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Protein

Myotonin-protein kinase

Gene

Dmpk

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

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 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei100ATPPROSITE-ProRule annotation1
Active sitei195Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi77 – 85ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • cellular calcium ion homeostasis Source: UniProtKB
  • muscle cell apoptotic process Source: UniProtKB
  • nuclear envelope organization Source: UniProtKB
  • peptidyl-serine phosphorylation Source: GO_Central
  • protein phosphorylation Source: UniProtKB
  • regulation of excitatory postsynaptic membrane potential involved in skeletal muscle contraction Source: MGI
  • regulation of heart contraction Source: UniProtKB
  • regulation of myotube differentiation Source: UniProtKB
  • regulation of skeletal muscle contraction by calcium ion signaling Source: UniProtKB
  • regulation of sodium ion transport Source: MGI
  • regulation of synapse structural plasticity Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 3474.
ReactomeiR-MMU-5578775. Ion homeostasis.

Names & Taxonomyi

Protein namesi
Recommended name:
Myotonin-protein kinase (EC:2.7.11.1)
Short name:
MT-PK
Alternative name(s):
DM-kinase
Short name:
DMK
DMPK
Myotonic dystrophy protein kinase
Short name:
MDPK
Gene namesi
Name:Dmpk
Synonyms:Dm15, Mdpk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:94906. Dmpk.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 592CytoplasmicSequence analysisAdd BLAST592
Transmembranei593 – 613Helical; Anchor for type IV membrane proteinSequence analysisAdd BLAST21
Topological domaini614 – 631LumenalSequence analysisAdd BLAST18

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB
  • integral component of mitochondrial outer membrane Source: UniProtKB
  • nuclear membrane Source: UniProtKB
  • nuclear outer membrane Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB
  • sarcoplasmic reticulum membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane, Nucleus, Sarcoplasmic reticulum

Pathology & Biotechi

Disruption phenotypei

Mice are fertile and no negative selection against the absence of the protein is apparent. Newborn do not display hypotonia, respiratory distress or gross anatomical abnormalities. However, a progressive muscle weakness a hall mark of myopathies is observed. Muscles from mature mice show variation in fiber size, increase fiber degeneration and fibrosis. They also display age-related progression in atrioventricular conduction defects that are reminiscent of congenital myotonic dystrophy.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859251 – 631Myotonin-protein kinaseAdd BLAST631

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei216Phosphoserine; by autocatalysisBy similarity1
Modified residuei228Phosphoserine; by autocatalysisBy similarity1
Modified residuei234Phosphothreonine; by autocatalysisBy similarity1

Post-translational modificationi

Phosphorylated. Autophosphorylates. Phosphorylation by RAF1 may result in activation of DMPK (By similarity).By similarity
Proteolytic processing of the C-terminus may remove the transmembrane domain and release the kinase from membranes stimulating its activity.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP54265.
PaxDbiP54265.
PeptideAtlasiP54265.
PRIDEiP54265.

PTM databases

PhosphoSitePlusiP54265.

Expressioni

Tissue specificityi

Expressed in all tissues tested, with a predominance in brain, skeletal muscle, heart, and other tissues containing smooth muscle. In the heart, expression is restricted to the cardiomyocytes in the ventricle and atrium.1 Publication

Developmental stagei

Primarily detected in striated muscle structures of the 14.5 day embryo, including all major muscles in the skeletal structures, cardiac muscle, diaphragm, and the smooth muscle of the lung and gut.1 Publication

Gene expression databases

BgeeiENSMUSG00000030409.
CleanExiMM_DMPK.
ExpressionAtlasiP54265. baseline and differential.
GenevisibleiP54265. MM.

Interactioni

Subunit structurei

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 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000032568.

Structurei

3D structure databases

ProteinModelPortaliP54265.
SMRiP54265.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini71 – 339Protein kinasePROSITE-ProRule annotationAdd BLAST269
Domaini340 – 415AGC-kinase C-terminalAdd BLAST76

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili464 – 532Sequence analysisAdd BLAST69

Domaini

The coiled coil domain is required for homodimerization and regulates the enzymatic activity.By similarity

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IT50. Eukaryota.
ENOG410YFQZ. LUCA.
GeneTreeiENSGT00760000118994.
HOGENOMiHOG000233033.
HOVERGENiHBG107817.
InParanoidiP54265.
KOiK08788.
OMAiFLQWVEP.
OrthoDBiEOG091G09EX.
PhylomeDBiP54265.
TreeFamiTF105337.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR014930. Myotonic_dystrophy_kinase_coil.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF08826. DMPK_coil. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
ProDomiPD011252. Myotonic_dystrophy_kinase_coil. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (10)i

Sequence statusi: Complete.

This entry describes 10 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P54265-1) [UniParc]FASTAAdd to basket
Also known as: DMPK A

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSAEVRLRQL QQLVLDPGFL GLEPLLDLLL GVHQELGASH LAQDKYVADF
60 70 80 90 100
LQWVEPIAAR LKEVRLQRDD FEILKVIGRG AFSEVAVVKM KQTGQVYAMK
110 120 130 140 150
IMNKWDMLKR GEVSCFREER DVLVKGDRRW ITQLHFAFQD ENYLYLVMEY
160 170 180 190 200
YVGGDLLTLL SKFGERIPAE MARFYLAEIV MAIDSVHRLG YVHRDIKPDN
210 220 230 240 250
ILLDRCGHIR LADFGSCLKL QPDGMVRSLV AVGTPDYLSP EILQAVGGGP
260 270 280 290 300
GAGSYGPECD WWALGVFAYE MFYGQTPFYA DSTAETYAKI VHYREHLSLP
310 320 330 340 350
LADTVVPEEA QDLIRGLLCP AEIRLGRGGA GDFQKHPFFF GLDWEGLRDS
360 370 380 390 400
VPPFTPDFEG ATDTCNFDVV EDRLTAMVSG GGETLSDMQE DMPLGVRLPF
410 420 430 440 450
VGYSYCCMAF RDNQVPDPTP MELEALQLPV SDLQGLDLQP PVSPPDQVAE
460 470 480 490 500
EADLVAVPAP VAEAETTVTL QQLQEALEEE VLTRQSLSRE LEAIRTANQN
510 520 530 540 550
FSSQLQEAEV RNRDLEAHVR QLQERMEMLQ APGAAAITGV PSPRATDPPS
560 570 580 590 600
HLDGPPAVAV GQCPLVGPGP MHRRHLLLPA RIPRPGLSEA RCLLLFAAAL
610 620 630
AAAATLGCTG LVAYTGGLTP VWCFPGATFA P
Length:631
Mass (Da):69,602
Last modified:October 1, 1996 - v1
Checksum:i5EE800A37EA81DF4
GO
Isoform 2 (identifier: P54265-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     328-356: Missing.

Show »
Length:602
Mass (Da):66,397
Checksum:i8A9EBB4E930E5EB0
GO
Isoform 3 (identifier: P54265-3) [UniParc]FASTAAdd to basket
Also known as: DMPK B

The sequence of this isoform differs from the canonical sequence as follows:
     378-382: Missing.

Show »
Length:626
Mass (Da):69,244
Checksum:i84F11B047BB340EF
GO
Isoform 4 (identifier: P54265-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     378-382: Missing.
     412-416: DNQVP → LKRPT
     417-631: Missing.

Show »
Length:411
Mass (Da):46,532
Checksum:i24F3F18634D0131C
GO
Isoform 5 (identifier: P54265-5) [UniParc]FASTAAdd to basket
Also known as: DMPK E

The sequence of this isoform differs from the canonical sequence as follows:
     536-537: AI → DP
     538-631: Missing.

Show »
Length:537
Mass (Da):60,161
Checksum:i21F148D98B3657BB
GO
Isoform 6 (identifier: P54265-6) [UniParc]FASTAAdd to basket
Also known as: DMPK F

The sequence of this isoform differs from the canonical sequence as follows:
     378-382: Missing.
     536-537: AI → DP
     538-631: Missing.

Show »
Length:532
Mass (Da):59,803
Checksum:iA79E9629B958241E
GO
Isoform 7 (identifier: P54265-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     536-557: AITGVPSPRATDPPSHLDGPPA → GESLTCFQPRGHWVEMGGMLGV
     558-631: Missing.

Show »
Length:557
Mass (Da):62,322
Checksum:iD0247256B70FD18C
GO
Isoform 8 (identifier: P54265-8) [UniParc]FASTAAdd to basket
Also known as: DMPK C

The sequence of this isoform differs from the canonical sequence as follows:
     552-631: LDGPPAVAVG...WCFPGATFAP → MAPRPWLWAS...SREPPSPPEP

Show »
Length:632
Mass (Da):70,329
Checksum:iD1576187FFBB8824
GO
Isoform 9 (identifier: P54265-9) [UniParc]FASTAAdd to basket
Also known as: DMPK D

The sequence of this isoform differs from the canonical sequence as follows:
     378-382: Missing.
     552-631: LDGPPAVAVG...WCFPGATFAP → MAPRPWLWAS...SREPPSPPEP

Show »
Length:627
Mass (Da):69,972
Checksum:iC5DD789C58BE9379
GO
Isoform 10 (identifier: P54265-10) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     552-562: LDGPPAVAVGQ → ASRQILPKGTP
     563-631: Missing.

Show »
Length:562
Mass (Da):62,682
Checksum:iC8D00A5C40223DBD
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004819328 – 356Missing in isoform 2. 1 PublicationAdd BLAST29
Alternative sequenceiVSP_004820378 – 382Missing in isoform 3, isoform 4, isoform 6 and isoform 9. 1 Publication5
Alternative sequenceiVSP_004821412 – 416DNQVP → LKRPT in isoform 4. 1 Publication5
Alternative sequenceiVSP_004822417 – 631Missing in isoform 4. 1 PublicationAdd BLAST215
Alternative sequenceiVSP_004825536 – 557AITGV…DGPPA → GESLTCFQPRGHWVEMGGML GV in isoform 7. CuratedAdd BLAST22
Alternative sequenceiVSP_004823536 – 537AI → DP in isoform 5 and isoform 6. 1 Publication2
Alternative sequenceiVSP_004824538 – 631Missing in isoform 5 and isoform 6. 1 PublicationAdd BLAST94
Alternative sequenceiVSP_004827552 – 631LDGPP…ATFAP → MAPRPWLWASARWWGQAPCT AVTCCSLPGSLGLAYPRRVA CSCSPLLWLLPPHWAALGWW PIPAVSPQSGVSREPPSPPE P in isoform 8 and isoform 9. 1 PublicationAdd BLAST80
Alternative sequenceiVSP_004828552 – 562LDGPPAVAVGQ → ASRQILPKGTP in isoform 10. CuratedAdd BLAST11
Alternative sequenceiVSP_004826558 – 631Missing in isoform 7. CuratedAdd BLAST74
Alternative sequenceiVSP_004829563 – 631Missing in isoform 10. CuratedAdd BLAST69

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z21503
, Z21504, Z21505, Z21506 Genomic DNA. Translation: CAA79715.1.
Z38015 Genomic DNA. Translation: CAA86113.1.
S60313 mRNA. Translation: AAC60667.1.
S60314 mRNA. Translation: AAC60666.1.
S60315 mRNA. Translation: AAC60665.1.
S60316 mRNA. Translation: AAC60664.1.
CCDSiCCDS39794.1. [P54265-1]
CCDS52054.1. [P54265-5]
PIRiI78393.
I78394.
I78395.
I78396.
S71829.
RefSeqiNP_001177420.1. NM_001190491.1. [P54265-5]
NP_115794.1. NM_032418.2. [P54265-1]
XP_006539581.1. XM_006539518.3. [P54265-9]
XP_006539582.1. XM_006539519.3. [P54265-3]
XP_011248735.1. XM_011250433.2. [P54265-8]
UniGeneiMm.6529.

Genome annotation databases

EnsembliENSMUST00000032568; ENSMUSP00000032568; ENSMUSG00000030409. [P54265-1]
ENSMUST00000108473; ENSMUSP00000104113; ENSMUSG00000030409. [P54265-5]
GeneIDi13400.
KEGGimmu:13400.
UCSCiuc009fkn.2. mouse. [P54265-1]
uc009fkp.2. mouse. [P54265-5]
uc009fkq.2. mouse. [P54265-8]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z21503
, Z21504, Z21505, Z21506 Genomic DNA. Translation: CAA79715.1.
Z38015 Genomic DNA. Translation: CAA86113.1.
S60313 mRNA. Translation: AAC60667.1.
S60314 mRNA. Translation: AAC60666.1.
S60315 mRNA. Translation: AAC60665.1.
S60316 mRNA. Translation: AAC60664.1.
CCDSiCCDS39794.1. [P54265-1]
CCDS52054.1. [P54265-5]
PIRiI78393.
I78394.
I78395.
I78396.
S71829.
RefSeqiNP_001177420.1. NM_001190491.1. [P54265-5]
NP_115794.1. NM_032418.2. [P54265-1]
XP_006539581.1. XM_006539518.3. [P54265-9]
XP_006539582.1. XM_006539519.3. [P54265-3]
XP_011248735.1. XM_011250433.2. [P54265-8]
UniGeneiMm.6529.

3D structure databases

ProteinModelPortaliP54265.
SMRiP54265.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000032568.

PTM databases

PhosphoSitePlusiP54265.

Proteomic databases

MaxQBiP54265.
PaxDbiP54265.
PeptideAtlasiP54265.
PRIDEiP54265.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000032568; ENSMUSP00000032568; ENSMUSG00000030409. [P54265-1]
ENSMUST00000108473; ENSMUSP00000104113; ENSMUSG00000030409. [P54265-5]
GeneIDi13400.
KEGGimmu:13400.
UCSCiuc009fkn.2. mouse. [P54265-1]
uc009fkp.2. mouse. [P54265-5]
uc009fkq.2. mouse. [P54265-8]

Organism-specific databases

CTDi1760.
MGIiMGI:94906. Dmpk.

Phylogenomic databases

eggNOGiENOG410IT50. Eukaryota.
ENOG410YFQZ. LUCA.
GeneTreeiENSGT00760000118994.
HOGENOMiHOG000233033.
HOVERGENiHBG107817.
InParanoidiP54265.
KOiK08788.
OMAiFLQWVEP.
OrthoDBiEOG091G09EX.
PhylomeDBiP54265.
TreeFamiTF105337.

Enzyme and pathway databases

BRENDAi2.7.11.1. 3474.
ReactomeiR-MMU-5578775. Ion homeostasis.

Miscellaneous databases

PROiP54265.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030409.
CleanExiMM_DMPK.
ExpressionAtlasiP54265. baseline and differential.
GenevisibleiP54265. MM.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR014930. Myotonic_dystrophy_kinase_coil.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF08826. DMPK_coil. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
ProDomiPD011252. Myotonic_dystrophy_kinase_coil. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDMPK_MOUSE
AccessioniPrimary (citable) accession number: P54265
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.