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MT000189

UniProt Annotations

Entry Information

Gene Name	dystrophia myotonica-protein kinase
Protein Entry	DMPK_HUMAN
UniProt ID	Q09013
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=12; Name=1; Synonyms=DMPK A; IsoId=Q09013-9; Sequence=Displayed; Name=2; Synonyms=DMPK B; IsoId=Q09013-11; Sequence=VSP_042101; Name=3; Synonyms=DMPK C; IsoId=Q09013-16; Sequence=VSP_042104; Note=No experimental confirmation available.; Name=4; Synonyms=DMPK D; IsoId=Q09013-15; Sequence=VSP_042101, VSP_042104; Name=5; Synonyms=DMPK E; IsoId=Q09013-10; Sequence=VSP_042102, VSP_042103; Note=No experimental confirmation available.; Name=6; Synonyms=DMPK F; IsoId=Q09013-12; Sequence=VSP_042101, VSP_042102, VSP_042103; Note=No experimental confirmation available.; Name=7; IsoId=Q09013-1; Sequence=VSP_042099; Name=8; IsoId=Q09013-2; Sequence=VSP_042098; Note=No experimental confirmation available.; Name=9; IsoId=Q09013-5; Sequence=VSP_042099, VSP_042100; Note=No experimental confirmation available.; Name=10; IsoId=Q09013-6; Sequence=VSP_042099, VSP_042101; Note=No experimental confirmation available.; Name=11; IsoId=Q09013-7; Sequence=VSP_042099, VSP_042105; Note=No experimental confirmation available.; Name=12; IsoId=Q09013-8; Sequence=VSP_042099, VSP_042102, VSP_042103; Note=No experimental confirmation available.;
Catalytic Activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Disease	Dystrophia myotonica 1 (DM1) [MIM:160900]: A muscular disorder characterized by myotonia, muscle wasting in the distal extremities, cataract, hypogonadism, defective endocrine functions, male baldness and cardiac arrhythmias. {ECO:0000269\|PubMed:1302022, ECO:0000269\|PubMed:1310900, ECO:0000269\|PubMed:1546326, ECO:0000269\|PubMed:19514047}. Note=The 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.
Domain	The coiled coil domain is required for homodimerization and regulates the enzymatic activity.
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. {ECO:0000269\|PubMed:10869570, ECO:0000269\|PubMed:10913253, ECO:0000269\|PubMed:12832055, ECO:0000269\|PubMed:9490724}.
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. {ECO:0000269\|PubMed:10811636, ECO:0000269\|PubMed:10913253, ECO:0000269\|PubMed:11287000, ECO:0000269\|PubMed:15598648, ECO:0000269\|PubMed:21457715, ECO:0000269\|PubMed:21949239}.
Interaction	P26678:PLN; NbExp=4; IntAct=EBI-692774, EBI-692836;
Ptm	Phosphorylated. Autophosphorylates. Phosphorylation by RAF1 may result in activation of DMPK. {ECO:0000269\|PubMed:10869570}.
Ptm	Proteolytic processing of the C-terminus may remove the transmembrane domain and release the kinase from membranes stimulating its activity. {ECO:0000269\|PubMed:10913253}.
Sequence Caution	Sequence=AAA64884.1; Type=Frameshift; Positions=56, 555, 568; Evidence={ECO:0000305}; Sequence=AAA87583.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
Similarity	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. DMPK subfamily. {ECO:0000305}.
Similarity	Contains 1 AGC-kinase C-terminal domain. {ECO:0000305}.
Similarity	Contains 1 protein kinase domain. {ECO:0000255\|PROSITE-ProRule:PRU00159}.
Subcellular Location	Endoplasmic reticulum membrane {ECO:0000250}; Single-pass type IV membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Nucleus outer membrane {ECO:0000305}; Single-pass type IV membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Mitochondrion outer membrane {ECO:0000305}; Single-pass type IV membrane protein {ECO:0000305}. Sarcoplasmic reticulum membrane {ECO:0000250}. Cell membrane {ECO:0000250}. Cytoplasm, cytosol {ECO:0000250}. Note=Localizes to sarcoplasmic reticulum membranes of cardiomyocytes. {ECO:0000250}.
Subcellular Location	Isoform 1: Mitochondrion membrane.
Subcellular Location	Isoform 3: Mitochondrion membrane.
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. {ECO:0000269\|PubMed:10869570, ECO:0000269\|PubMed:15598648, ECO:0000269\|PubMed:16770013, ECO:0000269\|PubMed:19309729, ECO:0000269\|PubMed:21949239, ECO:0000269\|PubMed:9490724}.
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. {ECO:0000269\|PubMed:7488138}.