Multidrug resistance-associated protein 1 (ABCC1)
The protein contains 1531 amino acids for an estimated molecular weight of 171591 Da.
Mediates export of organic anions and drugs from the cytoplasm (PubMed:7961706, PubMed:16230346, PubMed:9281595, PubMed:10064732, PubMed:11114332). Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics (PubMed:7961706, PubMed:16230346, PubMed:9281595, PubMed:10064732, PubMed:11114332). Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export (PubMed:9281595). Hydrolyzes ATP with low efficiency (PubMed:16230346). Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation (PubMed:17050692). Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthezing cells (By similarity). (updated: July 3, 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.
- 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.
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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Biological Process
Arachidonic acid metabolic process
Carboxylic acid transmembrane transport
Cell chemotaxis
Cellular response to amyloid-beta
Cobalamin metabolic process
Cobalamin transport
Drug transmembrane transport
Export across plasma membrane
Glutathione transmembrane transport
Heme catabolic process
Leukotriene metabolic process
Leukotriene transport
Phospholipid translocation
Positive regulation of inflammatory response
Response to drug
Small molecule metabolic process
Sphingolipid translocation
Transepithelial transport
Transmembrane transport
Transport
Transport across blood-brain barrier
Vitamin metabolic process
Water-soluble vitamin metabolic process
Xenobiotic transport
Xenobiotic transport across blood-brain barrier
Cellular Component
Apical plasma membrane
Basal plasma membrane
Basolateral plasma membrane
Cell surface
Extracellular exosome
Integral component of plasma membrane
Lateral plasma membrane
Membrane
Plasma membrane
Vacuolar membrane
Molecular Function
ABC-type glutathione S-conjugate transporter activity
ABC-type transporter activity
ABC-type xenobiotic transporter activity
ATP binding
ATPase
ATPase-coupled anion transmembrane transporter activity
ATPase-coupled lipid transmembrane transporter activity
ATPase-coupled transmembrane transporter activity
ATPase-coupled vitamin B12 transmembrane transporter activity
Carboxylic acid transmembrane transporter activity
Efflux transmembrane transporter activity
Glutathione transmembrane transporter activity
Organic anion transmembrane transporter activity
Phospholipid-translocating ATPase activity
Sphingolipid-translocating ATPase activity
Transporter activity
Xenobiotic transmembrane transporter activity
The reference OMIM entry for this protein is 158343
Atp-binding cassette, subfamily c, member 1; abcc1
Multidrug resistance-associated protein 1; mrp1
Multidrug resistance-associated protein; mrp
CLONING
Cole et al. (1992) identified a transporter protein whose gene is overexpressed in a multidrug-resistant variant of the small cell lung cancer cell line NCI-H69. Unlike most tumor cell lines that are resistant to multiple chemotherapeutic agents, it did not overexpress the transmembrane transport protein P-glycoprotein (MDR1; 171050). Cole et al. (1992) isolated cDNA clones corresponding to mRNAs overexpressed in the resistant H69 cells. One cDNA hybridized to an mRNA of 7.8 to 8.2 kb that was expressed 100- to 200-fold higher in the resistant cells than in the drug-sensitive H69 cells. Overexpression was associated with amplification of the cognate gene. The cDNA contained a single open reading frame of 1,522 amino acids encoding a protein that they designated MRP, for 'multidrug resistance-associated protein.' (Cole and Deeley (1993) corrected the predicted protein sequence to 1,531 amino acids.) Database analyses demonstrated similarities in primary sequence to the adenosine triphosphate (ATP)-binding cassette (ABC) superfamily of transport systems. Included in this superfamily are the genes for MDR1 and for the cystic fibrosis transmembrane conductance regulator (CFTR; 602421). Northern blot analysis readily detected MRP transcripts in lung, testis, and peripheral blood mononuclear cells; MRP transcripts were below the level of detection in placenta, brain, kidney, salivary gland, uterus, liver, and spleen.GENE FUNCTION
Zaman et al. (1994) described experiments leading them to conclude that MRP is a plasma membrane drug-efflux pump. Lorico et al. (2002) showed that glutathione is a cofactor in MRP-mediated resistance to heavy metal oxyanions: human fibrosarcoma cells overexpressing MRP1 together with the heavy (catalytic) subunit of gamma-glutamylcysteine synthetase (606857) showed increased resistance to sodium arsenite and antimony toxicity. Using flow cytometric analysis, Muller et al. (2002) found that when a FLAG epitope was introduced into the extracellular loops of membrane-spanning domain-1 (MSD1) or MSD3 of MRP1, it was accessible on the cell surface upon removal of N-glycosylation sites. In contrast, FLAG epitope inserted into MSD2 was not accessible even after removal of all 3 N-glycosylation sites, indicating that MSD2 is deeply buried in the plasma membrane. Using RT-PCR and Western blot analysis, Pascolo et al. (2003) found that MRP1 and MRP3 (ABCC3; 604323) were highly expressed in placenta, but only MRP1 was highly expressed in a trophoblastic cell line. MRP2 (ABCC2; 601107) and MRP5 (ABCC5; 605251) were only weakly expressed in placenta and the trophoblastic cell line. Third-trimester placenta expressed more MRP1 than first-trimester placenta. MRP1 expression increased markedly in the trophoblastic cell line upon polarization. Pascolo et al. (2003) concluded that MRP1 expression increases with trophoblast maturation. In cultured mouse astrocytes, Gennuso et al. (2004) found that unconjugated bilirubin induced increased expression and transient redistribution of Mrp1 from the Golgi apparatus to the plasma membrane and throughout the cytoplasm. Blocking Mrp1 efflux pumps increased the susceptibility of the cells to the toxic effects of unconjugated bilirubin, suggesting that Mrp1 is an important protector in this scenario. The authors noted the relevance of the findings to neonatal encephalopathy caused by increased bilirubin. Mitra et al. (2006) found that sphingosine-1-phosphate (S1P) ... More on the omim web site
July 4, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 158343 was added.