Affinage

DMPK

Myotonin-protein kinase · UniProt Q09013

Length
629 aa
Mass
69.4 kDa
Annotated
2026-06-09
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DMPK encodes a muscle- and heart-enriched serine/threonine protein kinase whose normal cellular role and disease-causing CTG repeat expansion represent two functionally distinct axes (PMID:15317754, PMID:9207102). As a kinase, DMPK regulates the actin cytoskeleton, with enzymatically active (but not kinase-dead) DMPK driving actin reorganization and membrane blebbing in a manner parallel to active RhoA (PMID:10658209). Alternative splicing generates multiple isoforms with distinct C-terminal tail anchors that target individual isoforms to either the outer mitochondrial membrane or the endoplasmic reticulum, defining DMPK as a tail-anchored kinase (PMID:10699184, PMID:15684391). At the mitochondrion, the kinase activity of long DMPK isoforms protects cells from oxidative stress and prevents permeability transition pore opening by assembling a complex with hexokinase II and active Src—which tyrosine-phosphorylates DMPK and stabilizes mitochondrial HK II localization under stress (PMID:24136222). DMPK also acts as a positive, muscle-specific modulator of insulin action, being required for correct trafficking of insulin/IGF-1 receptors and insulin-dependent GLUT4 trafficking (PMID:17987120). The DM1 disease mechanism operates through the expanded (CTG)n repeat in the DMPK 3'UTR: above a repeat-length threshold the mutant transcript is poorly processed and retained in the nucleus as discrete RNA foci, halving DMPK protein levels (haploinsufficiency), while flanking-gene transcripts are spared (PMID:8288237, PMID:9207102, PMID:11595515). The expanded CUG-repeat RNA additionally exerts a trans-dominant toxic gain of function, forming length-dependent hairpin structures (PMID:30700578) that sequester MBNL protein into nuclear foci (PMID:11433021) and reduce MyoD below the level needed to drive myogenic differentiation (PMID:12427866, PMID:10484765). The RNA helicase DDX6 binds and unwinds CUG-repeat duplexes, relocalizing the toxic transcript to the cytoplasm and relieving mis-splicing (PMID:24792155). Whether DMPK gene dosage is causally required for cardiac conduction is unresolved within the corpus: an early knockout study reported dose-dependent atrioventricular block (PMID:10021468), whereas a later knockout/ASO study found no cardiac or muscle functional deficit (PMID:27522499).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1993 Medium

    Established that CTG expansion does not simply abolish transcription but instead impairs transcript processing, reframing DM1 as a post-transcriptional rather than purely transcriptional defect.

    Evidence Somatic cell hybrids separating normal and mutant chromosome 19 alleles followed by RT-PCR

    PMID:8288237

    Open questions at the time
    • Did not localize where in processing the block occurs
    • Single-lab allele-specific design
  2. 1995 Medium

    Distinguished equal transcription from repeat-length-dependent impaired processing of the mutant allele, quantifying the haploinsufficiency mechanism.

    Evidence Quantitative allele-specific RT-PCR across patient tissues and cell lines

    PMID:7590731

    Open questions at the time
    • Mechanism of processing block not defined
    • No protein-level quantification
  3. 1995 Medium

    Defined DMPK protein size and subcellular localization, placing the kinase at neuromuscular junctions, intercalated discs, and synaptic sites.

    Evidence Immunoblotting and immunofluorescence with C-terminal DMPK antibody on muscle and brain tissue

    PMID:7655460

    Open questions at the time
    • Antibody could not distinguish isoforms functionally
    • Localization correlation with function not tested
  4. 1997 High

    Showed the mutant transcript is retained in the nucleus above a defined repeat threshold and that retention is gene-specific, establishing the physical basis for both haploinsufficiency and RNA toxicity.

    Evidence Subcellular RNA fractionation with allele-specific quantification in DM cell lines

    PMID:9207102

    Open questions at the time
    • Did not identify proteins mediating retention
    • Did not establish downstream toxicity
  5. 1999 High

    Demonstrated dose-dependent cardiac conduction disease in DMPK knockout and heterozygous mice, arguing that DMPK haploinsufficiency contributes to DM1 heart block.

    Evidence In vivo electrophysiology in DMPK-/- and DMPK+/- mice

    PMID:10021468

    Open questions at the time
    • Molecular substrate of conduction defect not identified
    • Later contradicted by negative knockout/ASO study
  6. 1999 High

    Separated cis (reduced reporter expression) from trans (myogenic differentiation block) effects of the expanded repeat, establishing the dual-mechanism framework for DM1.

    Evidence Chimeric reporter constructs and deletion analysis with Cre-loxP rescue in C2C12 myoblasts

    PMID:10484765

    Open questions at the time
    • Did not identify trans-acting factors mediating toxicity
    • Effects mapped to repeat region but not single nucleotide resolution
  7. 2000 High

    Catalogued six tissue-specific spliced isoforms with distinct C-termini, providing the molecular basis for differential isoform targeting and function.

    Evidence Transgenic DMPK-overexpressor mice and transfection of all six cDNAs

    PMID:10699184

    Open questions at the time
    • Functional differences between isoforms not yet assigned
    • Localization not yet mapped
  8. 2000 Medium

    Identified splicing factors binding 3' of the CUG repeat and a repeat-dependent splice event producing a non-retained, repeat-lacking isoform, hinting at an escape route from nuclear retention.

    Evidence RNA-binding protein identification and novel isoform characterization in DM cells

    PMID:10911990

    Open questions at the time
    • Physiological relevance of escape isoform not quantified
    • Single lab
  9. 2000 Medium

    Linked DMPK kinase activity to actin cytoskeletal reorganization and membrane blebbing, placing DMPK in a RhoA-related signaling network.

    Evidence Wild-type versus kinase-inactive DMPK overexpression compared with RhoA mutants in lens epithelial cells

    PMID:10658209

    Open questions at the time
    • Direct substrates not identified
    • Non-muscle cell model
  10. 2000 Medium

    Confirmed muscle-restricted DMPK expression and a shared catalytic-site epitope with the related kinases MRCK alpha/beta.

    Evidence 16-monoclonal-antibody tissue panel and phage-display epitope mapping

    PMID:10958655

    Open questions at the time
    • Functional consequence of MRCK relatedness not tested
    • Single lab
  11. 2001 Medium

    Provided direct imaging evidence that MBNL is sequestered onto expanded-repeat DMPK RNA foci, advancing the trans RNA-toxicity model.

    Evidence GFP-tagged MBNL co-localization with repeat RNA foci in DM1 cells

    PMID:11433021

    Open questions at the time
    • Co-localization not quantitatively binding affinity
    • Functional splicing consequences of sequestration not measured here
  12. 2001 Medium

    Quantified ~50% DMPK protein reduction in DM1 muscle cells alongside nuclear RNA foci, directly linking nuclear retention to haploinsufficiency.

    Evidence Immunoblotting and FISH in primary human DM1 myoblasts

    PMID:11595515

    Open questions at the time
    • Single lab
    • Causal contribution of 50% loss to phenotype not isolated
  13. 2001 Medium

    Connected CTG expansion to altered local chromatin structure and exon 13/14-deficient transcripts, adding a chromatin-level layer to expression silencing.

    Evidence Chromatin sensitivity assay and RT-PCR in somatic cell hybrids

    PMID:11592825

    Open questions at the time
    • Chromatin change mechanism not defined
    • Relative contribution versus RNA retention unclear
  14. 2002 High

    Pinpointed MyoD depletion below an activation threshold as the molecular cause of repeat-RNA-induced differentiation failure, with MyoD restoration rescuing the defect.

    Evidence (CUG)200 3'UTR constructs, MyoD immunoblot, E-box reporters, and rescue in C2C12

    PMID:12427866

    Open questions at the time
    • Mechanism linking RNA foci to MyoD reduction not fully defined
    • Cell-line model only
  15. 2004 High

    Demonstrated that DMPK overexpression alone reproduces DM1-like cardiac, skeletal, and smooth muscle pathology, implicating dosage in disease beyond loss of function.

    Evidence Transgenic mice with ~25 extra hDMPK copies; histology, electrophysiology, blood pressure

    PMID:15317754

    Open questions at the time
    • Overexpression level non-physiological
    • Does not separate kinase activity from gene dosage
  16. 2005 High

    Established isoform-specific tail-anchor targeting to mitochondria versus ER, identifying DMPK as the first tail-anchored protein kinase and giving a structural basis for compartmentalized function.

    Evidence Isoform expression, subcellular fractionation, alkaline resistance, tail-anchor mutagenesis, and imaging in myoblasts

    PMID:15684391

    Open questions at the time
    • Functional output at each organelle not yet defined
    • Targeting machinery not identified
  17. 2007 High

    Defined DMPK as a muscle-specific positive regulator of insulin signaling required for insulin/IGF-1 receptor and GLUT4 trafficking, linking DMPK loss to the insulin resistance of DM1.

    Evidence Knockout mice with glucose tolerance, uptake, and GLUT4 trafficking assays plus DMPK mutant cells

    PMID:17987120

    Open questions at the time
    • Direct kinase substrates in the trafficking pathway not identified
    • Molecular link between DMPK and receptor trafficking unresolved
  18. 2009 Medium

    Refined the tissue map of membrane-anchored versus cytosolic DMPK isoforms across muscle, visceral, and brain tissues, framing where each functional pool acts.

    Evidence Immunoblot and RT-PCR isoform profiling across mouse tissues and cell types

    PMID:19626675

    Open questions at the time
    • Functional consequence of isoform distribution not tested
    • Single lab
  19. 2013 High

    Resolved a mitochondrial protective mechanism in which long DMPK isoforms assemble an HK II–Src complex, are tyrosine-phosphorylated by Src, and prevent permeability transition pore opening under oxidative stress.

    Evidence Co-IP, fractionation, SH3 binding, kinase and PTP assays, and knockdown under oxidative stress

    PMID:24136222

    Open questions at the time
    • Direct DMPK phosphorylation substrates at the mitochondrion not identified
    • In vivo relevance to DM1 not established
  20. 2014 High

    Identified DDX6 as a CUG-repeat helicase that unwinds the toxic duplex, relocalizes the transcript to the cytoplasm, and relieves MBNL1 sequestration and mis-splicing, offering a route to counter RNA toxicity.

    Evidence Co-IP in DM1 fibroblasts, in vitro ATP-dependent unwinding, and reciprocal overexpression/knockdown

    PMID:24792155

    Open questions at the time
    • Endogenous regulation of DDX6 in DM1 tissue not addressed
    • Therapeutic feasibility untested
  21. 2019 High

    Provided a structural model of length-dependent CUG hairpins within a rigid flanking architecture and validated structure-guided antisense knockdown.

    Evidence SHAPE/DMS/CMCT/RNase T1 probing in vitro plus LNA antisense knockdown in cells

    PMID:30700578

    Open questions at the time
    • Structure of repeat in cellular context with bound proteins not resolved
    • Branched-structure functional consequence not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether DMPK gene dosage is causally required for cardiac conduction and muscle function in vivo remains unresolved, given directly contradictory knockout results.
  • Genetic background and modifier effects not reconciled
  • Direct kinase substrates underlying any cardiac role not identified
  • Relative weighting of haploinsufficiency versus RNA toxicity in cardiac disease unsettled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005739 mitochondrion 3 GO:0005634 nucleus 2 GO:0005783 endoplasmic reticulum 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2
Partners
DDX6HK2MBNL1SRC
Complex memberships
DMPK–hexokinase II–Src mitochondrial complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 DMPK mRNA transcription from wild-type and mutant (expanded CTG) alleles occurs at equal levels in skeletal muscle and cell lines of heterozygous DM patients, but post-transcriptional processing (splicing/maturation) of the mutant allele transcript is impaired in proportion to repeat size, resulting in reduced processed mRNA from the DM allele. Quantitative allele-specific RT-PCR on patient tissue samples and cell lines Genomics Medium 7590731
1993 Expansion of the CTG repeat in the DMPK 3'UTR results in both reduced levels of primary DMPK transcripts and impaired processing of those transcripts, leading to undetectable levels of processed DMPK mRNA from the mutant allele, as shown in somatic cell hybrids carrying either the normal or mutant allele. Somatic cell hybridization to isolate individual chromosome 19 homologues, followed by RT-PCR amplification of DMPK coding sequences Genomics Medium 8288237
1997 DMPK transcripts derived from expanded CTG alleles are retained within the nucleus and absent from the cytoplasm, above a critical threshold of 80–400 CTG repeats; this nuclear retention is specific to DMPK and does not affect mRNA levels of flanking genes SIX5 or DMWD. Subcellular fractionation of RNA combined with allele-specific analysis of DMPK transcripts in DM cell lines; quantitative RNA analysis Proceedings of the National Academy of Sciences of the United States of America High 9207102
1999 DMPK gene dosage is a critical determinant of cardiac conduction integrity: DMPK-/- mice develop first-, second-, and third-degree atrioventricular (A-V) block, with specific compromise of the A-V node and His-Purkinje regions; DMPK+/- mice develop first-degree heart block similar to human DM1 patients, establishing haploinsufficiency of DMPK as linked to cardiac conduction disease. In vivo murine electrophysiology in DMPK knockout mice on defined genetic backgrounds The Journal of clinical investigation High 10021468
1999 A mutant DMPK 3'UTR containing expanded CTG repeats acts in cis to reduce protein expression from the associated reporter gene, and the expanded CUG repeat-containing mRNA acts in trans to inhibit myogenic differentiation of C2C12 myoblasts; deletion analysis mapped both effects to the (CTG)n expansion itself and/or the 3' end of the DMPK 3'UTR. Chimeric reporter constructs with human DMPK 3'UTR in C2C12 mouse myoblasts; deletion analysis; Cre-loxP genetic rescue system Human molecular genetics High 10484765
2000 DMPK pre-mRNA undergoes alternative splicing producing six major isoforms with distinct C-terminal sequences and tissue-dependent expression: four ~74 kDa full-length isoforms (heart-, skeletal muscle-, brain-specific) and two ~68 kDa C-terminally truncated isoforms (smooth muscle-specific), arising from combinations of cryptic splice sites in exons 8 and 14 and regulated excision of exons 13/14. Transgenic DMPK-overexpressor mouse model; transfection of all six full-length mouse cDNAs into cells; characterization of mRNA and protein isoform distributions Human molecular genetics High 10699184
2000 Four RNA splicing factors—hnRNP C, U2AF, PTB (polypyrimidine tract binding protein), and PSF (PTB-associated splicing factor)—bind to two short regions 3' of the CUG repeat in DMPK 3'UTR; the CUG repeat acts as an essential cis element for a splicing event that produces a novel 3' DMPK exon generating an mRNA isoform that lacks the repeats and is not retained in the nucleus in DM cells. Identification of splicing factors binding to DMPK 3'UTR regions; characterization of novel splice isoform; analysis of nuclear retention of isoforms in DM cells Molecular cell Medium 10911990
2000 DMPK overexpression in cultured lens epithelial cells leads to apoptotic-like blebbing of the plasma membrane and reorganization of the actin cytoskeleton; enzymatically active DMPK (but not kinase-inactive mutant DMPK) is required for both effects, and active RhoA produces similar effects, suggesting DMPK and RhoA function in the same regulatory network. Overexpression of wild-type and kinase-inactive DMPK mutants in lens epithelial cells; comparison with constitutively active and GDP-state RhoA mutants; assessment of actin cytoskeletal morphology and membrane blebbing Cell motility and the cytoskeleton Medium 10658209
2001 GFP-tagged MBNL protein co-localizes with expanded DMPK repeat transcript nuclear foci in DM1 cell lines, forming discrete nuclear foci itself only in DM1 (not normal) cells, providing evidence that MBNL is sequestered by expanded CUG repeat DMPK transcripts. Indirect immunofluorescence and overexpression of GFP-tagged MBNL, CUG-BP, and hnRNP C in DM1 cell lines; co-localization with expanded repeat RNA foci Nucleic acids research Medium 11433021
2001 DMPK protein level is reduced by approximately 50% in DM1 fetal muscle cells relative to normal cells; mutant DMPK transcripts are retained in discrete nuclear foci, and DMPK mRNA levels increase sharply during myoblast differentiation. Immunoblotting with anti-DMPK antibody; fluorescence in situ hybridization for RNA foci in primary human DM1 myoblasts Neuromuscular disorders : NMD Medium 11595515
2002 Mutant DMPK 3'UTR transcripts containing (CUG)200 disrupt C2C12 myoblast differentiation by reducing MyoD protein levels below the threshold required to activate the differentiation program; restoring MyoD levels rescues the differentiation defect. C2C12 cell culture model with mutant DMPK 3'UTR expression constructs; MyoD protein measurement by immunoblot; E-box reporter assays; MyoD rescue experiment The Journal of cell biology High 12427866
2004 Transgenic overexpression of human DMPK in mice results in hypertrophic cardiomyopathy (myocardial hypertrophy, myocyte disarray, interstitial fibrosis, calcium overload), myotonic myopathy with sarcolemmal chloride channel deficit, and reduced blood pressure, demonstrating that DMPK overexpression in cardiac, skeletal, and smooth muscle cells causes DM1-like pathological changes. Aged transgenic mice carrying ~25 extra copies of complete hDMPK gene; cardiac and skeletal muscle histology, electrophysiology (myotonic discharges), blood pressure measurement, exercise testing Human molecular genetics High 15317754
2005 DMPK splice isoform A localizes predominantly to the outer mitochondrial membrane, while isoform C localizes to the endoplasmic reticulum (in mouse); unique sequence arrangements in C-terminal tail anchors control isoform-specific intracellular membrane targeting; expression of isoforms A/C caused clustering of ER or mitochondria respectively; mutagenesis of basic residues flanking putative transmembrane domains disrupted proper anchoring, identifying DMPK as the first kinase class of tail-anchored proteins. Expression of individual DMPK isoforms in C2C12 and DMPK-/- myoblast cells; subcellular fractionation; alkaline resistance assay; mutagenesis of tail-anchor basic residues; live-cell imaging of organelle distribution Molecular and cellular biology High 15684391
2007 DMPK is a positive modulator of insulin action specifically in muscle: DMPK-deficient mice exhibit impaired insulin signaling in muscle but not in adipocytes or liver (tissues lacking DMPK expression), abnormal glucose tolerance, reduced glucose uptake, and impaired insulin-dependent GLUT4 trafficking in muscle; DMPK mutant analysis showed DMPK is required for correct intracellular trafficking of insulin and IGF-1 receptors. DMPK knockout mice; glucose tolerance tests; glucose uptake assays; GLUT4 trafficking assays; DMPK mutant constructs in cultured muscle cells; tissue-specific phenotype analysis PloS one High 17987120
2013 The long DMPK isoforms (DMPK-A/B/C/D) are associated with the outer mitochondrial membrane; DMPK-A kinase activity protects cells from oxidative stress and prevents mitochondrial permeability transition pore (PTP) opening; DMPK forms a multimeric complex with hexokinase II (HK II) and the active form of the tyrosine kinase Src (binding its SH3 domain); DMPK is tyrosine-phosphorylated by Src; both the complex and tyrosine phosphorylation of DMPK increase under oxidative stress; DMPK increases mitochondrial localization of HK II; Src inhibition selectively enhances death in DMPK-expressing cells after HK II detachment. Co-immunoprecipitation; subcellular fractionation; SH3 domain binding assay; kinase activity assays; DMPK knockdown; oxidative stress treatments; permeability transition pore assay; in vitro myogenesis Cell death & disease High 24136222
2014 The DEAD-box helicase DDX6 interacts with CUG triplet-repeat DMPK mRNA in primary DM1 patient fibroblasts and with CUG-RNA in vitro; DDX6 overexpression reduces nuclear DMPK-mRNA foci and relieves DM1 mis-splicing without changing total CUG-expanded mRNA levels (causes re-localization to cytoplasm); DDX6 knockdown increases nuclear DMPK-mRNA foci and MBNL1 nuclear sequestration; DDX6 unwinds CUG-repeat duplexes in vitro in an ATP-dependent manner. Co-immunoprecipitation in primary DM1 fibroblasts; in vitro RNA unwinding assay; DDX6 overexpression and knockdown; fluorescence microscopy for RNA foci; splicing assays Nucleic acids research High 24792155
2016 Dmpk gene deletion or >90% ASO-mediated knockdown of DMPK in cardiac and skeletal muscle of mice does not compromise cardiac function (ECG intervals, ejection fraction) or muscle strength, even under cardiac stress (pressure overload) or muscle stress (myotonia), challenging earlier reports of cardiac defects in DMPK knockout mice. Dmpk knockout mice on two genetic backgrounds; heterozygous knockout mice treated with DMPK-targeting ASOs; ECG measurement, cardiac ejection fraction, muscle strength testing, pressure overload and myotonia stress models Human molecular genetics Medium 27522499
2009 Long membrane-anchored DMPK isoforms are the dominant form in heart, diaphragm, and skeletal muscle, while short cytosolic isoforms are highly expressed in bladder and stomach; both isoform types are present in diverse brain regions; DMPK protein is detectable in myoblasts, myotubes, cortical astrocytes, and related cell lines but not in hippocampal neurons. Immunoblotting and RT-PCR for DMPK isoforms in mouse tissue panels and cultured cell types Muscle & nerve Medium 19626675
2019 Expanded CUG repeats in DMPK 3'UTR RNA form length-dependent hairpin structures with conformational plasticity (including branched structures for long repeats), embedded in an otherwise rigid flanking architecture; SHAPE, DMS, CMCT, and RNase T1 probing showed the flanking sequences maintain fixed structure regardless of repeat length; LNA antisense oligonucleotides designed using this structural model confirmed DMPK knockdown in cells. SHAPE, DMS, CMCT, and RNase T1 RNA structure probing in vitro; LNA antisense oligonucleotide disruption of base-pairing; functional DMPK knockdown validation in cells RNA (New York, N.Y.) High 30700578
2001 CTG repeat expansion in the DMPK gene leads to a loss of a nuclease-hypersensitive chromatin site near the repeat, indicating altered chromatin structure; this chromatin change is associated with markedly reduced DMPK mRNA from expanded alleles, partially reduced SIX5 expression (in congenital DM), but no reduction of DMWD mRNA; most DMPK transcripts from expanded alleles lack exons 13 and 14, suggesting the expansion affects 3' splicing. PCR-based chromatin sensitivity assay in somatic cell hybrids carrying normal or expanded alleles; semiquantitative multiplex RT-PCR; nested RT-PCR for splice isoform analysis Molecular genetics and metabolism Medium 11592825
1995 DMPK protein (DMK) in human and rodent tissues is detected as ~74 kDa and ~82 kDa species in cardiac and skeletal muscle; by immunofluorescence, DMK localizes post-synaptically at neuromuscular junctions of skeletal muscle, at intercalated discs of cardiac tissue, and at the apical membrane of ependyma and choroid plexus; synaptic localization was also noted in cerebellum, hippocampus, midbrain and medulla. Immunoblotting with polyclonal antibody against C-terminal DMPK fusion protein; immunofluorescence microscopy on muscle and brain tissue sections Human molecular genetics Medium 7655460
2000 Using a panel of 16 monoclonal antibodies, DMPK was detected as a single ~80 kDa protein exclusively in skeletal muscle, cardiac muscle, and to a lesser extent smooth muscle; a shared epitope at the catalytic site of DMPK was identified using a phage-displayed random peptide library; DMPK shares epitopes with MRCK alpha and beta (related kinases). Monoclonal antibody panel immunoblotting across human tissue panel; phage-displayed random peptide library for epitope mapping; cDNA library screening Human molecular genetics Medium 10958655

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 A W-linked DM-domain gene, DM-W, participates in primary ovary development in Xenopus laevis. Proceedings of the National Academy of Sciences of the United States of America 369 18268317
2012 Sex and the singular DM domain: insights into sexual regulation, evolution and plasticity. Nature reviews. Genetics 296 22310892
2004 Two DM domain genes, DMY and DMRT1, involved in testicular differentiation and development in the medaka, Oryzias latipes. Developmental dynamics : an official publication of the American Association of Anatomists 235 15376325
1991 DM-GRASP, a novel immunoglobulin superfamily axonal surface protein that supports neurite extension. Neuron 202 1873027
2001 In vivo co-localisation of MBNL protein with DMPK expanded-repeat transcripts. Nucleic acids research 179 11433021
2009 The DM domain protein DMRT1 is a dose-sensitive regulator of fetal germ cell proliferation and pluripotency. Proceedings of the National Academy of Sciences of the United States of America 156 20007774
1993 Effect of the myotonic dystrophy (DM) mutation on mRNA levels of the DM gene. Nature genetics 147 8358430
1999 DMPK dosage alterations result in atrioventricular conduction abnormalities in a mouse myotonic dystrophy model. The Journal of clinical investigation 136 10021468
1993 Structure and genomic sequence of the myotonic dystrophy (DM kinase) gene. Human molecular genetics 128 8499920
1995 Effect of myotonic dystrophy trinucleotide repeat expansion on DMPK transcription and processing. Genomics 122 7590731
2020 Fundamental aspects of DMPK optimization of targeted protein degraders. Drug discovery today 121 32298797
1993 Absence of myotonic dystrophy protein kinase (DMPK) mRNA as a result of a triplet repeat expansion in myotonic dystrophy. Genomics 118 8288237
1997 Transcriptional abnormality in myotonic dystrophy affects DMPK but not neighboring genes. Proceedings of the National Academy of Sciences of the United States of America 117 9207102
1999 Cis and trans effects of the myotonic dystrophy (DM) mutation in a cell culture model. Human molecular genetics 114 10484765
2013 HLA-DM and HLA-DO, key regulators of MHC-II processing and presentation. Current opinion in immunology 103 24463216
2003 Evolutionary dynamics of the DM domain gene family in metazoans. Journal of molecular evolution 101 15008421
2015 Identification and characterization of modified antisense oligonucleotides targeting DMPK in mice and nonhuman primates for the treatment of myotonic dystrophy type 1. The Journal of pharmacology and experimental therapeutics 98 26330536
2000 Determination of the HLA-DM interaction site on HLA-DR molecules. Immunity 93 11070170
1995 The two novel MHC class II transactivators RFX5 and CIITA both control expression of HLA-DM genes. International immunology 91 7495736
2005 Cytoplasmic and nuclear retained DMPK mRNAs are targets for RNA interference in myotonic dystrophy cells. The Journal of biological chemistry 88 15722335
1996 Invariant chain and DM edit self-peptide presentation by major histocompatibility complex (MHC) class II molecules. The Journal of experimental medicine 88 8920863
2005 The relationship between immunodominance, DM editing, and the kinetic stability of MHC class II:peptide complexes. Immunological reviews 87 16181342
2007 Vertebrate DM domain proteins bind similar DNA sequences and can heterodimerize on DNA. BMC molecular biology 79 17605809
2006 Tumor cell expression of HLA-DM associates with a Th1 profile and predicts improved survival in breast carcinoma patients. International immunology 75 16987935
2001 Decreased levels of myotonic dystrophy protein kinase (DMPK) and delayed differentiation in human myotonic dystrophy myoblasts. Neuromuscular disorders : NMD 74 11595515
1999 Characterization of the expression of DMPK and SIX5 in the human eye and implications for pathogenesis in myotonic dystrophy. Human molecular genetics 63 9949207
1995 Characterization of myotonic dystrophy kinase (DMK) protein in human and rodent muscle and central nervous tissue. Human molecular genetics 58 7655460
2004 Intergenerational instability of the expanded CTG repeat in the DMPK gene: studies in human gametes and preimplantation embryos. American journal of human genetics 57 15185171
2002 HLA-DM, HLA-DO and tapasin: functional similarities and differences. Current opinion in immunology 57 11790529
2000 Constitutive and regulated modes of splicing produce six major myotonic dystrophy protein kinase (DMPK) isoforms with distinct properties. Human molecular genetics 56 10699184
2000 Myotonic dystrophy: the role of the CUG triplet repeats in splicing of a novel DMPK exon and altered cytoplasmic DMPK mRNA isoform ratios. Molecular cell 56 10911990
2021 Permissive HLA-DPB1 mismatches in HCT depend on immunopeptidome divergence and editing by HLA-DM. Blood 55 33025005
2008 Myotonic dystrophy protein kinase (DMPK) and its role in the pathogenesis of myotonic dystrophy 1. Cellular signalling 55 18583094
1994 The molecular cloning and characterization of potential chick DM-GRASP homologs in zebrafish and mouse. Journal of neurobiology 55 8089660
2021 Can remdesivir and its parent nucleoside GS-441524 be potential oral drugs? An in vitro and in vivo DMPK assessment. Acta pharmaceutica Sinica. B 53 34221871
2013 Myotonic dystrophy protein kinase (DMPK) prevents ROS-induced cell death by assembling a hexokinase II-Src complex on the mitochondrial surface. Cell death & disease 52 24136222
2007 Molecular cloning and sexually dimorphic expression of DM-domain genes in Daphnia magna. Genomics 52 18031985
2004 Transgenic overexpression of human DMPK accumulates into hypertrophic cardiomyopathy, myotonic myopathy and hypotension traits of myotonic dystrophy. Human molecular genetics 51 15317754
2002 Mutant DMPK 3'-UTR transcripts disrupt C2C12 myogenic differentiation by compromising MyoD. The Journal of cell biology 50 12427866
2000 DM determines the cryptic and immunodominant fate of T cell epitopes. The Journal of experimental medicine 49 10993909
2006 Mice mutant in the DM domain gene Dmrt4 are viable and fertile but have polyovular follicles. Molecular and cellular biology 48 16982677
2019 Genome Editing of Expanded CTG Repeats within the Human DMPK Gene Reduces Nuclear RNA Foci in the Muscle of DM1 Mice. Molecular therapy : the journal of the American Society of Gene Therapy 47 31253581
2017 Myotonic dystrophy type 1: role of CCG, CTC and CGG interruptions within DMPK alleles in the pathogenesis and molecular diagnosis. Clinical genetics 46 27991661
2009 Ganoderic acid DM: anti-androgenic osteoclastogenesis inhibitor. Bioorganic & medicinal chemistry letters 46 19289282
2008 Identification and expression of a factor of the DM family in the oyster Crassostrea gigas. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 46 18854223
2000 Characterization of a monoclonal antibody panel shows that the myotonic dystrophy protein kinase, DMPK, is expressed almost exclusively in muscle and heart. Human molecular genetics 45 10958655
2016 Dmpk gene deletion or antisense knockdown does not compromise cardiac or skeletal muscle function in mice. Human molecular genetics 44 27522499
2015 Sense and Antisense DMPK RNA Foci Accumulate in DM1 Tissues during Development. PloS one 44 26339785
2012 Altered replication in human cells promotes DMPK (CTG)(n) · (CAG)(n) repeat instability. Molecular and cellular biology 44 22354993
1999 HLA-DM and the MHC class II antigen presentation pathway. Immunologic research 44 10741860
2014 DDX6 regulates sequestered nuclear CUG-expanded DMPK-mRNA in dystrophia myotonica type 1. Nucleic acids research 42 24792155
2008 Expression of Dm-AMP1 in rice confers resistance to Magnaporthe oryzae and Rhizoctonia solani. Transgenic research 41 18618285
2006 Male-biased expression of X-chromosomal DM domain-less Dmrt8 genes in the mouse. Genomics 41 16488114
2023 Antisense oligonucleotide targeting DMPK in patients with myotonic dystrophy type 1: a multicentre, randomised, dose-escalation, placebo-controlled, phase 1/2a trial. The Lancet. Neurology 40 36804094
2016 Identification and characterization of 5' CCG interruptions in complex DMPK expanded alleles. European journal of human genetics : EJHG 40 27876818
2005 Genetics of diabetic nephropathy in type 2 DM: candidate gene analysis for the pathogenic role of inflammation. Nephrology (Carlton, Vic.) 38 16174285
2000 DM-GRASP is necessary for nonradial cell migration during chick diencephalic development. The Journal of neuroscience : the official journal of the Society for Neuroscience 38 10704504
2002 The influence of DMPK as an integrated partner in modern drug discovery. Current drug metabolism 35 12369896
2009 Xenopus W-linked DM-W induces Foxl2 and Cyp19 expression during ovary formation. Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 33 19339816
2007 Role of myotonic dystrophy protein kinase (DMPK) in glucose homeostasis and muscle insulin action. PloS one 33 17987120
2001 Effect of triplet repeat expansion on chromatin structure and expression of DMPK and neighboring genes, SIX5 and DMWD, in myotonic dystrophy. Molecular genetics and metabolism 33 11592825
2000 Manumycin inhibits ras signal transduction pathway and induces apoptosis in COLO320-DM human colon tumour cells. British journal of cancer 32 10732765
2003 DM loss in k haplotype mice reveals isotype-specific chaperone requirements. Journal of immunology (Baltimore, Md. : 1950) 31 12646641
1996 Myelin proteolipid protein (PLP), but not DM-20, is an inositol hexakisphosphate-binding protein. The Journal of biological chemistry 30 8910382
2001 In vivo and in vitro modulation of HLA-DM and HLA-DO is induced by B lymphocyte activation. Journal of immunology (Baltimore, Md. : 1950) 29 11739502
1998 MHC class II expression in double mutant mice lacking invariant chain and DM functions. Journal of immunology (Baltimore, Md. : 1950) 29 9551894
2022 Wound healing mechanism of antimicrobial peptide cathelicidin-DM. Frontiers in bioengineering and biotechnology 28 36425652
2001 Transmembrane domain-mediated colocalization of HLA-DM and HLA-DR is required for optimal HLA-DM catalytic activity. Journal of immunology (Baltimore, Md. : 1950) 28 11673529
2020 Systemic therapy in an RNA toxicity mouse model with an antisense oligonucleotide therapy targeting a non-CUG sequence within the DMPK 3'UTR RNA. Human molecular genetics 27 32242217
2015 Cooperation meets competition in microRNA-mediated DMPK transcript regulation. Nucleic acids research 27 26304544
2010 Detailed proteomic analysis on DM: insight into its hypoallergenicity. Frontiers in bioscience (Elite edition) 27 20036899
2010 Muscleblind1, but not Dmpk or Six5, contributes to a complex phenotype of muscular and motivational deficits in mouse models of myotonic dystrophy. PloS one 27 20360842
2004 In situ hybridization analysis of Dmpk mRNA in adult mouse tissues. Neuromuscular disorders : NMD 27 15336691
2000 Myotonic dystrophy protein kinase (DMPK) induces actin cytoskeletal reorganization and apoptotic-like blebbing in lens cells. Cell motility and the cytoskeleton 26 10658209
1997 How HLA-DM affects the peptide repertoire bound to HLA-DR molecules. Human immunology 26 9297535
1993 No imprinting involved in the expression of DM-kinase mRNAs in mouse and human tissues. Human molecular genetics 26 8401505
2019 Ganoderic acid A/DM-induced NDRG2 over-expression suppresses high-grade meningioma growth. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 25 31732915
2008 HLA-DM negatively regulates HLA-DR4-restricted collagen pathogenic peptide presentation and T cell recognition. European journal of immunology 25 18506881
2005 DM and DO shape the repertoire of peptide-MHC-class-II complexes. Current opinion in immunology 25 15653313
2002 Stabilization of soluble, low-affinity HLA-DM/HLA-DR1 complexes by leucine zippers. Journal of immunological methods 25 12009208
1987 Disproportional expression of proteolipid protein and DM-20 in the X-linked, dysmyelinating shaking pup mutant. Journal of neurochemistry 25 2445922
2018 Distinct editing functions of natural HLA-DM allotypes impact antigen presentation and CD4+ T cell activation. Cellular & molecular immunology 24 30467419
2002 Sex-specific gene regulation. The Doublesex DM motif is a bipartite DNA-binding domain. The Journal of biological chemistry 24 12198117
2022 The Perspective of DMPK on Recombinant Adeno-Associated Virus-Based Gene Therapy: Past Learning, Current Support, and Future Contribution. The AAPS journal 23 35102450
2019 DMPK gene DNA methylation levels are associated with muscular and respiratory profiles in DM1. Neurology. Genetics 23 31334355
2016 Epigenetics of the myotonic dystrophy-associated DMPK gene neighborhood. Epigenomics 22 26756355
1997 Expression of the dm-20 isoform of the plp gene in olfactory nerve ensheathing cells: evidence from developmental studies. Journal of neurocytology 22 9192285
2022 High Resolution Analysis of DMPK Hypermethylation and Repeat Interruptions in Myotonic Dystrophy Type 1. Genes 21 35741732
2016 Human leukocyte Antigen-DM polymorphisms in autoimmune diseases. Open biology 21 27534821
2016 Ki-67, p53, and p16 expression, and G691S RET polymorphism in desmoplastic melanoma (DM): A clinicopathologic analysis of predictors of outcome. Journal of the American Academy of Dermatology 21 27543214
2020 Recognition of emotions conveyed by facial expression and body postures in myotonic dystrophy (DM). Cortex; a journal devoted to the study of the nervous system and behavior 20 32169676
2015 pH-susceptibility of HLA-DO tunes DO/DM ratios to regulate HLA-DM catalytic activity. Scientific reports 20 26610428
2019 Expanded CUG repeats in DMPK transcripts adopt diverse hairpin conformations without influencing the structure of the flanking sequences. RNA (New York, N.Y.) 19 30700578
2019 DM-RPIs: Predicting ncRNA-protein interactions using stacked ensembling strategy. Computational biology and chemistry 19 31330489
2009 DMPK protein isoforms are differentially expressed in myogenic and neural cell lineages. Muscle & nerve 19 19626675
2005 Divergent mitochondrial and endoplasmic reticulum association of DMPK splice isoforms depends on unique sequence arrangements in tail anchors. Molecular and cellular biology 19 15684391
2005 Decreased expression of DMPK: correlation with CTG repeat expansion and fibre type composition in myotonic dystrophy type 1. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 19 16193250
2003 Association of TAP and HLA-DM genes with psoriasis in Koreans. The Journal of investigative dermatology 19 12648225
1999 Quality control of MHC class II associated peptides by HLA-DM/H2-M. Seminars in immunology 19 10625593
1999 BEN/SC1/DM-GRASP expression during neuromuscular development: a cell adhesion molecule regulated by innervation. The Journal of neuroscience : the official journal of the Society for Neuroscience 19 9952415

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