Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on Enzyme Commission mapping
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum.
Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6).
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Human full-length expression and vesicular transport establish ATP binding and glutathione-conjugate export
"We found that glutathione conjugates, including leukotriene C(4) and N-ethylmaleimide S-glutathione (NEM-GS), were actively transported by human ABCC6."
Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6).
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Human MRP6 in CHO vesicles supports defined substrate export and limited drug resistance
"Analysis of the drug sensitivity of MRP6-transfected cells revealed low levels of resistance to several natural product agents, including etoposide, teniposide, doxorubicin, and daunorubicin."
Subcellular localization and N-glycosylation of human ABCC6, expressed in MDCKII cells.
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Human protein in polarized canine MDCKII host cells establishes basolateral location
"human ABCC6, when expressed by retroviral transduction in polarized mammalian (MDCKII) cells, is exclusively localized to the basolateral membrane."
ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release.
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Abstract explicitly distinguishes ABCC6-dependent NTP release from direct NTP translocation. Human/rat expression and mouse PPi evidence. Full-text retrieval failed
"cells expressing ABCC6 excrete large amounts of nucleoside triphosphates, even though ABCC6 itself does not transport nucleoside triphosphates."
ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report.
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Full text read. Rat ABCC6 in human cell lines, mouse hepatocytes/perfusion, and human patient PPi are distinct experimental contexts. No direct ATP substrate assertion.
"Factors could be missing in vitro, however, that allows ABCC6 to transport ATP in vivo, or ABCC6 could indirectly stimulate ATP release by regulating vesicular transport or ion channels."
Ectopic calcification in pseudoxanthoma elasticum responds to inhibition of tissue-nonspecific alkaline phosphatase.
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Full text read. Patient fibroblasts and mouse genetic/metabolic studies support PPi/mineralization and TNAP effects. Proposed AMP/PPi secretion is explicitly hypothetical
"Here, both genetic and metabolic analyses provide compelling evidence that ABCC6 acts in concert with ENPP1 and CD73 to regulate extracellular PPi, a major physiologic inhibitor of calcification."
Localization of Xenobiotic Transporters Expressed at the Human Blood-Testis Barrier.
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Full text confirms human MRP6 basal Sertoli/peritubular staining. This does not establish specific substrate transport across the blood-testis barrier.
"OCTN2, multidrug resistance protein (MRP) 3, MRP6, and MRP7 localized to SC basal membranes and peritubular myoid cells (PMCs) surrounding the seminiferous tubules."
Quantitative fragmentomics allow affinity mapping of interactomes.
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Full paper and publisher Supplementary Dataset 1 inspected. ABCC6 target peptide, exact domain rows and IntAct exports are tabulated in the source audit. Quantified positives are separated from zero-coded affinities/10-molar export placeholders
"We quantified 18,332 unique dissociation constants, whereas 46,825 PDZ-PBM affinities representing 72% of the explored space remained below the assay’s quantification threshold."
The anthracycline resistance-associated (ara) gene, a novel gene associated with multidrug resistance in a human leukaemia cell line.
The ABCC family mediates organic anion transport
ABC-family proteins mediated transport
Defective ABCC6 does not transport organic anion from cytosol to extracellular region
ABCC6 is a basolateral plasma membrane protein.
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Full text read: native human/mouse liver and primary mouse hepatocyte staining supports basolateral localization and disputes earlier MAM attribution for full-length protein. Does not negate URG7 isoform ER data.
"Our results show unambiguously that in frozen sections of mouse and human livers, Abcc6/ABCC6 is colocalized with the plasma membrane markers cadherin (Figure 1A, D) and catenin (not shown) as well as the basolateral membrane marker Na,K-ATPase (Figure 1B)."
The hepatitis B x antigen anti-apoptotic effector URG7 is localized to the endoplasmic reticulum membrane.
Genetic modulation of nephrocalcinosis in mouse models of ectopic mineralization: the Abcc6(tm1Jfk) and Enpp1(asj) mutant mice.
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Full text read. Combined phosphate/magnesium diet and Abcc6/Enpp1 genetic effects on nephrocalcinosis
"No difference in serum calcium, inorganic phosphate or pyrophosphate concentrations was noted (Table 1)."
Oral administration of pyrophosphate inhibits connective tissue calcification.
Plasma PPi Deficiency Is the Major, but Not the Exclusive, Cause of Ectopic Mineralization in an Abcc6(-/-) Mouse Model of PXE.
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Full text read. ENPP1 overexpression incompletely rescues Abcc6 deficiency, supporting a major but not exclusive role for plasma PPi.
"In contrast, although significantly reduced mineralization was noted in Abcc6-/- mice expressing human ENPP1, small mineralization foci were still evident despite increased plasma PPi levels."
Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6.
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Full human primary genetic study read. Biallelic ABCC6 cases support overlapping GACI/PXE spectrum
"In 14 of these patients, we detected pathogenic ABCC6 mutations (biallelic mutations in eight patients, monoallelic mutations in six patients)."
Regulation of ABCC6 trafficking and stability by a conserved C-terminal PDZ-like sequence.
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Full text read: tail deletions affect biosynthesis/trafficking
"These data suggest that the conserved, PDZ-like sequence promotes the proper biosynthesis and trafficking of the ABCC6 protein."
Falcon research report for human ABCC6