myotonin kinase (myotonic dystrophy-associated protein kinase, DMPK)

Function

• modulation of cardiac contractility
• maintenance of proper cardiac conduction activity
• phosphorylates phospholamban
• activated in response to G protein second messengers

Cofactor: Mg+2

Structure

• belongs to the Ser/Thr protein kinase family, DMPK subfamily
  • classified as serine/threonine kinase because of homology to cAMP dependent protein kinase
• contains 1 protein kinase domain
• maintained in an inactive conformation by negative autoregulatory C-terminal coiled-coil region
• coiled-coil mediated oligomerization correlated with enhanced catalytic activity
• proteolytically cleavage near C-terminus correlated with enhanced catalytic activity

Alternative splicing

• named isoforms=12
• at least one isoform may be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay

Expression

• most isoforms are expressed in many tissues including heart, skeletal muscle, liver & brain
• isoform 2 is expressed in heart & skeletal muscle
• isoform 14 expressed only in brain, high levels in striatum, cerebellar cortex, pons

Pathology

• defects in DMPK are the cause of myotonic dystrophy 1

Laboratory

• DMPK genotyping
  • DMPK gene mutation
  • DMPK gene CTG repeats
• DMPK phenotype

More general terms

• serine/threonine kinase

Database

• OMIM: https://mirror.omim.org/entry/160900
• UniProt: http://www.uniprot.org/uniprot/Q09013.html