Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)
The protein contains 655 amino acids for an estimated molecular weight of 72314 Da.
Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, ca (updated: Oct. 16, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
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No binding partner found
Biological Process
Biotin transport
Cellular detoxification
Cellular iron ion homeostasis
Cholesterol efflux
Drug transmembrane transport
Export across plasma membrane
Heme biosynthetic process
Heme catabolic process
Heme transport
Organic anion transport
Response to drug
Riboflavin transport
Small molecule metabolic process
Transepithelial transport
Transmembrane transport
Transport
Transport across blood-brain barrier
Urate metabolic process
Urate salt excretion
Xenobiotic transport
Xenobiotic transport across blood-brain barrier
Cellular Component
Apical plasma membrane
Brush border membrane
Cell surface
External side of apical plasma membrane
Integral component of membrane
Membrane raft
Mitochondrial membrane
Nucleoplasm
Nucleus
Obsolete cell
Plasma membrane
Receptor complex
Molecular Function
ABC-type xenobiotic transporter activity
ATP binding
ATPase
ATPase-coupled transmembrane transporter activity
Biotin transmembrane transporter activity
Drug transmembrane transporter activity
Efflux transmembrane transporter activity
Heme transmembrane transporter activity
Identical protein binding
Organic anion transmembrane transporter activity
Protein homodimerization activity
Riboflavin transmembrane transporter activity
Transporter activity
Urate transmembrane transporter activity
Xenobiotic transmembrane transporter activity
The reference OMIM entry for this protein is 138900
Uric acid concentration, serum, quantitative trait locus 1; uaqtl1
Gout susceptibility 1; gout1
A number sign (#) is used with this entry because of evidence that serum uric acid concentration and susceptibility to gout can be conferred by variation in the ABCG2 gene (603756) on chromosome 4q22.
DESCRIPTION
Gout is a common disorder resulting from tissue deposition of monosodium urate crystals as a consequence of hyperuricemia. Patients with gout experience very painful attacks caused by precipitation of urate in joints, which triggers subsequent inflammation. Elevated serum uric acid concentration is a key risk factor for gout (summary from Matsuo et al., 2009 and Woodward et al., 2011). - Genetic Heterogeneity of Serum Uric Acid Concentration Quantitative Trait Loci See also UAQTL2 (see 612076), conferred by variation in the SLC2A9 gene (606142) on chromosome 4p; UAQTL4 (612671), conferred by variation in the SLC17A3 gene (611034) on chromosome 6p21; UAQTL5 (614746), associated with a SNP on chromosome 19q13; and UAQTL6 (614747), associated with a SNP on chromosome 1.MAPPING
The Pacific Austronesian population, including Taiwanese aborigines, has a remarkably high prevalence of hyperuricemia and gout, suggesting a founder effect across the Pacific region. Cheng et al. (2004) reported a genomewide linkage study of 21 multiplex pedigrees with gout from an aboriginal tribe in Taiwan. From observations of familial clustering, early onset of gout, and clinically severe manifestations, they hypothesized that a major gene plays a role in this trait. A highly significant linkage for gout at marker D4S2623 was found on 4q25. When alcohol consumption was included as a covariate in the model, the lod score increased to 5.66. By genomewide linkage analysis of 7,699 participants in the Framingham cohort and in 4,148 participants in a Rotterdam cohort, Dehghan et al. (2008) found a significant association between serum uric acid concentration and a gln141-to-lys (Q141K; 603756.0007) substitution (dbSNP rs2231142) in the ABCG2 gene on chromosome 4q22 (p = 9.0 x 10(-20) and p = 3.3 x 10(-9), respectively). The findings were replicated in the ARIC cohort of 11,024 white and 3,843 black individuals, yielding p values of 9.7 x 10(-30) and 9.8 x 10(-4), respectively. The combined p value for white individuals from all 3 cohorts was 2.5 x 10(-60), and further analysis showed that the SNP was direction-consistent with the development of gout in white participants (OR of 1.74; p = 3.3 x 10(-15)).PATHOGENESIS
Martinon et al. (2006) showed that monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD), both crystals found in gout, engage the caspase-1 (CASP1; 147678)-activating NALP3 (606416) inflammasome, resulting in the production of active interleukin (IL1)-1-beta (IL1B; 147720) and IL18 (IL18; 600953). Macrophages from mice deficient in various components of the inflammasome such as CASP1, ASC (606838), and NALP3 are defective in crystal-induced IL1B activation. Moreover, an impaired neutrophil influx was found in an in vivo model of crystal-induced peritonitis in inflammasome-deficient mice or mice deficient in the IL1B receptor (IL1R; 147810). Martinon et al. (2006) concluded that their findings provide insight into the molecular processing underlying the inflammatory conditions of gout and pseudogout, and further support a pivotal role of the inflammasome in several autoinflammatory diseases.INHERITANCE
Gout is a disorder in which, as in essential hypertension, diabetes mellitus, and hyperch ... More on the omim web siteThe reference OMIM entry for this protein is 614490
Blood group, junior system; jr
A number sign (#) is used with this entry because the Junior(a-) blood group phenotype is caused by homozygous or compound heterozygous mutation in the ABCG2 gene (603756) on chromosome 4q22.
DESCRIPTION
Individuals with Jr(a-) blood group lack the Jr(a) antigen on their red blood cells. These individuals may have anti-Jr(a) antibodies in their serum, which can cause transfusion reactions or hemolytic disease of the fetus or newborn. Although the clinical significance of the Jr(a-) blood group has been controversial, severe fatal hemolytic disease of the newborn has been reported. The Jr(a-) phenotype has a higher frequency in individuals of Asian descent, compared to those of European descent (summary by Kim et al., 2010 and Zelinski et al., 2012).CLINICAL FEATURES
Nakajima and Ito (1978) reported a 30-year-old Japanese woman with no history of blood transfusion whose child developed hemolytic disease of the newborn. The infant became jaundiced within 3 days of birth, and blood showed a strongly positive direct antiglobulin reaction. The maternal serum was found to contain anti-Jr(a) IgG antibodies. Red cells of the baby and the father carried the Jr(a) antigen, whereas those of the mother did not. The mother had a previous history of spontaneous abortion at 3 months' gestation. Peyrard et al. (2008) reported fatal hemolytic disease of the fetus and newborn associated with anti-Jr(a) antibodies. Prenatal ultrasound of a 28-year-old Caucasian woman of Gypsy Spanish origin at 29 weeks' gestation pregnancy showed fetal cardiomegaly and hepatomegaly. She had a history of 2 abortions and 1 full-term pregnancy, as well as a history of massive transfusion with Jr(a)-positive blood. In this pregnancy, an emergency cesarean section was performed at 36 weeks' gestation; the newborn was hydropic with severe anemia and died 30 hours after birth. The mother was found to have the Jr(a-) phenotype with anti-Jr(a) antibodies. Peyrard et al. (2008) stated that this was the first documented case of fatal hemolytic disease of the fetus or newborn due to anti-Jr(a), which provided new information about the clinical significance of anti-Jr(a). Kim et al. (2010) reported a 33-year-old nulliparous Korean woman with no history of transfusion who had the Jr(a-) red blood cell phenotype and anti-Jr(a) IgG antibodies. She delivered male twins with the Jr(a) phenotype, and circulating maternal Jr(a) antibodies were detected in the babies' serum. The twins had mild hemolytic disease of the newborn, which was successfully treated with phototherapy; they had no further complications.INHERITANCE
The Jr(a-) phenotype is inherited as an autosomal recessive trait (Zelinski et al., 2012).DIAGNOSIS
Miyazaki et al. (1994) developed a human monoclonal IgG3 antibody against the Jr(a) antigen using EBV-transformed lymphocytes derived from a Japanese woman with serum anti-Jr(a) antibodies hybridized with a mouse myeloma cell line. Studies on a panel of red cells demonstrated the specificity of the antibody for the Jr(a) antigen. Screening of 28,744 Japanese blood donor samples using the antibody detected 19 (0.07%) agglutination-negative samples, which were confirmed as Jr(a-) by conventional anti-Jr(a) antisera.MOLECULAR GENETICS
By SNP haplotype analysis of 4 probands with Jr(a) antibodies to red blood cells, indicating that their red blood cells were of the Jr(a-) phenotype, Zelinski et al. (2012) identified a share ... More on the omim web siteThe reference OMIM entry for this protein is 603756
Atp-binding cassette, subfamily g, member 2; abcg2
Atp-binding cassette transporter, placenta-specific; abcp
Breast cancer resistance protein; bcrp
Mitoxantrone-resistance protein; mrx
DESCRIPTION
The ABCG2 gene encodes a membrane transporter belonging to the ATP-binding cassette (ABC) superfamily of membrane transporters, which are involved in the trafficking of biologic molecules across cell membranes. ABCG2 was initially found to be a xenobiotic transporter that plays a role in the multidrug resistance phenotype of a specific human breast cancer (Doyle et al., 1998) and has since been shown to confer multidrug resistance in several cancer cells by actively exporting a wide variety of drugs across the plasma membrane. The ABCG2 protein is also a high capacity transporter for uric acid excretion in the kidney, liver, and gut (summary from Matsuo et al., 2009 and Saison et al., 2012). For general information on the ABC superfamily, see ABCA4 (601691).CLONING
Allikmets et al. (1998) characterized an ABC transporter gene, which they designated ABCP, that is highly expressed in the placenta. The ABCP gene produces 2 transcripts that differ at the 5-prime end and encode the same 655-amino acid protein. The predicted protein is closely related to the Drosophila White and the yeast ADP1 proteins. MCF-7/AdrVp is a multidrug-resistant human breast cancer subline that displays an ATP-dependent reduction in the intracellular accumulation of anthracycline anticancer drugs in the absence of overexpression of known multidrug resistance transporters such as P-glycoprotein (PGY1; 171050). By RNA fingerprinting, Doyle et al. (1998) identified a 2.4-kb mRNA that is overexpressed in these cells of the subline relative to parental MCF-7 cells. The mRNA encodes a 665-amino acid member of the ATP-binding cassette superfamily of transporters, which Doyle et al. (1998) termed the transporter breast cancer resistance protein (BCRP). Miyake et al. (1999) cloned 2 cDNAs for ABCG2, which they called MRX1 and MRX2, that were overexpressed in human colon carcinoma cells selected for mitoxantrone resistance. Northern blot analysis confirmed marked overexpression of mRNA between 2.89 and 3.4 kb in the resistant cells. Using porcine brain capillary endothelial cells as a model for the blood-brain barrier, Eisenblatter and Galla (2002) identified porcine ABCG2 mRNA overexpressed in hydrocortisone-treated cultures. Northern blot analysis revealed expression in brain, with predominant localization within endothelial cells isolated from porcine brain capillaries.GENE FUNCTION
Doyle et al. (1998) found that enforced expression of the full-length BCRP cDNA in MCF-7 breast cancer cells confers resistance to mitoxantrone, doxorubicin, and daunorubicin, reduces daunorubicin accumulation and retention, and causes an ATP-dependent enhancement of the efflux or rhodamine-123 in the cloned transfected cells. Thus, BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of a specific human breast cancer. Ozvegy et al. (2001) expressed ABCG2 as an underglycosylated recombinant protein in Sf9 insect cells. In vitro assays of isolated membrane preparations revealed a high-capacity, vanadate-sensitive ATPase activity associated with ABCG2 expression that was stimulated by compounds known to be transported by this protein. Ozvegy et al. (2001) concluded that ABCG2 is likely functioning as a homodimer or homooligomer in this expression system since it is unlikely that putative Sf9 transport partners would be overexpressed at similarly high levels. Ozvegy et al. (2002) expressed wildtype ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: OMIM entry 603756 was added.
July 1, 2021: Protein entry updated
Automatic update: OMIM entry 614490 was added.
July 1, 2021: Protein entry updated
Automatic update: OMIM entry 138900 was added.
April 11, 2021: Protein entry updated
Automatic update: OMIM entry 138900 was added.
April 11, 2021: Protein entry updated
Automatic update: OMIM entry 603756 was added.
April 11, 2021: Protein entry updated
Automatic update: OMIM entry 614490 was added.
Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 138900 was added.
Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 603756 was added.
Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 614490 was added.
Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 138900 was added.
Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 603756 was added.
Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 614490 was added.
Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 138900 was added.
Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 603756 was added.
Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 614490 was added.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 603756 was added.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 614490 was added.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 138900 was added.
April 25, 2020: Protein entry updated
Automatic update: OMIM entry 138900 was added.
April 25, 2020: Protein entry updated
Automatic update: OMIM entry 603756 was added.
April 25, 2020: Protein entry updated
Automatic update: OMIM entry 614490 was added.
March 4, 2020: Protein entry updated
Automatic update: OMIM entry 138900 was added.
March 4, 2020: Protein entry updated
Automatic update: OMIM entry 603756 was added.
March 4, 2020: Protein entry updated
Automatic update: OMIM entry 614490 was added.
Jan. 23, 2020: Protein entry updated
Automatic update: OMIM entry 138900 was added.
Jan. 23, 2020: Protein entry updated
Automatic update: OMIM entry 603756 was added.
Jan. 23, 2020: Protein entry updated
Automatic update: OMIM entry 614490 was added.
Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 138900 was added.
Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 603756 was added.
Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 614490 was added.
Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 138900 was added.
Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 603756 was added.
Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 614490 was added.
Oct. 27, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Sept. 22, 2019: Protein entry updated
Automatic update: OMIM entry 138900 was added.
Sept. 22, 2019: Protein entry updated
Automatic update: OMIM entry 603756 was added.
Sept. 22, 2019: Protein entry updated
Automatic update: OMIM entry 614490 was added.
Aug. 20, 2019: Protein entry updated
Automatic update: OMIM entry 138900 was added.
Aug. 20, 2019: Protein entry updated
Automatic update: OMIM entry 603756 was added.
Aug. 20, 2019: Protein entry updated
Automatic update: OMIM entry 614490 was added.
July 4, 2019: Protein entry updated
Automatic update: OMIM entry 614490 was added.
July 4, 2019: Protein entry updated
Automatic update: OMIM entry 138900 was added.
July 4, 2019: Protein entry updated
Automatic update: OMIM entry 603756 was added.
June 7, 2019: Protein entry updated
Automatic update: OMIM entry 138900 was added.
June 7, 2019: Protein entry updated
Automatic update: OMIM entry 603756 was added.
June 7, 2019: Protein entry updated
Automatic update: OMIM entry 614490 was added.
May 12, 2019: Protein entry updated
Automatic update: OMIM entry 138900 was added.
May 12, 2019: Protein entry updated
Automatic update: OMIM entry 603756 was added.
May 12, 2019: Protein entry updated
Automatic update: OMIM entry 614490 was added.
Jan. 21, 2019: Protein entry updated
Automatic update: OMIM entry 138900 was added.
Jan. 21, 2019: Protein entry updated
Automatic update: OMIM entry 603756 was added.
Jan. 21, 2019: Protein entry updated
Automatic update: OMIM entry 614490 was added.
Nov. 16, 2018: Protein entry updated
Automatic update: OMIM entry 138900 was added.
Nov. 16, 2018: Protein entry updated
Automatic update: OMIM entry 603756 was added.
Nov. 16, 2018: Protein entry updated
Automatic update: OMIM entry 614490 was added.
Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 138900 was added.
Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 603756 was added.
Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 614490 was added.
Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 138900 was added.
Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 603756 was added.
Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 614490 was added.
July 6, 2018: Protein entry updated
Automatic update: OMIM entry 138900 was added.
July 6, 2018: Protein entry updated
Automatic update: OMIM entry 603756 was added.
July 6, 2018: Protein entry updated
Automatic update: OMIM entry 614490 was added.
July 6, 2018: Protein entry updated
Automatic update: OMIM entry 138900 was added.
July 6, 2018: Protein entry updated
Automatic update: OMIM entry 603756 was added.
July 6, 2018: Protein entry updated
Automatic update: OMIM entry 614490 was added.
July 5, 2018: Protein entry updated
Automatic update: OMIM entry 138900 was added.
July 5, 2018: Protein entry updated
Automatic update: OMIM entry 603756 was added.
July 5, 2018: Protein entry updated
Automatic update: OMIM entry 614490 was added.
July 5, 2018: Protein entry updated
Automatic update: OMIM entry 138900 was added.
July 5, 2018: Protein entry updated
Automatic update: OMIM entry 603756 was added.
July 5, 2018: Protein entry updated
Automatic update: OMIM entry 614490 was added.
July 4, 2018: Protein entry updated
Automatic update: OMIM entry 138900 was added.
July 4, 2018: Protein entry updated
Automatic update: OMIM entry 603756 was added.
July 4, 2018: Protein entry updated
Automatic update: OMIM entry 614490 was added.
July 2, 2018: Protein entry updated
Automatic update: OMIM entry 138900 was added.
July 2, 2018: Protein entry updated
Automatic update: OMIM entry 603756 was added.
July 2, 2018: Protein entry updated
Automatic update: OMIM entry 614490 was added.
May 26, 2018: Protein entry updated
Automatic update: OMIM entry 138900 was added.
May 26, 2018: Protein entry updated
Automatic update: OMIM entry 603756 was added.
May 26, 2018: Protein entry updated
Automatic update: OMIM entry 614490 was added.
April 27, 2018: Protein entry updated
Automatic update: OMIM entry 138900 was added.
April 27, 2018: Protein entry updated
Automatic update: OMIM entry 603756 was added.
April 27, 2018: Protein entry updated
Automatic update: OMIM entry 614490 was added.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 138900 was added.