ABCC4 (MRP4) is a ubiquitously expressed, polytopic plasma-membrane ATP-binding cassette transporter of the ABCC/MRP subfamily. Using ATP binding and hydrolysis at its two nucleotide-binding domains, it catalyses primary active efflux of a broad range of organic anions out of cells. Physiological substrates include the cyclic nucleotides cAMP and cGMP, prostaglandins (PGE1/PGE2), leukotrienes B4 and C4, urate, reduced glutathione and glutathione S-conjugates, bile acids (cotransported with GSH), and steroid glucuronides and sulfates; it also effluxes many drugs and their metabolites (antivirals, 6-mercaptopurine, methotrexate, cephalosporins, chemotherapeutics), contributing to multidrug resistance. Its subcellular polarity is tissue-dependent, residing in the apical membrane of kidney proximal tubule and the basolateral (sinusoidal) membrane of hepatocytes, and it is present at blood-tissue barriers (blood-brain, blood-CSF, blood-testis) and in platelet dense-granule membranes, where it loads cyclic nucleotides. A C-terminal PDZ-binding motif recruits PDZ-domain scaffolds (e.g. SNX27, PDZK1, NHERF, MPP1) that govern its membrane localization and turnover. By exporting signalling molecules such as cyclic nucleotides and prostaglandins, ABCC4 influences processes including platelet mediator storage, cyclic-nucleotide signalling and prostaglandin-dependent ciliogenesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001409 guanine nucleotide transmembrane transporter activity | IDA PMID:15454390 Human organic anion transporter MRP4 (ABCC4) is an efflux pu... | ACCEPT | Summary: MRP4/ABCC4 mediates ATP-dependent efflux of the cyclic guanine nucleotide cGMP (a guanine nucleotide), shown directly in overexpressing vesicles (PMID:15454390). Reason: cGMP is a (cyclic) guanine nucleotide; ATP-dependent cGMP transport is directly demonstrated, so guanine-nucleotide transporter activity is a correct, core molecular function. Supporting Evidence: PMID:15454390 MRP4 could transport urate simultaneously with cAMP or cGMP |
| GO:0002576 platelet degranulation | TAS Reactome:R-HSA-114608 | KEEP AS NON CORE | Summary: Platelet degranulation: MRP4 in platelet dense-granule membranes loads cyclic nucleotides/nucleotides, contributing to mediator storage and release (PMID:15297306; Reactome). Reason: Genuine platelet-specific physiological role downstream of MRP4's nucleotide-transport activity, but peripheral to the core transporter function; retained as non-core. Supporting Evidence: PMID:15297306 a transport pump for cyclic nucleotides and nucleotide analogs |
| GO:0005515 protein binding | IPI PMID:22411990 Sorting nexin 27 interacts with multidrug resistance-associa... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q96L92 (UniProtKB:Q96L92); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. MRP4 carries a C-terminal class-I PDZ-binding motif (UniProt MOTIF 1322-1325; SUBUNIT: 'Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain)'). The interaction with the PDZ scaffold SNX27 (UniProtKB:Q96L92) is experimentally characterized and mediates MRP4 internalization and turnover, so the evidence supports the specific molecular function PDZ domain binding (GO:0030165). Proposed replacements: PDZ domain binding Supporting Evidence: PMID:22411990 MRP4 has a PDZ-binding motif, which is a potential sequence that modulates the membrane expression of MRP4 via interaction with PDZ adaptor proteins |
| GO:0005515 protein binding | IPI PMID:24550280 Large-scale interaction profiling of PDZ domains through pro... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q14160 (UniProtKB:Q14160); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is an in-vitro screen of isolated PDZ domains against C-terminal peptide ligands, detecting binding between MRP4's C-terminal class-I PDZ-binding motif and the PDZ domain of UniProtKB:Q14160. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:24550280 we screened the nine PSD-95/Dlg/ZO-1 (PDZ) domains of human Densin-180, Erbin, Scribble, and Disks large homolog 1 for peptide ligands |
| GO:0005515 protein binding | IPI PMID:29146910 An unexpected protein interaction promotes drug resistance i... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q00013 (UniProtKB:Q00013); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. MRP4's C-terminal class-I PDZ-binding motif (UniProt MOTIF 1322-1325) is engaged by the PDZ-domain scaffold MPP1 (UniProtKB:Q00013); this characterized interaction organizes MRP4 membrane localization and turnover (modulating MRP4-mediated drug resistance), so the evidence supports the specific molecular function PDZ domain binding (GO:0030165). Proposed replacements: PDZ domain binding Supporting Evidence: PMID:29146910 PDZ motifs mediate interactions with their cognate PDZ-binding domain proteins |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q15599 (UniProtKB:Q15599); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. This is a high-throughput AP-MS interactome hit (BioPlex) with no PDZ-specific statement in the source; the PDZ-domain-binding interpretation rests on UniProtKB:Q15599 being a PDZ-domain protein together with MRP4's C-terminal class-I PDZ-binding motif. On that basis the interaction is refined to the more precise molecular function PDZ domain binding (GO:0030165), with no trafficking, turnover or localization role asserted. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q5T2W1 (UniProtKB:Q5T2W1); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. This is a high-throughput AP-MS interactome hit (BioPlex) with no PDZ-specific statement in the source; the PDZ-domain-binding interpretation rests on UniProtKB:Q5T2W1 being a PDZ-domain protein together with MRP4's C-terminal class-I PDZ-binding motif. On that basis the interaction is refined to the more precise molecular function PDZ domain binding (GO:0030165), with no trafficking, turnover or localization role asserted. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:O00560 (UniProtKB:O00560); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:O00560. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:O15018 (UniProtKB:O15018); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:O15018. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:O75970 (UniProtKB:O75970); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:O75970. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:O95049 (UniProtKB:O95049); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:O95049. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:O96018 (UniProtKB:O96018); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:O96018. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:P78352 (UniProtKB:P78352); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:P78352. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q00013 (UniProtKB:Q00013); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q00013. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q02410 (UniProtKB:Q02410); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q02410. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q07157 (UniProtKB:Q07157); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q07157. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q12923 (UniProtKB:Q12923); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q12923. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q12959 (UniProtKB:Q12959); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q12959. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q14005 (UniProtKB:Q14005); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q14005. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q14160 (UniProtKB:Q14160); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q14160. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q15599 (UniProtKB:Q15599); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q15599. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q15700 (UniProtKB:Q15700); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q15700. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q5T2W1 (UniProtKB:Q5T2W1); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q5T2W1. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q5TCQ9 (UniProtKB:Q5TCQ9); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q5TCQ9. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q6ZMN7 (UniProtKB:Q6ZMN7); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q6ZMN7. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q70Z35 (UniProtKB:Q70Z35); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q70Z35. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q86UL8 (UniProtKB:Q86UL8); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q86UL8. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q86UT5 (UniProtKB:Q86UT5); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q86UT5. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q8N448 (UniProtKB:Q8N448); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q8N448. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q8NI35 (UniProtKB:Q8NI35); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q8NI35. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q8TBB1 (UniProtKB:Q8TBB1); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q8TBB1. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q8TDM6 (UniProtKB:Q8TDM6); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q8TDM6. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q8TEW0 (UniProtKB:Q8TEW0); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q8TEW0. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q8TEW8 (UniProtKB:Q8TEW8); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q8TEW8. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q96QZ7 (UniProtKB:Q96QZ7); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q96QZ7. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q99767 (UniProtKB:Q99767); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q99767. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q9C0E4 (UniProtKB:Q9C0E4); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q9C0E4. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q9H190 (UniProtKB:Q9H190); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q9H190. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q9H5P4 (UniProtKB:Q9H5P4); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q9H5P4. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q9P202 (UniProtKB:Q9P202); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q9P202. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q9UDY2 (UniProtKB:Q9UDY2); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q9UDY2. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q9UPQ7 (UniProtKB:Q9UPQ7); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q9UPQ7. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q9Y3R0 (UniProtKB:Q9Y3R0); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q9Y3R0. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: IPI interaction of MRP4 with UniProtKB:Q9Y6N9 (UniProtKB:Q9Y6N9); like MRP4's other characterized partners this is a PDZ-domain-containing protein that engages MRP4's C-terminal PDZ-binding motif. Reason: Bare 'protein binding' is uninformative. The supporting evidence is a large-scale in-vitro holdup affinity map measuring binding between a short peptide of MRP4's C-terminal class-I PDZ-binding motif and the isolated PDZ domain of UniProtKB:Q9Y6N9. This supports the more precise molecular function PDZ domain binding (GO:0030165). The evidence concerns isolated domains and short peptides in vitro, not an endogenous full-length complex, and does not establish a role in MRP4 trafficking, turnover or localization. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measured with unprecedented coverage and sensitivity ~65,000 PDZ-PBM affinities |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding: MRP4 has two nucleotide-binding domains that bind ATP to power transport (UniProt; PMID:15364914). Reason: Two ABC/NBD domains; ATP binding is required for the transport cycle. IEA/InterPro mapping is correct. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane (IBA): active-in the plasma membrane, the phylogenetically inferred location for this transporter clade. Reason: IBD node places this transporter family at the plasma membrane; MRP4 is a plasma-membrane protein (UniProt; multiple IDA), so the location claim holds. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Plasma membrane (immunofluorescence curation, GO_REF:0000052). Reason: Direct localization evidence; MRP4 is a plasma-membrane protein. |
| GO:0005886 plasma membrane | IDA PMID:15297306 The nucleotide transporter MRP4 (ABCC4) is highly expressed ... | ACCEPT | Summary: Plasma membrane in platelets (and dense granules) by immunofluorescence (PMID:15297306). Reason: Direct localization; plasma-membrane pool present alongside the predominant granule pool. Supporting Evidence: PMID:15297306 to a lower extent at the plasma membrane |
| GO:0005886 plasma membrane | IDA PMID:18619525 Subcellular localization of transporters along the rat blood... | ACCEPT | Summary: Plasma membrane at the blood-brain/CSF barrier by in vivo biotinylation (PMID:18619525). Reason: Surface-biotinylation localizes MRP4 to the plasma membrane; consistent with its role as a surface efflux pump. |
| GO:0005886 plasma membrane | IDA PMID:23137377 Quantitative targeted absolute proteomic analysis of transpo... | ACCEPT | Summary: Plasma membrane of human brain microvascular endothelium by targeted proteomics (PMID:23137377). Reason: Quantitative membrane proteomics places MRP4 at the plasma membrane. |
| GO:0005886 plasma membrane | IDA PMID:25173977 Prostaglandin signalling regulates ciliogenesis by modulatin... | ACCEPT | Summary: Plasma membrane localization used for PGE2 efflux assays (PMID:25173977). Reason: Direct plasma-membrane localization consistent with surface efflux function. Supporting Evidence: PMID:25173977 directly exports PGE2 across the plasma membrane |
| GO:0005886 plasma membrane | IDA PMID:28112518 LC-MS/MS Based Quantitation of ABC and SLC Transporter Prote... | ACCEPT | Summary: Plasma membrane of retinal pigment epithelium by LC-MS/MS transporter quantitation (PMID:28112518). Reason: Plasma-membrane proteomic localization. |
| GO:0005886 plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Plasma membrane (Ensembl ortholog projection). Reason: Consistent with experimental plasma-membrane localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1454916 | ACCEPT | Summary: Plasma membrane (Reactome, ABCC organic-anion transport). Reason: Curated pathway places MRP4 at the plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9750546 | ACCEPT | Summary: Plasma membrane (Reactome, TPMP efflux). Reason: Curated pathway localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9753283 | ACCEPT | Summary: Plasma membrane (Reactome, APAP conjugate transport). Reason: Curated pathway localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9753284 | ACCEPT | Summary: Plasma membrane (Reactome, APAP-Cys/Mer efflux). Reason: Curated pathway localization. |
| GO:0006805 xenobiotic metabolic process | TAS Reactome:R-HSA-9753281 | KEEP AS NON CORE | Summary: Xenobiotic metabolic process (ADME framing): MRP4 participates in drug disposition by effluxing xenobiotic conjugates (Reactome paracetamol ADME). Reason: Valid higher-level role in xenobiotic handling but broader/peripheral to the specific transport MF; retained as non-core pharmacological context. |
| GO:0006855 xenobiotic transmembrane transport | TAS Reactome:R-HSA-9750546 | ACCEPT | Summary: Xenobiotic transmembrane transport (BP): MRP4 exports xenobiotics/drug conjugates from cytosol to extracellular space (Reactome). Reason: Core BP for MRP4's xenobiotic efflux role; TAS from curated Reactome pathway. |
| GO:0008559 ABC-type xenobiotic transporter activity | EXP PMID:11856762 The MRP4/ABCC4 gene encodes a novel apical organic anion tra... | ACCEPT | Summary: ABC-type xenobiotic transporter activity: MRP4 effluxes a broad range of drugs/metabolites (antivirals, 6-MP, PMEA, methotrexate, cephalosporins), conferring resistance (PMID:11856762, PMID:12105214, PMID:15454390, PMID:17344354, PMID:18300232). Reason: Multispecific xenobiotic/drug efflux is a well-established core MRP4 activity. Supporting Evidence: PMID:11856762 ATP-dependent [(3)H]methotrexate and [(3)H]estradiol-17beta-D-glucuronide transport by MRP4 |
| GO:0008559 ABC-type xenobiotic transporter activity | EXP PMID:12105214 Expression of MRP4 confers resistance to ganciclovir and com... | ACCEPT | Summary: ABC-type xenobiotic transporter activity: MRP4 effluxes a broad range of drugs/metabolites (antivirals, 6-MP, PMEA, methotrexate, cephalosporins), conferring resistance (PMID:11856762, PMID:12105214, PMID:15454390, PMID:17344354, PMID:18300232). Reason: Multispecific xenobiotic/drug efflux is a well-established core MRP4 activity. Supporting Evidence: PMID:12105214 confers resistance to purine-based antiretroviral agents |
| GO:0008559 ABC-type xenobiotic transporter activity | EXP PMID:15454390 Human organic anion transporter MRP4 (ABCC4) is an efflux pu... | ACCEPT | Summary: ABC-type xenobiotic transporter activity: MRP4 effluxes a broad range of drugs/metabolites (antivirals, 6-MP, PMEA, methotrexate, cephalosporins), conferring resistance (PMID:11856762, PMID:12105214, PMID:15454390, PMID:17344354, PMID:18300232). Reason: Multispecific xenobiotic/drug efflux is a well-established core MRP4 activity. Supporting Evidence: PMID:15454390 Urate inhibited methotrexate transport |
| GO:0008559 ABC-type xenobiotic transporter activity | EXP PMID:17344354 Involvement of MRP4 (ABCC4) in the luminal efflux of ceftizo... | ACCEPT | Summary: ABC-type xenobiotic transporter activity: MRP4 effluxes a broad range of drugs/metabolites (antivirals, 6-MP, PMEA, methotrexate, cephalosporins), conferring resistance (PMID:11856762, PMID:12105214, PMID:15454390, PMID:17344354, PMID:18300232). Reason: Multispecific xenobiotic/drug efflux is a well-established core MRP4 activity. Supporting Evidence: PMID:17344354 Significant ATP-dependent transport of ceftizoxime (K(m), 18 microM), cefazolin (K(m), 80 microM), cefotaxime, and cefmetazole has been observed only in the membrane vesicles expressing hMRP4 |
| GO:0008559 ABC-type xenobiotic transporter activity | EXP PMID:18300232 6-mercaptopurine and 9-(2-phosphonyl-methoxyethyl) adenine (... | ACCEPT | Summary: ABC-type xenobiotic transporter activity: MRP4 effluxes a broad range of drugs/metabolites (antivirals, 6-MP, PMEA, methotrexate, cephalosporins), conferring resistance (PMID:11856762, PMID:12105214, PMID:15454390, PMID:17344354, PMID:18300232). Reason: Multispecific xenobiotic/drug efflux is a well-established core MRP4 activity. Supporting Evidence: PMID:18300232 participates in the transport of diverse antiviral and chemotherapeutic agents such as 6-mercaptopurine (6-MP) and 9-(2-phosphonyl methoxyethyl) adenine (PMEA) |
| GO:0008559 ABC-type xenobiotic transporter activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC 7.6.2.2 (ABC-type xenobiotic transporter) mapping, consistent with extensive experimental drug-transport data. Reason: IEA/EC mapping agrees with experimental xenobiotic transporter activity. |
| GO:0015132 prostaglandin transmembrane transporter activity | IMP PMID:15364914 Multidrug resistance protein 4 (ABCC4)-mediated ATP hydrolys... | ACCEPT | Summary: Prostaglandin transmembrane transporter activity: PGE1/PGE2 are MRP4 substrates and stimulate its ATPase (PMID:15364914). Reason: MRP4 is a bona fide prostaglandin efflux transporter; core MF. Supporting Evidence: PMID:15364914 the prostaglandins E1 and E2, stimulate ATP hydrolysis |
| GO:0015143 urate transmembrane transporter activity | IMP PMID:15454390 Human organic anion transporter MRP4 (ABCC4) is an efflux pu... | ACCEPT | Summary: Urate transmembrane transporter activity: MRP4 mediates ATP-dependent urate efflux with positive cooperativity (PMID:15454390). Reason: Directly demonstrated urate efflux; core renal/hepatic urate-handling activity. Supporting Evidence: PMID:15454390 mediates ATP-dependent urate transport via a positive cooperative mechanism |
| GO:0015216 purine nucleotide transmembrane transporter activity | IMP PMID:25986174 Characterization of efflux transport proteins of the human c... | ACCEPT | Summary: Purine-nucleotide transmembrane transporter activity: MRP4 effluxes cyclic purine nucleotides (cAMP, cGMP) and purine nucleotide analogs (PMID:25986174, PMID:11856762). Reason: The cyclic purine nucleotides cAMP/cGMP are core substrates; purine-nucleotide transporter activity is supported. |
| GO:0015431 ABC-type glutathione S-conjugate transporter activity | EXP PMID:11856762 The MRP4/ABCC4 gene encodes a novel apical organic anion tra... | ACCEPT | Summary: ABC-type glutathione S-conjugate transporter activity: MRP4 interacts with/transports anionic GSH conjugates such as DNP-SG (PMID:11856762) and transports the GSH-conjugate LTC4 (PMID:17959747). Reason: GSH S-conjugate (e.g. LTC4, DNP-SG) efflux is a core MRP4 activity. Supporting Evidence: PMID:11856762 S-(2,4-dinitrophenyl)-glutathione |
| GO:0015431 ABC-type glutathione S-conjugate transporter activity | IDA PMID:17959747 ATP-dependent transport of leukotrienes B4 and C4 by the mul... | ACCEPT | Summary: MRP4 is an ATP-dependent efflux pump for the glutathione S-conjugate leukotriene C4 (PMID:17959747). Reason: Direct demonstration of GSH-conjugate (LTC4) transport; core activity. Supporting Evidence: PMID:17959747 also functioned as an ATP-dependent efflux pump for LTC(4) |
| GO:0015431 ABC-type glutathione S-conjugate transporter activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC 7.6.2.3 (glutathione-conjugate-exporting ATPase) mapping, consistent with experimentally demonstrated LTC4/GSH-conjugate transport. Reason: IEA/EC mapping agrees with the experimental GSH S-conjugate transporter activity. |
| GO:0015432 ABC-type bile acid transporter activity | IMP PMID:16282361 Substrate specificity of human ABCC4 (MRP4)-mediated cotrans... | ACCEPT | Summary: ABC-type bile acid transporter activity: MRP4 cotransports taurine/glycine bile-acid conjugates and cholate together with GSH (PMID:16282361, PMID:12883481). Reason: Bile-acid/GSH cotransport is a directly demonstrated core activity, important for basolateral hepatocyte bile-acid handling. Supporting Evidence: PMID:16282361 has a high affinity for the taurine and glycine conjugates of the common natural bile acids as well as the unconjugated bile acid cholate |
| GO:0015562 efflux transmembrane transporter activity | IMP PMID:25986174 Characterization of efflux transport proteins of the human c... | ACCEPT | Summary: Efflux transmembrane transporter activity: ABCC4 is a unidirectional cellular efflux pump (PMID:25986174, PMID:16282361). Reason: Correct, slightly general MF capturing MRP4's efflux directionality; consistent with its ABC-type transporter activity. |
| GO:0015721 bile acid and bile salt transport | IMP PMID:16282361 Substrate specificity of human ABCC4 (MRP4)-mediated cotrans... | ACCEPT | Summary: Bile acid and bile salt transport: MRP4 exports bile acids across the basolateral hepatocyte membrane as a GSH cotransport (PMID:16282361, PMID:12883481). Reason: BP for the bile-acid cotransport function; core in hepatocytes. Supporting Evidence: PMID:16282361 mediates ATP-dependent unidirectional efflux of organic anions out of cells |
| GO:0015732 prostaglandin transport | IMP PMID:15364914 Multidrug resistance protein 4 (ABCC4)-mediated ATP hydrolys... | ACCEPT | Summary: Prostaglandin transport: MRP4 exports PGE1/PGE2 from cells (PMID:15364914, PMID:25173977). Reason: BP for the prostaglandin efflux function; core. Supporting Evidence: PMID:15364914 the prostaglandins E1 and E2, stimulate ATP hydrolysis |
| GO:0015747 urate transport | IMP PMID:15454390 Human organic anion transporter MRP4 (ABCC4) is an efflux pu... | ACCEPT | Summary: Urate transport (BP): MRP4 is a candidate apical efflux pump for urinary urate excretion (PMID:15454390). Reason: BP for the demonstrated urate transporter activity; core. Supporting Evidence: PMID:15454390 mediates ATP-dependent urate transport via a positive cooperative mechanism |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MODIFY | Summary: Membrane-protein evidence; the specific compartment is the plasma membrane. Reason: 'Membrane' is correct but uninformatively general; refine to plasma membrane (GO:0005886), MRP4's established membrane, which the gene already carries with direct evidence. Proposed replacements: plasma membrane |
| GO:0016020 membrane | IDA PMID:15297306 The nucleotide transporter MRP4 (ABCC4) is highly expressed ... | MODIFY | Summary: Membrane-protein evidence; the specific compartment is the plasma membrane. Reason: 'Membrane' is correct but uninformatively general; refine to plasma membrane (GO:0005886), MRP4's established membrane, which the gene already carries with direct evidence. Proposed replacements: plasma membrane |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Membrane-protein evidence; the specific compartment is the plasma membrane. Reason: 'Membrane' is correct but uninformatively general; refine to plasma membrane (GO:0005886), MRP4's established membrane, which the gene already carries with direct evidence. Proposed replacements: plasma membrane |
| GO:0016323 basolateral plasma membrane | EXP PMID:11106685 Analysis of the MRP4 drug resistance profile in transfected ... | ACCEPT | Summary: Basolateral plasma membrane: MRP4 localizes to the plasma membrane of transfected cells and basolaterally in prostate (PMID:11106685). Reason: Experimental localization read from full text by the curator; MRP4's polarity is tissue-dependent (basolateral in some epithelia). ACCEPT and defer to curator. Supporting Evidence: PMID:11106685 localized in the plasma membrane and cytoplasm of transfected cells |
| GO:0016323 basolateral plasma membrane | EXP PMID:12883481 Cotransport of reduced glutathione with bile salts by MRP4 (... | ACCEPT | Summary: Basolateral plasma membrane of hepatocytes: MRP4 localized to the basolateral (sinusoidal) membrane of human/rat/mouse hepatocytes (PMID:12883481). Reason: Direct, species-consistent basolateral localization; core location for hepatic GSH/bile-acid efflux. Supporting Evidence: PMID:12883481 localized the multidrug resistance protein 4 (MRP4; ABCC4) to the basolateral membrane of human, rat, and mouse hepatocytes |
| GO:0016323 basolateral plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Basolateral plasma membrane (IBA). Reason: Phylogenetically inferred basolateral localization, consistent with experimental data in hepatocytes/epithelia. |
| GO:0016323 basolateral plasma membrane | IDA PMID:24130369 Localization of multidrug resistance-associated proteins alo... | ACCEPT | Summary: Basolateral plasma membrane along the blood-testis barrier (PMID:24130369). Reason: Immunohistochemical localization of MRP4 in testis; tissue-specific basolateral pool. Supporting Evidence: PMID:24130369 MRP1, MRP4, MRP5, and MRP8 |
| GO:0016323 basolateral plasma membrane | IDA PMID:25986174 Characterization of efflux transport proteins of the human c... | ACCEPT | Summary: Basolateral plasma membrane in the choroid-plexus/blood-CSF model (PMID:25986174). Reason: Localization read from full text; tissue-dependent basolateral pool. ACCEPT and defer to curator. |
| GO:0016323 basolateral plasma membrane | IDA PMID:31791063 Quantitative Protein Expression in the Human Retinal Pigment... | ACCEPT | Summary: Basolateral plasma membrane of retinal pigment epithelium by comparative proteomics (PMID:31791063). Reason: Quantitative apical-vs-basolateral proteomics localizing MRP4; tissue-dependent polarity. |
| GO:0016323 basolateral plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Basolateral plasma membrane (UniProt subcellular-location IEA, SL-0026). Reason: Consistent with curated basolateral localization. |
| GO:0016324 apical plasma membrane | IDA PMID:11856762 The MRP4/ABCC4 gene encodes a novel apical organic anion tra... | ACCEPT | Summary: Apical plasma membrane of kidney proximal tubule: MRP4 is the apical cAMP/cGMP/urate efflux pump (PMID:11856762). Reason: Direct localization to the proximal-tubule apical membrane; core location for renal efflux. Supporting Evidence: PMID:11856762 MRP4 is localized to the proximal tubule apical membrane of human kidney |
| GO:0016324 apical plasma membrane | IDA PMID:25986174 Characterization of efflux transport proteins of the human c... | ACCEPT | Summary: Apical plasma membrane in the blood-CSF barrier model (PMID:25986174). Reason: Localization from full text; tissue-dependent apical pool. ACCEPT and defer to curator. |
| GO:0016324 apical plasma membrane | IDA PMID:31791063 Quantitative Protein Expression in the Human Retinal Pigment... | ACCEPT | Summary: Apical plasma membrane of retinal pigment epithelium by comparative proteomics (PMID:31791063). Reason: Quantitative proteomics localizing MRP4; polarity is tissue-dependent. |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Apical plasma membrane (UniProt subcellular-location IEA, SL-0015). Reason: Consistent with curated apical localization in kidney. |
| GO:0016404 15-hydroxyprostaglandin dehydrogenase (NAD+) activity | NAS PMID:7557451 Sequence of a novel mRNA coding for a C-terminal-truncated f... | REMOVE | Summary: 15-hydroxyprostaglandin dehydrogenase (NAD+) activity, NAS from PMID:7557451 — a paper about the HPGD (15-PGDH) enzyme, not ABCC4. Reason: ABCC4 is a polytopic ABC membrane transporter with ATP-driven efflux activity; it has no NAD(+)-dependent oxidoreductase/dehydrogenase domain and cannot perform 15-hydroxyprostaglandin dehydrogenation. PMID:7557451 ('a C-terminal-truncated form of human NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase') describes HPGD/15-PGDH, a soluble cytosolic enzyme. This NAS annotation is a gene/term mis-attribution and is biologically impossible for ABCC4; remove. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: ATP hydrolysis activity: MRP4 hydrolyzes ATP (Km 0.62 mM), stimulated by prostaglandin substrates (PMID:15364914). Reason: ATPase activity is experimentally demonstrated and mechanistically central; IEA mapping correct. Supporting Evidence: PMID:15364914 MRP4 hydrolyzes ATP (Km, 0.62 mm) |
| GO:0022857 transmembrane transporter activity | IEA GO_REF:0000107 | TOO GENERAL | Summary: Generic transmembrane transporter activity; true but uninformative here. Reason: This root-level transporter term is entailed by the specific transporter activities asserted elsewhere (ABC-type xenobiotic transporter activity GO:0008559, prostaglandin transmembrane transporter activity GO:0015132, and ABC-type glutathione S-conjugate transporter activity GO:0015431, all ACCEPT). It judges the term's granularity, not the truth of the claim. |
| GO:0031088 platelet dense granule membrane | IDA PMID:15297306 The nucleotide transporter MRP4 (ABCC4) is highly expressed ... | KEEP AS NON CORE | Summary: Platelet dense granule membrane: MRP4 colocalizes with delta-granule markers in platelets (PMID:15297306). Reason: Direct localization to a platelet-specific granule membrane where MRP4 loads cyclic nucleotides; a real but tissue-specific, non-core location. Supporting Evidence: PMID:15297306 largely colocalized with the accumulation of mepacrine as marker for delta-granules |
| GO:0031088 platelet dense granule membrane | TAS Reactome:R-HSA-429157 | KEEP AS NON CORE | Summary: Platelet dense granule membrane (TAS, Reactome: ABCC4 accumulation of dense granule contents). Reason: Curated pathway localization consistent with the IDA; tissue-specific, non-core. |
| GO:0032310 prostaglandin secretion | IDA PMID:25173977 Prostaglandin signalling regulates ciliogenesis by modulatin... | ACCEPT | Summary: Prostaglandin secretion: ABCC4 is the transporter that exports PGE2 out of cells, assayed directly by PGE2 efflux (PMID:25173977). Reason: ABCC4-mediated PGE2 efflux is cellular prostaglandin secretion; a direct, core consequence of its PG transporter activity. acts_upstream_of_or_within is appropriate. Supporting Evidence: PMID:25173977 we performed PGE2 efflux assays |
| GO:0034634 glutathione transmembrane transporter activity | IMP PMID:11856762 The MRP4/ABCC4 gene encodes a novel apical organic anion tra... | ACCEPT | Summary: Glutathione transmembrane transporter activity: MRP4 effluxes reduced GSH (and GSH conjugates), and cotransports GSH with bile acids (PMID:11856762, PMID:12883481, PMID:16282361). Reason: GSH efflux and GSH cotransport are experimentally established core activities. Supporting Evidence: PMID:11856762 S-(2,4-dinitrophenyl)-glutathione |
| GO:0034775 glutathione transmembrane transport | IEA GO_REF:0000108 | ACCEPT | Summary: Glutathione transmembrane transport (BP), inferred from glutathione transmembrane transporter activity. Reason: Correct BP inference from the supported GSH transporter MF. |
| GO:0042626 ATPase-coupled transmembrane transporter activity | IDA PMID:15364914 Multidrug resistance protein 4 (ABCC4)-mediated ATP hydrolys... | ACCEPT | Summary: ATPase-coupled transmembrane transporter activity: MRP4 couples ATP hydrolysis to vectorial substrate efflux (PMID:15364914, PMID:15454390; Reactome). Reason: Captures the primary active-transport mechanism; strongly supported by ATPase and vesicular transport assays. |
| GO:0042626 ATPase-coupled transmembrane transporter activity | IDA PMID:15454390 Human organic anion transporter MRP4 (ABCC4) is an efflux pu... | ACCEPT | Summary: ATPase-coupled transmembrane transporter activity: MRP4 couples ATP hydrolysis to vectorial substrate efflux (PMID:15364914, PMID:15454390; Reactome). Reason: Captures the primary active-transport mechanism; strongly supported by ATPase and vesicular transport assays. |
| GO:0042626 ATPase-coupled transmembrane transporter activity | IEA GO_REF:0000002 | ACCEPT | Summary: ATPase-coupled transmembrane transporter activity: MRP4 couples ATP hydrolysis to vectorial substrate efflux (PMID:15364914, PMID:15454390; Reactome). Reason: Captures the primary active-transport mechanism; strongly supported by ATPase and vesicular transport assays. |
| GO:0042626 ATPase-coupled transmembrane transporter activity | TAS Reactome:R-HSA-1454916 | ACCEPT | Summary: ATPase-coupled transmembrane transporter activity: MRP4 couples ATP hydrolysis to vectorial substrate efflux (PMID:15364914, PMID:15454390; Reactome). Reason: Captures the primary active-transport mechanism; strongly supported by ATPase and vesicular transport assays. |
| GO:0042626 ATPase-coupled transmembrane transporter activity | TAS Reactome:R-HSA-9750546 | ACCEPT | Summary: ATPase-coupled transmembrane transporter activity: MRP4 couples ATP hydrolysis to vectorial substrate efflux (PMID:15364914, PMID:15454390; Reactome). Reason: Captures the primary active-transport mechanism; strongly supported by ATPase and vesicular transport assays. |
| GO:0042626 ATPase-coupled transmembrane transporter activity | TAS Reactome:R-HSA-9753283 | ACCEPT | Summary: ATPase-coupled transmembrane transporter activity: MRP4 couples ATP hydrolysis to vectorial substrate efflux (PMID:15364914, PMID:15454390; Reactome). Reason: Captures the primary active-transport mechanism; strongly supported by ATPase and vesicular transport assays. |
| GO:0042626 ATPase-coupled transmembrane transporter activity | TAS Reactome:R-HSA-9753284 | ACCEPT | Summary: ATPase-coupled transmembrane transporter activity: MRP4 couples ATP hydrolysis to vectorial substrate efflux (PMID:15364914, PMID:15454390; Reactome). Reason: Captures the primary active-transport mechanism; strongly supported by ATPase and vesicular transport assays. |
| GO:0042910 xenobiotic transmembrane transporter activity | IDA PMID:11856762 The MRP4/ABCC4 gene encodes a novel apical organic anion tra... | ACCEPT | Summary: Xenobiotic transmembrane transporter activity: MRP4 transports organic-anion drugs and conjugates (PMID:11856762). Reason: Parent-level xenobiotic transporter MF, well supported by the drug-transport data; reinforces GO:0008559. Supporting Evidence: PMID:11856762 ATP-dependent [(3)H]methotrexate and [(3)H]estradiol-17beta-D-glucuronide transport by MRP4 |
| GO:0042910 xenobiotic transmembrane transporter activity | IMP PMID:25986174 Characterization of efflux transport proteins of the human c... | ACCEPT | Summary: Xenobiotic transporter activity of ABCC4 corroborated functionally at the blood-CSF barrier model (PMID:25986174). Reason: Supports multispecific xenobiotic efflux; consistent with directly demonstrated drug transport. Supporting Evidence: PMID:25986174 Functionality of ABCC1, ABCC4, ABCB1 and ABCG2 could be shown in uptake assays |
| GO:0055085 transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: Transmembrane transport (IBA): the phylogenetic family-level BP for this membrane-transporter clade. Reason: IBD-placed family BP; MRP4 is within the transporter clade. Correct pathway-level process, reinforced by the many specific transport processes demonstrated experimentally. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: Transmembrane transport (IEA/InterPro). Reason: Correct general transport BP from InterPro signature. |
| GO:0055085 transmembrane transport | TAS Reactome:R-HSA-382556 | ACCEPT | Summary: Transmembrane transport (TAS, Reactome ABC-family transport). Reason: Curated pathway assertion consistent with MRP4 function. |
| GO:0060271 cilium assembly | IMP PMID:25173977 Prostaglandin signalling regulates ciliogenesis by modulatin... | KEEP AS NON CORE | Summary: Cilium assembly (acts_upstream_of_or_within): ABCC4-mediated PGE2 export provides the extracellular PGE2 signal that promotes ciliogenesis via intraflagellar transport (PMID:25173977). Reason: ABCC4 does not build the cilium; it acts upstream by exporting the PGE2 signalling molecule. Genuine regulatory role (zebrafish lkt/abcc4), but indirect and peripheral to the core transport MF. Retained as non-core, consistent with acts_upstream_of_or_within. Supporting Evidence: PMID:25173977 These data reveal the molecular bases of Lkt/ABCC4 function, linking PGE2 export to ciliogenesis. |
| GO:0070730 cAMP transport | IDA PMID:11856762 The MRP4/ABCC4 gene encodes a novel apical organic anion tra... | ACCEPT | Summary: MRP4 is the apical renal efflux pump for cAMP; ATP-dependent cAMP transport shown in vesicles (PMID:11856762). Reason: cAMP efflux is a core physiological role of MRP4 (cyclic nucleotide extrusion). Supporting Evidence: PMID:11856762 exhibit ATP-dependent transport of [(3)H]cAMP and [(3)H]cGMP |
| GO:0070730 cAMP transport | IMP PMID:25986174 Characterization of efflux transport proteins of the human c... | ACCEPT | Summary: cAMP transport by ABCC4 corroborated functionally in the HIBCPP blood-CSF barrier model (PMID:25986174). Reason: Supports the cAMP efflux role; consistent with the directly demonstrated activity (PMID:11856762). Full text underlies this IMP; the core cyclic-nucleotide efflux function is well established. Supporting Evidence: PMID:25986174 Functionality of ABCC1, ABCC4, ABCB1 and ABCG2 could be shown in uptake assays |
| GO:0071716 leukotriene transport | IDA PMID:17959747 ATP-dependent transport of leukotrienes B4 and C4 by the mul... | ACCEPT | Summary: Leukotriene transport: MRP4 mediates ATP-dependent efflux of LTB4 (GSH-dependent) and LTC4 (PMID:17959747). Reason: Direct demonstration of LTB4/LTC4 efflux; core role in exporting proinflammatory lipid mediators. Supporting Evidence: PMID:17959747 human ABCC4 mediates the ATP-dependent efflux of LTB(4) in the presence of reduced glutathione (GSH) |
| GO:0071716 leukotriene transport | IEA GO_REF:0000117 | ACCEPT | Summary: Leukotriene transport (ARBA electronic), consistent with the experimentally demonstrated LTB4/LTC4 efflux (PMID:17959747). Reason: Electronic annotation agrees with experimental leukotriene transport. |
| GO:0098591 external side of apical plasma membrane | ISS PMID:18619525 Subcellular localization of transporters along the rat blood... | MARK AS OVER ANNOTATED | Summary: External side of apical plasma membrane, ISS-projected from rodent orthologs from a surface-biotinylation study (PMID:18619525). Reason: MRP4 is a polytopic (multi-pass) integral membrane transporter, not a protein peripherally attached to the external membrane face. Surface biotinylation shows apical surface exposure but does not support an 'external side' localization; the apical plasma-membrane location (GO:0016324) already captures this correctly. Over-annotation. |
| GO:0098591 external side of apical plasma membrane | ISS PMID:18619525 Subcellular localization of transporters along the rat blood... | MARK AS OVER ANNOTATED | Summary: External side of apical plasma membrane, ISS-projected from rodent orthologs from a surface-biotinylation study (PMID:18619525). Reason: MRP4 is a polytopic (multi-pass) integral membrane transporter, not a protein peripherally attached to the external membrane face. Surface biotinylation shows apical surface exposure but does not support an 'external side' localization; the apical plasma-membrane location (GO:0016324) already captures this correctly. Over-annotation. |
| GO:0140115 export across plasma membrane | IMP PMID:25986174 Characterization of efflux transport proteins of the human c... | ACCEPT | Summary: Export across plasma membrane: MRP4 is a plasma-membrane efflux pump that exports substrates out of the cell (PMID:25986174). Reason: Directly reflects MRP4's unidirectional efflux across the plasma membrane; core. Supporting Evidence: PMID:25986174 Functionality of ABCC1, ABCC4, ABCB1 and ABCG2 could be shown in uptake assays |
| GO:0140359 ABC-type transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: ABC-type transporter activity (IBA): the phylogenetically inherited family MF for this ABCC/ABC transporter clade. Reason: IBD node placement for the ABC transporter family is sound and MRP4 is within the clade; correct family-level MF, reinforced by experimental ATPase/transport data. |
| GO:0140359 ABC-type transporter activity | IEA GO_REF:0000002 | ACCEPT | Summary: ABC-type transporter activity (IEA/InterPro). Reason: Correct family-level MF from InterPro signature; agrees with IBA and experiment. |
| GO:0140359 ABC-type transporter activity | TAS Reactome:R-HSA-429157 | ACCEPT | Summary: ABC-type transporter activity (TAS, Reactome). Reason: Curated pathway assertion consistent with MRP4's ABC transporter mechanism. |
| GO:0150104 transport across blood-brain barrier | NAS PMID:26590417 Establishment and Dysfunction of the Blood-Brain Barrier. | KEEP AS NON CORE | Summary: Transport across blood-brain barrier: MRP4 is an efflux transporter expressed at the BBB (NAS, review). Reason: MRP4 contributes to efflux at the blood-brain barrier; a physiological context of its transporter activity rather than a distinct core function. Retained as non-core. |
| GO:0150104 transport across blood-brain barrier | NAS PMID:30280653 Blood-Brain Barrier: From Physiology to Disease and Back. | KEEP AS NON CORE | Summary: Transport across blood-brain barrier: MRP4 is an efflux transporter expressed at the BBB (NAS, review). Reason: MRP4 contributes to efflux at the blood-brain barrier; a physiological context of its transporter activity rather than a distinct core function. Retained as non-core. |
| GO:1903790 guanine nucleotide transmembrane transport | IEA GO_REF:0000120 | ACCEPT | Summary: Guanine-nucleotide (cGMP) transmembrane transport, logically inferred from the demonstrated cGMP transporter activity. Reason: BP counterpart of the directly supported cGMP efflux MF; correctly inferred from GO:0001409/GO:1905948. |
| GO:1905948 ABC-type 3',5'-cyclic GMP transmembrane transporter activity | EXP PMID:11856762 The MRP4/ABCC4 gene encodes a novel apical organic anion tra... | ACCEPT | Summary: ATP-dependent cGMP transport by human MRP4 demonstrated in Sf9 membrane vesicles (PMID:11856762). Reason: Direct biochemical demonstration of ATP-dependent cyclic GMP efflux; a defining core activity of MRP4. Supporting Evidence: PMID:11856762 exhibit ATP-dependent transport of [(3)H]cAMP and [(3)H]cGMP |
| GO:1905948 ABC-type 3',5'-cyclic GMP transmembrane transporter activity | EXP PMID:15454390 Human organic anion transporter MRP4 (ABCC4) is an efflux pu... | ACCEPT | Summary: cGMP transport by MRP4 confirmed, with positive-cooperative kinetics and modulation by urate (PMID:15454390). Reason: Independent biochemical confirmation of ATP-dependent cGMP efflux; core activity. Supporting Evidence: PMID:15454390 MRP4 could transport urate simultaneously with cAMP or cGMP |
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)