ABCG2_MACMU
ID ABCG2_MACMU Reviewed; 654 AA.
AC Q5MB13;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 96.
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 Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Kidney;
RX PubMed=15516692; DOI=10.1074/jbc.m409796200;
RA Ueda T., Brenner S., Malech H.L., Langemeijer S.M., Perl S., Kirby M.,
RA Phang O.A., Krouse A.E., Donahue R.E., Kang E.M., Tisdale J.F.;
RT "Cloning and functional analysis of the rhesus macaque ABCG2 gene. Forced
RT expression confers an SP phenotype among hematopoietic stem cell progeny in
RT vivo.";
RL J. Biol. Chem. 280:991-998(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 (PubMed:15516692).
CC {ECO:0000250|UniProtKB:Q7TMS5, ECO:0000250|UniProtKB:Q9UNQ0,
CC ECO:0000269|PubMed:15516692}.
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}.
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DR EMBL; AY841878; AAW28901.1; -; mRNA.
DR RefSeq; NP_001028091.1; NM_001032919.1.
DR AlphaFoldDB; Q5MB13; -.
DR SMR; Q5MB13; -.
DR STRING; 9544.ENSMMUP00000011540; -.
DR GeneID; 574307; -.
DR KEGG; mcc:574307; -.
DR CTD; 9429; -.
DR eggNOG; KOG0061; Eukaryota.
DR InParanoid; Q5MB13; -.
DR Proteomes; UP000006718; 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:0046983; F:protein dimerization activity; IEA:UniProt.
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; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR48041:SF92; PTHR48041:SF92; 1.
DR Pfam; PF01061; ABC2_membrane; 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 2: Evidence at transcript level;
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..654
FT /note="Broad substrate specificity ATP-binding cassette
FT transporter ABCG2"
FT /id="PRO_0000093387"
FT TOPO_DOM 1..394
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 395..415
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 416..427
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 428..448
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 449..476
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 477..497
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 498..505
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 506..526
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 527..534
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 535..555
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 556..629
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 630..650
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 651..654
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 37..286
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 388..650
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 BINDING 184..190
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9UNQ0"
FT BINDING 211
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9UNQ0"
FT BINDING 243
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9UNQ0"
FT CARBOHYD 417
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 556
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 595
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 599
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 591..607
FT /evidence="ECO:0000250|UniProtKB:Q9UNQ0"
FT DISULFID 602
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q9UNQ0"
SQ SEQUENCE 654 AA; 72459 MW; A9B3F3CC8305EC88 CRC64;
MSSSNVEVFI PMSQENTNGF PTTTSNDRKA FTEGAVLSFH NICYRVKVKS GFLPGRKPVE
KEILSNINGI MKPGLNAILG PTGGGKSSLL DVLAARKDPS GLSGDVLING ALRPTNFKCN
SGYVVQDDVV MGTLTVRENL QFSAALRLPT TMTNHEKNER INRVIQELGL DKVADSKVGT
QFIRGVSGGE RKRTSIGMEL ITDPSILFLD EPTTGLDSST ANAVLLLLKR MSKQGRTIIF
SIHQPRYSIF KLFDSLTLLA SGRLMFHGPA QEALGYFESA GYHCEAYNNP ADFFLDIING
DSTAVALNRE EDFKATEIIE PSKRDKPLVE KLAEIYVDSS FYKETKAELH QLSGGEKKKI
TVFKEISYTT SFCHQLRWVS KRSFKNLLGN PQASIAQIIV TVILGLVIGA IYFGLNNDST
GIQNRAGVLF FLTTNQCFSS VSAVELFVVE KKLFIHEYIS GYYRVSSYFF GKLLSDLLPM
RMLPSIIFTC IVYFMLGLKP TADAFFIMMF TLMMVAYSAS SMALAIAAGQ SVVSVATLLM
TICFVFMMIF SGLLVNLTTI ASWLSWLQYF SIPRYGFTAL QHNEFLGQNF CPGLNATVNN
TCNYATCTGE EYLAKQGIDL SPWGLWKNHV ALACMIVIFL TIAYLKLLFL KKYS
