Affinage

ABCC8

ATP-binding cassette sub-family C member 8 · UniProt Q09428

Length
1581 aa
Mass
177.0 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ABCC8 encodes SUR1, the regulatory subunit of the octameric K(ATP) channel (SUR1/Kir6.2), which couples cellular metabolic state to membrane excitability by sensing Mg-nucleotides: ATP binding at NBF1 and ADP binding/hydrolysis at NBF2 activate the channel, counterbalancing ATP-mediated inhibition at Kir6.2, thereby controlling insulin secretion in pancreatic beta cells and glucagon release in alpha cells (PMID:10581363, PMID:26682803, PMID:24621811). Gain-of-function mutations in ABCC8 cause neonatal diabetes by elevating MgATP-dependent channel open probability and impairing metabolic sensing, while loss-of-function mutations cause congenital hyperinsulinism through defective trafficking of the SUR1/Kir6.2 complex to the plasma membrane; both conditions remain responsive to sulfonylurea pharmacology (PMID:16885549, PMID:15579781, PMID:30354297). In the central nervous system, SUR1 co-assembles with TRPM4 (and AQP4) to form a heteromultimeric cation/water channel complex in astrocytes, neurons, and endothelial cells after ischemic injury; SUR1-TRPM4-mediated Na⁺ influx drives reverse-mode NCX1 signaling, calmodulin-dependent AQP4 translocation to the plasma membrane, and consequent cytotoxic edema (PMID:28906027, PMID:37279286). Loss-of-function ABCC8 variants also diminish K(ATP) channel currents in the pulmonary vasculature and are associated with pulmonary arterial hypertension (PMID:30354297).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1999 High

    Establishing how SUR1 senses metabolic state resolved the fundamental question of how an ABC transporter subunit couples nucleotide hydrolysis to ion channel gating: ATP binds NBF1 and ADP binds NBF2, with cooperative Mg-nucleotide interactions at SUR1 activating the channel to counterbalance ATP inhibition at Kir6.2.

    Evidence Biochemical nucleotide-binding/ATPase assays and functional reconstitution with NBF mutagenesis

    PMID:10581363

    Open questions at the time
    • Structural basis of NBF1–NBF2 cooperativity not resolved at atomic level
    • Stoichiometry of nucleotide occupancy states in the intact octamer unclear
  2. 2004 High

    Demonstrating that loss-of-function ABCC8 mutations cause congenital hyperinsulinism by trapping the SUR1/Kir6.2 complex intracellularly established that SUR1 controls channel trafficking in addition to gating, explaining a disease mechanism distinct from altered nucleotide sensitivity.

    Evidence Photolabeling in reconstituted system plus electrophysiology in patient beta cells

    PMID:15579781

    Open questions at the time
    • Specific ER quality-control machinery recognizing misfolded SUR1 not identified
    • Whether trafficking-defective mutants retain partial function if forced to the surface not systematically tested
  3. 2006 High

    Identifying activating ABCC8 mutations in neonatal diabetes patients showed that enhanced Mg-nucleotide-dependent stimulation of SUR1 is sufficient to hold channels open and prevent insulin secretion, establishing the gain-of-function disease mechanism and demonstrating sulfonylurea sensitivity of mutant channels.

    Evidence Patch-clamp electrophysiology of mutant channels in intact cells; mutation screening of 34 neonatal diabetes patients

    PMID:16885549

    Open questions at the time
    • Precise conformational change linking NBF activation to pore opening unknown
    • Genotype–phenotype correlations for sulfonylurea responsiveness incomplete
  4. 2007 High

    Deletion of NBF1 revealed that this domain is required not only for MgADP-dependent channel activation but also for stable SUR1 protein expression via a pathway independent of the ER retention checkpoint, showing NBF1 has a structural/stability role beyond nucleotide sensing.

    Evidence Electrophysiology of reconstituted split-SUR1 constructs; Western blotting with proteasomal inhibitor treatment

    PMID:18708750

    Open questions at the time
    • Degradation pathway for NBF1-deleted SUR1 not identified
    • Whether NBF1 directly mediates protein folding or chaperone recruitment unknown
  5. 2008 High

    Quantitative reconstitution of channels with varying numbers of mutant SUR1 subunits showed that hyperactivity rises exponentially with mutant subunit number and that tolbutamide inhibition is attenuated under stimulatory conditions, explaining variable clinical severity and sulfonylurea dose requirements.

    Evidence Electrophysiological dose-response analysis of Kir6.2-based channels with graded mutant SUR1

    PMID:18281290

    Open questions at the time
    • In vivo subunit stoichiometry in patient beta cells not directly measured
    • Whether heterozygous activating mutations produce clinically relevant hyperactivity not fully resolved
  6. 2013 High

    Discovery that EPAC binds directly to the SUR1 intracellular loop (aa 859–881) and reduces K(ATP) open probability revealed a cAMP-dependent regulatory input to channel gating, linking incretin signaling to channel modulation in neurons and affecting seizure susceptibility.

    Evidence Co-immunoprecipitation, direct binding assay, electrophysiology, and in vivo mouse seizure model with dominant-negative peptide

    PMID:23678128

    Open questions at the time
    • Whether EPAC–SUR1 interaction occurs in pancreatic beta cells and affects insulin secretion not tested
    • Structural basis of EPAC docking on the intracellular loop unknown
  7. 2015 Medium

    Co-immunoprecipitation and co-localization of SUR1 with TRPM4 in postmortem human stroke tissue, together with earlier negative FRET data in heterologous cells, framed a contested question about whether SUR1 physically associates with TRPM4 in a pathophysiologically relevant context.

    Evidence Co-IP and immunohistochemistry in human cerebral infarct tissue; pharmacological inhibition in rat stroke model; prior negative FRET in COSm6 cells

    PMID:22291026 PMID:26172285

    Open questions at the time
    • Contradictory FRET results in COSm6 cells versus co-IP in native tissue not reconciled
    • Whether an intermediate adaptor mediates the SUR1–TRPM4 interaction not excluded
    • Single-lab co-IP in tissue without reciprocal pulldown
  8. 2017 High

    Demonstration that SUR1, TRPM4, and AQP4 form a tripartite heteromultimeric complex required for high-capacity water transport resolved how SUR1 participates in cytotoxic edema beyond simple ion flux, and genetic ablation confirmed the complex's necessity for astrocyte swelling in vivo.

    Evidence Co-IP, FRET, calcein cell-swelling assay in COS-7 cells, and in vivo murine cold-injury model with genetic knockout

    PMID:28906027

    Open questions at the time
    • Stoichiometry and architecture of the SUR1-TRPM4-AQP4 complex not structurally resolved
    • Whether the tripartite complex forms in non-CNS tissues unknown
  9. 2018 High

    Identification of loss-of-function ABCC8 variants in pulmonary arterial hypertension patients, with functional rescue by diazoxide, extended K(ATP) channel pathophysiology beyond endocrine disease to vascular biology.

    Evidence Exome sequencing; patch-clamp and rubidium flux assays in COS cells; pharmacological rescue

    PMID:30354297

    Open questions at the time
    • Mechanism linking reduced K(ATP) current to pulmonary vascular remodeling not delineated
    • Whether SUR1 or SUR2 predominates in pulmonary vascular smooth muscle not clarified
  10. 2021 High

    Using isogenic iPSC-derived beta cells showed that ABCC8 deficiency increases both basal insulin secretion and beta-cell proliferation, with the proliferative phenotype recapitulated by pharmacological K(ATP) blockade, revealing a developmental role for K(ATP) channel activity in human islet biology.

    Evidence iPSC differentiation with CRISPR-Cas9 correction; insulin secretion assays; in vivo xenograft; pharmacological manipulation

    PMID:33404684

    Open questions at the time
    • Signaling pathway linking K(ATP) channel closure to proliferation not identified
    • Whether proliferative effect persists in mature beta cells unknown
  11. 2023 High

    A complete signaling cascade was mapped in perivascular astrocyte endfeet: SUR1-TRPM4 Na⁺ influx → reverse-mode NCX1 → Ca²⁺ rise → calmodulin-dependent AQP4 translocation → water influx and edema, establishing the molecular logic by which SUR1-TRPM4 amplifies brain swelling after stroke.

    Evidence Astrocyte-specific conditional knockout of SUR1-TRPM4 and NCX1 in mouse ischemic stroke model; calcium imaging; AQP4 surface localization assays

    PMID:37279286

    Open questions at the time
    • Whether this cascade operates in non-astrocytic CNS cell types not tested
    • Calmodulin target on AQP4 or intermediate kinase not identified
    • Relative contribution of this pathway versus other edema mechanisms not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite detailed functional understanding, high-resolution structural models of disease-mutant SUR1 channels and the SUR1-TRPM4-AQP4 complex are lacking, and the signaling pathways linking K(ATP) channel closure to beta-cell proliferation and pulmonary vascular remodeling remain uncharacterized.
  • Atomic-resolution structures of activating/trafficking-defective SUR1 mutants needed
  • Mechanism coupling K(ATP) channel state to cell proliferation unknown
  • Reconciliation of contradictory SUR1-TRPM4 FRET data across expression systems unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0140657 ATP-dependent activity 3 GO:0005215 transporter activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 4 R-HSA-382551 Transport of small molecules 4
Partners
AQP4KCNJ11RAPGEF3SLC8A1TRPM4
Complex memberships
K(ATP) channel (SUR1/Kir6.2 octamer)SUR1-TRPM4-AQP4 complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Activating mutations in ABCC8 (encoding SUR1) cause neonatal diabetes by elevating the basal magnesium-nucleotide-dependent stimulatory action of SUR1 on the Kir6.2 pore, resulting in markedly higher K(ATP) channel open probability in intact cells at physiological MgATP concentrations; these overactive channels remain sensitive to sulfonylurea blockade. Electrophysiological patch-clamp of mutant vs. wild-type K(ATP) channels in intact cells; clinical mutation screening of 34 neonatal diabetes patients The New England journal of medicine High 16885549
1999 SUR1 (ABCC8) binds ATP at NBF1 and ADP at NBF2, with the two nucleotide-binding folds working cooperatively; ADP binding/hydrolysis at SUR1 activates the K(ATP) channel, counterbalancing ATP-mediated inhibition through Kir6.2, thereby coupling metabolic state to channel activity. Biochemical nucleotide-binding and ATPase assays; functional reconstitution of K(ATP) channels with mutagenesis of NBF domains Biochimica et biophysica acta High 10581363
2004 Loss-of-function ABCC8 mutations causing congenital hyperinsulinism alter intracellular trafficking of the SUR1/Kir6.2 channel complex, preventing its delivery to the plasma membrane, as shown by photolabeling studies in a reconstituted system. Photolabeling studies with reconstituted system; functional electrophysiology of beta-cells from patients; direct sequencing of all ABCC8 coding exons The Journal of clinical endocrinology and metabolism High 15579781
2008 Diabetogenic activating mutations in SUR1 (ABCC8) cause MgATP-dependent hyper-stimulation that compromises K(ATP) channel metabolic sensing; channel hyperactivity rises exponentially with the number of mutant SUR subunits, and these channels show attenuated tolbutamide inhibition under stimulatory conditions. Electrophysiological analysis of Kir6.2-based channels reconstituted with mutant SUR1 subunits; dose-response analysis The Journal of biological chemistry High 18281290
2015 SUR1 NBF1 and NBF2 mediate nucleotide activation of the K(ATP) channel through an equilibrium allosteric mechanism; ATP/ADP binding to Kir6.2 inhibits the channel while Mg-nucleotide interactions with SUR activate it, and an allosteric model accounts for this dual regulation. Review synthesizing patch-clamp electrophysiology, mutagenesis, and equilibrium binding data; mechanistic allosteric modeling Biophysical journal High 26682803
2007 Deletion of SUR1 NBF1 severely impairs K(ATP) channel expression (reducing total SUR1 protein levels suggesting increased degradation) and abolishes MgADP stimulation; NBF1 plays a role in channel expression regulation independent of the ER retention checkpoint and proteasomal degradation pathway. Electrophysiology of reconstituted K(ATP) channels with NBF1 deletion constructs; Western blotting; proteasomal inhibitor (MG-132) treatment; 'split' SUR1 constructs Channels (Austin, Tex.) High 18708750
2013 EPAC (Exchange Protein Activated by cAMP) binds directly to the intracellular loop of SUR1 (ABCC8) at amino acids 859-881; EPAC-SUR1 interaction reduces KATP channel open probability, and ablation of EPAC or expression of the binding-intercepting peptide SUR1(859-881) increases channel open probability, inhibiting glutamate release and reducing seizure vulnerability. Co-immunoprecipitation/direct binding assay; electrophysiology; in vivo mouse seizure model; dominant-negative peptide expression The Journal of neuroscience High 23678128
2017 SUR1 (ABCC8) physically co-assembles with TRPM4 and AQP4 to form a novel heteromultimeric water/ion channel complex (SUR1-TRPM4-AQP4); the full tripartite complex is required for fast, high-capacity transmembrane water transport driving cell swelling; in a murine brain edema model, astrocytes upregulate SUR1-TRPM4, AQP4 co-associates with SUR1-TRPM4, and genetic inactivation of the SUR1-TRPM4-AQP4 solute pore blocks astrocyte swelling in vivo. Co-immunoprecipitation; Förster resonance energy transfer (FRET); calcein fluorescence cell-swelling assay in COS-7 cells; in vivo murine cold-injury model with diolistic labeling; genetic knockout Glia High 28906027
2015 SUR1 (ABCC8) co-localizes and co-associates with TRPM4 in human cerebral infarct neurons and endothelial cells; TRPM4 is transcriptionally upregulated after ischemia; pharmacologic blockade of SUR1 by glibenclamide mitigates perivascular TNF labeling in a rat stroke model. Immunohistochemistry and co-immunoprecipitation in postmortem human brain; in situ hybridization; rat middle cerebral artery occlusion model with pharmacologic inhibition Journal of neuropathology and experimental neurology Medium 26172285
2023 In perivascular astrocyte endfeet following ischemic stroke, SUR1-TRPM4 upregulation mediates Na+ influx, which drives reverse-mode NCX1 to elevate intracellular Ca2+, causing calmodulin-dependent AQP4 translocation to the plasma membrane and water influx, leading to cellular edema and brain swelling; astrocyte-specific deletion of SUR1-TRPM4 or NCX1 reduces brain swelling and improves neurological function. Mouse model of severe ischemic stroke; astrocyte-specific conditional knockout; pharmacological inhibition; calcium imaging; AQP4 surface localization assays Science signaling High 37279286
2022 SUR1-TRPM4 activation in BV2 microglia requires P2X7 receptor-mediated Ca2+ influx; SUR1-TRPM4-driven Na+ influx amplifies K+ efflux through K+ channels, leading to NLRP3 inflammasome activation; glibenclamide blocks SUR1-TRPM4 to inhibit this pathway and exerts direct anti-inflammatory neuroprotection independent of its anti-edema role. BV2 cell OGD/reperfusion and LPS models; Trpm4 siRNA knockdown; pharmacological inhibition with glibenclamide and 9-phenanthrol; Western blotting; rat cardiac arrest model Molecular neurobiology Medium 35972671
2012 SUR1 does not functionally or structurally associate with TRPM4 in COSm6 cells; TRPM4 currents are Ca2+-activated, ATP-inhibited, and insensitive to glibenclamide/tolbutamide regardless of SUR1 co-transfection; no FRET signal was detected between TRPM4 and SUR1, contrasting with efficient FRET between Kir6.2 and SUR1. Electrophysiology patch-clamp in COSm6 cells; FRET with fluorophore-tagged subunits; co-transfection of Kir6.2, SUR1, and TRPM4 The Journal of biological chemistry Medium 22291026
2018 Loss-of-function missense variants in ABCC8 are associated with pulmonary arterial hypertension; all evaluated ABCC8 variants decreased K(ATP) channel function in patch-clamp and rubidium flux assays in COS cells, and channel currents were pharmacologically rescued by the SUR1 activator diazoxide. Exome sequencing; patch-clamp electrophysiology; rubidium flux analysis in COS cells; pharmacological rescue with diazoxide Circulation. Genomic and precision medicine High 30354297
2007 Combining two ABCC8 coding mutations (D1193V and R1436Q) on a single allele causes intracellular retention of the SUR1/Kir6.2 channel complex, whereas each mutation individually results in plasma membrane-localized channels; separately, G228D and D1471N mutations in cis also cause intracellular retention and loss of K(ATP) channel function. Functional electrophysiology; intracellular localization studies of channel complex trafficking Clinical endocrinology Medium 17466004
2010 Activating mutations in ABCC8 account for approximately 40% of permanent neonatal diabetes cases; the K(ATP) channel composed of SUR1 and Kir6.2 is a key regulator of insulin release, with SUR1 mutations causing gain-of-channel function leading to persistent channel opening and failure of glucose-stimulated insulin secretion. Mutation screening; functional studies; clinical review Reviews in endocrine & metabolic disorders Medium 20922570
2017 An ABCC8 homozygous nonsense mutation (p.Glu747*) in exon 17 causes neonatal diabetes through absence of full-length SUR1 mRNA and expression of an alternatively spliced transcript lacking exon 17; the truncated transcript enhances K(ATP) channel sensitivity to Mg-ADP/ATP, representing a gain-of-function through altered splicing rather than typical gain-of-function missense mutation. RNA studies confirming absence of full-length transcript and presence of alternatively spliced form; clinical sulfonylurea transfer Journal of clinical research in pediatric endocrinology Medium 28663158
2013 Inhibition of SUR1 by glyburide decreases vascular permeability of cerebral metastases and reduces ZO-1 gap formation in endothelial cells, suggesting SUR1 modulates blood-tumor barrier integrity through regulation of tight junction protein ZO-1. Dynamic contrast-enhanced MRI of blood-tumor barrier permeability; immunofluorescence and Western blot for SUR1 and ZO-1; in vivo rat intracranial tumor model Neoplasia (New York, N.Y.) Medium 23633925
2022 Abcc8/SUR1 gene encodes alternatively spliced short isoforms (~65 kDa) in addition to the full-length protein; immunoprecipitation assays demonstrate that SUR2 short forms are part of functional channels coexisting with typical receptor forms, and SUR1 short forms alter ATP affinity; expression of SUR1 variants may be induced by brain conditions with decreased ATP (stroke, epilepsy). Western blotting with sulfonylurea binding assays; immunoprecipitation; review of experimental data Neural regeneration research Low 34380876
2014 Targeted deletion of Sur1/Abcc8 specifically in glucagon-expressing alpha-cells using a Cre-lox approach demonstrates that KATP channels play a regulatory role in pancreatic alpha-cells, with ~41-64% recombination efficiency depending on allele configuration. Conditional knockout (Abcc8 flox mice crossed with GCG-Cre); agonist-resistance quantification; ROSA-EYFP reporter PloS one Medium 24621811
2021 ABCC8-deficient (ABCC8V187D homozygous) iPSC-derived beta-like cells secrete 3.2-fold more insulin in low glucose and fail to respond to K(ATP) channel-acting drugs; loss of SUR1 increases SC-beta cell proliferation by 61% and this proliferative phenotype is recapitulated by pharmacological K(ATP) channel inactivation in SUR1-corrected cells, revealing a novel role for K(ATP) channel activity during human islet development. iPSC differentiation; CRISPR-Cas9 mutation correction; insulin secretion assays; in vivo mouse xenograft; pharmacological K(ATP) channel manipulation Diabetologia High 33404684

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2023 YaHS: yet another Hi-C scaffolding tool. Bioinformatics (Oxford, England) 1351 36525368
2007 Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nature medicine 1141 17767165
2012 Hi-C: a comprehensive technique to capture the conformation of genomes. Methods (San Diego, Calif.) 890 22652625
2006 Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. The New England journal of medicine 467 16885549
2014 Statistical confidence estimation for Hi-C data reveals regulatory chromatin contacts. Genome research 360 24501021
2017 Hi-C 2.0: An optimized Hi-C procedure for high-resolution genome-wide mapping of chromosome conformation. Methods (San Diego, Calif.) 243 28435001
1998 Novel insights into structure and function of MRP8 (S100A8) and MRP14 (S100A9). Biochimica et biophysica acta 231 9920411
2021 Myofibroblast transcriptome indicates SFRP2hi fibroblast progenitors in systemic sclerosis skin. Nature communications 207 34282151
1999 S100A12 is expressed exclusively by granulocytes and acts independently from MRP8 and MRP14. The Journal of biological chemistry 176 10464253
2010 Necrostatin decreases oxidative damage, inflammation, and injury after neonatal HI. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 164 20571523
2017 SUR1-TRPM4 and AQP4 form a heteromultimeric complex that amplifies ion/water osmotic coupling and drives astrocyte swelling. Glia 112 28906027
2000 Dynamics of microglial activation after human traumatic brain injury are revealed by delayed expression of macrophage-related proteins MRP8 and MRP14. Acta neuropathologica 103 10965802
2020 Hi-C Identifies Complex Genomic Rearrangements and TAD-Shuffling in Developmental Diseases. American journal of human genetics 91 32470376
2014 Alarmins MRP8 and MRP14 induce stress tolerance in phagocytes under sterile inflammatory conditions. Cell reports 90 25497086
1995 Increase of calcium levels in epithelial cells induces translocation of calcium-binding proteins migration inhibitory factor-related protein 8 (MRP8) and MRP14 to keratin intermediate filaments. The Biochemical journal 86 7542868
2018 Principles of Chromosome Architecture Revealed by Hi-C. Trends in biochemical sciences 85 29685368
2014 Peptidylarginine deiminases: novel drug targets for prevention of neuronal damage following hypoxic ischemic insult (HI) in neonates. Journal of neurochemistry 83 24762056
1990 Differential expression of the calcium-binding proteins MRP8 and MRP14 in granulomatous conditions: an immunohistochemical study. Clinical and experimental immunology 83 2199095
2015 Sur1-Trpm4 Cation Channel Expression in Human Cerebral Infarcts. Journal of neuropathology and experimental neurology 82 26172285
2003 Changing the conformation state of cytochrome b558 initiates NADPH oxidase activation: MRP8/MRP14 regulation. The Journal of biological chemistry 70 12719414
2003 Expression of calcium-binding proteins MRP8 and MRP14 in inflammatory muscle diseases. The American journal of pathology 70 12937135
2018 CscoreTool: fast Hi-C compartment analysis at high resolution. Bioinformatics (Oxford, England) 69 29244056
1998 Widespread expression of MRP8 and MRP14 in human cerebral malaria by microglial cells. Acta neuropathologica 68 9845287
2004 Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity. The Journal of clinical endocrinology and metabolism 66 15579781
2019 Sci-Hi-C: A single-cell Hi-C method for mapping 3D genome organization in large number of single cells. Methods (San Diego, Calif.) 65 31536770
2018 Loss-of-Function ABCC8 Mutations in Pulmonary Arterial Hypertension. Circulation. Genomic and precision medicine 65 30354297
2018 Hi-C analysis: from data generation to integration. Biophysical reviews 65 30570701
2015 The Effect of miR-132, miR-146a, and miR-155 on MRP8/TLR4-Induced Astrocyte-Related Inflammation. Journal of molecular neuroscience : MN 65 25957996
2010 Permanent neonatal diabetes due to activating mutations in ABCC8 and KCNJ11. Reviews in endocrine & metabolic disorders 65 20922570
2004 Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes. The Finnish Diabetes Prevention Study. The Journal of clinical endocrinology and metabolism 58 15579791
2003 Expression of MRP8 and MRP14 by macrophages is a marker for severe forms of glomerulonephritis. Journal of leukocyte biology 56 14597726
2022 dcHiC detects differential compartments across multiple Hi-C datasets. Nature communications 55 36369226
2009 Mrp-8 and -14 mediate CNS injury in focal cerebral ischemia. Biochimica et biophysica acta 53 19835955
2014 Injury-induced MRP8/MRP14 stimulates IP-10/CXCL10 in monocytes/macrophages. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 52 25342131
1999 The regulatory role of MRP8 (S100A8) and MRP14 (S100A9) in the transendothelial migration of human leukocytes. Pathobiology : journal of immunopathology, molecular and cellular biology 52 10725790
1999 Comparative aspects of the function and mechanism of SUR1 and MDR1 proteins. Biochimica et biophysica acta 51 10581363
2000 Calprotectin (MRP8/14 protein complex) release during mycobacterial infection in vitro and in vivo. FEMS immunology and medical microbiology 50 10967257
2022 Loop detection using Hi-C data with HiCExplorer. GigaScience 46 35809047
1992 The calcium binding proteins MRP8 and MRP14 in acute and chronic inflammation. Behring Institute Mitteilungen 46 1524561
2017 Software tools for visualizing Hi-C data. Genome biology 45 28159004
2013 Inhibition of SUR1 decreases the vascular permeability of cerebral metastases. Neoplasia (New York, N.Y.) 44 23633925
2012 Chromosome organization in the nucleus - charting new territory across the Hi-Cs. Current opinion in genetics & development 43 22265226
1998 Copurification of P6, MRP8, and MRP14 from human granulocytes and separation of individual proteins. Protein expression and purification 42 9693055
2020 PHi-C: deciphering Hi-C data into polymer dynamics. NAR genomics and bioinformatics 40 33575580
2019 The association between CD31hiEmcnhi endothelial cells and bone mineral density in Chinese women. Journal of bone and mineral metabolism 39 30919130
2023 Cation flux through SUR1-TRPM4 and NCX1 in astrocyte endfeet induces water influx through AQP4 and brain swelling after ischemic stroke. Science signaling 38 37279286
2017 Gas6 Promotes Inflammatory (CCR2hiCX3CR1lo) Monocyte Recruitment in Venous Thrombosis. Arteriosclerosis, thrombosis, and vascular biology 38 28450294
2010 Pharmacogenomics of human ABC transporter ABCC11 (MRP8): potential risk of breast cancer and chemotherapy failure. Anti-cancer agents in medicinal chemistry 32 21182469
2005 The subcellular distribution of myeloid-related protein 8 (MRP8) and MRP14 in human neutrophils. Journal of translational medicine 32 16191197
2020 Deficit of circulating CD19+ CD24hi CD38hi regulatory B cells in severe aplastic anaemia. British journal of haematology 30 32311088
2020 Defective CD19+CD24hiCD38hi transitional B-cell function in patients with relapsing-remitting MS. Multiple sclerosis (Houndmills, Basingstoke, England) 29 32924828
2008 Mutations in the ABCC8 (SUR1 subunit of the K(ATP) channel) gene are associated with a variable clinical phenotype. Clinical endocrinology 28 19021632
2003 Interleukin-10 influences the expression of MRP8 and MRP14 in human dendritic cells. International archives of allergy and immunology 28 14555857
2022 Glibenclamide Directly Prevents Neuroinflammation by Targeting SUR1-TRPM4-Mediated NLRP3 Inflammasome Activation In Microglia. Molecular neurobiology 27 35972671
2021 SUR1-mutant iPS cell-derived islets recapitulate the pathophysiology of congenital hyperinsulinism. Diabetologia 27 33404684
2020 BRG1 Stimulates Endothelial Derived Alarmin MRP8 to Promote Macrophage Infiltration in an Animal Model of Cardiac Hypertrophy. Frontiers in cell and developmental biology 27 32733885
2017 NAIP/NLRC4 inflammasome activation in MRP8+ cells is sufficient to cause systemic inflammatory disease. Nature communications 27 29263322
2014 ABCC8 genetic variants and risk of diabetes mellitus. Gene 27 24768178
2011 ABCC8 mutation allele frequency in the Ashkenazi Jewish population and risk of focal hyperinsulinemic hypoglycemia. Genetics in medicine : official journal of the American College of Medical Genetics 27 21716120
2015 The Nucleotide-Binding Sites of SUR1: A Mechanistic Model. Biophysical journal 26 26682803
2000 Identification of MRP-8 (calgranulin A) as a major responsive protein in chronic periodontitis. The Journal of pathology 26 11113873
2021 VEHiCLE: a Variationally Encoded Hi-C Loss Enhancement algorithm for improving and generating Hi-C data. Scientific reports 25 33893353
2001 Quantitative analysis of MRP-8 in gingival crevicular fluid in periodontal health and disease using microbore HPLC. Journal of clinical periodontology 25 11737516
2012 On potential interactions between non-selective cation channel TRPM4 and sulfonylurea receptor SUR1. The Journal of biological chemistry 24 22291026
2020 Characterization of rare ABCC8 variants identified in Spanish pulmonary arterial hypertension patients. Scientific reports 23 32934261
2020 Characterization of splenic MRC1hiMHCIIlo and MRC1loMHCIIhi cells from the monocyte/macrophage lineage of White Leghorn chickens. Veterinary research 22 32460863
2018 Iteratively improving Hi-C experiments one step at a time. Methods (San Diego, Calif.) 22 29723572
2000 MRP8/MRP14, CD11b and HLA-DR expression of alveolar macrophages in pneumonia. Immunology letters 22 10722871
2020 HI-511 overcomes melanoma drug resistance via targeting AURKB and BRAF V600E. Theranostics 21 32863956
2016 SUR1 Receptor Interaction with Hesperidin and Linarin Predicts Possible Mechanisms of Action of Valeriana officinalis in Parkinson. Frontiers in aging neuroscience 21 27199743
2020 GSDB: a database of 3D chromosome and genome structures reconstructed from Hi-C data. BMC molecular and cell biology 20 32758136
2021 A cookbook for DNase Hi-C. Epigenetics & chromatin 19 33743768
2013 EPAC inhibition of SUR1 receptor increases glutamate release and seizure vulnerability. The Journal of neuroscience : the official journal of the Society for Neuroscience 19 23678128
2007 Complex ABCC8 DNA variations in congenital hyperinsulinism: lessons from functional studies. Clinical endocrinology 19 17466004
2019 Decreased number of CD19+CD24hiCD38hi regulatory B cells in Diabetic nephropathy. Molecular immunology 18 31181422
2016 3D Genome Reconstruction with ShRec3D+ and Hi-C Data. IEEE/ACM transactions on computational biology and bioinformatics 18 26955049
2019 Heterogeneous Loop Model to Infer 3D Chromosome Structures from Hi-C. Biophysical journal 17 31337548
2008 A novel ABCC8 (SUR1)-dependent mechanism of metabolism-excitation uncoupling. The Journal of biological chemistry 17 18281290
2003 The time-dependent expression of fibronectin, MRP8, MRP14 and defensin in surgically treated human skin wounds. Forensic science international 17 12590055
2021 CD27hiCD38hi plasmablasts are activated B cells of mixed origin with distinct function. iScience 16 34113823
2020 CD19+CD24hiCD38hi B Cell Dysfunction in Primary Biliary Cholangitis. Mediators of inflammation 16 32104147
2020 The DLO Hi-C Tool for Digestion-Ligation-Only Hi-C Chromosome Conformation Capture Data Analysis. Genes 16 32164155
2019 Phenotype, genotype and glycaemic variability in people with activating mutations in the ABCC8 gene: response to appropriate therapy. Diabetic medicine : a journal of the British Diabetic Association 16 31562829
2017 Smoking reduces circulating CD26hiCD161hi MAIT cells in healthy individuals and patients with multiple sclerosis. Journal of leukocyte biology 16 28179539
2017 Modeling Congenital Hyperinsulinism with ABCC8-Deficient Human Embryonic Stem Cells Generated by CRISPR/Cas9. Scientific reports 16 28600547
2021 ABCC8 variants in MODY12: Review of the literature and report of a case with severe complications. Diabetes/metabolism research and reviews 15 34014594
2013 ABCC11/MRP8 polymorphisms affect 5-fluorouracil-induced severe toxicity and hepatic expression. Pharmacogenomics 15 24024896
2022 Wolbachia RNase HI contributes to virus blocking in the mosquito Aedes aegypti. iScience 14 36636344
2021 Extracting multi-way chromatin contacts from Hi-C data. PLoS computational biology 14 34871311
2014 The accumulation of macrophages expressing myeloid-related protein 8 (MRP8) and MRP14 in the spleen of BALB/cA mice during infection with Plasmodium berghei. Experimental parasitology 14 24440297
2024 ACKR1hiECs Promote Aortic Dissection Through Adjusting Macrophage Behavior. Circulation research 13 39692014
2019 Serum SUR1 and TRPM4 in patients with subarachnoid hemorrhage. Neurosurgical review 13 31707576
2014 Targeting SUR1/Abcc8-type neuroendocrine KATP channels in pancreatic islet cells. PloS one 13 24621811
2007 Regulation of KATP channel expression and activity by the SUR1 nucleotide binding fold 1. Channels (Austin, Tex.) 13 18708750
2022 The short form of the SUR1 and its functional implications in the damaged brain. Neural regeneration research 12 34380876
2021 Chromosome Modeling on Downsampled Hi-C Maps Enhances the Compartmentalization Signal. The journal of physical chemistry. B 12 34319725
2021 Clinical and Genetic Characteristics of ABCC8 Nonneonatal Diabetes Mellitus: A Systematic Review. Journal of diabetes research 12 34631896
2020 Ablation of Myeloid Cell MRP8 Ameliorates Nephrotoxic Serum-induced Glomerulonephritis by Affecting Macrophage Characterization through Intraglomerular Crosstalk. Scientific reports 12 32080297
2017 An ABCC8 Nonsense Mutation Causing Neonatal Diabetes Through Altered Transcript Expression. Journal of clinical research in pediatric endocrinology 12 28663158
2012 A role for MRP8 in in stent restenosis in diabetes. Atherosclerosis 12 22381691