ABCG2_BOVIN
ID ABCG2_BOVIN Reviewed; 655 AA.
AC Q4GZT4;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Broad substrate specificity ATP-binding cassette transporter ABCG2 {ECO:0000305};
DE EC=7.6.2.2 {ECO:0000250|UniProtKB:Q9UNQ0};
DE AltName: Full=ATP-binding cassette sub-family G member 2;
DE AltName: Full=Urate exporter;
DE AltName: CD_antigen=CD338;
GN Name=ABCG2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-578.
RC STRAIN=Holstein;
RX PubMed=15998908; DOI=10.1101/gr.3806705;
RA Cohen-Zinder M., Seroussi E., Larkin D.M., Loor J.J.,
RA Everts-van der Wind A., Lee J.-H., Drackley J.K., Band M.R.,
RA Hernandez A.G., Shani M., Lewin H.A., Weller J.I., Ron M.;
RT "Identification of a missense mutation in the bovine ABCG2 gene with a
RT major effect on the QTL on chromosome 6 affecting milk yield and
RT composition in Holstein cattle.";
RL Genome Res. 15:936-944(2005).
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 Involved in porphyrin homeostasis, mediating the export of
CC protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol
CC to extracellular space, it also functions in the cellular export of
CC heme. Also mediates the efflux of sphingosine-1-P from cells. Acts as a
CC urate exporter functioning in both renal and extrarenal urate excretion
CC (By similarity). In kidney, it also functions as a physiological
CC exporter of the uremic toxin indoxyl sulfate (By similarity). Also
CC involved in the excretion of steroids like estrone 3-sulfate/E1S,
CC 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates
CC (By similarity). Mediates the secretion of the riboflavin and biotin
CC vitamins into milk. 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. It confers to cells a resistance to multiple drugs and
CC other xenobiotics including mitoxantrone, pheophorbide, camptothecin,
CC methotrexate, azidothymidine, and the anthracyclines daunorubicin and
CC doxorubicin, through the control of their efflux (By similarity). In
CC placenta, it limits the penetration of drugs from the maternal plasma
CC into the fetus. May play a role in early stem cell self-renewal by
CC blocking differentiation (By similarity).
CC {ECO:0000250|UniProtKB:Q7TMS5, ECO:0000250|UniProtKB:Q9UNQ0}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate +
CC xenobioticSide 2.; EC=7.6.2.2;
CC Evidence={ECO:0000250|UniProtKB:Q9UNQ0};
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:0000250|UniProtKB:Q9UNQ0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16462;
CC Evidence={ECO:0000250|UniProtKB:Q9UNQ0};
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:0000250|UniProtKB:Q9UNQ0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38952;
CC Evidence={ECO:0000250|UniProtKB:Q9UNQ0};
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:0000250|UniProtKB:Q9UNQ0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61349;
CC Evidence={ECO:0000250|UniProtKB:Q9UNQ0};
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:0000250|UniProtKB:Q9UNQ0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61365;
CC Evidence={ECO:0000250|UniProtKB:Q9UNQ0};
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:0000250|UniProtKB:Q9UNQ0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61369;
CC Evidence={ECO:0000250|UniProtKB:Q9UNQ0};
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:0000250|UniProtKB:Q9UNQ0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61385;
CC Evidence={ECO:0000250|UniProtKB:Q9UNQ0};
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:0000250|UniProtKB:Q9UNQ0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61373;
CC Evidence={ECO:0000250|UniProtKB:Q9UNQ0};
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:0000250|UniProtKB:Q9UNQ0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61377;
CC Evidence={ECO:0000250|UniProtKB:Q9UNQ0};
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:0000250|UniProtKB:Q9UNQ0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60129;
CC Evidence={ECO:0000250|UniProtKB:Q9UNQ0};
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:0000250|UniProtKB:Q9UNQ0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61357;
CC Evidence={ECO:0000250|UniProtKB:Q9UNQ0};
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 -!- SUBUNIT: Homodimer; disulfide-linked. 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. {ECO:0000250|UniProtKB:Q9UNQ0}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9UNQ0};
CC Multi-pass membrane protein {ECO:0000255}. Apical cell membrane
CC {ECO:0000250|UniProtKB:Q9UNQ0}; Multi-pass membrane protein
CC {ECO:0000255}. Mitochondrion membrane {ECO:0000250|UniProtKB:Q9UNQ0};
CC Multi-pass membrane protein {ECO:0000255}. Note=Enriched in membrane
CC lipid rafts. {ECO:0000250|UniProtKB:Q9UNQ0}.
CC -!- DOMAIN: The extracellular loop 3 (ECL3) is involved in binding
CC porphyrins and transfer them to other carriers, probably albumin.
CC {ECO:0000250|UniProtKB:Q9UNQ0}.
CC -!- PTM: N-glycosylated. Glycosylation-deficient ABCG2 is normally
CC expressed and functional. {ECO:0000250|UniProtKB:Q9UNQ0}.
CC -!- PTM: Phosphorylated. Phosphorylation may regulate the localization to
CC the plasma membrane, the homooligomerization and therefore, the
CC activity of the transporter. {ECO:0000250|UniProtKB:Q9UNQ0}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCG family.
CC Eye pigment precursor importer (TC 3.A.1.204) subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAI38796.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AJ871176; CAI38796.1; ALT_INIT; Genomic_DNA.
DR RefSeq; XP_005207851.1; XM_005207794.2.
DR RefSeq; XP_005207852.1; XM_005207795.3.
DR RefSeq; XP_005207853.1; XM_005207796.2.
DR RefSeq; XP_005207854.1; XM_005207797.3.
DR RefSeq; XP_010804335.1; XM_010806033.2.
DR RefSeq; XP_010804337.1; XM_010806035.2.
DR AlphaFoldDB; Q4GZT4; -.
DR SMR; Q4GZT4; -.
DR STRING; 9913.ENSBTAP00000051068; -.
DR PaxDb; Q4GZT4; -.
DR PRIDE; Q4GZT4; -.
DR GeneID; 536203; -.
DR CTD; 9429; -.
DR eggNOG; KOG0061; Eukaryota.
DR HOGENOM; CLU_000604_57_8_1; -.
DR InParanoid; Q4GZT4; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0008559; F:ABC-type xenobiotic transporter activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015225; F:biotin transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015562; F:efflux transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0032217; F:riboflavin transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015143; F:urate transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015878; P:biotin transport; ISS:UniProtKB.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR GO; GO:0097744; P:renal urate salt excretion; ISS:UniProtKB.
DR GO; GO:0032218; P:riboflavin transport; ISS:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; ISS:UniProtKB.
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 3: Inferred from homology;
KW ATP-binding; Cell membrane; Disulfide bond; Glycoprotein; Lipid transport;
KW Membrane; Mitochondrion; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Translocase; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..655
FT /note="Broad substrate specificity ATP-binding cassette
FT transporter ABCG2"
FT /id="PRO_0000244032"
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 36..285
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 389..651
FT /note="ABC transmembrane type-2"
FT BINDING 79..86
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 183..189
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9UNQ0"
FT BINDING 210
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9UNQ0"
FT BINDING 242
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9UNQ0"
FT CARBOHYD 596
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 600
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 592..608
FT /evidence="ECO:0000250|UniProtKB:Q9UNQ0"
FT DISULFID 603
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q9UNQ0"
FT VARIANT 578
FT /note="Y -> S (affecting milk fat and protein
FT concentration)"
FT /evidence="ECO:0000269|PubMed:15998908"
SQ SEQUENCE 655 AA; 72725 MW; 8F1AD75742AD236E CRC64;
MSSNSYEVSI PMSKKLNGIP ETTSKDLQTL TEGAVLSFHN ICYRVKVKTG FLLCRKTIEK
EILANINGVM KPGLNAILGP TGGGKSSLLD ILAARKDPHG LSGDVLINGA PRPANFKCNS
GYVVQDDVVM GTLTVRENLQ FSAALRLPTT MTSYEKNERI NKVIQELGLD KVADSKVGTQ
FIRGVSGGER KRTSIAMELI TDPSILFLDE PTTGLDSSTA NAVLLLLKRM SKQGRTIIFS
IHQPRYSIFK LFDSLTLLAS GRLMFHGPAQ EALGYFGAIG FRCEPYNNPA DFFLDIINGD
SSAVVLNRED IGDEANETEE PSKKDTPLIE KLAEFYVNSS FFKETKVELD KFSGDQRRKK
LPSYKEVTYA TSFCHQLKWI SRRSFKNLLG NPQASIAQLI VTVFLGLVIG AIFYDLKNDP
AGIQNRAGVL FFLTTNQCFS SVSAVELLVV EKKLFIHEYI SGYYRVSSYF FGKLLSDLLP
MRMLPSIIFT CITYFLLGLK PKVEAFFIMM LTLMMVAYSA SSMALAIAAG QSVVSIATLL
MTISFVFMMI FSGLLVNLKT VVPWLSWLQY LSIPRYGYAA LQHNEFLGQN FCPGLNVTTN
NTCSYAICTG EEFLTNQGID ISPWGLWKNH VALACMIVIF LTIAYLKLLF LKKFS
