ABCG2

ATP-binding cassette super-family G member 2 is a protein that in humans is encoded by the ABCG2 gene.^[6][7] ABCG2 has also been designated as CDw338 (cluster of differentiation w338). ABCG2 is a translocation protein used to actively pump drugs and other compounds against their concentration gradient using the bonding and hydrolysis of ATP as the energy source.^[1]

ABCG2 with simulated plasma membrane^[1]

ABCG2
Identifiers
Aliases	ABCG2, ATP-binding cassette, sub-family G (WHITE), member 2 (Junior blood group), ABC15, ABCP, BCRP, BCRP1, BMDP, CD338, CDw338, EST157481, GOUT1, MRX, MXR, MXR1, UAQTL1, MXR-1, ATP binding cassette subfamily G member 2 (Junior blood group)
External IDs	OMIM: 603756; MGI: 1347061; HomoloGene: 55852; GeneCards: ABCG2; OMA:ABCG2 - orthologs
Gene location (Human) Chr. Chromosome 4 (human)[2] Band 4q22.1 Start 88,090,150 bp[2] End 88,231,628 bp[2]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[3] Band 6 B3|6 27.82 cM Start 58,561,508 bp[3] End 58,672,661 bp[3]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa mucosa of ileum endothelial cell mucosa of transverse colon seminal vesicula duodenum substantia nigra internal globus pallidus placenta C1 segment Top expressed in right kidney proximal tubule human kidney ileum fetal liver hematopoietic progenitor cell yolk sac jejunum tail of embryo sciatic nerve human fetus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding ABC-type xenobiotic transporter activity heme transmembrane transporter activity protein homodimerization activity transporter activity ATPase activity protein binding ATP binding ATPase-coupled transmembrane transporter activity cholesterol transfer activity identical protein binding xenobiotic transmembrane transporter activity Cellular component mitochondrial membranes membrane mitochondrion nucleus plasma membrane integral component of membrane apical plasma membrane receptor complex Biological process urate metabolic process cellular iron ion homeostasis heme transport xenobiotic transmembrane transport xenobiotic transport transmembrane transport cholesterol efflux cellular detoxification Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9429 26357 Ensembl ENSG00000118777 ENSMUSG00000029802 UniProt Q9UNQ0 Q7TMS5 RefSeq (mRNA) NM_001257386 NM_004827 NM_001348985 NM_001348986 NM_001348987 NM_001348988 NM_001348989 NM_011920 NM_001355477 NM_001381925 NM_001381926 NM_001381927 RefSeq (protein) NP_001244315 NP_004818 NP_001335914 NP_001335915 NP_001335916 NP_001335917 NP_001335918 NP_036050 NP_001342406 NP_001368854 NP_001368855 NP_001368856 Location (UCSC) Chr 4: 88.09 – 88.23 Mb Chr 6: 58.56 – 58.67 Mb PubMed search [4] [5]
Wikidata
View/Edit Human View/Edit Mouse

ABCG2 forms into a homodimer to assume its active transport conformation. The dimer weighs approximately 144 kDa. The expression of this transport protein is highly conserved throughout the animal kingdom, pointing to its importance.^[8]

Substrate binding with compounds occurs in the large central cavity. ABCG2 can bind to a broad range of compounds but binds strongest to flat, polycyclic chemicals with lots of hydrophobic character.^[1]

Function

The membrane-associated protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. The active transport of chemicals requires a source of energy to catalyze the conformational changes the protein undergoes. The nucleotide-binding domains (NBDs) found towards the N-terminus allow binding to ATP molecules. The NBD and the transmembrane domain (TMD) are the most conserved region of the transporter in various animal groups, highlighting the importance of these regions for overall protein function.^[8] Additionally, many ABC transporters have conserved NBD regions showing the strict conformation needed to bind ATP molecules.^[1]

ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. Alternatively referred to as the breast cancer resistance protein (BCRP), this protein functions as a xenobiotic transporter which may play a role in multi-drug resistance to chemotherapeutic agents including mitoxantrone and camptothecin analogues.^[8] Early observations of significant ABCG2-mediated resistance to anthracyclines were subsequently attributed mutations encountered in vitro but not in nature or the clinic. Significant expression of this protein has been observed in the placenta,^[9] and it has been shown to have a role in protecting the fetus from xenobiotics in the maternal circulation.^[10]

The transporter has been shown to play protective roles in blocking absorption at the apical membrane of the intestine, and at the blood–testis barrier,^[10] the blood–brain barrier,^[10] and the membranes of hematopoietic progenitor and other stem cells. At the apical membranes of the liver and kidney, it enhances excretion of xenobiotics. In the lactating mammary gland, it has a role on excreting vitamins such as riboflavin and biotin into milk.^[10] Xenobiotic toxins compete for the substrate binding domain of ABCG2 potentially causing toxins to concentrate in the breast milk.^[8] In the kidney and gastrointestinal tract, it has a role in urate excretion.

The protein also carries the Jr(a) antigen, which defines the Junior blood group system.^[11]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.[§ 1] [[File: [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] |alt=Fluorouracil (5-FU) Activity edit]] Fluorouracil (5-FU) Activity edit The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

Click on genes, proteins and metabolites below to link to respective articles. [§ 1] [[File: [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] [[ ]] |alt=Irinotecan Pathway edit]] Irinotecan Pathway edit The interactive pathway map can be edited at WikiPathways: "IrinotecanPathway_WP229".

Inhibition

It is inhibited by some calcium channel blockers such as amlodipine, felodipine and nifedipine.^[12] The fungal toxin fumitremorgin C (FTC) inhibits the protein but has neurotoxic side effects. A synthetic tetracyclic analog of FTC called Ko-143 inhibits ABCG2.^[13]

See also

• ATP-binding cassette transporter