View source for ABCG2

{{short description|Protein-coding gene in the species Homo sapiens}}
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[[File:ABCG2 with plasma membrane.jpg|thumb|ABCG2 with simulated plasma membrane<ref name=":1" />]]
{{Infobox_gene}}

'''ATP-binding cassette super-family G member 2''' is a [[protein]] that in humans is encoded by the ''ABCG2'' [[gene]].<ref name="pmid8894702">{{cite journal | vauthors = Allikmets R, Gerrard B, Hutchinson A, Dean M | title = Characterization of the human ABC superfamily: isolation and mapping of 21 new genes using the expressed sequence tags database | journal = Human Molecular Genetics | volume = 5 | issue = 10 | pages = 1649–1655 | date = October 1996 | pmid = 8894702 | doi = 10.1093/hmg/5.10.1649 | doi-access = free }}</ref><ref name="pmid9861027">{{cite journal | vauthors = Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK, Ross DD | title = A multidrug resistance transporter from human MCF-7 breast cancer cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 26 | pages = 15665–15670 | date = December 1998 | pmid = 9861027 | pmc = 28101 | doi = 10.1073/pnas.95.26.15665 | bibcode = 1998PNAS...9515665D | doi-access = free }}</ref> 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 [[Adenosine triphosphate|ATP]] as the energy source.<ref name=":1">{{cite journal | vauthors = Taylor NM, Manolaridis I, Jackson SM, Kowal J, Stahlberg H, Locher KP | title = Structure of the human multidrug transporter ABCG2 | journal = Nature | volume = 546 | issue = 7659 | pages = 504–509 | date = June 2017 | pmid = 28554189 | doi = 10.1038/nature22345 | bibcode = 2017Natur.546..504T | hdl = 20.500.11850/233014 | s2cid = 4461745 | hdl-access = free }}</ref>

ABCG2 forms into a [[Protein dimer|homodimer]] to assume its active transport conformation. The dimer weighs approximately 144 [[Dalton (unit)|kDa]]. The expression of this transport protein is highly conserved throughout the animal kingdom, pointing to its importance.<ref name=":0" />

[[Substrate (chemistry)|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 compound|polycyclic chemicals]] with lots of hydrophobic character.<ref name=":1" />

== Function ==

The membrane-associated protein encoded by this gene is included in the superfamily of [[ATP-binding cassette transporter|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.<ref name=":0" /> Additionally, many ABC transporters have conserved NBD regions showing the strict conformation needed to bind ATP molecules.<ref name=":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.<ref name=":0">{{cite journal | vauthors = Robey RW, To KK, Polgar O, Dohse M, Fetsch P, Dean M, Bates SE | title = ABCG2: a perspective | journal = Advanced Drug Delivery Reviews | volume = 61 | issue = 1 | pages = 3–13 | date = January 2009 | pmid = 19135109 | pmc = 3105088 | doi = 10.1016/j.addr.2008.11.003 }}</ref> 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]],<ref>{{cite web | title = Entrez Gene: ABCG2 ATP-binding cassette, sub-family G (WHITE), member 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9429}}</ref> and it has been shown to have a role in protecting the fetus from [[xenobiotic]]s in the maternal circulation.<ref name="Vlaming">{{cite journal | vauthors = Vlaming ML, Lagas JS, Schinkel AH | title = Physiological and pharmacological roles of ABCG2 (BCRP): recent findings in Abcg2 knockout mice | journal = Advanced Drug Delivery Reviews | volume = 61 | issue = 1 | pages = 14–25 | date = January 2009 | pmid = 19118589 | doi = 10.1016/j.addr.2008.08.007 }}</ref>

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]],<ref name = "Vlaming"/> the [[blood–brain barrier]],<ref name = "Vlaming"/> and the membranes of [[Hematopoietic stem cell|hematopoietic progenitor]] and other [[stem cell]]s. 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.<ref name = "Vlaming"/> Xenobiotic toxins compete for the substrate binding domain of ABCG2 potentially causing toxins to concentrate in the breast milk.<ref name=":0" /> 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]].<ref name="OMIM">{{cite web |title=OMIM entry # 614490 – BLOOD GROUP, JUNIOR SYSTEM; JR |author=Kniffin CL |work=[[Online Mendelian Inheritance in Man]] |date=2013 |access-date=1 September 2019 |url= https://www.omim.org/entry/614490}}</ref>

== Interactive pathway map ==
{|
|{{FluoropyrimidineActivity WP1601|highlight=ABCG2}}
|{{IrinotecanPathway_WP229|highlight=ABCG2}}
|}

==Inhibition==
It is inhibited by some calcium channel blockers such as [[amlodipine]], [[felodipine]] and [[nifedipine]].<ref name="Ghosh Sircar 2008 p=190">{{cite journal | vauthors = Ghosh S, Sircar M | title = Calcium channel blocker overdose: experience with amlodipine | journal = Indian Journal of Critical Care Medicine | volume = 12 | issue = 4 | pages = 190–193 | date = October 2008 | pmid = 19742263 | pmc = 2738322 | doi = 10.4103/0972-5229.45080 | publisher = Jaypee Brothers Medical Publishing | doi-access = free }}</ref> The fungal toxin [[fumitremorgin|fumitremorgin C]] (FTC) inhibits the protein but has neurotoxic side effects. A synthetic [[tetracyclic]] analog of FTC called Ko-143 inhibits ABCG2.<ref>{{cite journal | vauthors = Jackson SM, Manolaridis I, Kowal J, Zechner M, Taylor NM, Bause M, Bauer S, Bartholomaeus R, Bernhardt G, Koenig B, Buschauer A, Stahlberg H, Altmann KH, Locher KP | display-authors = 6 | title = Structural basis of small-molecule inhibition of human multidrug transporter ABCG2 | journal = Nature Structural & Molecular Biology | volume = 25 | issue = 4 | pages = 333–340 | date = April 2018 | pmid = 29610494 | doi = 10.1038/s41594-018-0049-1 | hdl = 20.500.11850/256191 | s2cid = 4617388 | hdl-access = free }}</ref>

== See also ==
* [[ATP-binding cassette transporter]]

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Hazai E, Bikádi Z | title = Homology modeling of breast cancer resistance protein (ABCG2) | journal = Journal of Structural Biology | volume = 162 | issue = 1 | pages = 63–74 | date = April 2008 | pmid = 18249138 | doi = 10.1016/j.jsb.2007.12.001 }}
* {{cite journal | vauthors = Abbott BL | title = ABCG2 (BCRP): a cytoprotectant in normal and malignant stem cells | journal = Clinical Advances in Hematology & Oncology | volume = 4 | issue = 1 | pages = 63–72 | date = January 2006 | pmid = 16562373 }}
* {{cite journal | vauthors = Schmitz G, Langmann T, Heimerl S | title = Role of ABCG1 and other ABCG family members in lipid metabolism | journal = Journal of Lipid Research | volume = 42 | issue = 10 | pages = 1513–1520 | date = October 2001 | pmid = 11590207 | doi = 10.1016/S0022-2275(20)32205-7 | doi-access = free }}
* {{cite journal | vauthors = Ejendal KF, Hrycyna CA | title = Multidrug resistance and cancer: the role of the human ABC transporter ABCG2 | journal = Current Protein & Peptide Science | volume = 3 | issue = 5 | pages = 503–511 | date = October 2002 | pmid = 12369998 | doi = 10.2174/1389203023380521 }}
* {{cite journal | vauthors = Doyle L, Ross DD | title = Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2) | journal = Oncogene | volume = 22 | issue = 47 | pages = 7340–7358 | date = October 2003 | pmid = 14576842 | doi = 10.1038/sj.onc.1206938 | s2cid = 9648841 | doi-access =  }}
* {{cite journal | vauthors = Sugimoto Y, Tsukahara S, Ishikawa E, Mitsuhashi J | title = Breast cancer resistance protein: molecular target for anticancer drug resistance and pharmacokinetics/pharmacodynamics | journal = Cancer Science | volume = 96 | issue = 8 | pages = 457–465 | date = August 2005 | pmid = 16108826 | doi = 10.1111/j.1349-7006.2005.00081.x | s2cid = 20734576 | doi-access =  | pmc = 11158713 }}
* {{cite journal | vauthors = Ishikawa T, Tamura A, Saito H, Wakabayashi K, Nakagawa H | title = Pharmacogenomics of the human ABC transporter ABCG2: from functional evaluation to drug molecular design | journal = Die Naturwissenschaften | volume = 92 | issue = 10 | pages = 451–463 | date = October 2005 | pmid = 16160819 | doi = 10.1007/s00114-005-0019-4 | bibcode = 2005NW.....92..451I | s2cid = 22151149 }}
* {{cite journal | vauthors = Krishnamurthy P, Schuetz JD | title = Role of ABCG2/BCRP in biology and medicine | journal = Annual Review of Pharmacology and Toxicology | volume = 46 | pages = 381–410 | year = 2006 | pmid = 16402910 | doi = 10.1146/annurev.pharmtox.46.120604.141238 }}
* {{cite journal | vauthors = Robey RW, Polgar O, Deeken J, To KW, Bates SE | title = ABCG2: determining its relevance in clinical drug resistance | journal = Cancer and Metastasis Reviews | volume = 26 | issue = 1 | pages = 39–57 | date = March 2007 | pmid = 17323127 | doi = 10.1007/s10555-007-9042-6 | s2cid = 11293439 | url = https://zenodo.org/record/1232789 }}
{{refend}}

== External links ==
* {{MeshName|ABCG2+protein,+human}}
* {{UCSC gene info|ABCG2}}
* {{PDBe-KB2|Q9UNQ0|Broad substrate specificity ATP-binding cassette transporter ABCG2}}

{{NLM content}}
{{Clusters of differentiation}}
{{ABC transporters}}

{{DEFAULTSORT:Abcg2}}
[[Category:Clusters of differentiation]]
[[Category:ATP-binding cassette transporters]]