ABCC1 (MRP1) is a 1531-residue, 17-transmembrane-helix ATP-binding cassette transporter of the ABCC subfamily that couples ATP binding and hydrolysis at its two cytoplasmic nucleotide-binding domains to the active, unidirectional efflux of organic anions across the plasma membrane. Its highest-affinity physiological substrate is the glutathione S-conjugate leukotriene C4, and it transports a broad range of glutathione-, glucuronide- and sulfate-conjugated compounds (e.g. estradiol-17-glucuronide, bilirubin glucuronides, sulfated bile acids, prostaglandin A2-glutathione conjugates) as well as free reduced and oxidized glutathione (GSH/GSSG). Many unmodified lipophilic drugs (anthracyclines, vinca alkaloids) are co-transported with glutathione, making MRP1 a major determinant of multidrug resistance in tumour cells. Beyond detoxification it exports the signaling lipid sphingosine-1-phosphate and the immunostimulatory cyclic dinucleotide 2'3'-cGAMP, thereby modulating mast-cell migration, inflammation and cGAS-STING-dependent type I interferon responses. In polarized epithelia MRP1 localizes predominantly to the basolateral membrane, where it contributes to cytoprotection, glutathione redox homeostasis, leukotriene release and xenobiotic efflux at tissue barriers (e.g. Sertoli cells of the blood-testis barrier, choroid plexus epithelium). Loss-of-function variants cause autosomal dominant non-syndromic hearing loss (DFNA77).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: MRP1 binds ATP at its two nucleotide-binding domains. Reason: The InterPro ABC ATP-binding signatures and the crystal structure of NBD1 bound to Mg-ATP establish ATP binding. Supporting Evidence: file:human/ABCC1/ABCC1-uniprot.txt hydrolyzes ATP to enable the active transport of organic |
| GO:0005886 plasma membrane | EXP PMID:16230346 Functional importance of three basic residues clustered at t... | ACCEPT | Summary: MRP1 functions at the plasma membrane where it effluxes drugs and organic anions. Reason: Functional efflux studies place MRP1 activity at the plasma membrane; this is the established site of transport. Supporting Evidence: PMID:16230346 The multidrug resistance protein 1 (MRP1) mediates drug and organic anion |
| GO:0005886 plasma membrane | EXP PMID:31273342 Extrusion pump ABCC1 was first linked with nonsyndromic hear... | ACCEPT | Summary: Endogenous/WT MRP1 localizes to the plasma membrane (cytomembrane). Reason: In the DFNA77 study wild-type ABCC1 was membrane-resident; mislocalization of the variant underlies the phenotype. Supporting Evidence: PMID:31273342 wild type was shown only in cytomembrane |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference (PANTHER node PTN002795584) that MRP1 is active in the plasma membrane. Reason: The PAINT node places plasma-membrane activity across the ABCC conjugate-transporter clade; consistent with direct human experimental evidence (e.g. PMID:16230346), so the ancestral assignment holds for ABCC1. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence localizes MRP1 to the plasma membrane. Reason: Direct immunofluorescence (HPA-type curation) agrees with the extensive functional and proteomic evidence for plasma-membrane localization. |
| GO:0005886 plasma membrane | IDA PMID:17050692 Role of ABCC1 in export of sphingosine-1-phosphate from mast... | ACCEPT | Summary: MRP1 is present at the cell surface, where it exports S1P. Reason: siRNA knockdown reduced MRP1 cell-surface expression and S1P export, confirming surface localization. Supporting Evidence: PMID:17050692 which decreased its cell surface expression |
| GO:0005886 plasma membrane | IDA PMID:23137377 Quantitative targeted absolute proteomic analysis of transpo... | ACCEPT | Summary: MRP1 detected in the plasma-membrane fraction of the hCMEC/D3 BBB model. Reason: Quantitative targeted proteomics of plasma-membrane fractions detected MRP1. Supporting Evidence: PMID:23137377 MRP1 and ATA1 were found only in hCMEC/D3 cells |
| GO:0005886 plasma membrane | IDA PMID:28112518 LC-MS/MS Based Quantitation of ABC and SLC Transporter Prote... | ACCEPT | Summary: MRP1 detected in plasma membranes of RPE cells. Reason: LC-MS/MS quantitation in RPE plasma-membrane fractions detected MRP1. Supporting Evidence: PMID:28112518 MRP1, MRP5, GLUT1, 4F2hc, TAUT, CAT1, |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Automated multi-method inference of plasma-membrane localization. Reason: Agrees with the direct experimental plasma-membrane evidence for MRP1. |
| GO:0005886 plasma membrane | TAS PMID:1360704 Overexpression of a transporter gene in a multidrug-resistan... | ACCEPT | Summary: The founding paper describes MRP1 as a transmembrane transport protein. Reason: MRP1 was identified as an ABC transmembrane transporter; plasma-membrane residence is well established. Supporting Evidence: PMID:1360704 member of the ATP-binding cassette transmembrane transporter superfamily |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1454916 | ACCEPT | Summary: Reactome models MRP1 transport reactions at the plasma membrane. Reason: Reactome places the ABCC1 efflux reactions at the plasma membrane, consistent with experimental evidence. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-266070 | ACCEPT | Summary: Reactome models MRP1 transport reactions at the plasma membrane. Reason: Reactome places the ABCC1 efflux reactions at the plasma membrane, consistent with experimental evidence. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-3095901 | ACCEPT | Summary: Reactome models MRP1 transport reactions at the plasma membrane. Reason: Reactome places the ABCC1 efflux reactions at the plasma membrane, consistent with experimental evidence. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9661405 | ACCEPT | Summary: Reactome models MRP1 transport reactions at the plasma membrane. Reason: Reactome places the ABCC1 efflux reactions at the plasma membrane, consistent with experimental evidence. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9753284 | ACCEPT | Summary: Reactome models MRP1 transport reactions at the plasma membrane. Reason: Reactome places the ABCC1 efflux reactions at the plasma membrane, consistent with experimental evidence. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9796074 | ACCEPT | Summary: Reactome models MRP1 transport reactions at the plasma membrane. Reason: Reactome places the ABCC1 efflux reactions at the plasma membrane, consistent with experimental evidence. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9843721 | ACCEPT | Summary: Reactome models MRP1 transport reactions at the plasma membrane. Reason: Reactome places the ABCC1 efflux reactions at the plasma membrane, consistent with experimental evidence. |
| GO:0006691 leukotriene metabolic process | TAS Reactome:R-HSA-2142691 | MODIFY | Summary: MRP1 exports LTC4; it transports rather than metabolizes leukotrienes. Reason: MRP1 performs no biosynthetic/catabolic step on leukotrienes; it mediates the cellular export of LTC4. The transport role is captured precisely by leukotriene transport, which the gene already carries. Proposed replacements: leukotriene transport |
| GO:0006805 xenobiotic metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: MRP1 is a phase-III efflux pump; it transports xenobiotics rather than chemically metabolizing them. Reason: The ARBA mapping to the broad metabolic-process term is better represented as xenobiotic transport, the efflux step MRP1 actually performs; the gene already carries GO:0042908. Proposed replacements: xenobiotic transport |
| GO:0006805 xenobiotic metabolic process | TAS Reactome:R-HSA-9753281 | MODIFY | Summary: In the paracetamol ADME pathway MRP1 exports the xenobiotic conjugates. Reason: MRP1 contributes the efflux (phase-III) step, not the chemical metabolism; xenobiotic transport is the accurate term. Proposed replacements: xenobiotic transport |
| GO:0008559 ABC-type xenobiotic transporter activity | EXP PMID:9281595 Pharmacological characterization of the murine and human ort... | ACCEPT | Summary: MRP1 is an ATP-dependent transporter of structurally diverse drugs (EC 7.6.2.2). Reason: Transport/resistance assays establish ABC-type xenobiotic transporter activity. Supporting Evidence: PMID:9281595 human MRP has also been shown to be a primary active transporter of a |
| GO:0008559 ABC-type xenobiotic transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference (node PTN002795564) of ABC-type xenobiotic transporter activity. Reason: The PAINT node assigns xenobiotic ABC-transporter activity across the clade; MRP1 has direct experimental support (PMID:9281595), so the ancestral assignment holds. |
| GO:0008559 ABC-type xenobiotic transporter activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated RHEA/EC mapping (EC 7.6.2.2, daunorubicin RHEA:33147) to ABC-type xenobiotic transporter activity. Reason: The electronic EC/RHEA mapping matches the experimentally demonstrated drug-efflux activity. |
| GO:0009410 response to xenobiotic stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: MRP1 participates in the cellular response to xenobiotics via efflux. Reason: Ortholog-based inference of a broad process; MRP1's contribution is the xenobiotic-efflux activity, so retain as a non-core contextual process rather than a core molecular claim. |
| GO:0009410 response to xenobiotic stimulus | TAS PMID:1360704 Overexpression of a transporter gene in a multidrug-resistan... | KEEP AS NON CORE | Summary: MRP1 overexpression confers the multidrug-resistant (xenobiotic-response) phenotype. Reason: Correct but broad process; the specific activity is xenobiotic transport. Retain as non-core. |
| GO:0009925 basal plasma membrane | IDA PMID:18619525 Subcellular localization of transporters along the rat blood... | ACCEPT | Summary: At the rat BBB MRP1 is primarily on the basal (abluminal) surface. Reason: In vivo biotinylation showed Mrp1 abluminal, consistent with the predominant basolateral/basal polarity of MRP1. Supporting Evidence: PMID:18619525 Mrp1 (Abcc1) appeared primarily abluminal by immunofluorescence |
| GO:0009925 basal plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-based inference of basal plasma-membrane localization. Reason: Consistent with direct basal/basolateral localization data. |
| GO:0015420 ABC-type vitamin B12 transporter activity | EXP PMID:21511966 Investigation of the ABC transporter MRP1 in selected patien... | KEEP AS NON CORE | Summary: MRP1 has a proposed role as a cellular cobalamin (vitamin B12) exporter. Reason: Cobalamin export by MRP1 is a documented but peripheral role (Beedholm-Ebsen 2010, the study this letter examines; corroborated by mouse ortholog inference and Reactome RCbl-export models). The cached entry is a clinical comment, so the activity is retained as non-core rather than a core claim. |
| GO:0015420 ABC-type vitamin B12 transporter activity | EXP PMID:22547309 Vitamin B12 transport from food to the body's cells--a sophi... | KEEP AS NON CORE | Summary: MRP1 is placed in the vitamin B12 trafficking pathway as a cellular cobalamin exporter. Reason: Review-level support for cobalamin export; kept as a non-core secondary substrate relative to the core organic-anion efflux function. |
| GO:0015420 ABC-type vitamin B12 transporter activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-based inference of ABC-type vitamin B12 transporter activity. Reason: Mouse ortholog (O35379) evidence propagated to human; consistent with the proposed cobalamin-export role, retained as non-core. |
| GO:0015431 ABC-type glutathione S-conjugate transporter activity | IEA GO_REF:0000120 | ACCEPT | Summary: ABC-type glutathione S-conjugate transporter activity (EC 7.6.2.3) - the defining MRP1 activity. Reason: The RHEA/EC mapping matches extensive experimental evidence that MRP1 is a glutathione-S-conjugate export pump (e.g. LTC4, DNP-GS). Supporting Evidence: PMID:7961706 ATP-dependent primary-active transport into the vesicles was demonstrated for |
| GO:0015431 ABC-type glutathione S-conjugate transporter activity | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog-based inference of ABC-type glutathione S-conjugate transporter activity. Reason: Consistent with the human experimental GS-conjugate transport data; a core function. |
| GO:0015562 efflux transmembrane transporter activity | IEA GO_REF:0000107 | ACCEPT | Summary: MRP1 is an efflux (outward) transmembrane transporter. Reason: Directional efflux is a correct and informative characterization of MRP1; it pumps substrates out of the cell. |
| GO:0015562 efflux transmembrane transporter activity | IMP PMID:25986174 Characterization of efflux transport proteins of the human c... | ACCEPT | Summary: Functional assays demonstrate MRP1 efflux activity at the blood-CSF barrier model. Reason: Uptake/permeation assays in HIBCPP cells confirmed functional ABCC1 efflux activity. Supporting Evidence: PMID:25986174 Functionality of ABCC1, ABCC4, ABCB1 |
| GO:0015562 efflux transmembrane transporter activity | ISS PMID:26200696 Dual pathways mediate Ξ²-amyloid stimulated glutathione relea... | ACCEPT | Summary: MRP1 effluxes glutathione from astrocytes (ortholog-supported). Reason: Astrocyte GSH-release data support efflux activity; consistent across species. |
| GO:0015889 cobalamin transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MRP1 is inferred to participate in cobalamin (vitamin B12) transport. Reason: Ortholog-based inference consistent with the proposed cellular cobalamin-export role; retained as a non-core secondary process. |
| GO:0015889 cobalamin transport | TAS Reactome:R-HSA-9758890 | KEEP AS NON CORE | Summary: Reactome models MRP1 in cobalamin (RCbl) transport within the body. Reason: Curated pathway placement of MRP1 in cobalamin export; kept non-core relative to the core organic-anion efflux function. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MODIFY | Summary: MRP1 detected in a membrane proteome; its specific location is the plasma membrane. Reason: A membrane-proteome MS survey yields the generic 'membrane' term; MRP1's membrane is the plasma membrane, which the gene already carries with direct evidence. Proposed replacements: plasma membrane |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: InterPro topology implies a membrane protein; the specific compartment is the plasma membrane. Reason: The InterPro signature only establishes membrane insertion; refine to plasma membrane per direct evidence. Proposed replacements: plasma membrane |
| GO:0016020 membrane | TAS PMID:1360704 Overexpression of a transporter gene in a multidrug-resistan... | MODIFY | Summary: MRP1 described as a transmembrane protein; specifically plasma-membrane localized. Reason: Refine the generic membrane term to plasma membrane, the established site of MRP1. Proposed replacements: plasma membrane |
| GO:0016323 basolateral plasma membrane | EXP PMID:9426231 Transport of glutathione prostaglandin A conjugates by the m... | ACCEPT | Summary: MRP1 localizes basolaterally/laterally in polarized epithelial cells. Reason: In polarized MDCKII monolayers MRP1 exports GS-conjugates to the basolateral side, matching its lateral localization. Supporting Evidence: PMID:9426231 the lateral localization of human MRP1 in these cells |
| GO:0016323 basolateral plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference (node PTN009085618) of basolateral plasma-membrane activity. Reason: The PAINT node places basolateral activity across the clade; well supported by direct human/primate data (PMID:24130369). |
| GO:0016323 basolateral plasma membrane | IDA PMID:24130369 Localization of multidrug resistance-associated proteins alo... | ACCEPT | Summary: MRP1 is restricted to the basolateral membrane of Sertoli cells (blood-testis barrier). Reason: Direct immunohistochemistry in rat, macaque and human testis localizes MRP1 to the Sertoli-cell basolateral membrane. Supporting Evidence: PMID:24130369 MRP1 was restricted to the basolateral membrane of Sertoli cells |
| GO:0016323 basolateral plasma membrane | IDA PMID:31791063 Quantitative Protein Expression in the Human Retinal Pigment... | ACCEPT | Summary: MRP1 present on the basolateral surface of RPE cells. Reason: Quantitative apical/basolateral proteomics detected MRP1 on the basolateral RPE membrane. Supporting Evidence: PMID:31791063 Most drug transporters showed similar abundance on both RPE surfaces |
| GO:0016323 basolateral plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to basolateral cell membrane. Reason: The SL-0026 mapping matches curated and experimental basolateral localization. |
| GO:0016323 basolateral plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog-based inference of basolateral plasma-membrane localization. Reason: Mouse ortholog (Q8CG09) supports the conserved basolateral localization. |
| GO:0016323 basolateral plasma membrane | ISS PMID:18619525 Subcellular localization of transporters along the rat blood... | ACCEPT | Summary: Basolateral localization inferred from mouse ortholog; Mrp1 basal-lateral in choroid plexus. Reason: In vivo biotinylation localized Mrp1 to the basal-lateral surface of choroid plexus epithelium. Supporting Evidence: PMID:18619525 Lat1, Mrp1 and Mrp4 were detected on the basal-lateral surface of lateral |
| GO:0016324 apical plasma membrane | IDA PMID:31791063 Quantitative Protein Expression in the Human Retinal Pigment... | KEEP AS NON CORE | Summary: MRP1 also detected on the apical RPE surface. Reason: RPE proteomics found MRP1 on both surfaces; apical localization is a tissue-specific/context observation, non-core relative to the characteristic basolateral localization. Supporting Evidence: PMID:31791063 Most drug transporters showed similar abundance on both RPE surfaces |
| GO:0016328 lateral plasma membrane | IDA PMID:31791063 Quantitative Protein Expression in the Human Retinal Pigment... | KEEP AS NON CORE | Summary: MRP1 detected at the lateral plasma membrane in RPE. Reason: Lateral localization is consistent with the basolateral polarity; retained as a fine-grained non-core location. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: MRP1 hydrolyzes ATP at its nucleotide-binding domains to power transport. Reason: ATP hydrolysis by the NBDs is intrinsic to MRP1's primary-active transport mechanism and is documented biochemically. Supporting Evidence: file:human/ABCC1/ABCC1-uniprot.txt hydrolyzes ATP to enable the active transport of organic |
| GO:0022857 transmembrane transporter activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: Generic transmembrane transporter activity; true but uninformative here. Reason: This root-level transporter term is entailed by the specific activities asserted elsewhere (ABC-type xenobiotic transporter activity GO:0008559 and xenobiotic transmembrane transporter activity GO:0042910, both ACCEPT). It judges the term's granularity, not the truth of the claim. |
| GO:0030054 cell junction | IDA GO_REF:0000052 | MARK AS OVER ANNOTATED | Summary: Immunofluorescence 'cell junction' call for a basolateral-membrane transporter. Reason: MRP1 is a basolateral/lateral plasma-membrane efflux pump, not a junctional protein; lateral-membrane staining in an IF screen is readily misread as cell-junction localization. Over-annotation. |
| GO:0030148 sphingolipid biosynthetic process | TAS Reactome:R-HSA-1660661 | MARK AS OVER ANNOTATED | Summary: MRP1 exports S1P but performs no sphingolipid biosynthetic step. Reason: MRP1 effluxes the end-product sphingosine-1-phosphate; it does not catalyse or contribute structure/cofactor to sphingolipid biosynthesis. Participation test fails, so the biosynthetic-process annotation is an over-annotation (the real role is S1P export). |
| GO:0034040 ATPase-coupled lipid transmembrane transporter activity | IMP PMID:17050692 Role of ABCC1 in export of sphingosine-1-phosphate from mast... | ACCEPT | Summary: MRP1 exports the signaling lipid S1P in an ATP-dependent manner. Reason: siRNA and inhibitor data show MRP1-mediated ATP-dependent S1P (a lipid) export; a demonstrated transport activity and a distinct physiological function of MRP1. Supporting Evidence: PMID:17050692 S1P is exported from mast cells independently of their degranulation |
| GO:0034599 cellular response to oxidative stress | TAS Reactome:R-HSA-9707564 | KEEP AS NON CORE | Summary: MRP1 exports GSH/GSSG, contributing to cytoprotection during oxidative stress. Reason: GSH/GSSG efflux by MRP1 helps limit oxidative damage; a contextual cytoprotective process, non-core relative to the transport activity itself. Supporting Evidence: file:human/ABCC1/ABCC1-uniprot.txt that limits cellular damage especially during oxidative stress |
| GO:0034634 glutathione transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference (node PTN002795564) of glutathione transmembrane transporter activity. Reason: MRP1 exports free GSH and GSSG (documented catalytic activities); the PAINT assignment is well grounded. |
| GO:0034634 glutathione transmembrane transporter activity | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-based inference of glutathione transmembrane transporter activity. Reason: Consistent with documented GSH/GSSG export by MRP1. |
| GO:0034634 glutathione transmembrane transporter activity | ISS PMID:26200696 Dual pathways mediate Ξ²-amyloid stimulated glutathione relea... | ACCEPT | Summary: MRP1 is the main pathway for GSH release from astrocytes. Reason: Astrocyte experiments identify ABCC1 as the principal GSH-release transporter. Supporting Evidence: PMID:26200696 the transporter ABCC1 (also referred to as MRP1) that is the main pathway for GSH release |
| GO:0034775 glutathione transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of involvement in glutathione transmembrane transport. Reason: The BP counterpart of MRP1's glutathione-export activity; well supported. |
| GO:0042167 heme catabolic process | TAS Reactome:R-HSA-189483 | KEEP AS NON CORE | Summary: MRP1 exports bilirubin-glucuronide conjugates, the catabolites of heme degradation. Reason: MRP1 mediates the elimination (export) step for bilirubin glucuronides rather than catalysing heme breakdown; retained as a non-core contribution to heme/bilirubin disposal. |
| GO:0042626 ATPase-coupled transmembrane transporter activity | TAS Reactome:R-HSA-1454916 | ACCEPT | Summary: MRP1 is a primary-active (ATP-hydrolysis-coupled) transmembrane transporter. Reason: Accurate description of the energetics of MRP1 transport; curated by Reactome. |
| GO:0042626 ATPase-coupled transmembrane transporter activity | TAS Reactome:R-HSA-9753284 | ACCEPT | Summary: MRP1 couples ATP hydrolysis to efflux of conjugates. Reason: Accurate ATP-coupled transporter characterization; curated by Reactome. |
| GO:0042908 xenobiotic transport | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference (node PTN002795564) of involvement in xenobiotic transport. Reason: Core process for MRP1; supported by direct human drug-efflux data. |
| GO:0042908 xenobiotic transport | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-based inference of xenobiotic transport. Reason: Consistent with the experimentally established drug/xenobiotic efflux role. |
| GO:0042908 xenobiotic transport | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog-based inference of xenobiotic transport. Reason: Consistent with MRP1's core xenobiotic-efflux role. |
| GO:0042910 xenobiotic transmembrane transporter activity | IDA PMID:7961706 The MRP gene encodes an ATP-dependent export pump for leukot... | ACCEPT | Summary: MRP1 transports xenobiotic/conjugate anions across the membrane (LTC4, DNP-GS). Reason: Direct ATP-dependent vesicular transport of conjugates demonstrates xenobiotic transmembrane transporter activity. Supporting Evidence: PMID:7961706 ATP-dependent primary-active transport into the vesicles was demonstrated for |
| GO:0042910 xenobiotic transmembrane transporter activity | IDA PMID:9281595 Pharmacological characterization of the murine and human ort... | ACCEPT | Summary: MRP1 transports diverse drugs across the membrane. Reason: Direct transport assays of drugs/conjugates demonstrate xenobiotic transmembrane transporter activity. Supporting Evidence: PMID:9281595 human MRP has also been shown to be a primary active transporter of a |
| GO:0042910 xenobiotic transmembrane transporter activity | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-based inference of xenobiotic transmembrane transporter activity. Reason: Consistent with direct human experimental evidence. |
| GO:0042910 xenobiotic transmembrane transporter activity | IMP PMID:25986174 Characterization of efflux transport proteins of the human c... | ACCEPT | Summary: Functional efflux of substrates demonstrated at the blood-CSF barrier model. Reason: HIBCPP uptake/permeation assays confirm MRP1 xenobiotic transport activity. Supporting Evidence: PMID:25986174 Functionality of ABCC1, ABCC4, ABCB1 |
| GO:0042910 xenobiotic transmembrane transporter activity | ISS PMID:26200696 Dual pathways mediate Ξ²-amyloid stimulated glutathione relea... | ACCEPT | Summary: Ortholog-supported xenobiotic transmembrane transporter activity. Reason: Consistent with MRP1's established transport of organic anions/xenobiotics. |
| GO:0045332 phospholipid translocation | IMP PMID:17050692 Role of ABCC1 in export of sphingosine-1-phosphate from mast... | MODIFY | Summary: The transported lipid is S1P, a sphingoid-base phosphate, not a glycerophospholipid. Reason: The S1P-export data are better represented by sphingolipid translocation (which the gene already carries from the same study) than by the generic phospholipid-translocation (flippase-like) term. Proposed replacements: sphingolipid translocation |
| GO:0046942 carboxylic acid transport | IEA GO_REF:0000117 | ACCEPT | Summary: MRP1 transports carboxylate-bearing organic anions. Reason: MRP1's organic-anion substrates (LTC4 and conjugates) are carboxylic acids; the broad ARBA term is correct, if less specific than the membrane-transport terms. |
| GO:0046943 carboxylic acid transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference (node PTN002795564) of carboxylic acid transmembrane transporter activity. Reason: MRP1 transports carboxylate-containing organic anions; the PAINT assignment is consistent with its substrate chemistry. |
| GO:0046943 carboxylic acid transmembrane transporter activity | IMP PMID:25986174 Characterization of efflux transport proteins of the human c... | ACCEPT | Summary: Functional organic-anion transport demonstrated at the blood-CSF barrier model. Reason: HIBCPP functional assays support carboxylic-acid (organic-anion) transmembrane transport. Supporting Evidence: PMID:25986174 Functionality of ABCC1, ABCC4, ABCB1 |
| GO:0050729 positive regulation of inflammatory response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: By exporting LTC4 (and S1P), MRP1 promotes inflammatory responses. Reason: An indirect, context-dependent consequence of MRP1 effluxing pro-inflammatory mediators; retained as non-core. |
| GO:0050729 positive regulation of inflammatory response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-based inference of positive regulation of inflammatory response. Reason: Indirect role via leukotriene/S1P export; non-core. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: MRP1 mediates transmembrane transport. Reason: Broad but correct process term for a membrane transporter; acceptable as an IEA that is more general than the specific transport processes. |
| GO:0055085 transmembrane transport | TAS Reactome:R-HSA-382556 | ACCEPT | Summary: Reactome: ABC-family-mediated transmembrane transport. Reason: Correct broad process; curated by Reactome. |
| GO:0060326 cell chemotaxis | ISS PMID:17050692 Role of ABCC1 in export of sphingosine-1-phosphate from mast... | KEEP AS NON CORE | Summary: MRP1-mediated S1P export influences mast-cell chemotaxis. Reason: MRP1 affects chemotaxis indirectly by exporting the chemotactic signaling lipid S1P; a downstream, context-specific role, retained as non-core. Supporting Evidence: PMID:17050692 Transport of S1P by ABCC1 influenced migration of mast cells toward antigen but not degranulation |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: MRP1 detected in B-cell exosome proteome. Reason: A single high-throughput exosome proteomics survey; plasma-membrane proteins commonly appear in exosomes. Non-core, functionally uninformative location. |
| GO:0070633 transepithelial transport | IMP PMID:25986174 Characterization of efflux transport proteins of the human c... | KEEP AS NON CORE | Summary: MRP1 contributes to transepithelial efflux at the blood-CSF barrier. Reason: Functional permeation studies show MRP1 participates in transepithelial transport at barriers; a context-specific physiological role, non-core. |
| GO:0070729 cyclic nucleotide transport | IEA GO_REF:0000107 | ACCEPT | Summary: MRP1 exports the cyclic dinucleotide 2'3'-cGAMP. Reason: Ortholog-based inference consistent with the experimentally demonstrated cGAMP export activity. |
| GO:0070729 cyclic nucleotide transport | IMP PMID:36070769 ABCC1 transporter exports the immunostimulatory cyclic dinuc... | ACCEPT | Summary: MRP1 is a direct ATP-dependent exporter of 2'3'-cGAMP, limiting STING signaling. Reason: Overexpression/knockout experiments in human and mouse cells establish MRP1 as the cGAMP exporter. Supporting Evidence: PMID:36070769 we identifed ABCC1 as a direct, ATP-dependent cGAMP exporter in mouse and human cells PMID:36070769 loss of ABCC1 reduced cGAMP export and potentiated STING signaling |
| GO:0071716 leukotriene transport | IEA GO_REF:0000107 | ACCEPT | Summary: MRP1 transports leukotrienes (LTC4 and related). Reason: Ortholog-based inference consistent with the defining LTC4-export activity of MRP1. |
| GO:0071716 leukotriene transport | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog-based inference of leukotriene transport. Reason: Consistent with the experimentally established LTC4 export; a core process. |
| GO:0099039 sphingolipid translocation | IMP PMID:17050692 Role of ABCC1 in export of sphingosine-1-phosphate from mast... | ACCEPT | Summary: MRP1 translocates the sphingolipid S1P across the plasma membrane. Reason: Direct knockdown/inhibitor evidence for ATP-dependent S1P export; the accurate specific term for the lipid moved. Supporting Evidence: PMID:17050692 S1P is exported from mast cells independently of their degranulation |
| GO:0140115 export across plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: MRP1 exports substrates across the plasma membrane. Reason: Export is the defining directionality of MRP1; ortholog-based inference is consistent. |
| GO:0140115 export across plasma membrane | IMP PMID:25986174 Characterization of efflux transport proteins of the human c... | ACCEPT | Summary: Functional export across the plasma membrane demonstrated. Reason: HIBCPP functional assays confirm MRP1-mediated export. Supporting Evidence: PMID:25986174 Functionality of ABCC1, ABCC4, ABCB1 |
| GO:0140115 export across plasma membrane | ISS PMID:26200696 Dual pathways mediate Ξ²-amyloid stimulated glutathione relea... | ACCEPT | Summary: MRP1 exports GSH across the plasma membrane (astrocytes). Reason: Ortholog-supported plasma-membrane export, consistent with GSH-release data. |
| GO:0140359 ABC-type transporter activity | EXP PMID:7961706 The MRP gene encodes an ATP-dependent export pump for leukot... | ACCEPT | Summary: MRP1 is an ATP-dependent (ABC-type) export pump. Reason: Direct demonstration of ATP-dependent conjugate transport establishes ABC-type transporter activity. Supporting Evidence: PMID:7961706 ATP-dependent primary-active transport into the vesicles was demonstrated for |
| GO:0140359 ABC-type transporter activity | IDA PMID:7961706 The MRP gene encodes an ATP-dependent export pump for leukot... | ACCEPT | Summary: ATP-dependent transport by MRP1 (photoaffinity-labeled 190-kDa protein). Reason: Direct biochemical evidence for ABC-type transporter activity. Supporting Evidence: PMID:7961706 The endogenous glutathione conjugate LTC4 had the highest affinity for this |
| GO:0140359 ABC-type transporter activity | IDA PMID:9281595 Pharmacological characterization of the murine and human ort... | ACCEPT | Summary: ATP-dependent transport of drugs/conjugates by MRP1. Reason: Direct transport assays establish ABC-type transporter activity. Supporting Evidence: PMID:9281595 mrp and MRP conferred similar drug resistance profiles, with the |
| GO:0140359 ABC-type transporter activity | IEA GO_REF:0000120 | ACCEPT | Summary: InterPro/ortholog inference of ABC-type transporter activity. Reason: Consistent with extensive direct evidence that MRP1 is an ABC transporter. |
| GO:0140359 ABC-type transporter activity | TAS Reactome:R-HSA-9661405 | ACCEPT | Summary: Reactome: MRP1 ABC-type transport reaction. Reason: Curated ABC-type transporter activity; consistent with experimental data. |
| GO:0150104 transport across blood-brain barrier | NAS PMID:26590417 Establishment and Dysfunction of the Blood-Brain Barrier. | KEEP AS NON CORE | Summary: MRP1 is discussed as an efflux transporter at the blood-brain barrier. Reason: Narrative (review) statement; MRP1's CNS-barrier role is more prominent at the blood-CSF barrier (choroid plexus) than at the BBB endothelium. Retained as a non-core contextual process. |
| GO:0150104 transport across blood-brain barrier | NAS PMID:30280653 Blood-Brain Barrier: From Physiology to Disease and Back. | KEEP AS NON CORE | Summary: MRP1 cited among BBB efflux transporters in a physiology review. Reason: Narrative review support; retained as a non-core contextual process. |
| GO:1904646 cellular response to amyloid-beta | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MRP1 expression responds to amyloid-beta in astrocytes. Reason: Ortholog-based inference of an amyloid-beta-responsive role (ABCC1 upregulation/GSH release); a disease-context process, non-core. |
| GO:1904646 cellular response to amyloid-beta | ISS PMID:26200696 Dual pathways mediate Ξ²-amyloid stimulated glutathione relea... | KEEP AS NON CORE | Summary: Monomeric amyloid-beta increases ABCC1 expression and GSH release in astrocytes. Reason: Context-specific (Alzheimer-related) response; retained as non-core. Supporting Evidence: PMID:26200696 cortical ABCC1 was significantly increased in temporal register with the surge of |
| GO:1905039 carboxylic acid transmembrane transport | IMP PMID:25986174 Characterization of efflux transport proteins of the human c... | ACCEPT | Summary: MRP1 mediates transmembrane transport of organic (carboxylic) acids. Reason: Functional efflux assays support carboxylic-acid (organic-anion) transmembrane transport. Supporting Evidence: PMID:25986174 Functionality of ABCC1, ABCC4, ABCB1 |
| GO:1990962 xenobiotic transport across blood-brain barrier | IMP PMID:25986174 Characterization of efflux transport proteins of the human c... | KEEP AS NON CORE | Summary: MRP1 limits xenobiotic entry at CNS barriers. Reason: The functional assay was at the blood-CSF barrier (choroid plexus); MRP1-mediated xenobiotic efflux at CNS barriers is a real but context-specific role, retained as non-core. Supporting Evidence: PMID:25986174 confirmed basolateral expression of ABCC1 |
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Download this section (compressed HTML)Q: Is MRP1 a bona fide physiological cobalamin (vitamin B12) exporter in humans, and does loss of this activity contribute to any clinical B12-handling phenotype?
Q: What is the relative physiological contribution of MRP1 to glutathione redox homeostasis in the CNS versus other GSH-export routes (e.g. connexin hemichannels)?
Experiment: Reconstitute purified human MRP1 in proteoliposomes and measure ATP-dependent cobalamin transport directly, to resolve whether cobalamin is a genuine MRP1 substrate.
Experiment: Use MRP1-selective inhibition/knockout in primary human astrocytes and brain endothelial/choroid-plexus cells to quantify MRP1's contribution to GSH export and xenobiotic efflux at CNS barriers under oxidative-stress conditions.
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