Multidrug resistance-associated protein 1
Also known as: ABCC1, MRP, MRP1
Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export. Hydrolyzes ATP with low efficiency. Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation. Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthesizing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export. Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway. Exports S-geranylgeranyl-glutathione (GGG) in lymphoid cells and stromal compartments of lymphoid organs. ABCC1 (via extracellular transport) with GGT5 (via GGG catabolism) establish GGG gradients within lymphoid tissues to position P2RY8-positive lymphocytes at germinal centers in lymphoid follicles and restrict their chemotactic transmigration from blood vessels to the bone marrow parenchyma (By similarity). Mediates basolateral export of GSH-conjugated R- and S-prostaglandin A2 diastereomers in polarized epithelial cells.
Classification
- Family (Pfam)
- PF00664 ABC_membrane, PF00005 ABC_tran, PF24357 TMD0_ABC
- InterPro
- AAA+_ATPase, ABC1_TM_dom, ABC1_TM_sf, ABC_transporter-like_ATP-bd, ABC_transporter-like_CS, ABC_transporter_C-like, MRP, P-loop_NTPase, TMD0_ABC
- Functional cluster
- G Protein-Coupled Receptors
Experimental structures · PDB · 5
A predicted model is available from AlphaFold.
Gene Ontology · 43
- GO:0016324 apical plasma membrane
- GO:0009925 basal plasma membrane
- GO:0016323 basolateral plasma membrane
- GO:0030054 cell junction
- GO:0070062 extracellular exosome
- GO:0016328 lateral plasma membrane
- GO:0016020 membrane
- GO:0005886 plasma membrane
- GO:0015431 ABC-type glutathione S-conjugate transporter activity
- GO:0140359 ABC-type transporter activity
- GO:0015420 ABC-type vitamin B12 transporter activity
- GO:0008559 ABC-type xenobiotic transporter activity
- GO:0005524 ATP binding
- GO:0016887 ATP hydrolysis activity
- GO:0034040 ATPase-coupled lipid transmembrane transporter activity
- GO:0042626 ATPase-coupled transmembrane transporter activity
- GO:0046943 carboxylic acid transmembrane transporter activity
- GO:0015562 efflux transmembrane transporter activity
- GO:0034634 glutathione transmembrane transporter activity
- GO:0046624 sphingolipid transporter activity
- GO:0042910 xenobiotic transmembrane transporter activity
- GO:1905039 carboxylic acid transmembrane transport
- GO:0060326 cell chemotaxis
- GO:1904646 cellular response to amyloid-beta
- GO:0034599 cellular response to oxidative stress
- GO:0015889 cobalamin transport
- GO:0070729 cyclic nucleotide transport
- GO:0140115 export across plasma membrane
- GO:0034775 glutathione transmembrane transport
- GO:0042167 heme catabolic process
- GO:0006691 leukotriene metabolic process
- GO:0071716 leukotriene transport
- GO:0045332 phospholipid translocation
- GO:0050729 positive regulation of inflammatory response
- GO:0009410 response to xenobiotic stimulus
- GO:0030148 sphingolipid biosynthetic process
- GO:0099039 sphingolipid translocation
- GO:0070633 transepithelial transport
- GO:0055085 transmembrane transport
- GO:0150104 transport across blood-brain barrier
- GO:0006805 xenobiotic metabolic process
- GO:0042908 xenobiotic transport
- GO:1990962 xenobiotic transport across blood-brain barrier
Disease associations
- hearing loss, autosomal dominant 77 MONDO:0030058
Drugs targeting this protein · 1
- BIRICODAR inhibitor
Related proteins · sequence + function similarity
- Multidrug resistance-associated protein 1 1.00
- Multidrug resistance-associated protein 1 1.00
- Multidrug resistance-associated protein 1 0.99
- Multidrug resistance-associated protein 1 0.99
- Multidrug resistance-associated protein 1 0.98
- Multidrug resistance-associated protein 1 0.97
- ATP-binding cassette sub-family C member 3 0.90
- ATP-binding cassette sub-family C member 2 0.90
- ATP-binding cassette sub-family C member 2 0.89
- ATP-binding cassette sub-family C member 2 0.89
- ABC transporter C family member 2 0.88
- ATP-binding cassette sub-family C member 4 0.88
Co-cited proteins · studied together in the literature
- Multidrug resistance-associated protein 1 2 shared papers
- Multidrug resistance-associated protein 1 1 shared papers
- BOS complex subunit NOMO1 2 shared papers
- ATP-binding cassette sub-family C member 6 3 shared papers
- Protein UL138 1 shared papers
- ATP-binding cassette sub-family C member 2 1 shared papers
- Dihydropyrimidine dehydrogenase [NADP(+)] 1 shared papers
- Histone-lysine N-methyltransferase, H3 lysine-36 specific 1 shared papers
- Aromatase 1 shared papers
- Adhesion G protein-coupled receptor A1 1 shared papers
- Myosin-1 1 shared papers
- Disks large homolog 5 1 shared papers
Literature · 39 cited papers
- ABCC1 transporter exports the immunostimulatory cyclic dinucleotide cGAMP. Immunity · 2022
- Extrusion pump ABCC1 was first linked with nonsyndromic hearing loss in humans by stepwise genetic analysis. Genet. Med. · 2019
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Latency-associated degradation of the MRP1 drug transporter during latent human cytomegalovirus infection. Science · 2013
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
- Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
- Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
- DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature · 2008
- Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell · 2008
- … and 27 more in the literature graph