DMPK dystrophia myotonica-protein kinase [Homo sapiens] - Gene

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Summary

Official Symbol: DMPKprovided by HGNC
Official Full Name: dystrophia myotonica-protein kinaseprovided by HGNC
Primary source: HGNC:2933
See related: Ensembl:ENSG00000104936; HPRD:05645; MIM:605377
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DM; DM1; DMK; MDPK; DM1PK; MT-PK
Summary: The protein encoded by this gene is a serine-threonine kinase that is closely related to other kinases that interact with members of the Rho family of small GTPases. Substrates for this enzyme include myogenin, the beta-subunit of the L-type calcium channels, and phospholemman. The 3' untranslated region of this gene contains 5-37 copies of a CTG trinucleotide repeat. Expansion of this unstable motif to 50-5,000 copies causes myotonic dystrophy type I, which increases in severity with increasing repeat element copy number. Repeat expansion is associated with condensation of local chromatin structure that disrupts the expression of genes in this region. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 19q13.3

Sequence :: Chromosome: 19; NC_000019.9 (46272975..46285815, complement)

See DMPK in Epigenomics, MapViewer

Chromosome 19 - NC_000019.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

reduced DMPK may contribute to NE instability, a common mechanism of skeletal muscle wasting in muscular dystrophies.
Title: Myotonic dystrophy protein kinase is critical for nuclear envelope integrity.
The results of this study suggested that peripheral neuropathy can be linked to a large CTG expansion and a severe form of DM1.
Title: Peripheral neuropathy is linked to a severe form of myotonic dystrophy in transgenic mice.
analysis of CTG repeats at the DMPK gene in myotonic dystrophy patients and healthy individuals from the Mexican population
Title: Distribution of CTG repeats at the DMPK gene in myotonic dystrophy patients and healthy individuals from the Mexican population.
NMR spectroscopy and molecular dynamics simulation show that the 5'CUG/3'GUC motif found in DM1 RNAs is dynamic.
Title: NMR spectroscopy and molecular dynamics simulation of r(CCGCUGCGG)₂ reveal a dynamic UU internal loop found in myotonic dystrophy type 1.
Only seven typical patients with myotonic dystrophy from six unrelated families were identified, all with large pathological CTG repeat expansions (> 400 repeats) in the DMPK gene
Title: CTG repeat lengths of the DMPK gene in myotonic dystrophy patients compared to healthy controls in Thailand.
Methylation of the CpG sites in DMPK locus does not correlate with CTG expansion size or with the congenital form of the disease. The size range of the repeat expansions with methylation was from as small as 300 to as large as 2800 repeats.
Title: Methylation of the CpG sites in the myotonic dystrophy locus does not correlate with CTG expansion size or with the congenital form of the disease.
An aberrant MTMR1 expression and signs of altered myofiber maturation were documented in DM1. There was more severe dysregulation of MTMR1 expression in DM1.
Title: Analysis of MTMR1 expression and correlation with muscle pathological features in juvenile/adult onset myotonic dystrophy type 1 (DM1) and in myotonic dystrophy type 2 (DM2).
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
This study showedthat an abnormal activation of the proteolytic Fbox32/ubiquitin-proteasome pathway may contribute to muscle atrophy in these mice and could be involved in the progressive muscle loss observed in the myotonic dystrophy type 1 patients.
Title: Progressive skeletal muscle weakness in transgenic mice expressing CTG expansions is associated with the activation of the ubiquitin-proteasome pathway.
Steinert's disease caused by a dynamic mutation of (CTG) trinucleotide repeats in the 3' untranslated region of the myotonic dystrophy protein kinase gene (DMPK).
Title: A rapid polymerase chain reaction-based test for screening Steinert's disease (DM1).

Submit: New GeneRIF Correction See all (57)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Myotonic dystrophy type 1 (DM1) is a multisystem disorder that affects skeletal and smooth muscle as well as the eye, heart, endocrine system, and central nervous system. The clinical findings, which span a continuum from mild to severe, have been categorized into three somewhat overlapping phenotypes: mild, classic, and congenital. Mild DM1 is characterized by cataract and mild myotonia (sustained muscle contraction); life span is normal. Classic DM1 is characterized by muscle weakness and wasting, myotonia, cataract, and often cardiac conduction abnormalities; adults may become physically disabled and may have a shortened life span. Congenital DM1 is characterized by hypotonia and severe generalized weakness at birth, often with respiratory insufficiency and early death; intellectual disability is common.

Diagnosis Testing

DM1 is caused by expansion of a CTG trinucleotide repeat in the non-coding region of DMPK. The diagnosis of DM1 is suspected in individuals with characteristic muscle weakness and is confirmed by molecular genetic testing of DMPK. CTG repeat length exceeding 34 repeats is abnormal. Molecular genetic testing detects mutations in nearly 100% of affected individuals and is clinically available.

Genetic Counseling

DM1 is inherited in an autosomal dominant manner. Offspring of an individual with an expanded allele have a 50% chance of inheriting the mutant allele. Disease-causing alleles may expand in length during gametogenesis, resulting in the transmission of longer trinucleotide repeat alleles that may be associated with earlier onset and more severe disease than that observed in the parent. Prenatal testing is possible for pregnancies at increased risk when the diagnosis of DM1 has been confirmed by molecular genetic testing in an affected family member.

References

PMID: 20301344

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Interactions

Products	Interactant	Other Gene	Source	Pubs	Description
NM_004409.2	NP_006551.1	CELF1	BIND	PubMed	Mutant DMPK mRNA interacts with CUGBP1.
NM_004409.2	NP_000957.1	RARG	BIND	PubMed	Mutant DMPK mRNA interacts with RAR-gamma.
NM_004409.2	NP_612482.2	SP1	BIND	PubMed	Mutant DMPK mRNA interacts with Sp1.
NP_004400.4	NP_002471.1	PPP1R12A	BIND	PubMed	DMPK interacts with MYPT1. This interaction was modelled on a demonstrated interaction between chicken MYPT1 and DMPK from an unspecified source.
Q09013	P54259	ATN1	HPRD	PubMed
Q09013	P54253	ATXN1	HPRD	PubMed
Q09013	Q92879	CELF1	HPRD	PubMed
Q09013	O00168	FXYD1	HPRD	PubMed
Q09013	O95166	GABARAP	HPRD	PubMed
Q09013	Q16082	HSPB2	HPRD	PubMed
Q09013	P26678	PLN	HPRD	PubMed
Q09013	O14974	PPP1R12A	HPRD	PubMed
Q09013	P04049	RAF1	HPRD	PubMed
Q09013	Q9NRR5	UBQLN4	HPRD	PubMed
BioGRID:108100	BioGRID:106807	ANXA7	BioGRID	PubMed	Two-hybrid
BioGRID:108100	BioGRID:109548	HSPB2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:108100	BioGRID:111317	PIN1	BioGRID	PubMed	Two-hybrid
BioGRID:108100	BioGRID:111817	RAC1	BioGRID	PubMed	Reconstituted Complex
BioGRID:108100	BioGRID:112118	RPS10	BioGRID	PubMed	Two-hybrid
BioGRID:108100	BioGRID:112490	SMN1	BioGRID	PubMed	Two-hybrid
BioGRID:108100	BioGRID:112938	TK1	BioGRID	PubMed	Two-hybrid
BioGRID:108100	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

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General gene information

Markers

PMC104374P1 (e-PCR)
- UniSTS:270110

RH11440 (e-PCR)
- UniSTS:35122

D19S261 (e-PCR)
- UniSTS:147775

D19S201 (e-PCR)
- UniSTS:147034

GDB:186209 (e-PCR)
- UniSTS:155482

RH75247 (e-PCR)
- UniSTS:87387

GDB:186796 (e-PCR)
- UniSTS:155505

RH78049 (e-PCR)
- UniSTS:51338

G60275 (e-PCR)
- UniSTS:137380

Dmpk (e-PCR), detects polymorphism
- UniSTS:265659

G64289 (e-PCR)
- UniSTS:158663

G15898 (e-PCR)
- UniSTS:34269

GDB:196904 (e-PCR)
- UniSTS:155894

GDB:196905 (e-PCR)
- UniSTS:155895

Genotypes

Potential readthrough

Included gene: DMWD

Homology

Homologs of the DMPK gene: The DMPK gene is conserved in chimpanzee, , dog, cow, and mouse.
Map Viewer (Mouse)

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IDA Inferred from Direct Assay more info	PubMed
metal ion binding	IEA Inferred from Electronic Annotation more info
myosin phosphatase regulator activity	IDA Inferred from Direct Assay more info	PubMed
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
cellular calcium ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
muscle cell apoptosis	IDA Inferred from Direct Assay more info	PubMed
nuclear envelope organization	IMP Inferred from Mutant Phenotype more info
protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
regulation of excitatory postsynaptic membrane potential involved in skeletal muscle contraction	IEA Inferred from Electronic Annotation more info
regulation of heart contraction	IDA Inferred from Direct Assay more info	PubMed
regulation of myotube differentiation	ISS Inferred from Sequence or Structural Similarity more info
regulation of sodium ion transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytoplasm	IEA Inferred from Electronic Annotation more info
cytosol	ISS Inferred from Sequence or Structural Similarity more info
endoplasmic reticulum membrane	ISS Inferred from Sequence or Structural Similarity more info
integral to membrane	IEA Inferred from Electronic Annotation more info
integral to mitochondrial outer membrane	IDA Inferred from Direct Assay more info	PubMed
mitochondrial outer membrane	IEA Inferred from Electronic Annotation more info
mitochondrion	IEA Inferred from Electronic Annotation more info
nuclear membrane	ISS Inferred from Sequence or Structural Similarity more info
nuclear outer membrane	IEA Inferred from Electronic Annotation more info
nucleus	IEA Inferred from Electronic Annotation more info
plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
sarcoplasmic reticulum membrane	ISS Inferred from Sequence or Structural Similarity more info

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General protein information

Preferred Names: myotonin-protein kinase

Names: myotonin-protein kinase; DM-kinase; DM protein kinase; DM1 protein kinase; thymopoietin homolog; myotonin protein kinase A; myotonic dystrophy protein kinase; myotonic dystrophy associated protein kinase

NP_001075029.1

EC 2.7.11.1

NP_001075031.1

EC 2.7.11.1

NP_001075032.1

EC 2.7.11.1

NP_004400.4

EC 2.7.11.1

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009784.1 RefSeqGene

Range

5001..17841

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001081560.1 → NP_001075029.1 myotonin-protein kinase isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) has multiple differences in the presence and absence of exons at its 5' end and in the CDS, compared to variant 1. These differences produce a distinct 5' UTR, cause translation initiation at an alternative start codon, and the loss of an in-frame portion of the coding region, compared to variant 1. The encoded protein (isoform 3, also known as isoform 11) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

AC011530, AV655848, BC062553, L19268

Consensus CDS

CCDS46118.1

UniProtKB/TrEMBL

E5KR07

UniProtKB/Swiss-Prot

Q09013

Related

ENSP00000413417, ENST00000447742

Conserved Domains (3) summary

pfam08826
Location:465 – 525
Blast Score: 246

DMPK_coil; DMPK coiled coil domain like

cd05597
Location:69 – 401
Blast Score: 1662

STKc_DMPK_like; Catalytic domain of Myotonic Dystrophy protein kinase-like Protein Serine/Threonine Kinases

smart00220
Location:71 – 339
Blast Score: 701

S_TKc; Serine/Threonine protein kinases, catalytic domain
NM_001081562.1 → NP_001075031.1 myotonin-protein kinase isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) has multiple differences in the presence and absence of exons at its 5' end and in the CDS, compared to variant 1. These differences produce a distinct 5' UTR, and cause translation initiation at an alternative start codon, the loss of an in-frame portion of the coding region and a frameshift in the 3' coding region, compared to variant 1. The encoded protein (isoform 4) has a distinct N-terminus and a unique C-terminus, and is shorter than isoform 1.

Source sequence(s)

AC011530, AV655848, BC062553, S72883

Consensus CDS

CCDS46117.1

UniProtKB/TrEMBL

E5KR05

UniProtKB/Swiss-Prot

Q09013

Related

ENSP00000401753, ENST00000458663

Conserved Domains (3) summary

pfam08826
Location:465 – 525
Blast Score: 249

DMPK_coil; DMPK coiled coil domain like

cd05597
Location:69 – 401
Blast Score: 1666

STKc_DMPK_like; Catalytic domain of Myotonic Dystrophy protein kinase-like Protein Serine/Threonine Kinases

smart00220
Location:71 – 339
Blast Score: 709

S_TKc; Serine/Threonine protein kinases, catalytic domain
NM_001081563.1 → NP_001075032.1 myotonin-protein kinase isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1), also known as Form I.

Source sequence(s)

AC011530, AV655848, BC062553, M87312

Consensus CDS

CCDS46119.1

UniProtKB/TrEMBL

E5KR08

UniProtKB/Swiss-Prot

Q09013

Related

ENSP00000345997, ENST00000343373

Conserved Domains (3) summary

pfam08826
Location:480 – 540
Blast Score: 258

DMPK_coil; DMPK coiled coil domain like

cd05597
Location:79 – 416
Blast Score: 1645

STKc_DMPK_like; Catalytic domain of Myotonic Dystrophy protein kinase-like Protein Serine/Threonine Kinases

smart00220
Location:81 – 349
Blast Score: 706

S_TKc; Serine/Threonine protein kinases, catalytic domain
NM_004409.3 → NP_004400.4 myotonin-protein kinase isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) has multiple differences in the presence and absence of exons at its 5' end, compared to variant 1. These differences produce a distinct 5' UTR and cause translation initiation at an alternative start codon, compared to variant 1. The encoded protein (isoform 2, also known as isoform 9) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

AC011530, AV655848, BC062553, BG706056

Consensus CDS

CCDS12674.1

UniProtKB/TrEMBL

E5KR06

UniProtKB/Swiss-Prot

Q09013

Related

ENSP00000291270, ENST00000291270

Conserved Domains (3) summary

pfam08826
Location:470 – 530
Blast Score: 247

DMPK_coil; DMPK coiled coil domain like

cd05597
Location:69 – 406
Blast Score: 1647

STKc_DMPK_like; Catalytic domain of Myotonic Dystrophy protein kinase-like Protein Serine/Threonine Kinases

smart00220
Location:71 – 339
Blast Score: 702

S_TKc; Serine/Threonine protein kinases, catalytic domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000019.9 Reference GRCh37.p5 Primary Assembly

Range

46272975..46285815, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000151.1 Alternate HuRef

Range

42701722..42714534, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC011530.6 (26351..29601)	None
genomic	AC074212.5 (30720..40310)	None
genomic	CH471126.1	EAW57380.1
		EAW57381.1
		EAW57382.1
		EAW57383.1
		EAW57384.1
		EAW57385.1
genomic	HQ205626.1	ADP91334.1
		ADP91335.1
		ADP91336.1
		ADP91337.1
genomic	HQ205627.1	ADP91338.1
		ADP91339.1
		ADP91340.1
		ADP91341.1
genomic	HQ205628.1	ADP91342.1
		ADP91343.1
		ADP91344.1
		ADP91345.1
genomic	HQ205629.1	ADP91346.1
		ADP91347.1
		ADP91348.1
		ADP91349.1
genomic	HQ205630.1	ADP91350.1
		ADP91351.1
		ADP91352.1
		ADP91353.1
genomic	HQ205631.1	ADP91354.1
		ADP91355.1
		ADP91356.1
		ADP91357.1
genomic	HQ205632.1	ADP91358.1
		ADP91359.1
		ADP91360.1
		ADP91361.1
genomic	HQ205633.1	ADP91362.1
		ADP91363.1
		ADP91364.1
		ADP91365.1
genomic	HQ205634.1	ADP91366.1
		ADP91367.1
		ADP91368.1
		ADP91369.1
genomic	HQ205635.1	ADP91370.1
		ADP91371.1
		ADP91372.1
		ADP91373.1
genomic	HQ205636.1	ADP91374.1
		ADP91375.1
		ADP91376.1
		ADP91377.1
genomic	HQ205637.1	ADP91378.1
		ADP91379.1
		ADP91380.1
		ADP91381.1
genomic	HQ205638.1	ADP91382.1
		ADP91383.1
		ADP91384.1
		ADP91385.1
genomic	HQ205639.1	ADP91386.1
		ADP91387.1
		ADP91388.1
		ADP91389.1
genomic	HQ205640.1	ADP91390.1
		ADP91391.1
		ADP91392.1
		ADP91393.1
genomic	HQ205641.1	ADP91394.1
		ADP91395.1
		ADP91396.1
		ADP91397.1
genomic	HQ205642.1	ADP91398.1
		ADP91399.1
		ADP91400.1
		ADP91401.1
genomic	HQ205643.1	ADP91402.1
		ADP91403.1
		ADP91404.1
		ADP91405.1
genomic	HQ205644.1	ADP91406.1
		ADP91407.1
		ADP91408.1
		ADP91409.1
genomic	HQ205645.1	ADP91410.1
		ADP91411.1
		ADP91412.1
		ADP91413.1
genomic	HQ205646.1	ADP91414.1
		ADP91415.1
		ADP91416.1
		ADP91417.1
genomic	HQ205647.1	ADP91418.1
		ADP91419.1
		ADP91420.1
		ADP91421.1
genomic	HQ205648.1	ADP91422.1
		ADP91423.1
		ADP91424.1
		ADP91425.1
genomic	HQ205649.1	ADP91426.1
		ADP91427.1
		ADP91428.1
		ADP91429.1
genomic	HQ205650.1	ADP91430.1
		ADP91431.1
		ADP91432.1
		ADP91433.1
genomic	HQ205651.1	ADP91434.1
		ADP91435.1
		ADP91436.1
		ADP91437.1
genomic	HQ205652.1	ADP91438.1
		ADP91439.1
		ADP91440.1
		ADP91441.1
genomic	HQ205653.1	ADP91442.1
		ADP91443.1
		ADP91444.1
		ADP91445.1
genomic	HQ205654.1	ADP91446.1
		ADP91447.1
		ADP91448.1
		ADP91449.1
genomic	HQ205655.1	ADP91450.1
		ADP91451.1
		ADP91452.1
		ADP91453.1
genomic	HQ205656.1	ADP91454.1
		ADP91455.1
		ADP91456.1
		ADP91457.1
genomic	HQ205657.1	ADP91458.1
		ADP91459.1
		ADP91460.1
		ADP91461.1
genomic	HQ205658.1	ADP91462.1
		ADP91463.1
		ADP91464.1
		ADP91465.1
genomic	HQ205659.1	ADP91466.1
		ADP91467.1
		ADP91468.1
		ADP91469.1
genomic	HQ205660.1	ADP91470.1
		ADP91471.1
		ADP91472.1
		ADP91473.1
genomic	HQ205661.1	ADP91474.1
		ADP91475.1
		ADP91476.1
		ADP91477.1
genomic	HQ205662.1	ADP91478.1
		ADP91479.1
		ADP91480.1
		ADP91481.1
genomic	HQ205663.1	ADP91482.1
		ADP91483.1
		ADP91484.1
		ADP91485.1
genomic	HQ205664.1	ADP91486.1
		ADP91487.1
		ADP91488.1
		ADP91489.1
genomic	HQ205665.1	ADP91490.1
		ADP91491.1
		ADP91492.1
		ADP91493.1
genomic	L00727.1	AAA75235.1
		AAA75236.1
		AAA75237.1
		AAA75238.1
		AAA75239.1
		AAA75240.1
genomic	L08835.1	AAC14448.1
		AAC14449.1
		AAC14450.1
		AAC14451.1
genomic	L19266.1	AAA36205.1
mRNA	AB209363.1	BAD92600.1
mRNA	AK297299.1	BAG59767.1
mRNA	AK302874.1	BAG64054.1
mRNA	AK304749.1	BAH14251.1
mRNA	AV655848.1	None
mRNA	BC026328.1	AAH26328.1
mRNA	BC062553.1	AAH62553.1
mRNA	BG706056.1	None
mRNA	L19268.1	AAA36206.1
mRNA	M87312.1	None
mRNA	M94203.1	AAA64884.1
mRNA	S72883.1	AAB31800.1
mRNA	S86455.1	None
mRNA	U46546.1	AAA87583.1