DMPK_HUMAN
ID DMPK_HUMAN Reviewed; 629 AA.
AC Q09013; E5KR08; Q16205; Q6P5Z6;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 3.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Myotonin-protein kinase;
DE Short=MT-PK;
DE EC=2.7.11.1;
DE AltName: Full=DM-kinase;
DE Short=DMK;
DE AltName: Full=DM1 protein kinase;
DE AltName: Full=DMPK;
DE AltName: Full=Myotonic dystrophy protein kinase;
GN Name=DMPK; Synonyms=DM1PK, MDPK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), AND INVOLVEMENT IN DM1.
RX PubMed=1546326; DOI=10.1126/science.1546326;
RA Fu Y.-H., Pizzuti A., Fenwick R.G. Jr., King J., Rajnarayan S., Dunne P.W.,
RA Dubel J., Nasser G.A., Ashizawa T., de Jong P.J., Wieringa B., Korneluk R.,
RA Perryman M.B., Epstein H.F., Caskey C.T.;
RT "An unstable triplet repeat in a gene related to myotonic muscular
RT dystrophy.";
RL Science 255:1256-1258(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2), AND VARIANT VAL-423.
RC TISSUE=Brain, and Muscle;
RX PubMed=7905855; DOI=10.1016/s0888-7543(05)80372-6;
RA Shaw D.J., McCurrach M., Rundle S.A., Harley H.G., Crow S.R., Sohn R.,
RA Thirion J.-P., Hamshere M.G., Buckler A.J., Harper P.S., Housman D.E.,
RA Brook J.D.;
RT "Genomic organization and transcriptional units at the myotonic dystrophy
RT locus.";
RL Genomics 18:673-679(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2; 5; 6), AND VARIANT
RP VAL-423.
RX PubMed=8499920; DOI=10.1093/hmg/2.3.299;
RA Mahadevan M.S., Amemiya C., Jansen G., Sabourin L., Baird S., Neville C.E.,
RA Wormskamp N., Segers B., Batzer M., Lamerdin J., de Jong P.J., Wieringa B.,
RA Korneluk R.G.;
RT "Structure and genomic sequence of the myotonic dystrophy (DM kinase)
RT gene.";
RL Hum. Mol. Genet. 2:299-304(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 7; 8; 9; 10; 11 AND 12), AND
RP VARIANT VAL-423.
RX PubMed=8469976; DOI=10.1126/science.8469976;
RA Fu Y.-H., Friedman D.L., Richards S., Pearlman J.A., Gibbs R.A.,
RA Pizzuti A., Ashizawa T., Perryman M.B., Scarlato G., Fenwick R.G. Jr.,
RA Caskey C.T.;
RT "Decreased expression of myotonin-protein kinase messenger RNA and protein
RT in adult form of myotonic dystrophy.";
RL Science 260:235-238(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC TISSUE=Muscle;
RX PubMed=8076686; DOI=10.1016/0014-5793(94)00808-6;
RA Sasagawa N., Sorimachi H., Maruyama K., Arahata K., Ishiura S., Suzuki K.;
RT "Expression of a novel human myotonin protein kinase (MtPK) cDNA clone
RT which encodes a protein with a thymopoietin-like domain in COS cells.";
RL FEBS Lett. 351:22-26(1994).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 7).
RX PubMed=20843780; DOI=10.1093/nar/gkq750;
RA Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R.,
RA Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M.,
RA Speed T.P., Scharfe C.;
RT "Identification of rare DNA variants in mitochondrial disorders with
RT improved array-based sequencing.";
RL Nucleic Acids Res. 39:44-58(2011).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7).
RC TISSUE=Fetal brain;
RX PubMed=24722188; DOI=10.1038/ncomms4650;
RA Corominas R., Yang X., Lin G.N., Kang S., Shen Y., Ghamsari L., Broly M.,
RA Rodriguez M., Tam S., Wanamaker S.A., Fan C., Yi S., Tasan M., Lemmens I.,
RA Kuang X., Zhao N., Malhotra D., Michaelson J.J., Vacic V., Calderwood M.A.,
RA Roth F.P., Tavernier J., Horvath S., Salehi-Ashtiani K., Korkin D.,
RA Sebat J., Hill D.E., Hao T., Vidal M., Iakoucheva L.M.;
RT "Protein interaction network of alternatively spliced isoforms from brain
RT links genetic risk factors for autism.";
RL Nat. Commun. 5:3650-3650(2014).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 43-629 (ISOFORM 2), INVOLVEMENT IN DM1, AND
RP VARIANT VAL-423.
RX PubMed=1310900; DOI=10.1016/0092-8674(92)90154-5;
RA Brook J.D., McCurrach M., Harley H.G., Buckler A.J., Church D.,
RA Aburatani H., Hunter K., Stanton V.P., Thirion J.-P., Hudson T., Sohn R.,
RA Zemelman B., Snell R.G., Rundle S.A., Crow S., Davies J., Shelbourne P.,
RA Buxton J., Jones C., Juvonen V., Johnson K., Harper P.S., Shaw D.J.,
RA Housman D.E.;
RT "Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG)
RT repeat at the 3' end of a transcript encoding a protein kinase family
RT member.";
RL Cell 68:799-808(1992).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 550-619 (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=7488138; DOI=10.1006/bbrc.1995.2649;
RA Gennarelli M., Lucarelli M., Zelano G., Pizzuti A., Novelli G.,
RA Dallapiccola B.;
RT "Different expression of the myotonin protein kinase gene in discrete areas
RT of human brain.";
RL Biochem. Biophys. Res. Commun. 216:489-494(1995).
RN [12]
RP ALTERNATIVE SPLICING, AND INVOLVEMENT IN DM1.
RC TISSUE=Brain, and Heart;
RX PubMed=1302022; DOI=10.1038/ng0792-261;
RA Jansen G., Mahadevan M.S., Amemiya C., Wormskamp N., Segers B.,
RA Hendriks W., O'Hoy K., Baird S., Sabourin L., Lennon G., Jap P.L., Iles D.,
RA Coerwinkel M., Hofker M., Carrano A.V., de Jong P.J., Korneluk R.G.,
RA Wieringa B.;
RT "Characterization of the myotonic dystrophy region predicts multiple
RT protein isoform-encoding mRNAs.";
RL Nat. Genet. 1:261-266(1992).
RN [13]
RP INTERACTION WITH HSPB2, AND ACTIVITY REGULATION.
RC TISSUE=Muscle;
RX PubMed=9490724; DOI=10.1083/jcb.140.5.1113;
RA Suzuki A., Sugiyama Y., Hayashi Y., Nyu-i N., Yoshida M., Nonaka I.,
RA Ishiura S., Arahata K., Ohno S.;
RT "MKBP, a novel member of the small heat shock protein family, binds and
RT activates the myotonic dystrophy protein kinase.";
RL J. Cell Biol. 140:1113-1124(1998).
RN [14]
RP FUNCTION, ACTIVITY REGULATION, HOMODIMERIZATION, SUBCELLULAR LOCATION, AND
RP PROTEOLYTIC PROCESSING.
RX PubMed=10913253; DOI=10.1021/bi992142f;
RA Bush E.W., Helmke S.M., Birnbaum R.A., Perryman M.B.;
RT "Myotonic dystrophy protein kinase domains mediate localization,
RT oligomerization, novel catalytic activity, and autoinhibition.";
RL Biochemistry 39:8480-8490(2000).
RN [15]
RP INTERACTION WITH RAC1, PHOSPHORYLATION BY RAF1, AND ACTIVITY REGULATION.
RX PubMed=10869570; DOI=10.1016/s0014-5793(00)01692-6;
RA Shimizu M., Wang W., Walch E.T., Dunne P.W., Epstein H.F.;
RT "Rac-1 and Raf-1 kinases, components of distinct signaling pathways,
RT activate myotonic dystrophy protein kinase.";
RL FEBS Lett. 475:273-277(2000).
RN [16]
RP ALTERNATIVE SPLICING (ISOFORMS 1; 2; 3; 4; 5 AND 6).
RX PubMed=10699184; DOI=10.1093/hmg/9.4.605;
RA Groenen P.J.T.A., Wansink D.G., Coerwinkel M., van den Broek W., Jansen G.,
RA Wieringa B.;
RT "Constitutive and regulated modes of splicing produce six major myotonic
RT dystrophy protein kinase (DMPK) isoforms with distinct properties.";
RL Hum. Mol. Genet. 9:605-616(2000).
RN [17]
RP FUNCTION IN PHOSPHORYLATION OF FXYD1/PLM.
RX PubMed=10811636; DOI=10.1074/jbc.m000899200;
RA Mounsey J.P., John J.E. III, Helmke S.M., Bush E.W., Gilbert J.,
RA Roses A.D., Perryman M.B., Jones L.R., Moorman J.R.;
RT "Phospholemman is a substrate for myotonic dystrophy protein kinase.";
RL J. Biol. Chem. 275:23362-23367(2000).
RN [18]
RP FUNCTION IN PHOSPHORYLATION OF PPP1R12A.
RX PubMed=11287000; DOI=10.1016/s0014-5793(01)02283-9;
RA Muranyi A., Zhang R., Liu F., Hirano K., Ito M., Epstein H.F.,
RA Hartshorne D.J.;
RT "Myotonic dystrophy protein kinase phosphorylates the myosin phosphatase
RT targeting subunit and inhibits myosin phosphatase activity.";
RL FEBS Lett. 493:80-84(2001).
RN [19]
RP HOMODIMERIZATION, AND ACTIVITY REGULATION.
RX PubMed=12832055; DOI=10.1016/s0014-5793(03)00601-x;
RA Zhang R., Epstein H.F.;
RT "Homodimerization through coiled-coil regions enhances activity of the
RT myotonic dystrophy protein kinase.";
RL FEBS Lett. 546:281-287(2003).
RN [20]
RP FUNCTION IN PHOSPHORYLATION OF PLN, MUTAGENESIS OF LYS-100, AND INTERACTION
RP WITH PLN.
RX PubMed=15598648; DOI=10.1074/jbc.m412845200;
RA Kaliman P., Catalucci D., Lam J.T., Kondo R., Gutierrez J.C., Reddy S.,
RA Palacin M., Zorzano A., Chien K.R., Ruiz-Lozano P.;
RT "Myotonic dystrophy protein kinase phosphorylates phospholamban and
RT regulates calcium uptake in cardiomyocyte sarcoplasmic reticulum.";
RL J. Biol. Chem. 280:8016-8021(2005).
RN [21]
RP ALTERNATIVE SPLICING, AND SUBCELLULAR LOCATION.
RX PubMed=15684391; DOI=10.1128/mcb.25.4.1402-1414.2005;
RA van Herpen R.E., Oude Ophuis R.J., Wijers M., Bennink M.B.,
RA van de Loo F.A., Fransen J., Wieringa B., Wansink D.G.;
RT "Divergent mitochondrial and endoplasmic reticulum association of DMPK
RT splice isoforms depends on unique sequence arrangements in tail anchors.";
RL Mol. Cell. Biol. 25:1402-1414(2005).
RN [22]
RP INVOLVEMENT IN DM1.
RX PubMed=19514047; DOI=10.1002/ajmg.a.32987;
RA Musova Z., Mazanec R., Krepelova A., Ehler E., Vales J., Jaklova R.,
RA Prochazka T., Koukal P., Marikova T., Kraus J., Havlovicova M.,
RA Sedlacek Z.;
RT "Highly unstable sequence interruptions of the CTG repeat in the myotonic
RT dystrophy gene.";
RL Am. J. Med. Genet. A 149:1365-1374(2009).
RN [23]
RP FUNCTION IN PHOSPHORYLATION OF PPP1R12A.
RX PubMed=21457715; DOI=10.1016/j.febslet.2011.03.054;
RA Tan I., Lai J., Yong J., Li S.F., Leung T.;
RT "Chelerythrine perturbs lamellar actomyosin filaments by selective
RT inhibition of myotonic dystrophy kinase-related Cdc42-binding kinase.";
RL FEBS Lett. 585:1260-1268(2011).
RN [24]
RP FUNCTION IN NUCLEAR ENVELOPE STABILITY, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH LMNA.
RX PubMed=21949239; DOI=10.1074/jbc.m111.241455;
RA Harmon E.B., Harmon M.L., Larsen T.D., Yang J., Glasford J.W.,
RA Perryman M.B.;
RT "Myotonic dystrophy protein kinase is critical for nuclear envelope
RT integrity.";
RL J. Biol. Chem. 286:40296-40306(2011).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 460-537, AND COILED-COIL DOMAIN.
RX PubMed=15583383; DOI=10.1107/s0907444904026873;
RA Garcia P., Marino M., Mayans O.;
RT "Crystallization and preliminary X-ray analysis of the coiled-coil domain
RT of dystrophia myotonica kinase.";
RL Acta Crystallogr. D 60:2336-2339(2004).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 460-537, SUBUNIT, AND COILED-COIL
RP DOMAIN.
RX PubMed=16770013; DOI=10.1096/fj.05-5262com;
RA Garcia P., Ucurum Z., Bucher R., Svergun D.I., Huber T., Lustig A.,
RA Konarev P.V., Marino M., Mayans O.;
RT "Molecular insights into the self-assembly mechanism of dystrophia
RT myotonica kinase.";
RL FASEB J. 20:1142-1151(2006).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 11-430 IN COMPLEX WITH INHIBITOR
RP BIM-8, AND SUBUNIT.
RX PubMed=19309729; DOI=10.1002/pro.82;
RA Elkins J.M., Amos A., Niesen F.H., Pike A.C.W., Fedorov O., Knapp S.;
RT "Structure of dystrophia myotonica protein kinase.";
RL Protein Sci. 18:782-791(2009).
RN [28]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-428.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Non-receptor serine/threonine protein kinase which is
CC necessary for the maintenance of skeletal muscle structure and
CC function. May play a role in myocyte differentiation and survival by
CC regulating the integrity of the nuclear envelope and the expression of
CC muscle-specific genes. May also phosphorylate PPP1R12A and inhibit the
CC myosin phosphatase activity to regulate myosin phosphorylation. Also
CC critical to the modulation of cardiac contractility and to the
CC maintenance of proper cardiac conduction activity probably through the
CC regulation of cellular calcium homeostasis. Phosphorylates PLN, a
CC regulator of calcium pumps and may regulate sarcoplasmic reticulum
CC calcium uptake in myocytes. May also phosphorylate FXYD1/PLM which is
CC able to induce chloride currents. May also play a role in synaptic
CC plasticity. {ECO:0000269|PubMed:10811636, ECO:0000269|PubMed:10913253,
CC ECO:0000269|PubMed:11287000, ECO:0000269|PubMed:15598648,
CC ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:21949239}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Coiled-coil-mediated oligomerization enhances the
CC catalytic activity. Proteolytic processing of the C-terminus may
CC release the protein from membranes and constitute a mean to regulate
CC the enzyme. May be regulated by HSPB2, RAC1, RAF1 and G-protein second
CC messengers. {ECO:0000269|PubMed:10869570, ECO:0000269|PubMed:10913253,
CC ECO:0000269|PubMed:12832055, ECO:0000269|PubMed:9490724}.
CC -!- SUBUNIT: Homodimer; homodimerization stimulates the kinase activity.
CC Interacts with HSPB2; may enhance DMPK kinase activity. Interacts with
CC PLN; phosphorylates PLN. May interact with RAC1; may regulate DMPK
CC kinase activity. Interacts with LMNA; may regulate nuclear envelope
CC stability. {ECO:0000269|PubMed:10869570, ECO:0000269|PubMed:15598648,
CC ECO:0000269|PubMed:16770013, ECO:0000269|PubMed:19309729,
CC ECO:0000269|PubMed:21949239, ECO:0000269|PubMed:9490724}.
CC -!- INTERACTION:
CC Q09013; P54253: ATXN1; NbExp=5; IntAct=EBI-692774, EBI-930964;
CC Q09013; P26678: PLN; NbExp=4; IntAct=EBI-692774, EBI-692836;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Single-pass type IV membrane protein {ECO:0000250}; Cytoplasmic side
CC {ECO:0000250}. Nucleus outer membrane {ECO:0000305}; Single-pass type
CC IV membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC Mitochondrion outer membrane {ECO:0000305}; Single-pass type IV
CC membrane protein {ECO:0000305}. Sarcoplasmic reticulum membrane
CC {ECO:0000250}. Cell membrane {ECO:0000250}. Cytoplasm, cytosol
CC {ECO:0000250}. Note=Localizes to sarcoplasmic reticulum membranes of
CC cardiomyocytes. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion membrane.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Mitochondrion membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=12;
CC Name=1; Synonyms=DMPK A;
CC IsoId=Q09013-9; Sequence=Displayed;
CC Name=2; Synonyms=DMPK B;
CC IsoId=Q09013-11; Sequence=VSP_042101;
CC Name=3; Synonyms=DMPK C;
CC IsoId=Q09013-16; Sequence=VSP_042104;
CC Name=4; Synonyms=DMPK D;
CC IsoId=Q09013-15; Sequence=VSP_042101, VSP_042104;
CC Name=5; Synonyms=DMPK E;
CC IsoId=Q09013-10; Sequence=VSP_042102, VSP_042103;
CC Name=6; Synonyms=DMPK F;
CC IsoId=Q09013-12; Sequence=VSP_042101, VSP_042102, VSP_042103;
CC Name=7;
CC IsoId=Q09013-1; Sequence=VSP_042099;
CC Name=8;
CC IsoId=Q09013-2; Sequence=VSP_042098;
CC Name=9;
CC IsoId=Q09013-5; Sequence=VSP_042099, VSP_042100;
CC Name=10;
CC IsoId=Q09013-6; Sequence=VSP_042099, VSP_042101;
CC Name=11;
CC IsoId=Q09013-7; Sequence=VSP_042099, VSP_042105;
CC Name=12;
CC IsoId=Q09013-8; Sequence=VSP_042099, VSP_042102, VSP_042103;
CC -!- TISSUE SPECIFICITY: Most isoforms are expressed in many tissues
CC including heart, skeletal muscle, liver and brain, except for isoform 2
CC which is only found in the heart and skeletal muscle, and isoform 14
CC which is only found in the brain, with high levels in the striatum,
CC cerebellar cortex and pons. {ECO:0000269|PubMed:7488138}.
CC -!- DOMAIN: The coiled coil domain is required for homodimerization and
CC regulates the enzymatic activity.
CC -!- PTM: Phosphorylated. Autophosphorylates. Phosphorylation by RAF1 may
CC result in activation of DMPK. {ECO:0000269|PubMed:10869570}.
CC -!- PTM: Proteolytic processing of the C-terminus may remove the
CC transmembrane domain and release the kinase from membranes stimulating
CC its activity. {ECO:0000269|PubMed:10913253}.
CC -!- DISEASE: Dystrophia myotonica 1 (DM1) [MIM:160900]: A muscular disorder
CC characterized by myotonia, muscle wasting in the distal extremities,
CC cataract, hypogonadism, defective endocrine functions, male baldness
CC and cardiac arrhythmias. {ECO:0000269|PubMed:1302022,
CC ECO:0000269|PubMed:1310900, ECO:0000269|PubMed:1546326,
CC ECO:0000269|PubMed:19514047}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. The causative mutation is
CC a CTG expansion in the 3'-UTR of the DMPK gene. A length exceeding 50
CC CTG repeats is pathogenic, while normal individuals have 5 to 37
CC repeats. Intermediate alleles with 35-49 triplets are not disease-
CC causing but show instability in intergenerational transmissions.
CC Disease severity varies with the number of repeats: mildly affected
CC persons have 50 to 150 repeats, patients with classic DM have 100 to
CC 1,000 repeats, and those with congenital onset can have more than 2,000
CC repeats. {ECO:0000269|PubMed:1310900, ECO:0000269|PubMed:19514047}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. DMPK subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA64884.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAA87583.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; M87312; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; L19268; AAA36206.1; -; mRNA.
DR EMBL; L19266; AAA36205.1; -; Genomic_DNA.
DR EMBL; L08835; AAC14449.1; -; Genomic_DNA.
DR EMBL; L08835; AAC14451.1; -; Genomic_DNA.
DR EMBL; L08835; AAC14448.1; -; Genomic_DNA.
DR EMBL; L08835; AAC14450.1; -; Genomic_DNA.
DR EMBL; L00727; AAA75235.1; -; Genomic_DNA.
DR EMBL; L00727; AAA75236.1; -; Genomic_DNA.
DR EMBL; L00727; AAA75237.1; -; Genomic_DNA.
DR EMBL; L00727; AAA75238.1; -; Genomic_DNA.
DR EMBL; L00727; AAA75239.1; -; Genomic_DNA.
DR EMBL; L00727; AAA75240.1; -; Genomic_DNA.
DR EMBL; S72883; AAB31800.1; -; mRNA.
DR EMBL; HQ205626; ADP91337.1; -; Genomic_DNA.
DR EMBL; HQ205627; ADP91341.1; -; Genomic_DNA.
DR EMBL; HQ205628; ADP91345.1; -; Genomic_DNA.
DR EMBL; HQ205629; ADP91349.1; -; Genomic_DNA.
DR EMBL; HQ205630; ADP91353.1; -; Genomic_DNA.
DR EMBL; HQ205631; ADP91357.1; -; Genomic_DNA.
DR EMBL; HQ205632; ADP91361.1; -; Genomic_DNA.
DR EMBL; HQ205633; ADP91365.1; -; Genomic_DNA.
DR EMBL; HQ205634; ADP91369.1; -; Genomic_DNA.
DR EMBL; HQ205635; ADP91373.1; -; Genomic_DNA.
DR EMBL; HQ205636; ADP91377.1; -; Genomic_DNA.
DR EMBL; HQ205637; ADP91381.1; -; Genomic_DNA.
DR EMBL; HQ205638; ADP91385.1; -; Genomic_DNA.
DR EMBL; HQ205639; ADP91389.1; -; Genomic_DNA.
DR EMBL; HQ205640; ADP91393.1; -; Genomic_DNA.
DR EMBL; HQ205641; ADP91397.1; -; Genomic_DNA.
DR EMBL; HQ205642; ADP91401.1; -; Genomic_DNA.
DR EMBL; HQ205643; ADP91405.1; -; Genomic_DNA.
DR EMBL; HQ205644; ADP91409.1; -; Genomic_DNA.
DR EMBL; HQ205645; ADP91413.1; -; Genomic_DNA.
DR EMBL; HQ205646; ADP91417.1; -; Genomic_DNA.
DR EMBL; HQ205647; ADP91421.1; -; Genomic_DNA.
DR EMBL; HQ205648; ADP91425.1; -; Genomic_DNA.
DR EMBL; HQ205649; ADP91429.1; -; Genomic_DNA.
DR EMBL; HQ205650; ADP91433.1; -; Genomic_DNA.
DR EMBL; HQ205651; ADP91437.1; -; Genomic_DNA.
DR EMBL; HQ205652; ADP91441.1; -; Genomic_DNA.
DR EMBL; HQ205653; ADP91445.1; -; Genomic_DNA.
DR EMBL; HQ205654; ADP91449.1; -; Genomic_DNA.
DR EMBL; HQ205655; ADP91453.1; -; Genomic_DNA.
DR EMBL; HQ205656; ADP91457.1; -; Genomic_DNA.
DR EMBL; HQ205657; ADP91461.1; -; Genomic_DNA.
DR EMBL; HQ205658; ADP91465.1; -; Genomic_DNA.
DR EMBL; HQ205659; ADP91469.1; -; Genomic_DNA.
DR EMBL; HQ205660; ADP91473.1; -; Genomic_DNA.
DR EMBL; HQ205661; ADP91477.1; -; Genomic_DNA.
DR EMBL; HQ205662; ADP91481.1; -; Genomic_DNA.
DR EMBL; HQ205663; ADP91485.1; -; Genomic_DNA.
DR EMBL; HQ205664; ADP91489.1; -; Genomic_DNA.
DR EMBL; HQ205665; ADP91493.1; -; Genomic_DNA.
DR EMBL; KJ534827; AHW56467.1; -; mRNA.
DR EMBL; CH471126; EAW57380.1; -; Genomic_DNA.
DR EMBL; CH471126; EAW57382.1; -; Genomic_DNA.
DR EMBL; BC062553; AAH62553.1; -; mRNA.
DR EMBL; M94203; AAA64884.1; ALT_FRAME; mRNA.
DR EMBL; U46546; AAA87583.1; ALT_SEQ; mRNA.
DR CCDS; CCDS12674.1; -. [Q09013-9]
DR CCDS; CCDS46117.1; -. [Q09013-15]
DR CCDS; CCDS46118.1; -. [Q09013-11]
DR CCDS; CCDS46119.1; -. [Q09013-1]
DR CCDS; CCDS74400.1; -. [Q09013-12]
DR PIR; B49364; B49364.
DR RefSeq; NP_001075029.1; NM_001081560.2. [Q09013-11]
DR RefSeq; NP_001075031.1; NM_001081562.2. [Q09013-15]
DR RefSeq; NP_001075032.1; NM_001081563.2. [Q09013-1]
DR RefSeq; NP_001275694.1; NM_001288765.1.
DR RefSeq; NP_004400.4; NM_004409.4. [Q09013-9]
DR PDB; 1WT6; X-ray; 1.60 A; A/B/D=460-537.
DR PDB; 2VD5; X-ray; 2.80 A; A/B=11-420.
DR PDBsum; 1WT6; -.
DR PDBsum; 2VD5; -.
DR AlphaFoldDB; Q09013; -.
DR SASBDB; Q09013; -.
DR SMR; Q09013; -.
DR BioGRID; 108100; 26.
DR IntAct; Q09013; 17.
DR MINT; Q09013; -.
DR STRING; 9606.ENSP00000345997; -.
DR BindingDB; Q09013; -.
DR ChEMBL; CHEMBL5320; -.
DR DrugBank; DB01946; Bisindolylmaleimide VIII.
DR DrugCentral; Q09013; -.
DR GuidetoPHARMACOLOGY; 1505; -.
DR iPTMnet; Q09013; -.
DR PhosphoSitePlus; Q09013; -.
DR BioMuta; DMPK; -.
DR DMDM; 363548519; -.
DR REPRODUCTION-2DPAGE; Q09013; -.
DR EPD; Q09013; -.
DR jPOST; Q09013; -.
DR MassIVE; Q09013; -.
DR MaxQB; Q09013; -.
DR PaxDb; Q09013; -.
DR PeptideAtlas; Q09013; -.
DR PRIDE; Q09013; -.
DR ProteomicsDB; 58699; -. [Q09013-9]
DR ProteomicsDB; 58700; -. [Q09013-1]
DR ProteomicsDB; 58701; -. [Q09013-10]
DR ProteomicsDB; 58702; -. [Q09013-11]
DR ProteomicsDB; 58703; -. [Q09013-12]
DR ProteomicsDB; 58704; -. [Q09013-15]
DR ProteomicsDB; 58705; -. [Q09013-16]
DR ProteomicsDB; 58706; -. [Q09013-2]
DR ProteomicsDB; 58707; -. [Q09013-5]
DR ProteomicsDB; 58708; -. [Q09013-6]
DR ProteomicsDB; 58709; -. [Q09013-7]
DR ProteomicsDB; 58710; -. [Q09013-8]
DR TopDownProteomics; Q09013-11; -. [Q09013-11]
DR Antibodypedia; 2044; 301 antibodies from 30 providers.
DR DNASU; 1760; -.
DR Ensembl; ENST00000291270.9; ENSP00000291270.4; ENSG00000104936.20. [Q09013-9]
DR Ensembl; ENST00000343373.10; ENSP00000345997.4; ENSG00000104936.20. [Q09013-16]
DR Ensembl; ENST00000354227.9; ENSP00000346168.5; ENSG00000104936.20. [Q09013-12]
DR Ensembl; ENST00000447742.6; ENSP00000413417.1; ENSG00000104936.20. [Q09013-11]
DR Ensembl; ENST00000458663.6; ENSP00000401753.1; ENSG00000104936.20. [Q09013-15]
DR Ensembl; ENST00000683086.1; ENSP00000508381.1; ENSG00000104936.20. [Q09013-10]
DR GeneID; 1760; -.
DR KEGG; hsa:1760; -.
DR MANE-Select; ENST00000291270.9; ENSP00000291270.4; NM_004409.5; NP_004400.4.
DR UCSC; uc002pdd.3; human. [Q09013-9]
DR CTD; 1760; -.
DR DisGeNET; 1760; -.
DR GeneCards; DMPK; -.
DR GeneReviews; DMPK; -.
DR HGNC; HGNC:2933; DMPK.
DR HPA; ENSG00000104936; Tissue enhanced (skeletal).
DR MalaCards; DMPK; -.
DR MIM; 160900; phenotype.
DR MIM; 605377; gene.
DR neXtProt; NX_Q09013; -.
DR OpenTargets; ENSG00000104936; -.
DR Orphanet; 589821; Congenital-onset Steinert myotonic dystrophy.
DR PharmGKB; PA27380; -.
DR VEuPathDB; HostDB:ENSG00000104936; -.
DR eggNOG; KOG0612; Eukaryota.
DR GeneTree; ENSGT00940000162019; -.
DR HOGENOM; CLU_000288_140_4_1; -.
DR InParanoid; Q09013; -.
DR OMA; EYFEFPP; -.
DR OrthoDB; 1366218at2759; -.
DR TreeFam; TF105337; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; Q09013; -.
DR Reactome; R-HSA-5578775; Ion homeostasis.
DR SignaLink; Q09013; -.
DR SIGNOR; Q09013; -.
DR BioGRID-ORCS; 1760; 11 hits in 1114 CRISPR screens.
DR ChiTaRS; DMPK; human.
DR EvolutionaryTrace; Q09013; -.
DR GeneWiki; Myotonin-protein_kinase; -.
DR GenomeRNAi; 1760; -.
DR Pharos; Q09013; Tchem.
DR PRO; PR:Q09013; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q09013; protein.
DR Bgee; ENSG00000104936; Expressed in apex of heart and 166 other tissues.
DR ExpressionAtlas; Q09013; baseline and differential.
DR Genevisible; Q09013; HS.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; ISS:UniProtKB.
DR GO; GO:0005640; C:nuclear outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017020; F:myosin phosphatase regulator activity; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0010657; P:muscle cell apoptotic process; IDA:UniProtKB.
DR GO; GO:0006998; P:nuclear envelope organization; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0014853; P:regulation of excitatory postsynaptic membrane potential involved in skeletal muscle contraction; IEA:Ensembl.
DR GO; GO:0008016; P:regulation of heart contraction; IDA:UniProtKB.
DR GO; GO:0010830; P:regulation of myotube differentiation; ISS:UniProtKB.
DR GO; GO:0014722; P:regulation of skeletal muscle contraction by calcium ion signaling; IBA:GO_Central.
DR GO; GO:0002028; P:regulation of sodium ion transport; IEA:Ensembl.
DR GO; GO:0051823; P:regulation of synapse structural plasticity; IEA:Ensembl.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR014930; Myotonic_dystrophy_kinase_coil.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF08826; DMPK_coil; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cataract; Cell membrane;
KW Coiled coil; Cytoplasm; Endoplasmic reticulum; Kinase; Magnesium; Membrane;
KW Metal-binding; Mitochondrion; Mitochondrion outer membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Sarcoplasmic reticulum; Serine/threonine-protein kinase; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..629
FT /note="Myotonin-protein kinase"
FT /id="PRO_0000085924"
FT TOPO_DOM 1..590
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 591..611
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 612..629
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 71..339
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 340..415
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT COILED 457..536
FT /evidence="ECO:0000269|PubMed:15583383,
FT ECO:0000269|PubMed:16770013"
FT ACT_SITE 195
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 77..85
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 100
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 216
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 228
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 234
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..89
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000305"
FT /id="VSP_042098"
FT VAR_SEQ 1..53
FT /note="MSAEVRLRRLQQLVLDPGFLGLEPLLDLLLGVHQELGASELAQDKYVADFLQ
FT W -> MGGHFWPPEPYTVFMWGSPWEADSPRVKLRGREKGRQTEGGAFPLVSSALSGDP
FT RFFSPTTPP (in isoform 7, isoform 9, isoform 10, isoform 11
FT and isoform 12)"
FT /evidence="ECO:0000303|PubMed:1546326,
FT ECO:0000303|PubMed:24722188"
FT /id="VSP_042099"
FT VAR_SEQ 226..275
FT /note="Missing (in isoform 9)"
FT /evidence="ECO:0000305"
FT /id="VSP_042100"
FT VAR_SEQ 378..382
FT /note="Missing (in isoform 2, isoform 4, isoform 6 and
FT isoform 10)"
FT /evidence="ECO:0000303|PubMed:1310900,
FT ECO:0000303|PubMed:7905855, ECO:0000303|PubMed:8076686"
FT /id="VSP_042101"
FT VAR_SEQ 534..535
FT /note="AV -> GP (in isoform 5, isoform 6 and isoform 12)"
FT /evidence="ECO:0000305"
FT /id="VSP_042102"
FT VAR_SEQ 536..629
FT /note="Missing (in isoform 5, isoform 6 and isoform 12)"
FT /evidence="ECO:0000305"
FT /id="VSP_042103"
FT VAR_SEQ 550..629
FT /note="LDGPPAVAVGQCPLVGPGPMHRRHLLLPARVPRPGLSEALSLLLFAVVLSRA
FT AALGCIGLVAHAGQLTAVWRRPGAARAP -> MAPRPWLWASARWWGQAPCTAATCCSL
FT PGSLGLAYRRRFPCSCSPLFCLVPPPWAALGWWPTPANSPQSGAAQEPPALPEP (in
FT isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:8076686"
FT /id="VSP_042104"
FT VAR_SEQ 550..579
FT /note="Missing (in isoform 11)"
FT /evidence="ECO:0000305"
FT /id="VSP_042105"
FT VARIANT 423
FT /note="L -> V (in dbSNP:rs527221)"
FT /evidence="ECO:0000269|PubMed:1310900,
FT ECO:0000269|PubMed:7905855, ECO:0000269|PubMed:8469976,
FT ECO:0000269|PubMed:8499920"
FT /id="VAR_058334"
FT VARIANT 428
FT /note="L -> V (in a lung small cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040452"
FT MUTAGEN 100
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15598648"
FT CONFLICT 474
FT /note="A -> P (in Ref. 5; AAB31800)"
FT /evidence="ECO:0000305"
FT HELIX 12..15
FT /evidence="ECO:0007829|PDB:2VD5"
FT TURN 17..19
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 22..37
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 40..43
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 45..64
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:2VD5"
FT STRAND 71..79
FT /evidence="ECO:0007829|PDB:2VD5"
FT STRAND 84..90
FT /evidence="ECO:0007829|PDB:2VD5"
FT TURN 91..93
FT /evidence="ECO:0007829|PDB:2VD5"
FT STRAND 96..103
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 104..110
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 116..125
FT /evidence="ECO:0007829|PDB:2VD5"
FT TURN 128..130
FT /evidence="ECO:0007829|PDB:2VD5"
FT STRAND 134..139
FT /evidence="ECO:0007829|PDB:2VD5"
FT STRAND 141..148
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 156..163
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 169..188
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 198..200
FT /evidence="ECO:0007829|PDB:2VD5"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:2VD5"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 235..237
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 240..247
FT /evidence="ECO:0007829|PDB:2VD5"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 258..273
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 283..291
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 293..296
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 308..315
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 321..323
FT /evidence="ECO:0007829|PDB:2VD5"
FT TURN 325..329
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 330..334
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 337..339
FT /evidence="ECO:0007829|PDB:2VD5"
FT STRAND 378..382
FT /evidence="ECO:0007829|PDB:2VD5"
FT TURN 385..387
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 398..400
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 412..414
FT /evidence="ECO:0007829|PDB:2VD5"
FT HELIX 468..528
FT /evidence="ECO:0007829|PDB:1WT6"
SQ SEQUENCE 629 AA; 69385 MW; 46783ED4AE65B493 CRC64;
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
