DMPK_HUMAN » Myotonin-protein kinase

DMPK_HUMAN » Myotonin-protein kinase
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Topology in Mitochondrial outer membrane
Topologyintermembrane space
cytoplasmic side
DMPK_HUMAN » Myotonin-protein kinase » MT-PK; DM-kinase;DMK; DM1 protein kinase;DMPK;Myotonic dystrophy protein kinase;
Hydrophobic Thickness 21.2 ± 1.8 Å
Tilt Angle 0 ± 0°
ΔGtransfer -17.6 kcal/mol
ΔGfold -8.4 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology In
TM Segments 587-615 (587-618)
Pathways none
PDB 1wt6 (A/B/D=460-537), 2vd5 (A/B=11-420)
OPM none
Complexes

DMPK:DMPK_HUMAN

Interactions

DMPK, Complex: Homodimer of myotonic dystrophy protein kinase, PDBID: 2VD5

PLB1, Complex: PLB1:DMPK, PubMed

PLM, Complex: PLM:DMPK, PubMed

PPLA, Complex: DMPK:PPLA, PubMed

Domains

AA: 71-339, PDBID: 2VD5, Subunit B, Seq Identity:100%, Protein kinase domain

AA: 470-530, PDBID: 1WT6, Subunit D, Seq Identity:100%, DMPK coiled coil domain like

UniProt annotation for DMPK_HUMAN » Myotonin-protein kinase
FUNCTION: Non-receptor serine/threonine protein kinase which is necessary for the maintenance of skeletal muscle structure and function. May play a role in myocyte differentiation and survival by regulating the integrity of the nuclear envelope and the expression of muscle-specific genes. May also phosphorylate PPP1R12A and inhibit the myosin phosphatase activity to regulate myosin phosphorylation. Also critical to the modulation of cardiac contractility and to the maintenance of proper cardiac conduction activity probably through the regulation of cellular calcium homeostasis. Phosphorylates PLN, a regulator of calcium pumps and may regulate sarcoplasmic reticulum calcium uptake in myocytes. May also phosphorylate FXYD1/PLM which is able to induce chloride currents. May also play a role in synaptic plasticity.

CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.

ENZYME REGULATION: Coiled-coil-mediated oligomerization enhances the catalytic activity. Proteolytic processing of the C-terminus may release the protein from membranes and constitute a mean to regulate the enzyme. May be regulated by HSPB2, RAC1, RAF1 and G- protein second messengers.

SUBUNIT: Homodimer; homodimerization stimulates the kinase activity. Interacts with HSPB2; may enhance DMPK kinase activity. Interacts with PLN; phosphorylates PLN. May interact with RAC1; may regulate DMPK kinase activity. Interacts with LMNA; may regulate nuclear envelope stability.

TISSUE SPECIFICITY: Most isoforms are expressed in many tissues including heart, skeletal muscle, liver and brain, except for isoform 2 which is only found in the heart and skeletal muscle, and isoform 14 which is only found in the brain, with high levels in the striatum, cerebellar cortex and pons.

DOMAIN: The coiled coil domain is required for homodimerization and regulates the enzymatic activity.

DISEASE: Dystrophia myotonica 1 (DM1) OMIM: A muscular disorder characterized by myotonia, muscle wasting in the distal extremities, cataract, hypogonadism, defective endocrine functions, male baldness and cardiac arrhythmias. disease is caused by mutations affecting the gene represented in this entry. The causative mutation is a CTG expansion in the 3"- UTR of the DMPK gene. A length exceeding 50 CTG repeats is pathogenic, while normal individuals have 5 to 37 repeats. Intermediate alleles with 35-49 triplets are not disease-causing but show instability in intergenerational transmissions. Disease severity varies with the number of repeats: mildly affected persons have 50 to 150 repeats, patients with classic DM have 100 to 1,000 repeats, and those with congenital onset can have more than 2,000 repeats.

UniProt features for DMPK_HUMAN » Myotonin-protein kinase
CHAIN 1 629 Myotonin-protein kinase.
DOMAIN 71 339 Protein kinase.
DOMAIN 340 415 AGC-kinase C-terminal.
COILED 457 536
ACT_SITE 195 195 Proton acceptor (By similarity).
Amino Acid Sequence for DMPK_HUMAN » Myotonin-protein kinase
MSAEVRLRRL QQLVLDPGFL GLEPLLDLLL GVHQELGASE LAQDKYVADF LQWAEPIVVR LKEVRLQRDD FEILKVIGRG AFSEVAVVKM KQTGQVYAMK IMNKWDMLKR GEVSCFREER DVLVNGDRRW ITQLHFAFQD ENYLYLVMEY YVGGDLLTLL SKFGERIPAE MARFYLAEIV MAIDSVHRLG YVHRDIKPDN ILLDRCGHIR LADFGSCLKL RADGTVRSLV AVGTPDYLSP EILQAVGGGP GTGSYGPECD WWALGVFAYE MFYGQTPFYA DSTAETYGKI VHYKEHLSLP LVDEGVPEEA RDFIQRLLCP PETRLGRGGA GDFRTHPFFF GLDWDGLRDS VPPFTPDFEG ATDTCNFDLV EDGLTAMVSG GGETLSDIRE GAPLGVHLPF VGYSYSCMAL RDSEVPGPTP MELEAEQLLE PHVQAPSLEP SVSPQDETAE VAVPAAVPAA EAEAEVTLRE LQEALEEEVL TRQSLSREME AIRTDNQNFA SQLREAEARN RDLEAHVRQL QERMELLQAE GATAVTGVPS PRATDPPSHL DGPPAVAVGQ CPLVGPGPMH RRHLLLPARV PRPGLSEALS LLLFAVVLSR AAALGCIGLV AHAGQLTAVW RRPGAARAP