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FLASH GENE

Symbol

DMPK

contributors: mct/npt/shn - updated : 01-04-2016

HGNC name	dystrophia myotonica-protein kinase
HGNC id	2933

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive salivary gland       highly Nervous brain       specific   nerve cranial nerve     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular smooth       Muscular striatum cardiac     Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

Text	expressed in postmitotic cardiac and skeletal myocytes and developmental signaling centers

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	five distinct domains
	N terminal stretch leucine-rich
	a kinase domain S/T type subfamily, with presence, also in LATS2, of two negative pockets in the peptide binding groove provides an explanation for the substrate preference
	a coiled-coil domain modulating multimerization, substrate binding, kinase activity and subcellular localization characteristics
	a five AA sequence with unknown function
	an hydrophobic C terminus
	an alpha helical domain at various C termini possibly acting as self-association domain or membrane anchor

HOMOLOGY

interspecies	ortholog to DMPK, Pan troglodytes
	ortholog to Dmpk, Rattus norvegicus
	ortholog to Dmpk, Mus musculus

intraspecies

homolog to DMR-B15

Homologene

FAMILY

multidomain protein kinases

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytosolic
	intracellular,nuclear envelope
text	localised prominently at sites of neuromuscular and myotendinous junctions and rodent skeletal muscles
	highly enriched in the sarcoplasmic reticulum of cardiac myocytes
	DMPK A and C proteins both localized to mitochondria

basic FUNCTION	myotonin serine threonine kinase, modulator of the Ca++ homeostasis in skeletal muscle cell presenting a replication discrepancy between the normal and the mutant allele in cells with the CTG repeat expansion
	involved in the organization of sarcoplasmic reticulum in skeletal muscle
	playing a critical role for the modulation of cardiac contractility and the maintenance of proper cardiac conduction activity
	phosphorylating phospholamban and regulating calcium uptake in cardiomyocyte sarcoplasmic reticulum
	a kinase with pronounced expression in diverse muscle and neural tissues that are affected in DM1 (Oude 20096)
	a key role in myocyte differentiation
	necessary for myogenin expression in differentiating C2C12 myoblasts
	a critical component of the nuclear envelope

CELLULAR PROCESS

cell organization/biogenesis

PHYSIOLOGICAL PROCESS

text	Ca2+ homeostasis in skeletal muscle

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	DMPK-binding protein, MKBP
	actin cytoskeleton-linked GTPase Rac-1 and Raf-1 kinase
	phospholamban, PLN
	Lamin-A/C
	DDX6 can remodel and release nuclear DMPK messenger ribonucleoprotein foci, leading to normalization of pathogenic alternative splicing events

cell & other

REGULATION

activated by

HSPB2, RAC1, RAF1 suggesting that DMPK plays a role as a nexus between the repetitive pathways af these signals

induced by

intracellular signaling pathways that induce myotonic dystrophy protein kinase expression during myogenesis

Other

enhanced by DMPK-binding protein, MKBP

ASSOCIATED DISORDERS

corresponding disease(s)

DM1

Susceptibility

Variant & Polymorphism repeat	associated to spontaneous chromosome loss and colcemid resistance in lymphocytes of DM1

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	mice expressing the CUG expansion in an unrelated mRNA develop myotonia and myopathy, and show abnormal tau expression in the brain
	overexpression of the DMPK 3'-UTR including either wild-type (11) or expanded (91) CTG repeats results in aberrant and delayed muscle development in fetal transgenic mice, and mice display muscle atrophy at 3 months of age
	overexpression of DMPK mRNA and protein transgene products in cardiac, skeletal and smooth muscles of transgenic murine line carrying approximately 25 extra copies of a complete hDMPK gene with all exons and an intact promoter region resulted in deficient exercise endurance, hypertrophic cardiomyopathy, myotonic myopathy and hypotension traits of myotonic dystrophy
	PLN is hypo-phosphorylated in SR vesicles from DMPK(-/-) mice compared with wild-type mice
	mice overexpressing a normal DMPK 3' UTR mRNA reproduced cardinal features of myotonic dystrophy, including myotonia, cardiac conduction abnormalities, histopathology and RNA splicing defects in the absence of detectable nuclear inclusion
	inductible DM1 mouse model misregulation of developmentally regulated alternative splicing events, myotonia, characteristic histological abnormalities, and increased CUGBP1 protein levels
	Overexpression of DMPK induces cell rounding and apoptosis in myocytes
	Overexpression of DMPK in HeLa cells or C2C12 myoblasts disrupts Lamin-A/C and Lamin-B1 localization and causes nuclear fragmentation, and depletion of DMPK disrupts nuclear envelope lamina