ABCG2_HUMAN
ID ABCG2_HUMAN Reviewed; 655 AA.
AC Q9UNQ0; A0A1W3; A8K1T5; O95374; Q4W5I3; Q53ZQ1; Q569L4; Q5YLG4; Q86V64;
AC Q8IX16; Q96LD6; Q96TA8; Q9BY73; Q9NUS0;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 3.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Broad substrate specificity ATP-binding cassette transporter ABCG2 {ECO:0000305};
DE EC=7.6.2.2 {ECO:0000269|PubMed:11306452, ECO:0000269|PubMed:31254042};
DE AltName: Full=ATP-binding cassette sub-family G member 2;
DE AltName: Full=Breast cancer resistance protein;
DE AltName: Full=CDw338;
DE AltName: Full=Mitoxantrone resistance-associated protein;
DE AltName: Full=Placenta-specific ATP-binding cassette transporter;
DE AltName: Full=Urate exporter;
DE AltName: CD_antigen=CD338;
GN Name=ABCG2; Synonyms=ABCP, BCRP, BCRP1, MXR;
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), VARIANTS GLU-166 AND SER-208, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=9850061;
RA Allikmets R., Schriml L.M., Hutchinson A., Romano-Spica V., Dean M.;
RT "A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome
RT 4q22 that is involved in multidrug resistance.";
RL Cancer Res. 58:5337-5339(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Mammary cancer;
RX PubMed=9861027; DOI=10.1073/pnas.95.26.15665;
RA Doyle L.A., Yang W., Abruzzo L.V., Krogmann T., Gao Y., Rishi A.K.,
RA Ross D.D.;
RT "A multidrug resistance transporter from human MCF-7 breast cancer cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:15665-15670(1998).
RN [3]
RP ERRATUM OF PUBMED:9861027.
RA Doyle L.A., Yang W., Abruzzo L.V., Krogmann T., Gao Y., Rishi A.K.,
RA Ross D.D.;
RL Proc. Natl. Acad. Sci. U.S.A. 96:2569-2569(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Kage K., Tsukahara S., Sugiyama T., Asada S., Ishikawa E., Tsuruo T.,
RA Sugimoto Y.;
RT "Breast cancer resistance protein constitutes a 140-kDa complex as a
RT homodimer.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11306452;
RA Komatani H., Kotani H., Hara Y., Nakagawa R., Matsumoto M., Arakawa H.,
RA Nishimura S.;
RT "Identification of breast cancer resistant protein/mitoxantrone
RT resistance/placenta-specific, ATP-binding cassette transporter as a
RT transporter of NB-506 and J-107088, topoisomerase I inhibitors with an
RT indolocarbazole structure.";
RL Cancer Res. 61:2827-2832(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11533706; DOI=10.1038/nm0901-1028;
RA Zhou S., Schuetz J.D., Bunting K.D., Colapietro A.M., Sampath J.,
RA Morris J.J., Lagutina I., Grosveld G.C., Osawa M., Nakauchi H.,
RA Sorrentino B.P.;
RT "The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem
RT cells and is a molecular determinant of the side-population phenotype.";
RL Nat. Med. 7:1028-1034(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP TISSUE SPECIFICITY, AND VARIANTS GLU-166 AND SER-208.
RC TISSUE=Brain endothelium;
RX PubMed=12958161; DOI=10.1096/fj.02-1131fje;
RA Zhang W., Mojsilovic-Petrovic J., Andrade M.F., Zhang H., Ball M.,
RA Stanimirovic D.B.;
RT "The expression and functional characterization of ABCG2 in brain
RT endothelial cells and vessels.";
RL FASEB J. 17:2085-2087(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT LYS-141.
RA Yoshikawa M., Yabuuchi H., Ikegami Y., Ishikawa T.;
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PRO-316.
RA Sudarikov A., Makarik T., Andreeff M.;
RT "Cell line K562 resistant to Hoechst 33342.";
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hippocampus, and Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-12; LYS-141; HIS-296
RP AND THR-528.
RG SeattleSNPs variation discovery resource;
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
RN [12]
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 [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP LYS-141.
RC TISSUE=Pancreas, and PNS;
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 [14]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 294-655 (ISOFORM 1).
RX PubMed=9892175;
RA Miyake K., Mickley L., Litman T., Zhan Z., Robey R.W., Cristensen B.,
RA Brangi M., Greenberger L., Dean M., Fojo T., Bates S.E.;
RT "Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-
RT resistant cells: demonstration of homology to ABC transport genes.";
RL Cancer Res. 59:8-13(1999).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=12477054;
RA Allen J.D., van Loevezijn A., Lakhai J.M., van der Valk M.,
RA van Tellingen O., Reid G., Schellens J.H., Koomen G.J., Schinkel A.H.;
RT "Potent and specific inhibition of the breast cancer resistance protein
RT multidrug transporter in vitro and in mouse intestine by a novel analogue
RT of fumitremorgin C.";
RL Mol. Cancer Ther. 1:417-425(2002).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12682043; DOI=10.1074/jbc.m212399200;
RA Suzuki M., Suzuki H., Sugimoto Y., Sugiyama Y.;
RT "ABCG2 transports sulfated conjugates of steroids and xenobiotics.";
RL J. Biol. Chem. 278:22644-22649(2003).
RN [17]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=15001581; DOI=10.1074/jbc.m310785200;
RA Xu J., Liu Y., Yang Y., Bates S., Zhang J.T.;
RT "Characterization of oligomeric human half-ABC transporter ATP-binding
RT cassette G2.";
RL J. Biol. Chem. 279:19781-19789(2004).
RN [18]
RP SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-596, LACK OF GLYCOSYLATION AT
RP ASN-418 AND ASN-557, AND MUTAGENESIS OF ASN-418; ASN-557 AND ASN-596.
RX PubMed=15807535; DOI=10.1021/bi0479858;
RA Diop N.K., Hrycyna C.A.;
RT "N-linked glycosylation of the human ABC transporter ABCG2 on asparagine
RT 596 is not essential for expression, transport activity, or trafficking to
RT the plasma membrane.";
RL Biochemistry 44:5420-5429(2005).
RN [19]
RP FUNCTION, AND MUTAGENESIS OF ARG-482.
RX PubMed=15670731; DOI=10.1016/j.bbamem.2004.11.005;
RA Oezvegy-Laczka C., Koebloes G., Sarkadi B., Varadi A.;
RT "Single amino acid (482) variants of the ABCG2 multidrug transporter: major
RT differences in transport capacity and substrate recognition.";
RL Biochim. Biophys. Acta 1668:53-63(2005).
RN [20]
RP MUTAGENESIS OF LYS-86, SUBCELLULAR LOCATION, AND HOMODIMERIZATION.
RX PubMed=15769853; DOI=10.1242/jcs.01729;
RA Henriksen U., Gether U., Litman T.;
RT "Effect of Walker A mutation (K86M) on oligomerization and surface
RT targeting of the multidrug resistance transporter ABCG2.";
RL J. Cell Sci. 118:1417-1426(2005).
RN [21]
RP SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=17686774; DOI=10.1074/jbc.c700133200;
RA Wakabayashi K., Nakagawa H., Tamura A., Koshiba S., Hoshijima K.,
RA Komada M., Ishikawa T.;
RT "Intramolecular disulfide bond is a critical check point determining
RT degradative fates of ATP-binding cassette (ABC) transporter ABCG2
RT protein.";
RL J. Biol. Chem. 282:27841-27846(2007).
RN [22]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, PHOSPHORYLATION AT THR-362, AND
RP MUTAGENESIS OF THR-362.
RX PubMed=18056989; DOI=10.1074/jbc.m707773200;
RA Xie Y., Xu K., Linn D.E., Yang X., Guo Z., Shimelis H., Nakanishi T.,
RA Ross D.D., Chen H., Fazli L., Gleave M.E., Qiu Y.;
RT "The 44-kDa Pim-1 kinase phosphorylates BCRP/ABCG2 and thereby promotes its
RT multimerization and drug-resistant activity in human prostate cancer
RT cells.";
RL J. Biol. Chem. 283:3349-3356(2008).
RN [23]
RP POLYMORPHISM, AND INVOLVEMENT IN UAQTL1 AND GOUT.
RX PubMed=18834626; DOI=10.1016/s0140-6736(08)61343-4;
RA Dehghan A., Kottgen A., Yang Q., Hwang S.J., Kao W.L., Rivadeneira F.,
RA Boerwinkle E., Levy D., Hofman A., Astor B.C., Benjamin E.J.,
RA van Duijn C.M., Witteman J.C., Coresh J., Fox C.S.;
RT "Association of three genetic loci with uric acid concentration and risk of
RT gout: a genome-wide association study.";
RL Lancet 372:1953-1961(2008).
RN [24]
RP POLYMORPHISM, INVOLVEMENT IN UAQTL1, ASSOCIATION OF VARIANT LYS-141 WITH
RP GOUT, CHARACTERIZATION OF VARIANT LYS-141, FUNCTION, CATALYTIC ACTIVITY,
RP AND SUBCELLULAR LOCATION.
RX PubMed=19506252; DOI=10.1073/pnas.0901249106;
RA Woodward O.M., Kottgen A., Coresh J., Boerwinkle E., Guggino W.B.,
RA Kottgen M.;
RT "Identification of a urate transporter, ABCG2, with a common functional
RT polymorphism causing gout.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:10338-10342(2009).
RN [25]
RP FUNCTION, CATALYTIC ACTIVITY, POLYMORPHISM, INVOLVEMENT IN UAQTL1, AND
RP ASSOCIATION OF VARIANT LYS-141 WITH GOUT.
RX PubMed=20368174; DOI=10.1126/scitranslmed.3000237;
RA Matsuo H., Takada T., Ichida K., Nakamura T., Nakayama A., Ikebuchi Y.,
RA Ito K., Kusanagi Y., Chiba T., Tadokoro S., Takada Y., Oikawa Y., Inoue H.,
RA Suzuki K., Okada R., Nishiyama J., Domoto H., Watanabe S., Fujita M.,
RA Morimoto Y., Naito M., Nishio K., Hishida A., Wakai K., Asai Y., Niwa K.,
RA Kamakura K., Nonoyama S., Sakurai Y., Hosoya T., Kanai Y., Suzuki H.,
RA Hamajima N., Shinomiya N.;
RT "Common defects of ABCG2, a high-capacity urate exporter, cause gout: a
RT function-based genetic analysis in a Japanese population.";
RL Sci. Transl. Med. 1:5RA11-5RA11(2009).
RN [26]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20110355; DOI=10.1074/jbc.m109.064162;
RA Takabe K., Kim R.H., Allegood J.C., Mitra P., Ramachandran S.,
RA Nagahashi M., Harikumar K.B., Hait N.C., Milstien S., Spiegel S.;
RT "Estradiol induces export of sphingosine 1-phosphate from breast cancer
RT cells via ABCC1 and ABCG2.";
RL J. Biol. Chem. 285:10477-10486(2010).
RN [27]
RP CAUTION.
RX PubMed=20332504; DOI=10.1074/jbc.m109.090506;
RA Brechbuhl H.M., Gould N., Kachadourian R., Riekhof W.R., Voelker D.R.,
RA Day B.J.;
RT "Glutathione transport is a unique function of the ATP-binding cassette
RT protein ABCG2.";
RL J. Biol. Chem. 285:16582-16587(2010).
RN [28]
RP FUNCTION, DOMAIN, AND MUTAGENESIS OF HIS-583; CYS-603 AND TYR-605.
RX PubMed=20705604; DOI=10.1074/jbc.m110.139170;
RA Desuzinges-Mandon E., Arnaud O., Martinez L., Huche F., Di Pietro A.,
RA Falson P.;
RT "ABCG2 transports and transfers heme to albumin through its large
RT extracellular loop.";
RL J. Biol. Chem. 285:33123-33133(2010).
RN [29]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22132962; DOI=10.1080/15257770.2011.633953;
RA Nakayama A., Matsuo H., Takada T., Ichida K., Nakamura T., Ikebuchi Y.,
RA Ito K., Hosoya T., Kanai Y., Suzuki H., Shinomiya N.;
RT "ABCG2 is a high-capacity urate transporter and its genetic impairment
RT increases serum uric acid levels in humans.";
RL Nucleosides Nucleotides Nucleic Acids 30:1091-1097(2011).
RN [30]
RP POLYMORPHISM, INVOLVEMENT IN JR, AND VARIANT MET-12.
RX PubMed=22246507; DOI=10.1038/ng.1075;
RA Zelinski T., Coghlan G., Liu X.Q., Reid M.E.;
RT "ABCG2 null alleles define the Jr(a-) blood group phenotype.";
RL Nat. Genet. 44:131-132(2012).
RN [31]
RP POLYMORPHISM, AND INVOLVEMENT IN JR.
RX PubMed=22246505; DOI=10.1038/ng.1070;
RA Saison C., Helias V., Ballif B.A., Peyrard T., Puy H., Miyazaki T.,
RA Perrot S., Vayssier-Taussat M., Waldner M., Le Pennec P.Y., Cartron J.P.,
RA Arnaud L.;
RT "Null alleles of ABCG2 encoding the breast cancer resistance protein define
RT the new blood group system Junior.";
RL Nat. Genet. 44:174-177(2012).
RN [32]
RP FUNCTION, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=23189181; DOI=10.1371/journal.pone.0050082;
RA Kobuchi H., Moriya K., Ogino T., Fujita H., Inoue K., Shuin T., Yasuda T.,
RA Utsumi K., Utsumi T.;
RT "Mitochondrial localization of ABC transporter ABCG2 and its function in 5-
RT aminolevulinic acid-mediated protoporphyrin IX accumulation.";
RL PLoS ONE 7:E50082-E50082(2012).
RN [33]
RP CAUTION.
RX PubMed=24312054; DOI=10.3389/fphar.2013.00138;
RA Gauthier C., Ozvegy-Laczka C., Szakacs G., Sarkadi B., Di Pietro A.;
RT "ABCG2 is not able to catalyze glutathione efflux and does not contribute
RT to GSH-dependent collateral sensitivity.";
RL Front. Pharmacol. 4:138-138(2013).
RN [34]
RP SUBCELLULAR LOCATION.
RX PubMed=28623970; DOI=10.1016/j.placenta.2017.04.006;
RA Szilagyi J.T., Vetrano A.M., Laskin J.D., Aleksunes L.M.;
RT "Localization of the placental BCRP/ABCG2 transporter to lipid rafts: Role
RT for cholesterol in mediating efflux activity.";
RL Placenta 55:29-36(2017).
RN [35]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, CHARACTERIZATION OF
RP VARIANT LYS-141; TRP-147; MET-153; LYS-360 DEL; CYS-373; MET-434 AND
RP PRO-476, AND MUTAGENESIS OF MET-71; LYS-86 AND ARG-383.
RX PubMed=31254042; DOI=10.1007/s00018-019-03186-2;
RA Zambo B., Mozner O., Bartos Z., Toeroek G., Varady G., Telbisz A.,
RA Homolya L., Orban T.I., Sarkadi B.;
RT "Cellular expression and function of naturally occurring variants of the
RT human ABCG2 multidrug transporter.";
RL Cell. Mol. Life Sci. 77:365-378(2020).
RN [36]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.78 ANGSTROMS) OF 2-655, FUNCTION,
RP CATALYTIC ACTIVITY, SUBUNIT, DISULFIDE BOND, GLYCOSYLATION AT ASN-596, AND
RP MUTAGENESIS OF GLU-211.
RX PubMed=28554189; DOI=10.1038/nature22345;
RA Taylor N.M.I., Manolaridis I., Jackson S.M., Kowal J., Stahlberg H.,
RA Locher K.P.;
RT "Structure of the human multidrug transporter ABCG2.";
RL Nature 546:504-509(2017).
RN [37]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.10 ANGSTROMS) IN COMPLEX WITH
RP INHIBITORS.
RX PubMed=29610494; DOI=10.1038/s41594-018-0049-1;
RA Jackson S.M., Manolaridis I., Kowal J., Zechner M., Taylor N.M.I.,
RA Bause M., Bauer S., Bartholomaeus R., Bernhardt G., Koenig B.,
RA Buschauer A., Stahlberg H., Altmann K.H., Locher K.P.;
RT "Structural basis of small-molecule inhibition of human multidrug
RT transporter ABCG2.";
RL Nat. Struct. Mol. Biol. 25:333-340(2018).
RN [38]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.09 ANGSTROMS) OF MUTANT GLN-211 IN
RP COMPLEX WITH ATP, MUTAGENESIS OF GLU-211; THR-435; ASN-436; PHE-439;
RP VAL-546; MET-549; LEU-554 AND LEU-555, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30405239; DOI=10.1038/s41586-018-0680-3;
RA Manolaridis I., Jackson S.M., Taylor N.M.I., Kowal J., Stahlberg H.,
RA Locher K.P.;
RT "Cryo-EM structures of a human ABCG2 mutant trapped in ATP-bound and
RT substrate-bound states.";
RL Nature 563:426-430(2018).
RN [39]
RP VARIANTS MET-12 AND LYS-141.
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 [40]
RP VARIANTS LEU-431 AND LEU-489.
RX PubMed=15618737; DOI=10.2133/dmpk.18.212;
RA Itoda M., Saito Y., Shirao K., Minami H., Ohtsu A., Yoshida T., Saijo N.,
RA Suzuki H., Sugiyama Y., Ozawa S., Sawada J.;
RT "Eight novel single nucleotide polymorphisms in ABCG2/BCRP in Japanese
RT cancer patients administered irinotacan.";
RL Drug Metab. Pharmacokinet. 18:212-217(2003).
RN [41]
RP VARIANTS MET-12; LYS-141; LEU-206 AND TYR-590.
RX PubMed=12544509; DOI=10.1097/00008571-200301000-00004;
RA Zamber C.P., Lamba J.K., Yasuda K., Farnum J., Thummel K., Schuetz J.D.,
RA Schuetz E.G.;
RT "Natural allelic variants of breast cancer resistance protein (BCRP) and
RT their relationship to BCRP expression in human intestine.";
RL Pharmacogenetics 13:19-28(2003).
RN [42]
RP CHARACTERIZATION OF VARIANTS MET-12; LYS-141 AND ASN-620.
RX PubMed=15838659; DOI=10.1007/s00280-004-0931-x;
RA Morisaki K., Robey R.W., Oezvegy-Laczka C., Honjo Y., Polgar O.,
RA Steadman K., Sarkadi B., Bates S.E.;
RT "Single nucleotide polymorphisms modify the transporter activity of
RT ABCG2.";
RL Cancer Chemother. Pharmacol. 56:161-172(2005).
RN [43]
RP VARIANTS MET-12; LEU-13; LYS-141; GLN-160; ARG-354; LEU-431; ASN-441 AND
RP LEU-489.
RX PubMed=16702730; DOI=10.2133/dmpk.21.109;
RA Maekawa K., Itoda M., Sai K., Saito Y., Kaniwa N., Shirao K., Hamaguchi T.,
RA Kunitoh H., Yamamoto N., Tamura T., Minami H., Kubota K., Ohtsu A.,
RA Yoshida T., Saijo N., Kamatani N., Ozawa S., Sawada J.;
RT "Genetic variation and haplotype structure of the ABC transporter gene
RT ABCG2 in a Japanese population.";
RL Drug Metab. Pharmacokinet. 21:109-121(2006).
RN [44]
RP VARIANTS TRP-147; MET-153; LYS-360 DEL; CYS-373; ALA-421; MET-434; PRO-476;
RP ARG-572 AND ASN-620, CHARACTERIZATION OF VARIANTS LYS-141; TRP-147;
RP MET-153; LYS-360 DEL; CYS-373; ALA-421; MET-434; PRO-476; ARG-572 AND
RP ASN-620, FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=31003562; DOI=10.3390/cells8040363;
RA Toyoda Y., Mancikova A., Krylov V., Morimoto K., Pavelcova K., Bohata J.,
RA Pavelka K., Pavlikova M., Suzuki H., Matsuo H., Takada T., Stiburkova B.;
RT "Functional Characterization of Clinically-Relevant Rare Variants in ABCG2
RT Identified in a Gout and Hyperuricemia Cohort.";
RL Cells 8:0-0(2019).
CC -!- FUNCTION: Broad substrate specificity ATP-dependent transporter of the
CC ATP-binding cassette (ABC) family that actively extrudes a wide variety
CC of physiological compounds, dietary toxins and xenobiotics from cells
CC (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604,
CC PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in
CC porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX)
CC from both mitochondria to cytosol and cytosol to extracellular space,
CC it also functions in the cellular export of heme (PubMed:20705604,
CC PubMed:23189181). Also mediates the efflux of sphingosine-1-P from
CC cells (PubMed:20110355). Acts as a urate exporter functioning in both
CC renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174,
CC PubMed:22132962, PubMed:31003562). In kidney, it also functions as a
CC physiological exporter of the uremic toxin indoxyl sulfate (By
CC similarity). Also involved in the excretion of steroids like estrone 3-
CC sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other
CC sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239).
CC Mediates the secretion of the riboflavin and biotin vitamins into milk
CC (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin
CC catabolite of chlorophyll, reducing its bioavailability (By
CC similarity). Plays an important role in the exclusion of xenobiotics
CC from the brain (Probable). It confers to cells a resistance to multiple
CC drugs and other xenobiotics including mitoxantrone, pheophorbide,
CC camptothecin, methotrexate, azidothymidine, and the anthracyclines
CC daunorubicin and doxorubicin, through the control of their efflux
CC (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989,
CC PubMed:31254042). In placenta, it limits the penetration of drugs from
CC the maternal plasma into the fetus (By similarity). May play a role in
CC early stem cell self-renewal by blocking differentiation (By
CC similarity). {ECO:0000250|UniProtKB:Q7TMS5,
CC ECO:0000269|PubMed:11306452, ECO:0000269|PubMed:12477054,
CC ECO:0000269|PubMed:12682043, ECO:0000269|PubMed:12958161,
CC ECO:0000269|PubMed:15670731, ECO:0000269|PubMed:18056989,
CC ECO:0000269|PubMed:19506252, ECO:0000269|PubMed:20110355,
CC ECO:0000269|PubMed:20368174, ECO:0000269|PubMed:20705604,
CC ECO:0000269|PubMed:22132962, ECO:0000269|PubMed:23189181,
CC ECO:0000269|PubMed:28554189, ECO:0000269|PubMed:30405239,
CC ECO:0000269|PubMed:31003562, ECO:0000269|PubMed:31254042,
CC ECO:0000305|PubMed:12958161}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate +
CC xenobioticSide 2.; EC=7.6.2.2; Evidence={ECO:0000269|PubMed:11306452,
CC ECO:0000269|PubMed:12477054, ECO:0000269|PubMed:12958161,
CC ECO:0000269|PubMed:31254042};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + urate(in) = ADP + H(+) + phosphate + urate(out);
CC Xref=Rhea:RHEA:16461, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17775, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000305|PubMed:19506252,
CC ECO:0000305|PubMed:20368174, ECO:0000305|PubMed:22132962,
CC ECO:0000305|PubMed:31003562};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16462;
CC Evidence={ECO:0000269|PubMed:22132962};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + indoxyl sulfate(in) = ADP + H(+) + indoxyl
CC sulfate(out) + phosphate; Xref=Rhea:RHEA:61332, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:144643, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q7TMS5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61333;
CC Evidence={ECO:0000250|UniProtKB:Q7TMS5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + sphing-4-enine 1-phosphate(in) = ADP + H(+) +
CC phosphate + sphing-4-enine 1-phosphate(out); Xref=Rhea:RHEA:38951,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:60119, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:20110355};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38952;
CC Evidence={ECO:0000269|PubMed:20110355};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + estrone 3-sulfate(in) + H2O = ADP + estrone 3-
CC sulfate(out) + H(+) + phosphate; Xref=Rhea:RHEA:61348,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:60050, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:12682043, ECO:0000269|PubMed:28554189,
CC ECO:0000269|PubMed:30405239};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61349;
CC Evidence={ECO:0000269|PubMed:12682043};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + dehydroepiandrosterone 3-sulfate(in) + H2O = ADP +
CC dehydroepiandrosterone 3-sulfate(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:61364, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57905,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:12682043};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61365;
CC Evidence={ECO:0000269|PubMed:12682043};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-methylumbelliferone sulfate(in) + ATP + H2O = 4-
CC methylumbelliferone sulfate(out) + ADP + H(+) + phosphate;
CC Xref=Rhea:RHEA:61368, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:144581,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:12682043};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61369;
CC Evidence={ECO:0000269|PubMed:12682043};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl)-1,3-
CC benzothiazol-6-yl beta-D-glucuronate(in) + ATP + H2O = 5,7-dimethyl-
CC 2-methylamino-4-(3-pyridylmethyl)-1,3-benzothiazol-6-yl beta-D-
CC glucuronate(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:61384,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:144584, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:12682043};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61385;
CC Evidence={ECO:0000269|PubMed:12682043};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-methylumbelliferone beta-D-glucuronate(in) + ATP + H2O = 4-
CC methylumbelliferone beta-D-glucuronate(out) + ADP + H(+) + phosphate;
CC Xref=Rhea:RHEA:61372, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:144582,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:12682043};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61373;
CC Evidence={ECO:0000269|PubMed:12682043};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl)-1,3-
CC benzothiazol-6-yl sulfate(in) + ATP + H2O = 5,7-dimethyl-2-
CC methylamino-4-(3-pyridylmethyl)-1,3-benzothiazol-6-yl sulfate(out) +
CC ADP + H(+) + phosphate; Xref=Rhea:RHEA:61376, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:144583, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:12682043};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61377;
CC Evidence={ECO:0000269|PubMed:12682043};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol 17-O-(beta-D-glucuronate)(in) + ATP + H2O =
CC 17beta-estradiol 17-O-(beta-D-glucuronate)(out) + ADP + H(+) +
CC phosphate; Xref=Rhea:RHEA:60128, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:82961, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:12682043};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60129;
CC Evidence={ECO:0000269|PubMed:12682043};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + methotrexate(in) = ADP + H(+) + methotrexate(out)
CC + phosphate; Xref=Rhea:RHEA:61356, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:50681, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:12682043};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61357;
CC Evidence={ECO:0000269|PubMed:12682043};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + riboflavin(in) = ADP + H(+) + phosphate +
CC riboflavin(out); Xref=Rhea:RHEA:61352, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57986, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q7TMS5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61353;
CC Evidence={ECO:0000250|UniProtKB:Q7TMS5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + pheophorbide a(in) = ADP + H(+) + pheophorbide
CC a(out) + phosphate; Xref=Rhea:RHEA:61360, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58687, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q7TMS5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61361;
CC Evidence={ECO:0000250|UniProtKB:Q7TMS5};
CC -!- ACTIVITY REGULATION: Specifically inhibited by the fungal toxin
CC fumitremorgin C and Ko143. {ECO:0000269|PubMed:12477054}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=16.6 uM for estrone 3-sulfate {ECO:0000269|PubMed:12682043};
CC KM=1.23 mM for ATP {ECO:0000269|PubMed:12682043};
CC KM=12.9 uM for 4-methylumbelliferone sulfate
CC {ECO:0000269|PubMed:12682043};
CC KM=26.9 uM for 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-
CC pyridylmethyl)benzothiazole sulfate {ECO:0000269|PubMed:12682043};
CC KM=8.24 mM for urate {ECO:0000269|PubMed:22132962};
CC Vmax=2.34 nmol/min/mg enzyme for estrone 3-sulfate transport
CC {ECO:0000269|PubMed:12682043};
CC Vmax=6.96 nmol/min/mg enzyme for urate transport
CC {ECO:0000269|PubMed:22132962};
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:15001581, PubMed:17686774,
CC PubMed:18056989, PubMed:28554189). The minimal functional unit is a
CC homodimer, but the major oligomeric form in plasma membrane is a
CC homotetramer with possibility of higher order oligomerization up to
CC homododecamers (PubMed:15001581). {ECO:0000269|PubMed:15001581,
CC ECO:0000269|PubMed:17686774, ECO:0000269|PubMed:18056989,
CC ECO:0000269|PubMed:28554189}.
CC -!- INTERACTION:
CC Q9UNQ0; Q9UNQ0: ABCG2; NbExp=5; IntAct=EBI-1569435, EBI-1569435;
CC Q9UNQ0; P11309-2: PIM1; NbExp=5; IntAct=EBI-1569435, EBI-1018633;
CC Q9UNQ0; P0CG48: UBC; NbExp=2; IntAct=EBI-1569435, EBI-3390054;
CC Q9UNQ0-1; Q9UNQ0-1: ABCG2; NbExp=3; IntAct=EBI-20717342, EBI-20717342;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15001581,
CC ECO:0000269|PubMed:15769853, ECO:0000269|PubMed:15807535,
CC ECO:0000269|PubMed:18056989, ECO:0000269|PubMed:31003562,
CC ECO:0000269|PubMed:31254042}; Multi-pass membrane protein
CC {ECO:0000255}. Apical cell membrane {ECO:0000269|PubMed:19506252};
CC Multi-pass membrane protein {ECO:0000255}. Mitochondrion membrane
CC {ECO:0000269|PubMed:23189181}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Enriched in membrane lipid rafts.
CC {ECO:0000269|PubMed:28623970}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UNQ0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UNQ0-2; Sequence=VSP_014232, VSP_014233;
CC -!- TISSUE SPECIFICITY: Highly expressed in placenta (PubMed:9850061). Low
CC expression in small intestine, liver and colon (PubMed:9861027).
CC Expressed in brain (at protein level) (PubMed:12958161).
CC {ECO:0000269|PubMed:12958161, ECO:0000269|PubMed:9850061,
CC ECO:0000269|PubMed:9861027}.
CC -!- DOMAIN: The extracellular loop 3 (ECL3) is involved in binding
CC porphyrins and transfer them to other carriers, probably albumin.
CC {ECO:0000269|PubMed:20705604}.
CC -!- PTM: N-glycosylated (PubMed:15807535, PubMed:23189181). Glycosylation-
CC deficient ABCG2 is normally expressed and functional.
CC {ECO:0000269|PubMed:15807535, ECO:0000269|PubMed:23189181}.
CC -!- PTM: Phosphorylated. Phosphorylation at Thr-362 by PIM1 is induced by
CC drugs like mitoxantrone and is associated with cells increased drug
CC resistance. It regulates the localization to the plasma membrane, the
CC homooligomerization and therefore, the activity of the transporter.
CC {ECO:0000269|PubMed:18056989}.
CC -!- POLYMORPHISM: Genetic variations in ABCG2 define the blood group Junior
CC system (JR) [MIM:614490]. Individuals with Jr(a-) blood group lack the
CC Jr(a) antigen on their red blood cells. These individuals may have
CC anti-Jr(a) antibodies in their serum, which can cause transfusion
CC reactions or hemolytic disease of the fetus or newborn. Although the
CC clinical significance of the Jr(a-) blood group has been controversial,
CC severe fatal hemolytic disease of the newborn has been reported. The
CC Jr(a-) phenotype has a higher frequency in individuals of Asian
CC descent, compared to those of European descent. The Jr(a-) phenotype is
CC inherited as an autosomal recessive trait.
CC {ECO:0000269|PubMed:22246505, ECO:0000269|PubMed:22246507}.
CC -!- POLYMORPHISM: Genetic variations in ABCG2 influence the variance in
CC serum uric acid concentrations and define the serum uric acid
CC concentration quantitative trait locus 1 (UAQTL1) [MIM:138900]. Excess
CC serum accumulation of uric acid can lead to the development of gout, a
CC common disorder characterized by tissue deposition of monosodium urate
CC crystals as a consequence of hyperuricemia (PubMed:18834626,
CC PubMed:19506252, PubMed:20368174). {ECO:0000269|PubMed:18834626,
CC ECO:0000269|PubMed:19506252, ECO:0000269|PubMed:20368174}.
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: Was originally proposed to function as a glutathione
CC transporter (PubMed:20332504). However, some evidences suggest it is
CC not the case (PubMed:24312054). {ECO:0000269|PubMed:20332504,
CC ECO:0000269|PubMed:24312054}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AF093771; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AF093772; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/abcg2/";
CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins;
CC URL="http://abcm2.hegelab.org/search";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The unwalkable disease
CC - Issue 222 of February 2020;
CC URL="https://web.expasy.org/spotlight/back_issues/222/";
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DR EMBL; AF103796; AAD09188.1; -; mRNA.
DR EMBL; AF098951; AAC97367.1; -; mRNA.
DR EMBL; AB056867; BAB39212.1; -; mRNA.
DR EMBL; AB051855; BAB46933.1; -; mRNA.
DR EMBL; AY017168; AAG52982.1; -; mRNA.
DR EMBL; AY289766; AAP44087.1; -; mRNA.
DR EMBL; AY288307; AAP31310.1; -; mRNA.
DR EMBL; AF463519; AAO14617.1; -; mRNA.
DR EMBL; AY333755; AAQ92941.1; -; mRNA.
DR EMBL; AY333756; AAQ92942.1; -; mRNA.
DR EMBL; AK002040; BAA92050.1; -; mRNA.
DR EMBL; AK290000; BAF82689.1; -; mRNA.
DR EMBL; DQ996467; ABI97388.1; -; Genomic_DNA.
DR EMBL; AC084732; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC097484; AAY40902.1; -; Genomic_DNA.
DR EMBL; BC021281; AAH21281.1; -; mRNA.
DR EMBL; BC092408; AAH92408.1; -; mRNA.
DR EMBL; AF093771; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF093772; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS3628.1; -. [Q9UNQ0-1]
DR CCDS; CCDS58910.1; -. [Q9UNQ0-2]
DR RefSeq; NP_001244315.1; NM_001257386.1. [Q9UNQ0-2]
DR RefSeq; NP_004818.2; NM_004827.2. [Q9UNQ0-1]
DR RefSeq; XP_005263412.1; XM_005263355.3. [Q9UNQ0-1]
DR RefSeq; XP_011530722.1; XM_011532420.2. [Q9UNQ0-1]
DR PDB; 5NJ3; EM; 3.78 A; A/B=2-655.
DR PDB; 5NJG; EM; 3.78 A; A/B=2-655.
DR PDB; 6ETI; EM; 3.10 A; A/B=1-655.
DR PDB; 6FEQ; EM; 3.60 A; A/B=1-655.
DR PDB; 6FFC; EM; 3.56 A; A/B=2-655.
DR PDB; 6HBU; EM; 3.09 A; A/B=1-655.
DR PDB; 6HCO; EM; 3.58 A; A/B=2-655.
DR PDB; 6HIJ; EM; 3.56 A; A/B=1-655.
DR PDB; 6HZM; EM; 3.09 A; A/B=1-655.
DR PDB; 6VXF; EM; 3.50 A; A/B=1-655.
DR PDB; 6VXH; EM; 4.00 A; A/B=1-655.
DR PDB; 6VXI; EM; 3.70 A; A/B=1-655.
DR PDB; 6VXJ; EM; 4.10 A; A/B=1-655.
DR PDB; 7NEQ; EM; 3.12 A; A/B=1-655.
DR PDB; 7NEZ; EM; 3.39 A; A/B=1-655.
DR PDB; 7NFD; EM; 3.51 A; A/B=1-655.
DR PDB; 7OJ8; EM; 3.40 A; A/B=2-655.
DR PDB; 7OJH; EM; 3.10 A; A/B=2-655.
DR PDB; 7OJI; EM; 3.40 A; A/B=2-655.
DR PDBsum; 5NJ3; -.
DR PDBsum; 5NJG; -.
DR PDBsum; 6ETI; -.
DR PDBsum; 6FEQ; -.
DR PDBsum; 6FFC; -.
DR PDBsum; 6HBU; -.
DR PDBsum; 6HCO; -.
DR PDBsum; 6HIJ; -.
DR PDBsum; 6HZM; -.
DR PDBsum; 6VXF; -.
DR PDBsum; 6VXH; -.
DR PDBsum; 6VXI; -.
DR PDBsum; 6VXJ; -.
DR PDBsum; 7NEQ; -.
DR PDBsum; 7NEZ; -.
DR PDBsum; 7NFD; -.
DR PDBsum; 7OJ8; -.
DR PDBsum; 7OJH; -.
DR PDBsum; 7OJI; -.
DR AlphaFoldDB; Q9UNQ0; -.
DR SMR; Q9UNQ0; -.
DR BioGRID; 114821; 60.
DR DIP; DIP-29162N; -.
DR IntAct; Q9UNQ0; 19.
DR MINT; Q9UNQ0; -.
DR STRING; 9606.ENSP00000237612; -.
DR BindingDB; Q9UNQ0; -.
DR ChEMBL; CHEMBL5393; -.
DR DrugBank; DB12001; Abemaciclib.
DR DrugBank; DB08916; Afatinib.
DR DrugBank; DB11363; Alectinib.
DR DrugBank; DB00437; Allopurinol.
DR DrugBank; DB12015; Alpelisib.
DR DrugBank; DB03496; Alvocidib.
DR DrugBank; DB06288; Amisulpride.
DR DrugBank; DB11901; Apalutamide.
DR DrugBank; DB06605; Apixaban.
DR DrugBank; DB09274; Artesunate.
DR DrugBank; DB12597; Asciminib.
DR DrugBank; DB16098; Atogepant.
DR DrugBank; DB06237; Avanafil.
DR DrugBank; DB15233; Avapritinib.
DR DrugBank; DB11995; Avatrombopag.
DR DrugBank; DB11817; Baricitinib.
DR DrugBank; DB00394; Beclomethasone dipropionate.
DR DrugBank; DB16703; Belumosudil.
DR DrugBank; DB15982; Berotralstat.
DR DrugBank; DB04851; Biricodar.
DR DrugBank; DB12267; Brigatinib.
DR DrugBank; DB12151; Brincidofovir.
DR DrugBank; DB00921; Buprenorphine.
DR DrugBank; DB06772; Cabazitaxel.
DR DrugBank; DB11751; Cabotegravir.
DR DrugBank; DB00201; Caffeine.
DR DrugBank; DB04690; Camptothecin.
DR DrugBank; DB08907; Canagliflozin.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB11791; Capmatinib.
DR DrugBank; DB00958; Carboplatin.
DR DrugBank; DB00482; Celecoxib.
DR DrugBank; DB00439; Cerivastatin.
DR DrugBank; DB04540; Cholesterol.
DR DrugBank; DB00515; Cisplatin.
DR DrugBank; DB00242; Cladribine.
DR DrugBank; DB00631; Clofarabine.
DR DrugBank; DB00845; Clofazimine.
DR DrugBank; DB09065; Cobicistat.
DR DrugBank; DB05239; Cobimetinib.
DR DrugBank; DB00286; Conjugated estrogens.
DR DrugBank; DB12483; Copanlisib.
DR DrugBank; DB00091; Cyclosporine.
DR DrugBank; DB08912; Dabrafenib.
DR DrugBank; DB09102; Daclatasvir.
DR DrugBank; DB11963; Dacomitinib.
DR DrugBank; DB00970; Dactinomycin.
DR DrugBank; DB02115; Daidzin.
DR DrugBank; DB12941; Darolutamide.
DR DrugBank; DB09183; Dasabuvir.
DR DrugBank; DB01254; Dasatinib.
DR DrugBank; DB00694; Daunorubicin.
DR DrugBank; DB11943; Delafloxacin.
DR DrugBank; DB01234; Dexamethasone.
DR DrugBank; DB14649; Dexamethasone acetate.
DR DrugBank; DB00255; Diethylstilbestrol.
DR DrugBank; DB01248; Docetaxel.
DR DrugBank; DB08930; Dolutegravir.
DR DrugBank; DB00843; Donepezil.
DR DrugBank; DB05928; Dovitinib.
DR DrugBank; DB00997; Doxorubicin.
DR DrugBank; DB00470; Dronabinol.
DR DrugBank; DB11952; Duvelisib.
DR DrugBank; DB04881; Elacridar.
DR DrugBank; DB06210; Eltrombopag.
DR DrugBank; DB09038; Empagliflozin.
DR DrugBank; DB13874; Enasidenib.
DR DrugBank; DB00530; Erlotinib.
DR DrugBank; DB11827; Ertugliflozin.
DR DrugBank; DB00783; Estradiol.
DR DrugBank; DB13952; Estradiol acetate.
DR DrugBank; DB13953; Estradiol benzoate.
DR DrugBank; DB13954; Estradiol cypionate.
DR DrugBank; DB13955; Estradiol dienanthate.
DR DrugBank; DB13956; Estradiol valerate.
DR DrugBank; DB00655; Estrone.
DR DrugBank; DB00773; Etoposide.
DR DrugBank; DB00973; Ezetimibe.
DR DrugBank; DB04854; Febuxostat.
DR DrugBank; DB12500; Fedratinib.
DR DrugBank; DB09279; Fimasartan.
DR DrugBank; DB00544; Fluorouracil.
DR DrugBank; DB00158; Folic acid.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB11796; Fostemsavir.
DR DrugBank; DB02703; Fusidic acid.
DR DrugBank; DB00317; Gefitinib.
DR DrugBank; DB01645; Genistein.
DR DrugBank; DB12141; Gilteritinib.
DR DrugBank; DB11978; Glasdegib.
DR DrugBank; DB13879; Glecaprevir.
DR DrugBank; DB01016; Glyburide.
DR DrugBank; DB01094; Hesperetin.
DR DrugBank; DB14538; Hydrocortisone aceponate.
DR DrugBank; DB14539; Hydrocortisone acetate.
DR DrugBank; DB14540; Hydrocortisone butyrate.
DR DrugBank; DB14541; Hydrocortisone cypionate.
DR DrugBank; DB14542; Hydrocortisone phosphate.
DR DrugBank; DB14543; Hydrocortisone probutate.
DR DrugBank; DB14544; Hydrocortisone valerate.
DR DrugBank; DB09054; Idelalisib.
DR DrugBank; DB00619; Imatinib.
DR DrugBank; DB11886; Infigratinib.
DR DrugBank; DB00762; Irinotecan.
DR DrugBank; DB11633; Isavuconazole.
DR DrugBank; DB11757; Istradefylline.
DR DrugBank; DB00602; Ivermectin.
DR DrugBank; DB00709; Lamivudine.
DR DrugBank; DB00448; Lansoprazole.
DR DrugBank; DB14723; Larotrectinib.
DR DrugBank; DB11732; Lasmiditan.
DR DrugBank; DB09027; Ledipasvir.
DR DrugBank; DB01097; Leflunomide.
DR DrugBank; DB09078; Lenvatinib.
DR DrugBank; DB12070; Letermovir.
DR DrugBank; DB06448; Lonafarnib.
DR DrugBank; DB13125; Lusutrombopag.
DR DrugBank; DB06234; Maribavir.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB00563; Methotrexate.
DR DrugBank; DB01204; Mitoxantrone.
DR DrugBank; DB16390; Mobocertinib.
DR DrugBank; DB00688; Mycophenolate mofetil.
DR DrugBank; DB14011; Nabiximols.
DR DrugBank; DB03467; Naringenin.
DR DrugBank; DB00220; Nelfinavir.
DR DrugBank; DB11820; Nifurtimox.
DR DrugBank; DB04868; Nilotinib.
DR DrugBank; DB09079; Nintedanib.
DR DrugBank; DB00698; Nitrofurantoin.
DR DrugBank; DB01051; Novobiocin.
DR DrugBank; DB09074; Olaparib.
DR DrugBank; DB09296; Ombitasvir.
DR DrugBank; DB00338; Omeprazole.
DR DrugBank; DB11632; Opicapone.
DR DrugBank; DB09330; Osimertinib.
DR DrugBank; DB00526; Oxaliplatin.
DR DrugBank; DB12612; Ozanimod.
DR DrugBank; DB09073; Palbociclib.
DR DrugBank; DB00213; Pantoprazole.
DR DrugBank; DB09297; Paritaprevir.
DR DrugBank; DB06589; Pazopanib.
DR DrugBank; DB15102; Pemigatinib.
DR DrugBank; DB13878; Pibrentasvir.
DR DrugBank; DB08860; Pitavastatin.
DR DrugBank; DB08901; Ponatinib.
DR DrugBank; DB06813; Pralatrexate.
DR DrugBank; DB15822; Pralsetinib.
DR DrugBank; DB01708; Prasterone.
DR DrugBank; DB00175; Pravastatin.
DR DrugBank; DB00457; Prazosin.
DR DrugBank; DB00396; Progesterone.
DR DrugBank; DB04216; Quercetin.
DR DrugBank; DB01129; Rabeprazole.
DR DrugBank; DB00481; Raloxifene.
DR DrugBank; DB08896; Regorafenib.
DR DrugBank; DB11853; Relugolix.
DR DrugBank; DB11855; Revefenacin.
DR DrugBank; DB08864; Rilpivirine.
DR DrugBank; DB00740; Riluzole.
DR DrugBank; DB12457; Rimegepant.
DR DrugBank; DB08931; Riociguat.
DR DrugBank; DB14840; Ripretinib.
DR DrugBank; DB15305; Risdiplam.
DR DrugBank; DB00503; Ritonavir.
DR DrugBank; DB06228; Rivaroxaban.
DR DrugBank; DB09291; Rolapitant.
DR DrugBank; DB01098; Rosuvastatin.
DR DrugBank; DB12332; Rucaparib.
DR DrugBank; DB06654; Safinamide.
DR DrugBank; DB01232; Saquinavir.
DR DrugBank; DB15685; Selpercatinib.
DR DrugBank; DB11689; Selumetinib.
DR DrugBank; DB06290; Simeprevir.
DR DrugBank; DB08934; Sofosbuvir.
DR DrugBank; DB00398; Sorafenib.
DR DrugBank; DB15569; Sotorasib.
DR DrugBank; DB00795; Sulfasalazine.
DR DrugBank; DB00391; Sulpiride.
DR DrugBank; DB00669; Sumatriptan.
DR DrugBank; DB01268; Sunitinib.
DR DrugBank; DB11644; Tafamidis.
DR DrugBank; DB11760; Talazoparib.
DR DrugBank; DB00675; Tamoxifen.
DR DrugBank; DB04348; Taurocholic acid.
DR DrugBank; DB12887; Tazemetostat.
DR DrugBank; DB01079; Tegaserod.
DR DrugBank; DB00966; Telmisartan.
DR DrugBank; DB00853; Temozolomide.
DR DrugBank; DB00444; Teniposide.
DR DrugBank; DB09299; Tenofovir alafenamide.
DR DrugBank; DB15133; Tepotinib.
DR DrugBank; DB08880; Teriflunomide.
DR DrugBank; DB00624; Testosterone.
DR DrugBank; DB13943; Testosterone cypionate.
DR DrugBank; DB13944; Testosterone enanthate.
DR DrugBank; DB13946; Testosterone undecanoate.
DR DrugBank; DB11712; Tezacaftor.
DR DrugBank; DB11800; Tivozanib.
DR DrugBank; DB01685; Topiroxostat.
DR DrugBank; DB01030; Topotecan.
DR DrugBank; DB14962; Trastuzumab deruxtecan.
DR DrugBank; DB15442; Trilaciclib.
DR DrugBank; DB11652; Tucatinib.
DR DrugBank; DB15328; Ubrogepant.
DR DrugBank; DB15091; Upadacitinib.
DR DrugBank; DB05294; Vandetanib.
DR DrugBank; DB11613; Velpatasvir.
DR DrugBank; DB08881; Vemurafenib.
DR DrugBank; DB11581; Venetoclax.
DR DrugBank; DB00285; Venlafaxine.
DR DrugBank; DB15456; Vericiguat.
DR DrugBank; DB00541; Vincristine.
DR DrugBank; DB08828; Vismodegib.
DR DrugBank; DB12026; Voxilaprevir.
DR DrugBank; DB00549; Zafirlukast.
DR DrugBank; DB00495; Zidovudine.
DR DrugCentral; Q9UNQ0; -.
DR GuidetoPHARMACOLOGY; 792; -.
DR TCDB; 3.A.1.204.2; the atp-binding cassette (abc) superfamily.
DR GlyGen; Q9UNQ0; 1 site.
DR iPTMnet; Q9UNQ0; -.
DR PhosphoSitePlus; Q9UNQ0; -.
DR BioMuta; ABCG2; -.
DR DMDM; 67462103; -.
DR EPD; Q9UNQ0; -.
DR jPOST; Q9UNQ0; -.
DR MassIVE; Q9UNQ0; -.
DR MaxQB; Q9UNQ0; -.
DR PaxDb; Q9UNQ0; -.
DR PeptideAtlas; Q9UNQ0; -.
DR PRIDE; Q9UNQ0; -.
DR ProteomicsDB; 85323; -. [Q9UNQ0-1]
DR ProteomicsDB; 85324; -. [Q9UNQ0-2]
DR ABCD; Q9UNQ0; 1 sequenced antibody.
DR Antibodypedia; 14577; 364 antibodies from 45 providers.
DR DNASU; 9429; -.
DR Ensembl; ENST00000237612.8; ENSP00000237612.3; ENSG00000118777.12. [Q9UNQ0-1]
DR Ensembl; ENST00000515655.5; ENSP00000426917.1; ENSG00000118777.12. [Q9UNQ0-2]
DR Ensembl; ENST00000650821.1; ENSP00000498246.1; ENSG00000118777.12. [Q9UNQ0-1]
DR GeneID; 9429; -.
DR KEGG; hsa:9429; -.
DR MANE-Select; ENST00000237612.8; ENSP00000237612.3; NM_004827.3; NP_004818.2.
DR UCSC; uc003hrg.4; human. [Q9UNQ0-1]
DR CTD; 9429; -.
DR DisGeNET; 9429; -.
DR GeneCards; ABCG2; -.
DR HGNC; HGNC:74; ABCG2.
DR HPA; ENSG00000118777; Tissue enhanced (intestine).
DR MalaCards; ABCG2; -.
DR MIM; 138900; phenotype.
DR MIM; 603756; gene.
DR MIM; 614490; phenotype.
DR neXtProt; NX_Q9UNQ0; -.
DR OpenTargets; ENSG00000118777; -.
DR PharmGKB; PA390; -.
DR VEuPathDB; HostDB:ENSG00000118777; -.
DR eggNOG; KOG0061; Eukaryota.
DR GeneTree; ENSGT00940000162658; -.
DR HOGENOM; CLU_000604_57_8_1; -.
DR InParanoid; Q9UNQ0; -.
DR OMA; WCARMSS; -.
DR OrthoDB; 1022017at2759; -.
DR PhylomeDB; Q9UNQ0; -.
DR TreeFam; TF105211; -.
DR BRENDA; 7.6.2.2; 2681.
DR BRENDA; 7.6.2.3; 2681.
DR PathwayCommons; Q9UNQ0; -.
DR Reactome; R-HSA-189451; Heme biosynthesis.
DR Reactome; R-HSA-189483; Heme degradation.
DR Reactome; R-HSA-2161517; Abacavir transmembrane transport.
DR Reactome; R-HSA-917937; Iron uptake and transport.
DR Reactome; R-HSA-9753281; Paracetamol ADME.
DR SABIO-RK; Q9UNQ0; -.
DR SignaLink; Q9UNQ0; -.
DR SIGNOR; Q9UNQ0; -.
DR BioGRID-ORCS; 9429; 12 hits in 1072 CRISPR screens.
DR ChiTaRS; ABCG2; human.
DR GeneWiki; ABCG2; -.
DR GenomeRNAi; 9429; -.
DR Pharos; Q9UNQ0; Tchem.
DR PRO; PR:Q9UNQ0; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9UNQ0; protein.
DR Bgee; ENSG00000118777; Expressed in jejunal mucosa and 160 other tissues.
DR ExpressionAtlas; Q9UNQ0; baseline and differential.
DR Genevisible; Q9UNQ0; HS.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; IDA:UniProtKB.
DR GO; GO:0098591; C:external side of apical plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0008559; F:ABC-type xenobiotic transporter activity; IDA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0015225; F:biotin transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015562; F:efflux transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008514; F:organic anion transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0032217; F:riboflavin transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015143; F:urate transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0015878; P:biotin transport; ISS:UniProtKB.
DR GO; GO:1990748; P:cellular detoxification; IDA:GO_Central.
DR GO; GO:0140115; P:export across plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR GO; GO:0015711; P:organic anion transport; ISS:ARUK-UCL.
DR GO; GO:0097744; P:renal urate salt excretion; IMP:UniProtKB.
DR GO; GO:0032218; P:riboflavin transport; IDA:UniProtKB.
DR GO; GO:0070633; P:transepithelial transport; IDA:ARUK-UCL.
DR GO; GO:0055085; P:transmembrane transport; IMP:UniProtKB.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR GO; GO:0046415; P:urate metabolic process; IMP:UniProtKB.
DR GO; GO:1990962; P:xenobiotic transport across blood-brain barrier; IDA:ARUK-UCL.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR013525; ABC_2_trans.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR030256; ABCG2.
DR InterPro; IPR043926; ABCG_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR48041:SF92; PTHR48041:SF92; 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; SSF52540; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Disulfide bond; Glycoprotein; Lipid transport; Membrane; Mitochondrion;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Translocase;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..655
FT /note="Broad substrate specificity ATP-binding cassette
FT transporter ABCG2"
FT /id="PRO_0000093386"
FT TOPO_DOM 1..395
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 396..416
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 417..428
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 429..449
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 450..477
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 478..498
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 499..506
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 507..527
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 528..535
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 536..556
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 557..630
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 631..651
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 652..655
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 37..286
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 389..651
FT /note="ABC transmembrane type-2"
FT BINDING 80..87
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434,
FT ECO:0000269|PubMed:30405239, ECO:0007744|PDB:6HBU,
FT ECO:0007744|PDB:6HZM"
FT BINDING 184..190
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:30405239,
FT ECO:0007744|PDB:6HBU, ECO:0007744|PDB:6HZM"
FT BINDING 211
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:30405239,
FT ECO:0007744|PDB:6HBU, ECO:0007744|PDB:6HZM"
FT BINDING 243
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:30405239,
FT ECO:0007744|PDB:6HBU, ECO:0007744|PDB:6HZM"
FT SITE 418
FT /note="Not glycosylated"
FT /evidence="ECO:0000269|PubMed:15807535"
FT SITE 557
FT /note="Not glycosylated"
FT /evidence="ECO:0000269|PubMed:15807535"
FT MOD_RES 362
FT /note="Phosphothreonine; by PIM1"
FT /evidence="ECO:0000269|PubMed:18056989"
FT CARBOHYD 596
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15807535,
FT ECO:0000269|PubMed:28554189, ECO:0007744|PDB:5NJ3,
FT ECO:0007744|PDB:5NJG"
FT DISULFID 592..608
FT /evidence="ECO:0000269|PubMed:17686774,
FT ECO:0000269|PubMed:28554189, ECO:0007744|PDB:5NJ3,
FT ECO:0007744|PDB:5NJG"
FT DISULFID 603
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:17686774,
FT ECO:0000269|PubMed:28554189, ECO:0007744|PDB:5NJ3,
FT ECO:0007744|PDB:5NJG"
FT VAR_SEQ 550..611
FT /note="IFSGLLVNLTTIASWLSWLQYFSIPRYGFTALQHNEFLGQNFCPGLNATGNN
FT PCNYATCTGE -> VCWSISQPLHLGCHGFSTSAFHDMDLRLCSIMNFWDKTSAQDSMQ
FT QETILVTMQHVLAKNIW (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014232"
FT VAR_SEQ 612..655
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014233"
FT VARIANT 12
FT /note="V -> M (found in Jr(a-) blood group phenotype;
FT dbSNP:rs2231137)"
FT /evidence="ECO:0000269|PubMed:12111378,
FT ECO:0000269|PubMed:12544509, ECO:0000269|PubMed:15838659,
FT ECO:0000269|PubMed:16702730, ECO:0000269|PubMed:22246507,
FT ECO:0000269|Ref.11"
FT /id="VAR_020779"
FT VARIANT 13
FT /note="S -> L (in dbSNP:rs1319203095)"
FT /evidence="ECO:0000269|PubMed:16702730"
FT /id="VAR_067363"
FT VARIANT 141
FT /note="Q -> K (associated with high serum levels of uric
FT acid and increased risk of gout; results in lower urate
FT transport rates compared to wild-type; decreased protein
FT abundance; dbSNP:rs2231142)"
FT /evidence="ECO:0000269|PubMed:12111378,
FT ECO:0000269|PubMed:12544509, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:15838659, ECO:0000269|PubMed:16702730,
FT ECO:0000269|PubMed:19506252, ECO:0000269|PubMed:31003562,
FT ECO:0000269|PubMed:31254042, ECO:0000269|Ref.11,
FT ECO:0000269|Ref.8"
FT /id="VAR_020780"
FT VARIANT 147
FT /note="R -> W (loss of protein expression; loss of
FT localization to the plasma membrane; dbSNP:rs372192400)"
FT /evidence="ECO:0000269|PubMed:31003562,
FT ECO:0000269|PubMed:31254042"
FT /id="VAR_082302"
FT VARIANT 153
FT /note="T -> M (decreased protein abundance; no effect on
FT localization to the plasma membrane; no effect on substrate
FT transmembrane transport; decreased ATPase activity; no
FT effect on ATPase-coupled transmembrane transporter
FT activity; dbSNP:rs753759474)"
FT /evidence="ECO:0000269|PubMed:31003562,
FT ECO:0000269|PubMed:31254042"
FT /id="VAR_082303"
FT VARIANT 160
FT /note="R -> Q (in dbSNP:rs528655917)"
FT /evidence="ECO:0000269|PubMed:16702730"
FT /id="VAR_067364"
FT VARIANT 166
FT /note="Q -> E (in dbSNP:rs1061017)"
FT /evidence="ECO:0000269|PubMed:12958161,
FT ECO:0000269|PubMed:9850061"
FT /id="VAR_022704"
FT VARIANT 206
FT /note="I -> L (in dbSNP:rs12721643)"
FT /evidence="ECO:0000269|PubMed:12544509"
FT /id="VAR_022705"
FT VARIANT 208
FT /note="F -> S (in dbSNP:rs1061018)"
FT /evidence="ECO:0000269|PubMed:12958161,
FT ECO:0000269|PubMed:9850061"
FT /id="VAR_022706"
FT VARIANT 248
FT /note="S -> P (in dbSNP:rs3116448)"
FT /id="VAR_022707"
FT VARIANT 296
FT /note="D -> H (in dbSNP:rs41282401)"
FT /evidence="ECO:0000269|Ref.11"
FT /id="VAR_030357"
FT VARIANT 316
FT /note="T -> P"
FT /evidence="ECO:0000269|Ref.9"
FT /id="VAR_022443"
FT VARIANT 354
FT /note="G -> R (in dbSNP:rs138606116)"
FT /evidence="ECO:0000269|PubMed:16702730"
FT /id="VAR_067365"
FT VARIANT 360
FT /note="Missing (no effect on protein abundance; no effect
FT on localization to the plasma membrane; no effect on ATPase
FT activity; no effect on substrate transmembrane transport)"
FT /evidence="ECO:0000269|PubMed:31003562,
FT ECO:0000269|PubMed:31254042"
FT /id="VAR_082304"
FT VARIANT 373
FT /note="F -> C (decreased protein abundance; decreased
FT localization to the plasma membrane; no effect on ATPase-
FT coupled transmembrane transporter activity;
FT dbSNP:rs752626614)"
FT /evidence="ECO:0000269|PubMed:31003562,
FT ECO:0000269|PubMed:31254042"
FT /id="VAR_082305"
FT VARIANT 421
FT /note="T -> A (no effect on protein abundance; no effect on
FT substrate transmembrane transport; dbSNP:rs199854112)"
FT /evidence="ECO:0000269|PubMed:31003562"
FT /id="VAR_082306"
FT VARIANT 431
FT /note="F -> L"
FT /evidence="ECO:0000269|PubMed:15618737,
FT ECO:0000269|PubMed:16702730"
FT /id="VAR_018349"
FT VARIANT 434
FT /note="T -> M (no effect on protein abundance; no effect on
FT localization to the plasma membrane; increased ATPase
FT activity; decreased ATPase-coupled transmembrane
FT transporter activity; dbSNP:rs769734146)"
FT /evidence="ECO:0000269|PubMed:31003562,
FT ECO:0000269|PubMed:31254042"
FT /id="VAR_082307"
FT VARIANT 441
FT /note="S -> N (in dbSNP:rs1354553769)"
FT /evidence="ECO:0000269|PubMed:16702730"
FT /id="VAR_067366"
FT VARIANT 476
FT /note="S -> P (no effect on protein abundance; no effect on
FT localization to the plasma membrane; no effect on ATPase
FT activity; decreased ATPase-coupled transmembrane
FT transporter activity; dbSNP:rs1274428653)"
FT /evidence="ECO:0000269|PubMed:31003562,
FT ECO:0000269|PubMed:31254042"
FT /id="VAR_082308"
FT VARIANT 489
FT /note="F -> L (in dbSNP:rs192169063)"
FT /evidence="ECO:0000269|PubMed:15618737,
FT ECO:0000269|PubMed:16702730"
FT /id="VAR_018350"
FT VARIANT 528
FT /note="A -> T (in dbSNP:rs45605536)"
FT /evidence="ECO:0000269|Ref.11"
FT /id="VAR_030358"
FT VARIANT 571
FT /note="F -> I (in dbSNP:rs9282571)"
FT /id="VAR_022708"
FT VARIANT 572
FT /note="S -> R (decreased protein abundance; loss of
FT localization to the plasma membrane; dbSNP:rs200894058)"
FT /evidence="ECO:0000269|PubMed:31003562"
FT /id="VAR_082309"
FT VARIANT 590
FT /note="N -> Y (in dbSNP:rs34264773)"
FT /evidence="ECO:0000269|PubMed:12544509"
FT /id="VAR_035355"
FT VARIANT 620
FT /note="D -> N (no effect on protein abundance; no effect on
FT substrate transmembrane transport; dbSNP:rs34783571)"
FT /evidence="ECO:0000269|PubMed:15838659,
FT ECO:0000269|PubMed:31003562"
FT /id="VAR_022709"
FT MUTAGEN 71
FT /note="M->V: Decreased protein abundance. No effect on
FT substrate transmembrane transport."
FT /evidence="ECO:0000269|PubMed:31254042"
FT MUTAGEN 86
FT /note="K->M: Decreased protein abundance. Decreased
FT localization to the plasma membrane and retained
FT intracellularly. Loss of ATPase-coupled transmembrane
FT transporter activity."
FT /evidence="ECO:0000269|PubMed:15769853,
FT ECO:0000269|PubMed:31254042"
FT MUTAGEN 211
FT /note="E->Q: Decreased estrone-3 sulfate ATPase-coupled
FT transmembrane transporter activity. Decreased substrate-
FT induced ATP hydrolysis. Decreased substrate transport."
FT /evidence="ECO:0000269|PubMed:28554189,
FT ECO:0000269|PubMed:30405239"
FT MUTAGEN 362
FT /note="T->A: Loss of phosphorylation by PIM1. Decreased
FT localization to the plasma membrane. Decreased
FT homooligomerization. Loss of function in resistance to drug
FT treatment."
FT /evidence="ECO:0000269|PubMed:18056989"
FT MUTAGEN 362
FT /note="T->D: Loss of phosphorylation by PIM1. Constitutive
FT drug resistance independent of PIM1."
FT /evidence="ECO:0000269|PubMed:18056989"
FT MUTAGEN 383
FT /note="R->C: Loss of protein expression."
FT /evidence="ECO:0000269|PubMed:31254042"
FT MUTAGEN 418
FT /note="N->Q: No effect."
FT /evidence="ECO:0000269|PubMed:15807535"
FT MUTAGEN 435
FT /note="T->A: No effect on stability. Increased estrone-3
FT sulfate ATPase-coupled transmembrane transporter activity.
FT Increased substrate-induced ATP hydrolysis. Increased
FT substrate transport."
FT /evidence="ECO:0000269|PubMed:30405239"
FT MUTAGEN 435
FT /note="T->F: No effect on stability. Decreased estrone-3
FT sulfate ATPase-coupled transmembrane transporter activity.
FT Decreased substrate-induced ATP hydrolysis. Decreased
FT substrate transport."
FT /evidence="ECO:0000269|PubMed:30405239"
FT MUTAGEN 436
FT /note="N->A: No effect on stability. Decreased estrone-3
FT sulfate ATPase-coupled transmembrane transporter activity.
FT Decreased substrate-induced ATP hydrolysis. Decreased
FT substrate transport."
FT /evidence="ECO:0000269|PubMed:30405239"
FT MUTAGEN 439
FT /note="F->A: No effect on stability. Decreased estrone-3
FT sulfate ATPase-coupled transmembrane transporter activity.
FT Decreased substrate-induced ATP hydrolysis. Decreased
FT substrate transport."
FT /evidence="ECO:0000269|PubMed:30405239"
FT MUTAGEN 482
FT /note="R->D: Decreases ATPase activity."
FT /evidence="ECO:0000269|PubMed:15670731"
FT MUTAGEN 482
FT /note="R->G,N,S,T: Increases ATPase activity."
FT /evidence="ECO:0000269|PubMed:15670731"
FT MUTAGEN 482
FT /note="R->K,I,M,Y: No change in ATPase activity."
FT /evidence="ECO:0000269|PubMed:15670731"
FT MUTAGEN 482
FT /note="R->T,Y: Decreases transport activity."
FT /evidence="ECO:0000269|PubMed:15670731"
FT MUTAGEN 546
FT /note="V->A: No effect on stability. No effect on estrone-3
FT sulfate ATPase-coupled transmembrane transporter activity.
FT No effect on substrate-induced ATP hydrolysis. No effect on
FT substrate transport."
FT /evidence="ECO:0000269|PubMed:30405239"
FT MUTAGEN 546
FT /note="V->F: No effect on stability. Decreased estrone-3
FT sulfate ATPase-coupled transmembrane transporter activity.
FT Increased basal and substrate-induced ATP hydrolysis.
FT Decreased substrate transport."
FT /evidence="ECO:0000269|PubMed:30405239"
FT MUTAGEN 549
FT /note="M->A: No effect on stability. No effect on estrone-3
FT sulfate ATPase-coupled transmembrane transporter activity.
FT No effect on substrate-induced ATP hydrolysis. No effect on
FT substrate transport."
FT /evidence="ECO:0000269|PubMed:30405239"
FT MUTAGEN 554
FT /note="L->A: No effect on stability. Increased estrone-3
FT sulfate ATPase-coupled transmembrane transporter activity.
FT Increased basal and substrate-induced ATP hydrolysis.
FT Increased substrate transport."
FT /evidence="ECO:0000269|PubMed:30405239"
FT MUTAGEN 555
FT /note="L->A: Loss of protein expression."
FT /evidence="ECO:0000269|PubMed:30405239"
FT MUTAGEN 557
FT /note="N->Q: No effect."
FT /evidence="ECO:0000269|PubMed:15807535"
FT MUTAGEN 583
FT /note="H->A: Strongly reduced binding to hemin but not to
FT PPIX."
FT /evidence="ECO:0000269|PubMed:20705604"
FT MUTAGEN 596
FT /note="N->Q: Loss of glycosylation."
FT /evidence="ECO:0000269|PubMed:15807535"
FT MUTAGEN 603
FT /note="C->A: Strongly reduced binding to hemin but not to
FT PPIX."
FT /evidence="ECO:0000269|PubMed:20705604"
FT MUTAGEN 605
FT /note="Y->A: No effect on hemin binding."
FT /evidence="ECO:0000269|PubMed:20705604"
FT CONFLICT 24
FT /note="A -> V (in Ref. 1; AAD09188 and 7; AAP44087)"
FT /evidence="ECO:0000305"
FT CONFLICT 315..316
FT /note="Missing (in Ref. 10; BAA92050)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="G -> V (in Ref. 13; AAH92408)"
FT /evidence="ECO:0000305"
FT CONFLICT 482
FT /note="R -> G (in Ref. 14; AF093771/AF093772)"
FT /evidence="ECO:0000305"
FT CONFLICT 482
FT /note="R -> T (in Ref. 2; AAC97367)"
FT /evidence="ECO:0000305"
FT CONFLICT 484..485
FT /note="LP -> FT (in Ref. 14; AF093772)"
FT /evidence="ECO:0000305"
FT CONFLICT 501
FT /note="P -> A (in Ref. 6; AAG52982)"
FT /evidence="ECO:0000305"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:6HBU"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:7OJ8"
FT STRAND 60..64
FT /evidence="ECO:0007829|PDB:7OJ8"
FT STRAND 66..71
FT /evidence="ECO:0007829|PDB:6HBU"
FT STRAND 73..79
FT /evidence="ECO:0007829|PDB:6HBU"
FT TURN 82..85
FT /evidence="ECO:0007829|PDB:7NEQ"
FT HELIX 86..93
FT /evidence="ECO:0007829|PDB:6HBU"
FT TURN 99..101
FT /evidence="ECO:0007829|PDB:6ETI"
FT STRAND 104..108
FT /evidence="ECO:0007829|PDB:6HBU"
FT TURN 116..120
FT /evidence="ECO:0007829|PDB:6HBU"
FT STRAND 121..124
FT /evidence="ECO:0007829|PDB:6HBU"
FT STRAND 132..135
FT /evidence="ECO:0007829|PDB:7NEQ"
FT HELIX 136..147
FT /evidence="ECO:0007829|PDB:6HBU"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:7OJ8"
FT HELIX 154..168
FT /evidence="ECO:0007829|PDB:6HBU"
FT TURN 172..175
FT /evidence="ECO:0007829|PDB:6HBU"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 188..198
FT /evidence="ECO:0007829|PDB:6HBU"
FT TURN 199..202
FT /evidence="ECO:0007829|PDB:6HBU"
FT STRAND 205..211
FT /evidence="ECO:0007829|PDB:6HBU"
FT TURN 212..215
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 218..232
FT /evidence="ECO:0007829|PDB:6HBU"
FT TURN 233..235
FT /evidence="ECO:0007829|PDB:6HBU"
FT STRAND 237..241
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 247..250
FT /evidence="ECO:0007829|PDB:6HBU"
FT STRAND 254..260
FT /evidence="ECO:0007829|PDB:6HBU"
FT STRAND 263..268
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 270..272
FT /evidence="ECO:0007829|PDB:7NEQ"
FT HELIX 274..277
FT /evidence="ECO:0007829|PDB:6HBU"
FT TURN 278..281
FT /evidence="ECO:0007829|PDB:6HBU"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:7NEQ"
FT HELIX 290..297
FT /evidence="ECO:0007829|PDB:6HBU"
FT TURN 298..301
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 303..307
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 328..337
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 340..352
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 373..390
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 393..412
FT /evidence="ECO:0007829|PDB:6HBU"
FT TURN 413..415
FT /evidence="ECO:0007829|PDB:7OJH"
FT STRAND 418..421
FT /evidence="ECO:0007829|PDB:6VXF"
FT HELIX 423..439
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 440..447
FT /evidence="ECO:0007829|PDB:6HBU"
FT TURN 448..451
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 452..460
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 466..478
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 479..483
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 484..492
FT /evidence="ECO:0007829|PDB:6HBU"
FT TURN 493..497
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 504..528
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 535..550
FT /evidence="ECO:0007829|PDB:6HBU"
FT STRAND 553..556
FT /evidence="ECO:0007829|PDB:6HBU"
FT TURN 558..560
FT /evidence="ECO:0007829|PDB:6HBU"
FT TURN 563..567
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 568..570
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 573..585
FT /evidence="ECO:0007829|PDB:6HBU"
FT STRAND 586..588
FT /evidence="ECO:0007829|PDB:6HBU"
FT STRAND 597..599
FT /evidence="ECO:0007829|PDB:6HBU"
FT STRAND 602..605
FT /evidence="ECO:0007829|PDB:6ETI"
FT HELIX 610..617
FT /evidence="ECO:0007829|PDB:6HBU"
FT HELIX 624..649
FT /evidence="ECO:0007829|PDB:6HBU"
SQ SEQUENCE 655 AA; 72314 MW; A8AF66B96034C5A8 CRC64;
MSSSNVEVFI PVSQGNTNGF PATASNDLKA FTEGAVLSFH NICYRVKLKS GFLPCRKPVE
KEILSNINGI MKPGLNAILG PTGGGKSSLL DVLAARKDPS GLSGDVLING APRPANFKCN
SGYVVQDDVV MGTLTVRENL QFSAALRLAT TMTNHEKNER INRVIQELGL DKVADSKVGT
QFIRGVSGGE RKRTSIGMEL ITDPSILFLD EPTTGLDSST ANAVLLLLKR MSKQGRTIIF
SIHQPRYSIF KLFDSLTLLA SGRLMFHGPA QEALGYFESA GYHCEAYNNP ADFFLDIING
DSTAVALNRE EDFKATEIIE PSKQDKPLIE KLAEIYVNSS FYKETKAELH QLSGGEKKKK
ITVFKEISYT TSFCHQLRWV SKRSFKNLLG NPQASIAQII VTVVLGLVIG AIYFGLKNDS
TGIQNRAGVL FFLTTNQCFS SVSAVELFVV EKKLFIHEYI SGYYRVSSYF LGKLLSDLLP
MRMLPSIIFT CIVYFMLGLK PKADAFFVMM FTLMMVAYSA SSMALAIAAG QSVVSVATLL
MTICFVFMMI FSGLLVNLTT IASWLSWLQY FSIPRYGFTA LQHNEFLGQN FCPGLNATGN
NPCNYATCTG EEYLVKQGID LSPWGLWKNH VALACMIVIF LTIAYLKLLF LKKYS
