=1-651. DR PDB; 7R88; EM; 3.50 A; A=1-651. DR PDB; 7R89; EM; 2.60 A; A=1-651. DR PDB; 7R8A; EM; 2.90 A; A=1-651. DR PDB; 7R8B; EM; 3.10 A; A=1-651. DR PDB; 8CUB; X-ray; 4.05 A; A/C=3-651. DR PDBsum; 5DO7; -. DR PDBsum; 7JR7; -. DR PDBsum; 7R87; -. DR PDBsum; 7R88; -. DR PDBsum; 7R89; -. DR PDBsum; 7R8A; -. DR PDBsum; 7R8B; -. DR PDBsum; 8CUB; -. DR AlphaFoldDB; Q9H222; -. DR EMDB; EMD-22443; -. DR EMDB; EMD-24310; -. DR EMDB; EMD-24311; -. DR EMDB; EMD-24312; -. DR EMDB; EMD-24313; -. DR EMDB; EMD-24314; -. DR SMR; Q9H222; -. DR BioGRID; 122124; 2. DR CORUM; Q9H222; -. DR DIP; DIP-42630N; -. DR IntAct; Q9H222; 5. DR MINT; Q9H222; -. DR STRING; 9606.ENSP00000384513; -. DR DrugBank; DB08834; Tauroursodeoxycholic acid. DR DrugBank; DB11635; Tocofersolan. DR TCDB; 3.A.1.204.5; the atp-binding cassette (abc) superfamily. DR GlyCosmos; Q9H222; 2 sites, No reported glycans. DR GlyGen; Q9H222; 2 sites. DR iPTMnet; Q9H222; -. DR PhosphoSitePlus; Q9H222; -. DR BioMuta; ABCG5; -. DR DMDM; 17432917; -. DR MassIVE; Q9H222; -. DR PaxDb; 9606-ENSP00000260645; -. DR PeptideAtlas; Q9H222; -. DR Antibodypedia; 14899; 257 antibodies from 31 providers. DR DNASU; 64240; -. DR Ensembl; ENST00000405322.8; ENSP00000384513.2; ENSG00000138075.14. [Q9H222-1] DR GeneID; 64240; -. DR KEGG; hsa:64240; -. DR MANE-Select; ENST00000405322.8; ENSP00000384513.2; NM_022436.3; NP_071881.1. DR UCSC; uc002rtn.3; human. [Q9H222-1] DR AGR; HGNC:13886; -. DR CTD; 64240; -. DR DisGeNET; 64240; -. DR GeneCards; ABCG5; -. DR GeneReviews; ABCG5; -. DR HGNC; HGNC:13886; ABCG5. DR HPA; ENSG00000138075; Group enriched (intestine, liver). DR MalaCards; ABCG5; -. DR MIM; 605459; gene. DR MIM; 618666; phenotype. DR neXtProt; NX_Q9H222; -. DR OpenTargets; ENSG00000138075; -. DR Orphanet; 391665; Homozygous familial hypercholesterolemia. DR Orphanet; 2882; Sitosterolemia. DR PharmGKB; PA24411; -. DR VEuPathDB; HostDB:ENSG00000138075; -. DR eggNOG; KOG0061; Eukaryota. DR GeneTree; ENSGT00940000157985; -. DR HOGENOM; CLU_000604_57_9_1; -. DR InParanoid; Q9H222; -. DR OMA; RVRPWWD; -. DR OrthoDB; 936137at2759; -. DR PhylomeDB; Q9H222; -. DR TreeFam; TF105212; -. DR PathwayCommons; Q9H222; -. 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; Q9H222; -. DR SIGNOR; Q9H222; -. DR BioGRID-ORCS; 64240; 10 hits in 1149 CRISPR screens. DR ChiTaRS; ABCG5; human. DR GeneWiki; ABCG5; -. DR GenomeRNAi; 64240; -. DR Pharos; Q9H222; Tbio. DR PRO; PR:Q9H222; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9H222; Protein. DR Bgee; ENSG00000138075; Expressed in jejunal mucosa and 43 other cell types or tissues. 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:0005886; C:plasma membrane; ISS:UniProtKB. 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:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; 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:0010212; P:response to ionizing radiation; 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 CDD; cd03234; ABCG_White; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR013525; ABC2_TM. DR InterPro; IPR003439; ABC_transporter-like_ATP-bd. DR InterPro; IPR043926; ABCG_dom. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR48041; ABC TRANSPORTER G FAMILY MEMBER 28; 1. DR PANTHER; PTHR48041:SF113; ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 5; 1. DR Pfam; PF01061; ABC2_membrane; 1. DR Pfam; PF19055; ABC2_membrane_7; 1. DR Pfam; PF00005; ABC_tran; 1. DR SMART; SM00382; AAA; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1. DR Genevisible; Q9H222; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; KW Disease variant; Glycoprotein; Lipid transport; Magnesium; Membrane; KW Metal-binding; Nucleotide-binding; Reference proteome; Translocase; KW Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..651 FT /note="ATP-binding cassette sub-family G member 5" FT /id="PRO_0000093393" FT TOPO_DOM 1..383 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:27144356" FT TRANSMEM 384..404 FT /note="Helical; Name=1" FT /evidence="ECO:0000269|PubMed:27144356" FT TOPO_DOM 405..421 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:27144356" FT TRANSMEM 422..442 FT /note="Helical; Name=2" FT /evidence="ECO:0000269|PubMed:27144356" FT TOPO_DOM 443..467 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:27144356" FT TRANSMEM 468..489 FT /note="Helical; Name=3" FT /evidence="ECO:0000269|PubMed:27144356" FT TOPO_DOM 490..500 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:27144356" FT TRANSMEM 501..521 FT /note="Helical; Name=4" FT /evidence="ECO:0000269|PubMed:27144356" FT TOPO_DOM 522..528 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:27144356" FT TRANSMEM 529..549 FT /note="Helical; Name=5" FT /evidence="ECO:0000269|PubMed:27144356" FT TOPO_DOM 550..623 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:27144356" FT TRANSMEM 624..644 FT /note="Helical; Name=6" FT /evidence="ECO:0000269|PubMed:27144356" FT TOPO_DOM 645..651 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:27144356" FT DOMAIN 52..293 FT /note="ABC transporter" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434" FT DOMAIN 388..645 FT /note="ABC transmembrane type-2" FT REGION 1..32 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..28 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 86..93 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434" FT CARBOHYD 584 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 591 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 1..395 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_055770" FT VARIANT 50 FT /note="R -> C (in dbSNP:rs6756629)" FT /id="VAR_048142" FT VARIANT 99 FT /note="M -> R (in STSL2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:35557526" FT /id="VAR_086593" FT VARIANT 146 FT /note="E -> Q (in STSL2; decreased maturation of glycan FT chains; dbSNP:rs758551848)" FT /evidence="ECO:0000269|PubMed:11452359, FT ECO:0000269|PubMed:15054092" FT /id="VAR_012244" FT VARIANT 389 FT /note="R -> H (in STSL2; loss of normal maturation of FT glycan chains; dbSNP:rs119480069)" FT /evidence="ECO:0000269|PubMed:11138003, FT ECO:0000269|PubMed:11452359, ECO:0000269|PubMed:15054092" FT /id="VAR_012245" FT VARIANT 419 FT /note="R -> H (in STSL2; loss of normal maturation of FT glycan chains; dbSNP:rs119479067)" FT /evidence="ECO:0000269|PubMed:11138003, FT ECO:0000269|PubMed:11452359, ECO:0000269|PubMed:15054092" FT /id="VAR_012246" FT VARIANT 419 FT /note="R -> P (in STSL2; strongly decreased maturation of FT glycan chains; dbSNP:rs119479067)" FT /evidence="ECO:0000269|PubMed:11138003, FT ECO:0000269|PubMed:11452359, ECO:0000269|PubMed:15054092" FT /id="VAR_012247" FT VARIANT 437 FT /note="N -> K (in STSL2; loss of normal maturation of FT glycan chains; dbSNP:rs575266356)" FT /evidence="ECO:0000269|PubMed:11668628, FT ECO:0000269|PubMed:15054092" FT /id="VAR_020781" FT VARIANT 517 FT /note="T -> S (in dbSNP:rs17031672)" FT /id="VAR_033457" FT VARIANT 523 FT /note="I -> V (in dbSNP:rs140899003)" FT /evidence="ECO:0000269|PubMed:11668628" FT /id="VAR_020782" FT VARIANT 550 FT /note="R -> S (in STSL2)" FT /evidence="ECO:0000269|PubMed:11452359" FT /id="VAR_012248" FT VARIANT 600 FT /note="C -> Y (in dbSNP:rs779109455)" FT /evidence="ECO:0000269|PubMed:11668628" FT /id="VAR_020783" FT VARIANT 604 FT /note="Q -> E (in dbSNP:rs6720173)" FT /evidence="ECO:0000269|PubMed:11099417, FT ECO:0000269|PubMed:11138003, ECO:0000269|PubMed:11452359, FT ECO:0000269|PubMed:11668628" FT /id="VAR_012249" FT VARIANT 622 FT /note="M -> V (in dbSNP:rs140374206)" FT /evidence="ECO:0000269|PubMed:11668628" FT /id="VAR_020784" FT MUTAGEN 92..93 FT /note="KT->RA: Abolishes increase of the very low basal FT ATPase activity by cholate." FT /evidence="ECO:0000269|PubMed:20210363" FT MUTAGEN 432 FT /note="Y->A: Strongly decreases cholesterol secretion into FT bile." FT /evidence="ECO:0000269|PubMed:27144356" FT MUTAGEN 540 FT /note="A->F: Strongly decreases cholesterol secretion into FT bile." FT /evidence="ECO:0000269|PubMed:27144356" FT STRAND 37..45 FT /evidence="ECO:0007829|PDB:7R89" FT STRAND 69..77 FT /evidence="ECO:0007829|PDB:7R89" FT STRAND 81..86 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 88..90 FT /evidence="ECO:0007829|PDB:7R8B" FT HELIX 92..100 FT /evidence="ECO:0007829|PDB:7R89" FT TURN 104..106 FT /evidence="ECO:0007829|PDB:7R8B" FT STRAND 109..115 FT /evidence="ECO:0007829|PDB:7R89" FT STRAND 118..120 FT /evidence="ECO:0007829|PDB:7R8A" FT TURN 126..128 FT /evidence="ECO:0007829|PDB:7R89" FT STRAND 129..132 FT /evidence="ECO:0007829|PDB:7R89" FT STRAND 140..143 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 144..155 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 161..174 FT /evidence="ECO:0007829|PDB:7R89" FT TURN 179..182 FT /evidence="ECO:0007829|PDB:7R89" FT TURN 188..191 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 195..207 FT /evidence="ECO:0007829|PDB:7R89" FT STRAND 212..217 FT /evidence="ECO:0007829|PDB:7R89" FT TURN 219..222 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 225..240 FT /evidence="ECO:0007829|PDB:7R89" FT STRAND 244..248 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 254..256 FT /evidence="ECO:0007829|PDB:7R89" FT TURN 257..259 FT /evidence="ECO:0007829|PDB:7R89" FT STRAND 261..267 FT /evidence="ECO:0007829|PDB:7R89" FT STRAND 270..275 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 277..286 FT /evidence="ECO:0007829|PDB:7R89" FT STRAND 293..295 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 297..304 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 312..330 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 333..346 FT /evidence="ECO:0007829|PDB:7R89" FT STRAND 349..351 FT /evidence="ECO:0007829|PDB:7R8B" FT HELIX 364..380 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 383..404 FT /evidence="ECO:0007829|PDB:7R89" FT TURN 412..414 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 415..453 FT /evidence="ECO:0007829|PDB:7R89" FT TURN 454..456 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 460..490 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 496..523 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 527..544 FT /evidence="ECO:0007829|PDB:7R89" FT STRAND 546..550 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 552..554 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 557..563 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 567..579 FT /evidence="ECO:0007829|PDB:7R89" FT STRAND 580..582 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 605..612 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 614..616 FT /evidence="ECO:0007829|PDB:7R87" FT HELIX 617..619 FT /evidence="ECO:0007829|PDB:7R89" FT HELIX 620..648 FT /evidence="ECO:0007829|PDB:7R89" SQ SEQUENCE 651 AA; 72504 MW; 950BABFCBB6A1536 CRC64; MGDLSSLTPG GSMGLQVNRG SQSSLEGAPA TAPEPHSLGI LHASYSVSHR VRPWWDITSC RQQWTRQILK DVSLYVESGQ IMCILGSSGS GKTTLLDAMS GRLGRAGTFL GEVYVNGRAL RREQFQDCFS YVLQSDTLLS SLTVRETLHY TALLAIRRGN PGSFQKKVEA VMAELSLSHV ADRLIGNYSL GGISTGERRR VSIAAQLLQD PKVMLFDEPT TGLDCMTANQ IVVLLVELAR RNRIVVLTIH QPRSELFQLF DKIAILSFGE LIFCGTPAEM LDFFNDCGYP CPEHSNPFDF YMDLTSVDTQ SKEREIETSK RVQMIESAYK KSAICHKTLK NIERMKHLKT LPMVPFKTKD SPGVFSKLGV LLRRVTRNLV RNKLAVITRL LQNLIMGLFL LFFVLRVRSN VLKGAIQDRV GLLYQFVGAT PYTGMLNAVN LFPVLRAVSD QESQDGLYQK WQMMLAYALH VLPFSVVATM IFSSVCYWTL GLHPEVARFG YFSAALLAPH LIGEFLTLVL LGIVQNPNIV NSVVALLSIA GVLVGSGFLR NIQEMPIPFK IISYFTFQKY CSEILVVNEF YGLNFTCGSS NVSVTTNPMC AFTQGIQFIE KTCPGATSRF TMNFLILYSF IPALVILGIV VFKIRDHLIS R //