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 27-MAR-2024, entry version 225. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 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; 33. 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; 9606-ENSP00000345997; -. DR PeptideAtlas; 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 Pumba; Q09013; -. DR TopDownProteomics; Q09013-11; -. [Q09013-11] DR Antibodypedia; 2044; 319 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 AGR; HGNC:2933; -. DR CTD; 1760; -. DR DisGeNET; 1760; -. DR GeneCards; DMPK; -. DR GeneReviews; DMPK; -. DR HGNC; HGNC:2933; DMPK. DR HPA; ENSG00000104936; Low tissue specificity. DR MalaCards; DMPK; -. DR MIM; 160900; phenotype. DR MIM; 605377; gene. DR neXtProt; NX_Q09013; -. DR OpenTargets; ENSG00000104936; -. DR Orphanet; 589830; Adult-onset Steinert myotonic dystrophy. DR Orphanet; 589824; Childhood-onset Steinert myotonic dystrophy. DR Orphanet; 589821; Congenital-onset Steinert myotonic dystrophy. DR Orphanet; 589827; Juvenile-onset Steinert myotonic dystrophy. DR Orphanet; 589833; Late-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; YFEFPPG; -. DR OrthoDB; 988261at2759; -. 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; 17 hits in 1192 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 168 other cell types or tissues. DR ExpressionAtlas; Q09013; baseline and differential. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0005741; C: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:intracellular calcium ion homeostasis; ISS:UniProtKB. DR GO; GO:0010657; P:muscle cell apoptotic process; IDA:UniProtKB. DR GO; GO:0006998; P:nuclear envelope organization; IMP:UniProtKB. 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 CDD; cd05597; STKc_DMPK_like; 1. DR Gene3D; 1.20.5.340; -; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR22988:SF72; LOW QUALITY PROTEIN: MYOTONIN-PROTEIN KINASE; 1. DR PANTHER; PTHR22988; MYOTONIC DYSTROPHY S/T KINASE-RELATED; 1. 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; Protein kinase-like (PK-like); 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. DR Genevisible; Q09013; HS. 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 //