InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DMPK

Summary

InnateDB Protein

IDBP-382063.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

DMPK

Protein Name

dystrophia myotonica-protein kinase

Synonyms

DM; DM1; DM1PK; DMK; MDPK; MT-PK;

Species

Homo sapiens

Ensembl Protein

ENSP00000401753

InnateDB Gene

IDBG-57994 (DMPK)

Protein Structure

UniProt Annotation

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:0000269PubMed:10811636, ECO:0000269PubMed:10913253, ECO:0000269PubMed:11287000, ECO:0000269PubMed:15598648, ECO:0000269PubMed:21457715, ECO:0000269PubMed:21949239}.

Subcellular Localization

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}.Isoform 1: Mitochondrion membrane.Isoform 3: Mitochondrion membrane.

Disease Associations

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:0000269PubMed:1302022, ECO:0000269PubMed:1310900, ECO:0000269PubMed:1546326, ECO:0000269PubMed: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.

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:0000269PubMed:7488138}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 28 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	28 [view]
Protein-Protein	24 [view]
Protein-DNA	0
Protein-RNA	3 [view]
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0017020	myosin phosphatase regulator activity
GO:0046872	metal ion binding

Biological Process

GO:0006468	protein phosphorylation
GO:0006874	cellular calcium ion homeostasis
GO:0006998	nuclear envelope organization
GO:0008016	regulation of heart contraction
GO:0010657	muscle cell apoptotic process
GO:0010830	regulation of myotube differentiation
GO:0050790	regulation of catalytic activity

Cellular Component

GO:0005640	nuclear outer membrane
GO:0005789	endoplasmic reticulum membrane
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0031307	integral component of mitochondrial outer membrane
GO:0031965	nuclear membrane
GO:0033017	sarcoplasmic reticulum membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR000961 AGC-kinase, C-terminal
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR014930 Myotonic dystrophy protein kinase, coiled coil
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF08826

PRINTS

PR00109

PIRSF

SMART

SM00133
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt