ID ACTS_HUMAN Reviewed; 377 AA. AC P68133; P02568; P99020; Q5T8M9; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 27-MAR-2024, entry version 190. DE RecName: Full=Actin, alpha skeletal muscle; DE EC=3.6.4.- {ECO:0000250|UniProtKB:P68137}; DE AltName: Full=Alpha-actin-1; DE Contains: DE RecName: Full=Actin, alpha skeletal muscle, intermediate form; DE Flags: Precursor; GN Name=ACTA1; Synonyms=ACTA; 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]. RC TISSUE=Skeletal muscle; RX PubMed=6190133; DOI=10.1093/nar/11.11.3503; RA Hanauer A., Levin M., Heilig R., Daegelen D., Kahn A., Mandel J.-L.; RT "Isolation and characterization of cDNA clones for human skeletal muscle RT alpha actin."; RL Nucleic Acids Res. 11:3503-3516(1983). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2907503; DOI=10.1016/0888-7543(88)90123-1; RA Taylor A., Erba H.P., Muscat G.E.O., Kedes L.; RT "Nucleotide sequence and expression of the human skeletal alpha-actin gene: RT evolution of functional regulatory domains."; RL Genomics 3:323-336(1988). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CMYP2A ARG-17; TYR-42; SER-117; RP VAL-134; LEU-165; ASP-184; CYS-185; HIS-258; LEU-265; LYS-282; GLY-288 AND RP PHE-372, AND VARIANTS CMYP2B PRO-96 AND VAL-261. RX PubMed=10508519; DOI=10.1038/13837; RA Nowak K.J., Wattanasirichaigoon D., Goebel H.H., Wilce M., Pelin K., RA Donner K., Jacob R.L., Hubner C., Oexle K., Anderson J.R., Verity C.M., RA North K.N.; RT "Mutations in the skeletal muscle alpha-actin gene in patients with actin RT myopathy and nemaline myopathy."; RL Nat. Genet. 23:208-212(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skeletal muscle; 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 [8] RP INTERACTION WITH TTID. RX PubMed=10958653; DOI=10.1093/hmg/9.14.2141; RA Hauser M.A., Horrigan S.K., Salmikangas P., Torian U.M., Viles K.D., RA Dancel R., Tim R.W., Taivainen A., Bartoloni L., Gilchrist J.M., RA Stajich J.M., Gaskell P.C., Gilbert J.R., Vance J.M., Pericak-Vance M.A., RA Carpen O., Westbrook C.A., Speer M.C.; RT "Myotilin is mutated in limb girdle muscular dystrophy 1A."; RL Hum. Mol. Genet. 9:2141-2147(2000). RN [9] RP INTERACTION WITH USP25. RX PubMed=16501887; DOI=10.1007/s00018-005-5533-1; RA Bosch-Comas A., Lindsten K., Gonzalez-Duarte R., Masucci M.G., Marfany G.; RT "The ubiquitin-specific protease USP25 interacts with three sarcomeric RT proteins."; RL Cell. Mol. Life Sci. 63:723-734(2006). RN [10] RP CROSS-LINK BY V.CHOLERAE TOXIN RTXA (MICROBIAL INFECTION). RX PubMed=19015515; DOI=10.1073/pnas.0808082105; RA Kudryashov D.S., Durer Z.A., Ytterberg A.J., Sawaya M.R., Pashkov I., RA Prochazkova K., Yeates T.O., Loo R.R., Loo J.A., Satchell K.J., Reisler E.; RT "Connecting actin monomers by iso-peptide bond is a toxicity mechanism of RT the Vibrio cholerae MARTX toxin."; RL Proc. Natl. Acad. Sci. U.S.A. 105:18537-18542(2008). RN [11] RP MALONYLATION AT LYS-63. RX PubMed=21908771; DOI=10.1074/mcp.m111.012658; RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y., He W., RA Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C., Dai J., RA Verdin E., Ye Y., Zhao Y.; RT "The first identification of lysine malonylation substrates and its RT regulatory enzyme."; RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011). RN [12] RP METHYLATION AT LYS-86, AND DEMETHYLATION BY ALKBH4. RX PubMed=23673617; DOI=10.1038/ncomms2863; RA Li M.M., Nilsen A., Shi Y., Fusser M., Ding Y.H., Fu Y., Liu B., Niu Y., RA Wu Y.S., Huang C.M., Olofsson M., Jin K.X., Lv Y., Xu X.Z., He C., RA Dong M.Q., Rendtlew Danielsen J.M., Klungland A., Yang Y.G.; RT "ALKBH4-dependent demethylation of actin regulates actomyosin dynamics."; RL Nat. Commun. 4:1832-1832(2013). RN [13] RP CROSS-LINK BY V.CHOLERAE TOXIN RTXA (MICROBIAL INFECTION). RX PubMed=26228148; DOI=10.1126/science.aab4090; RA Heisler D.B., Kudryashova E., Grinevich D.O., Suarez C., Winkelman J.D., RA Birukov K.G., Kotha S.R., Parinandi N.L., Vavylonis D., Kovar D.R., RA Kudryashov D.S.; RT "ACD toxin-produced actin oligomers poison formin-controlled actin RT polymerization."; RL Science 349:535-539(2015). RN [14] RP METHYLATION AT HIS-75. RX PubMed=30626964; DOI=10.1038/s41586-018-0821-8; RA Wilkinson A.W., Diep J., Dai S., Liu S., Ooi Y.S., Song D., Li T.M., RA Horton J.R., Zhang X., Liu C., Trivedi D.V., Ruppel K.M., RA Vilches-Moure J.G., Casey K.M., Mak J., Cowan T., Elias J.E., RA Nagamine C.M., Spudich J.A., Cheng X., Carette J.E., Gozani O.; RT "SETD3 is an actin histidine methyltransferase that prevents primary RT dystocia."; RL Nature 565:372-376(2019). RN [15] RP VARIANTS CMYP2A SER-117; MET-138; GLY-185; CYS-270 AND LEU-359. RX PubMed=11333380; DOI=10.1086/320605; RA Ilkovski B., Cooper S.T., Nowak K., Ryan M.M., Yang N., Schnell C., RA Durling H.J., Roddick L.G., Wilkinson I., Kornberg A.J., Collins K.J., RA Wallace G., Gunning P., Hardeman E.C., Laing N.G., North K.N.; RT "Nemaline myopathy caused by mutations in the muscle alpha-skeletal-actin RT gene."; RL Am. J. Hum. Genet. 68:1333-1343(2001). RN [16] RP REVIEW ON VARIANTS, AND INVOLVEMENT IN CMYP2B. RX PubMed=12921789; DOI=10.1016/s0960-8966(03)00101-9; RA Sparrow J.C., Nowak K.J., Durling H.J., Beggs A.H., Wallgren-Pettersson C., RA Romero N., Nonaka I., Laing N.G.; RT "Muscle disease caused by mutations in the skeletal muscle alpha-actin gene RT (ACTA1)."; RL Neuromuscul. Disord. 13:519-531(2003). RN [17] RP VARIANTS CMYP2A VAL-134 AND ARG-271. RX PubMed=11166164; DOI=10.1016/s0960-8966(00)00167-x; RA Jungbluth H., Sewry C.A., Brown S.C., Nowak K.J., Laing N.G., RA Wallgren-Pettersson C., Pelin K., Manzur A.Y., Mercuri E., Dubowitz V., RA Muntoni F.; RT "Mild phenotype of nemaline myopathy with sleep hypoventilation due to a RT mutation in the skeletal muscle alpha-actin (ACTA1) gene."; RL Neuromuscul. Disord. 11:35-40(2001). RN [18] RP VARIANTS CMYP2A LEU-37; LEU-40; TYR-42; ARG-43; ASN-66; LEU-75; ARG-75; RP LEU-77; ALA-79; LYS-85; ALA-136; ASP-148; GLY-181; ASP-184; GLY-185; RP SER-199; GLY-226; VAL-229; ILE-229; ARG-248; ASP-253; CYS-270; HIS-281; RP LYS-282; GLY-288 AND GLN-375. RX PubMed=15236405; DOI=10.1002/ana.20157; RA Agrawal P.B., Strickland C.D., Midgett C., Morales A., Newburger D.E., RA Poulos M.A., Tomczak K.K., Ryan M.M., Iannaccone S.T., Crawford T.O., RA Laing N.G., Beggs A.H.; RT "Heterogeneity of nemaline myopathy cases with skeletal muscle alpha-actin RT gene mutations."; RL Ann. Neurol. 56:86-96(2004). RN [19] RP VARIANTS CMYP2C PRO-223; VAL-294 AND SER-334. RX PubMed=15468086; DOI=10.1002/ana.20260; RA Laing N.G., Clarke N.F., Dye D.E., Liyanage K., Walker K.R., Kobayashi Y., RA Shimakawa S., Hagiwara T., Ouvrier R., Sparrow J.C., Nishino I., RA North K.N., Nonaka I.; RT "Actin mutations are one cause of congenital fibre type disproportion."; RL Ann. Neurol. 56:689-694(2004). RN [20] RP VARIANTS CMYP2A ILE-68; LYS-74; SER-117; MET-138; LEU-165; MET-165; RP GLY-185; CYS-270 AND LEU-359. RX PubMed=15198992; DOI=10.1093/hmg/ddh185; RA Ilkovski B., Nowak K.J., Domazetovska A., Maxwell A.L., Clement S., RA Davies K.E., Laing N.G., North K.N., Cooper S.T.; RT "Evidence for a dominant-negative effect in ACTA1 nemaline myopathy caused RT by abnormal folding, aggregation and altered polymerization of mutant actin RT isoforms."; RL Hum. Mol. Genet. 13:1727-1743(2004). RN [21] RP VARIANTS CMYP2A TYR-3 AND ALA-336. RX PubMed=15520409; DOI=10.1136/jmg.2004.020271; RA Kaindl A.M., Rueschendorf F., Krause S., Goebel H.-H., Koehler K., RA Becker C., Pongratz D., Mueller-Hoecker J., Nuernberg P., RA Stoltenburg-Didinger G., Lochmueller H., Huebner A.; RT "Missense mutations of ACTA1 cause dominant congenital myopathy with RT cores."; RL J. Med. Genet. 41:842-848(2004). RN [22] RP VARIANTS CMYP2A ASP-270 AND GLU-375. RX PubMed=15336687; DOI=10.1016/j.nmd.2004.05.016; RA Ohlsson M., Tajsharghi H., Darin N., Kyllerman M., Oldfors A.; RT "Follow-up of nemaline myopathy in two patients with novel mutations in the RT skeletal muscle alpha-actin gene (ACTA1)."; RL Neuromuscul. Disord. 14:471-475(2004). RN [23] RP VARIANT CMYP2A MET-165. RX PubMed=16427282; DOI=10.1016/j.nmd.2005.11.004; RA Hutchinson D.O., Charlton A., Laing N.G., Ilkovski B., North K.N.; RT "Autosomal dominant nemaline myopathy with intranuclear rods due to RT mutation of the skeletal muscle ACTA1 gene: clinical and pathological RT variability within a kindred."; RL Neuromuscul. Disord. 16:113-121(2006). RN [24] RP VARIANT CMYP2A GLU-338. RX PubMed=16945537; DOI=10.1016/j.nmd.2006.07.005; RA D'Amico A., Graziano C., Pacileo G., Petrini S., Nowak K.J., Boldrini R., RA Jacques A., Feng J.-J., Porfirio B., Sewry C.A., Santorelli F.M., RA Limongelli G., Bertini E., Laing N., Marston S.B.; RT "Fatal hypertrophic cardiomyopathy and nemaline myopathy associated with RT ACTA1 K336E mutation."; RL Neuromuscul. Disord. 16:548-552(2006). RN [25] RP CHARACTERIZATION OF VARIANT CMYP2C VAL-294. RX PubMed=17387733; DOI=10.1002/ana.21112; RA Clarke N.F., Ilkovski B., Cooper S., Valova V.A., Robinson P.J., Nonaka I., RA Feng J.-J., Marston S., North K.; RT "The pathogenesis of ACTA1-related congenital fiber type disproportion."; RL Ann. Neurol. 61:552-561(2007). RN [26] RP CHARACTERIZATION OF VARIANT CMYP2A MET-165. RX PubMed=17705262; DOI=10.1002/ana.21200; RA Domazetovska A., Ilkovski B., Kumar V., Valova V.A., Vandebrouck A., RA Hutchinson D.O., Robinson P.J., Cooper S.T., Sparrow J.C., Peckham M., RA North K.N.; RT "Intranuclear rod myopathy: molecular pathogenesis and mechanisms of RT weakness."; RL Ann. Neurol. 62:597-608(2007). RN [27] RP VARIANT CMYP2A ASN-328, AND CHARACTERIZATION OF VARIANT CMYP2A ASN-328. RX PubMed=22442437; DOI=10.1212/wnl.0b013e31824e8ebe; RA Jain R.K., Jayawant S., Squier W., Muntoni F., Sewry C.A., Manzur A., RA Quinlivan R., Lillis S., Jungbluth H., Sparrow J.C., Ravenscroft G., RA Nowak K.J., Memo M., Marston S.B., Laing N.G.; RT "Nemaline myopathy with stiffness and hypertonia associated with an ACTA1 RT mutation."; RL Neurology 78:1100-1103(2012). RN [28] RP VARIANT CMYP2A CYS-358. RX PubMed=23650303; DOI=10.1542/peds.2012-1139; RA Gatayama R., Ueno K., Nakamura H., Yanagi S., Ueda H., Yamagishi H., RA Yasui S.; RT "Nemaline myopathy with dilated cardiomyopathy in childhood."; RL Pediatrics 131:E1986-E1990(2013). RN [29] RP INVOLVEMENT IN SHPM, VARIANT SHPM ASP-197, CHARACTERIZATION OF VARIANT SHPM RP ASP-197, AND CHARACTERIZATION OF VARIANT CMYP2A GLY-288. RX PubMed=25938801; DOI=10.1001/jamaneurol.2015.37; RA Zukosky K., Meilleur K., Traynor B.J., Dastgir J., Medne L., Devoto M., RA Collins J., Rooney J., Zou Y., Yang M.L., Gibbs J.R., Meier M., RA Stetefeld J., Finkel R.S., Schessl J., Elman L., Felice K., Ferguson T.A., RA Ceyhan-Birsoy O., Beggs A.H., Tennekoon G., Johnson J.O., Boennemann C.G.; RT "Association of a Novel ACTA1 Mutation With a Dominant Progressive RT Scapuloperoneal Myopathy in an Extended Family."; RL JAMA Neurol. 72:689-698(2015). RN [30] RP VARIANTS CMYP2A ARG-72 AND VAL-116. RX PubMed=25635128; DOI=10.1136/jmedgenet-2014-102819; RA Chae J.H., Vasta V., Cho A., Lim B.C., Zhang Q., Eun S.H., Hahn S.H.; RT "Utility of next generation sequencing in genetic diagnosis of early onset RT neuromuscular disorders."; RL J. Med. Genet. 52:208-216(2015). RN [31] RP VARIANT CMYP2A SER-17. RX PubMed=29274205; DOI=10.1002/ajmg.a.38577; RA Ahmed A.A., Skaria P., Safina N.P., Thiffault I., Kats A., Taboada E., RA Habeebu S., Saunders C.; RT "Arthrogryposis and pterygia as lethal end manifestations of genetically RT defined congenital myopathies."; RL Am. J. Med. Genet. A 176:359-367(2018). CC -!- FUNCTION: Actins are highly conserved proteins that are involved in CC various types of cell motility and are ubiquitously expressed in all CC eukaryotic cells. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; CC Evidence={ECO:0000250|UniProtKB:P68137}; CC -!- SUBUNIT: Polymerization of globular actin (G-actin) leads to a CC structural filament (F-actin) in the form of a two-stranded helix. Each CC actin can bind to 4 others. Interacts with alpha-actinin (By CC similarity). Identified in a complex composed of ACTA1, COBL, GSN AND CC TMSB4X (By similarity). Interacts with TTID (PubMed:10958653). CC Interacts (via its C-terminus) with USP25; the interaction occurs for CC all USP25 isoforms but is strongest for isoform USP25m in muscle CC differentiating cells (PubMed:16501887). {ECO:0000250|UniProtKB:P68135, CC ECO:0000269|PubMed:10958653, ECO:0000269|PubMed:16501887}. CC -!- INTERACTION: CC P68133; Q6XD76: ASCL4; NbExp=3; IntAct=EBI-367510, EBI-10254793; CC P68133; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-367510, EBI-1383687; CC P68133; Q0VD86: INCA1; NbExp=3; IntAct=EBI-367510, EBI-6509505; CC P68133; Q6ZQX7-4: LIAT1; NbExp=3; IntAct=EBI-367510, EBI-25830459; CC P68133; Q96PV4: PNMA5; NbExp=3; IntAct=EBI-367510, EBI-10171633; CC P68133; Q9H7C4: SYNC; NbExp=3; IntAct=EBI-367510, EBI-11285923; CC P68133; P17024: ZNF20; NbExp=3; IntAct=EBI-367510, EBI-717634; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. CC -!- PTM: Oxidation of Met-46 and Met-49 by MICALs (MICAL1, MICAL2 or CC MICAL3) to form methionine sulfoxide promotes actin filament CC depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The CC (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promotes actin CC repolymerization. {ECO:0000250|UniProtKB:P68134}. CC -!- PTM: Monomethylation at Lys-86 (K84me1) regulates actin-myosin CC interaction and actomyosin-dependent processes. Demethylation by ALKBH4 CC is required for maintaining actomyosin dynamics supporting normal CC cleavage furrow ingression during cytokinesis and cell migration. CC {ECO:0000269|PubMed:23673617}. CC -!- PTM: [Actin, alpha skeletal muscle, intermediate form]: N-terminal CC cleavage of acetylated cysteine of intermediate muscle actin by ACTMAP. CC {ECO:0000250|UniProtKB:P68134}. CC -!- PTM: Methylated at His-75 by SETD3. {ECO:0000269|PubMed:30626964}. CC -!- PTM: (Microbial infection) Monomeric actin is cross-linked by CC V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins CC mediate the cross-link between Lys-52 of one monomer and Glu-272 of CC another actin monomer, resulting in formation of highly toxic actin CC oligomers that cause cell rounding (PubMed:19015515). The toxin can be CC highly efficient at very low concentrations by acting on formin CC homology family proteins: toxic actin oligomers bind with high affinity CC to formins and adversely affect both nucleation and elongation CC abilities of formins, causing their potent inhibition in both profilin- CC dependent and independent manners (PubMed:26228148). CC {ECO:0000305|PubMed:19015515, ECO:0000305|PubMed:26228148}. CC -!- DISEASE: Congenital myopathy 2A, typical, autosomal dominant (CMYP2A) CC [MIM:161800]: A muscular disorder characterized by generalized muscle CC weakness, delayed motor milestones, hypotonia, and muscle fiber CC abnormalities on histologic examination. Histologic findings include CC abnormal thread- or rod-like structures (nemaline rods), intranuclear CC rods, clumped filaments, cores, or fiber-type disproportion. The CC spectrum of clinical phenotypes ranges from severe neonatal CC presentations to onset of a milder disorder in childhood. CC {ECO:0000269|PubMed:10508519, ECO:0000269|PubMed:11166164, CC ECO:0000269|PubMed:11333380, ECO:0000269|PubMed:15198992, CC ECO:0000269|PubMed:15236405, ECO:0000269|PubMed:15336687, CC ECO:0000269|PubMed:15520409, ECO:0000269|PubMed:16427282, CC ECO:0000269|PubMed:16945537, ECO:0000269|PubMed:17705262, CC ECO:0000269|PubMed:22442437, ECO:0000269|PubMed:23650303, CC ECO:0000269|PubMed:25635128, ECO:0000269|PubMed:25938801, CC ECO:0000269|PubMed:29274205}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Congenital myopathy 2B, severe infantile, autosomal recessive CC (CMYP2B) [MIM:620265]: An autosomal recessive skeletal muscle disorder CC characterized by severe hypotonia with lack of spontaneous movements CC and respiratory insufficiency, usually leading to death in infancy or CC early childhood. Longer survival has been reported. CC {ECO:0000269|PubMed:10508519, ECO:0000269|PubMed:12921789}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Congenital myopathy 2C, severe infantile, autosomal dominant CC (CMYP2C) [MIM:620278]: An autosomal dominant skeletal muscle disorder CC characterized by severe congenital weakness usually resulting in death CC from respiratory failure in the first year or so of life. Patients CC present at birth with hypotonia, lack of antigravity movements, poor CC head control, and difficulties feeding or breathing, often requiring CC tube-feeding and mechanical ventilation. Decreased fetal movements may CC be observed in some cases. {ECO:0000269|PubMed:15468086, CC ECO:0000269|PubMed:17387733}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Myopathy, scapulohumeroperoneal (SHPM) [MIM:616852]: An CC autosomal dominant muscular disorder characterized by progressive CC muscle weakness with initial scapulo-humeral-peroneal and distal CC distribution. Over time, muscle weakness progresses to proximal muscle CC groups. Clinical characteristics include scapular winging, mild lower CC facial weakness, foot drop due to foot eversion and dorsiflexion CC weakness, and selective muscle atrophy. Age at onset and disease CC progression are variable. {ECO:0000269|PubMed:25938801}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: In vertebrates 3 main groups of actin isoforms, alpha, CC beta and gamma have been identified. The alpha actins are found in CC muscle tissues and are a major constituent of the contractile CC apparatus. The beta and gamma actins coexist in most cell types as CC components of the cytoskeleton and as mediators of internal cell CC motility. CC -!- SIMILARITY: Belongs to the actin family. {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; J00068; AAB59376.1; -; mRNA. DR EMBL; M20543; AAA60296.1; -; Genomic_DNA. DR EMBL; AF182035; AAF02694.1; -; Genomic_DNA. DR EMBL; CR536516; CAG38754.1; -; mRNA. DR EMBL; CR541796; CAG46595.1; -; mRNA. DR EMBL; AL160004; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471098; EAW69898.1; -; Genomic_DNA. DR EMBL; BC012597; AAH12597.1; -; mRNA. DR CCDS; CCDS1578.1; -. DR PIR; A31251; ATHU. DR RefSeq; NP_001091.1; NM_001100.3. DR PDB; 7RNS; X-ray; 1.14 A; B=52-60. DR PDB; 7RNU; X-ray; 1.45 A; B/D/F/H=52-60. DR PDB; 7RNV; X-ray; 2.15 A; B=52-60. DR PDBsum; 7RNS; -. DR PDBsum; 7RNU; -. DR PDBsum; 7RNV; -. DR AlphaFoldDB; P68133; -. DR SMR; P68133; -. DR BioGRID; 106573; 284. DR IntAct; P68133; 61. DR MINT; P68133; -. DR STRING; 9606.ENSP00000355645; -. DR DrugBank; DB04151; 1-Methylhistidine. DR DrugBank; DB04629; Aplyronine A. DR DrugBank; DB03850; Jaspisamide A. DR DrugBank; DB03616; Kabiramide C. DR DrugBank; DB02621; Latrunculin A. DR DrugBank; DB08080; Latrunculin B. DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester. DR DrugBank; DB04774; Reidispongiolide A. DR DrugBank; DB04775; Reidispongiolide C. DR DrugBank; DB04783; Sphinxolide B. DR DrugBank; DB02772; Sucrose. DR DrugBank; DB03903; Tmr. DR DrugBank; DB03021; Ulapualide A. DR GlyCosmos; P68133; 4 sites, 1 glycan. DR GlyGen; P68133; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; P68133; -. DR MetOSite; P68133; -. DR PhosphoSitePlus; P68133; -. DR SwissPalm; P68133; -. DR BioMuta; ACTA1; -. DR DMDM; 61218043; -. DR CPTAC; CPTAC-5857; -. DR CPTAC; CPTAC-5882; -. DR EPD; P68133; -. DR jPOST; P68133; -. DR MassIVE; P68133; -. DR MaxQB; P68133; -. DR PaxDb; 9606-ENSP00000355645; -. DR PeptideAtlas; P68133; -. DR PRIDE; P68133; -. DR ProteomicsDB; 57532; -. DR Pumba; P68133; -. DR Antibodypedia; 3508; 1451 antibodies from 45 providers. DR DNASU; 58; -. DR Ensembl; ENST00000366684.7; ENSP00000355645.3; ENSG00000143632.15. DR GeneID; 58; -. DR KEGG; hsa:58; -. DR MANE-Select; ENST00000366684.7; ENSP00000355645.3; NM_001100.4; NP_001091.1. DR UCSC; uc001htm.4; human. DR AGR; HGNC:129; -. DR CTD; 58; -. DR DisGeNET; 58; -. DR GeneCards; ACTA1; -. DR HGNC; HGNC:129; ACTA1. DR HPA; ENSG00000143632; Tissue enriched (skeletal). DR MalaCards; ACTA1; -. DR MIM; 102610; gene. DR MIM; 161800; phenotype. DR MIM; 616852; phenotype. DR MIM; 620265; phenotype. DR MIM; 620278; phenotype. DR neXtProt; NX_P68133; -. DR OpenTargets; ENSG00000143632; -. DR Orphanet; 171439; Childhood-onset nemaline myopathy. DR Orphanet; 2020; Congenital fiber-type disproportion myopathy. DR Orphanet; 98904; Congenital myopathy with excess of thin filaments. DR Orphanet; 171433; Intermediate nemaline myopathy. DR Orphanet; 447977; Progressive scapulohumeroperoneal distal myopathy. DR Orphanet; 97244; Rigid spine syndrome. DR Orphanet; 171430; Severe congenital nemaline myopathy. DR Orphanet; 171436; Typical nemaline myopathy. DR Orphanet; 97240; Zebra body myopathy. DR PharmGKB; PA24455; -. DR VEuPathDB; HostDB:ENSG00000143632; -. DR eggNOG; KOG0676; Eukaryota. DR GeneTree; ENSGT00940000156048; -. DR InParanoid; P68133; -. DR OMA; DTMCDED; -. DR OrthoDB; 4646155at2759; -. DR PhylomeDB; P68133; -. DR TreeFam; TF354237; -. DR PathwayCommons; P68133; -. DR Reactome; R-HSA-390522; Striated Muscle Contraction. DR SignaLink; P68133; -. DR SIGNOR; P68133; -. DR BioGRID-ORCS; 58; 21 hits in 1153 CRISPR screens. DR ChiTaRS; ACTA1; human. DR EvolutionaryTrace; P68133; -. DR GeneWiki; Actin,_alpha_1; -. DR GenomeRNAi; 58; -. DR Pharos; P68133; Tbio. DR PRO; PR:P68133; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P68133; Protein. DR Bgee; ENSG00000143632; Expressed in skeletal muscle tissue of biceps brachii and 132 other cell types or tissues. DR ExpressionAtlas; P68133; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; IMP:UniProtKB. DR GO; GO:0005884; C:actin filament; IDA:UniProtKB. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0044297; C:cell body; ISS:AgBase. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0030175; C:filopodium; ISS:AgBase. DR GO; GO:0030027; C:lamellipodium; ISS:AgBase. DR GO; GO:0030017; C:sarcomere; IDA:UniProtKB. DR GO; GO:0001725; C:stress fiber; IDA:UniProtKB. DR GO; GO:0005865; C:striated muscle thin filament; IDA:UniProtKB. DR GO; GO:0043531; F:ADP binding; TAS:UniProtKB. DR GO; GO:0005524; F:ATP binding; TAS:UniProtKB. DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW. DR GO; GO:0017022; F:myosin binding; TAS:UniProtKB. DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:UniProtKB. DR GO; GO:0071417; P:cellular response to organonitrogen compound; IEA:Ensembl. DR GO; GO:0090131; P:mesenchyme migration; ISS:AgBase. DR GO; GO:0006936; P:muscle contraction; TAS:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; ISS:AgBase. DR GO; GO:0009991; P:response to extracellular stimulus; IEA:Ensembl. DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0048545; P:response to steroid hormone; IEA:Ensembl. DR GO; GO:0043503; P:skeletal muscle fiber adaptation; IEA:Ensembl. DR GO; GO:0048741; P:skeletal muscle fiber development; ISS:UniProtKB. DR GO; GO:0030240; P:skeletal muscle thin filament assembly; IMP:UniProtKB. DR CDD; cd00012; NBD_sugar-kinase_HSP70_actin; 1. DR Gene3D; 3.30.420.40; -; 2. DR InterPro; IPR004000; Actin. DR InterPro; IPR020902; Actin/actin-like_CS. DR InterPro; IPR004001; Actin_CS. DR InterPro; IPR043129; ATPase_NBD. DR PANTHER; PTHR11937; ACTIN; 1. DR PANTHER; PTHR11937:SF193; ACTIN, ALPHA SKELETAL MUSCLE; 1. DR Pfam; PF00022; Actin; 1. DR PRINTS; PR00190; ACTIN. DR SMART; SM00268; ACTIN; 1. DR SUPFAM; SSF53067; Actin-like ATPase domain; 2. DR PROSITE; PS00406; ACTINS_1; 1. DR PROSITE; PS00432; ACTINS_2; 1. DR PROSITE; PS01132; ACTINS_ACT_LIKE; 1. DR Genevisible; P68133; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Cytoplasm; Cytoskeleton; KW Disease variant; Hydrolase; Isopeptide bond; Methylation; Muscle protein; KW Nemaline myopathy; Nucleotide-binding; Oxidation; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT CHAIN 2..377 FT /note="Actin, alpha skeletal muscle, intermediate form" FT /evidence="ECO:0000250|UniProtKB:P62737" FT /id="PRO_0000442803" FT CHAIN 3..377 FT /note="Actin, alpha skeletal muscle" FT /evidence="ECO:0000250|UniProtKB:P68135" FT /id="PRO_0000442804" FT REGION 112..125 FT /note="Interaction with alpha-actinin" FT /evidence="ECO:0000250|UniProtKB:P68135" FT REGION 360..372 FT /note="Interaction with alpha-actinin" FT /evidence="ECO:0000250|UniProtKB:P68135" FT MOD_RES 2 FT /note="N-acetylcysteine; in intermediate form" FT /evidence="ECO:0000250|UniProtKB:P68134" FT MOD_RES 46 FT /note="Methionine (R)-sulfoxide" FT /evidence="ECO:0000250|UniProtKB:P68134" FT MOD_RES 49 FT /note="Methionine (R)-sulfoxide" FT /evidence="ECO:0000250|UniProtKB:P68134" FT MOD_RES 63 FT /note="N6-malonyllysine" FT /evidence="ECO:0000269|PubMed:21908771" FT MOD_RES 75 FT /note="Tele-methylhistidine" FT /evidence="ECO:0000269|PubMed:30626964" FT MOD_RES 86 FT /note="N6-methyllysine" FT /evidence="ECO:0000269|PubMed:23673617" FT CROSSLNK 52 FT /note="Isoglutamyl lysine isopeptide (Lys-Glu) (interchain FT with E-272); by Vibrio toxins RtxA and VgrG1" FT /evidence="ECO:0000250|UniProtKB:P60709" FT CROSSLNK 272 FT /note="Isoglutamyl lysine isopeptide (Glu-Lys) (interchain FT with K-52); by Vibrio toxins RtxA and VgrG1" FT /evidence="ECO:0000250|UniProtKB:P60709" FT VARIANT 3 FT /note="D -> Y (in CMYP2A; some patients have core lesions FT on muscle biopsy; dbSNP:rs121909527)" FT /evidence="ECO:0000269|PubMed:15520409" FT /id="VAR_062424" FT VARIANT 17 FT /note="G -> R (in CMYP2A; dbSNP:rs121909521)" FT /evidence="ECO:0000269|PubMed:10508519" FT /id="VAR_011680" FT VARIANT 17 FT /note="G -> S (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:29274205" FT /id="VAR_085717" FT VARIANT 27 FT /note="D -> N (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062425" FT VARIANT 37 FT /note="V -> L (in CMYP2A; dbSNP:rs1553255521)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062426" FT VARIANT 40 FT /note="P -> L (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062427" FT VARIANT 42 FT /note="H -> Y (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:10508519, FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15236405" FT /id="VAR_015579" FT VARIANT 43 FT /note="Q -> R (in CMYP2A; dbSNP:rs1659984269)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062428" FT VARIANT 44 FT /note="G -> V (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062429" FT VARIANT 45 FT /note="V -> F (in CMYP2A; dbSNP:rs398123562)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062430" FT VARIANT 66 FT /note="I -> N (in CMYP2A; dbSNP:rs1553255502)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062431" FT VARIANT 68 FT /note="T -> I (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:15198992" FT /id="VAR_062432" FT VARIANT 72 FT /note="P -> R (in CMYP2A; dbSNP:rs1659978909)" FT /evidence="ECO:0000269|PubMed:25635128" FT /id="VAR_083589" FT VARIANT 74 FT /note="E -> K (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:15198992" FT /id="VAR_062433" FT VARIANT 75 FT /note="H -> L (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062434" FT VARIANT 75 FT /note="H -> R (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062435" FT VARIANT 77 FT /note="I -> L (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:15236405" FT /id="VAR_062436" FT VARIANT 79 FT /note="T -> A (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062437" FT VARIANT 85 FT /note="E -> K (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:15236405" FT /id="VAR_062438" FT VARIANT 96 FT /note="L -> P (in CMYP2B; dbSNP:rs121909519)" FT /evidence="ECO:0000269|PubMed:10508519, FT ECO:0000269|PubMed:12921789" FT /id="VAR_011681" FT VARIANT 116 FT /note="A -> T (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062439" FT VARIANT 116 FT /note="A -> V (in CMYP2A; dbSNP:rs1659975747)" FT /evidence="ECO:0000269|PubMed:25635128" FT /id="VAR_083590" FT VARIANT 117 FT /note="N -> S (in CMYP2A; dbSNP:rs121909520)" FT /evidence="ECO:0000269|PubMed:10508519, FT ECO:0000269|PubMed:11333380, ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15198992" FT /id="VAR_011682" FT VARIANT 117 FT /note="N -> T (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062440" FT VARIANT 118 FT /note="R -> H (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062441" FT VARIANT 134 FT /note="M -> V (in CMYP2A; dbSNP:rs1659974377)" FT /evidence="ECO:0000269|PubMed:10508519, FT ECO:0000269|PubMed:11166164, ECO:0000269|PubMed:12921789" FT /id="VAR_013470" FT VARIANT 136 FT /note="V -> A (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062442" FT VARIANT 138 FT /note="I -> M (in CMYP2A; dbSNP:rs121909526)" FT /evidence="ECO:0000269|PubMed:11333380, FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15198992" FT /id="VAR_011683" FT VARIANT 140 FT /note="A -> P (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062443" FT VARIANT 142 FT /note="L -> P (in CMYP2A; dbSNP:rs1553255482)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062444" FT VARIANT 148 FT /note="G -> D (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062445" FT VARIANT 150 FT /note="T -> N (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062446" FT VARIANT 156 FT /note="D -> N (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062447" FT VARIANT 165 FT /note="V -> L (in CMYP2A; dbSNP:rs121909522)" FT /evidence="ECO:0000269|PubMed:10508519, FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15198992" FT /id="VAR_011684" FT VARIANT 165 FT /note="V -> M (in CMYP2A; results in sequestration of FT sarcomeric and Z line proteins into intranuclear FT aggregates; there is some evidence of muscle regeneration FT suggesting a compensatory effect; dbSNP:rs121909522)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15198992, ECO:0000269|PubMed:16427282, FT ECO:0000269|PubMed:17705262" FT /id="VAR_062448" FT VARIANT 172 FT /note="A -> G (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062449" FT VARIANT 181 FT /note="D -> G (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:15236405" FT /id="VAR_062450" FT VARIANT 181 FT /note="D -> H (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062451" FT VARIANT 181 FT /note="D -> N (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062452" FT VARIANT 184 FT /note="G -> D (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:10508519, FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15236405" FT /id="VAR_015580" FT VARIANT 185 FT /note="R -> C (in CMYP2A; dbSNP:rs1064794287)" FT /evidence="ECO:0000269|PubMed:10508519, FT ECO:0000269|PubMed:12921789" FT /id="VAR_015582" FT VARIANT 185 FT /note="R -> D (in CMYP2A; requires 2 nucleotide FT substitutions)" FT /id="VAR_062453" FT VARIANT 185 FT /note="R -> G (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:11333380, FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15198992, FT ECO:0000269|PubMed:15236405" FT /id="VAR_015581" FT VARIANT 185 FT /note="R -> S (in CMYP2A; dbSNP:rs1064794287)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062454" FT VARIANT 197 FT /note="E -> D (in SHPM; no effect on cytoskeleton FT structure; dbSNP:rs869312739)" FT /evidence="ECO:0000269|PubMed:25938801" FT /id="VAR_076426" FT VARIANT 198 FT /note="R -> L (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062455" FT VARIANT 199 FT /note="G -> S (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:15236405" FT /id="VAR_062456" FT VARIANT 223 FT /note="L -> P (in CMYP2C; dbSNP:rs121909530)" FT /evidence="ECO:0000269|PubMed:15468086" FT /id="VAR_032917" FT VARIANT 226 FT /note="E -> G (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062457" FT VARIANT 226 FT /note="E -> Q (in CMYP2A; dbSNP:rs1057521118)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062458" FT VARIANT 227 FT /note="N -> V (in CMYP2A; requires 2 nucleotide FT substitutions)" FT /id="VAR_062459" FT VARIANT 229 FT /note="M -> I (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062460" FT VARIANT 229 FT /note="M -> T (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062461" FT VARIANT 229 FT /note="M -> V (in CMYP2A; dbSNP:rs794727714)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062462" FT VARIANT 243 FT /note="E -> K (in CMYP2A; dbSNP:rs367543051)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062463" FT VARIANT 248 FT /note="Q -> K (in CMYP2A; dbSNP:rs1659954634)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062464" FT VARIANT 248 FT /note="Q -> R (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062465" FT VARIANT 253 FT /note="G -> D (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062466" FT VARIANT 258 FT /note="R -> H (in CMYP2A; dbSNP:rs1659953887)" FT /evidence="ECO:0000269|PubMed:10508519, FT ECO:0000269|PubMed:12921789" FT /id="VAR_015583" FT VARIANT 258 FT /note="R -> L (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062467" FT VARIANT 261 FT /note="E -> V (in CMYP2B; dbSNP:rs121909523)" FT /evidence="ECO:0000269|PubMed:10508519, FT ECO:0000269|PubMed:12921789" FT /id="VAR_011685" FT VARIANT 265 FT /note="Q -> L (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:10508519, FT ECO:0000269|PubMed:12921789" FT /id="VAR_015584" FT VARIANT 270 FT /note="G -> C (in CMYP2A; dbSNP:rs121909525)" FT /evidence="ECO:0000269|PubMed:11333380, FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15198992, FT ECO:0000269|PubMed:15236405" FT /id="VAR_011686" FT VARIANT 270 FT /note="G -> D (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:15336687" FT /id="VAR_062468" FT VARIANT 270 FT /note="G -> R (in CMYP2A; dbSNP:rs121909525)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062469" FT VARIANT 271 FT /note="M -> R (in CMYP2A; dbSNP:rs1553255360)" FT /evidence="ECO:0000269|PubMed:11166164, FT ECO:0000269|PubMed:12921789" FT /id="VAR_013471" FT VARIANT 274 FT /note="A -> E (in CMYP2A; dbSNP:rs1553255357)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062470" FT VARIANT 281 FT /note="Y -> H (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062471" FT VARIANT 282 FT /note="N -> K (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:10508519, FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15236405" FT /id="VAR_015585" FT VARIANT 285 FT /note="M -> K (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062472" FT VARIANT 288 FT /note="D -> G (in CMYP2A; formation of rod-like structure)" FT /evidence="ECO:0000269|PubMed:10508519, FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15236405, FT ECO:0000269|PubMed:25938801" FT /id="VAR_015586" FT VARIANT 294 FT /note="D -> V (in CMYP2C; results in decreased motility due FT to abnormal interactions between actin and tropomyosin with FT tropomyosin stabilized in the 'off' position; the mutant FT protein incorporates into actin filaments and does not FT result in increased actin aggregation or disruption of the FT sarcomere; dbSNP:rs121909529)" FT /evidence="ECO:0000269|PubMed:15468086, FT ECO:0000269|PubMed:17387733" FT /id="VAR_032918" FT VARIANT 328 FT /note="K -> N (in CMYP2A; no effect on actin structure; FT higher sensitivity to calcium; dbSNP:rs398122936)" FT /evidence="ECO:0000269|PubMed:22442437" FT /id="VAR_076427" FT VARIANT 334 FT /note="P -> S (in CMYP2C; dbSNP:rs121909531)" FT /evidence="ECO:0000269|PubMed:15468086" FT /id="VAR_032919" FT VARIANT 336 FT /note="E -> A (in CMYP2A; dbSNP:rs121909528)" FT /evidence="ECO:0000269|PubMed:15520409" FT /id="VAR_062473" FT VARIANT 338 FT /note="K -> E (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:16945537" FT /id="VAR_062474" FT VARIANT 338 FT /note="K -> I (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062475" FT VARIANT 350 FT /note="S -> L (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062476" FT VARIANT 358 FT /note="W -> C (in CMYP2A; found in a patient with a rare FT combination of CMYP2A and dilated cardiomyopathy; FT dbSNP:rs587777354)" FT /evidence="ECO:0000269|PubMed:23650303" FT /id="VAR_076428" FT VARIANT 359 FT /note="I -> L (in CMYP2A; dbSNP:rs121909524)" FT /evidence="ECO:0000269|PubMed:11333380, FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15198992" FT /id="VAR_015587" FT VARIANT 372 FT /note="V -> F (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:10508519, FT ECO:0000269|PubMed:12921789" FT /id="VAR_011687" FT VARIANT 374 FT /note="R -> S (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789" FT /id="VAR_062477" FT VARIANT 375 FT /note="K -> E (in CMYP2A; dbSNP:rs1571892209)" FT /evidence="ECO:0000269|PubMed:15336687" FT /id="VAR_062478" FT VARIANT 375 FT /note="K -> Q (in CMYP2A)" FT /evidence="ECO:0000269|PubMed:12921789, FT ECO:0000269|PubMed:15236405" FT /id="VAR_062479" FT STRAND 53..55 FT /evidence="ECO:0007829|PDB:7RNS" SQ SEQUENCE 377 AA; 42051 MW; DF2A3A046346A179 CRC64; MCDEDETTAL VCDNGSGLVK AGFAGDDAPR AVFPSIVGRP RHQGVMVGMG QKDSYVGDEA QSKRGILTLK YPIEHGIITN WDDMEKIWHH TFYNELRVAP EEHPTLLTEA PLNPKANREK MTQIMFETFN VPAMYVAIQA VLSLYASGRT TGIVLDSGDG VTHNVPIYEG YALPHAIMRL DLAGRDLTDY LMKILTERGY SFVTTAEREI VRDIKEKLCY VALDFENEMA TAASSSSLEK SYELPDGQVI TIGNERFRCP ETLFQPSFIG MESAGIHETT YNSIMKCDID IRKDLYANNV MSGGTTMYPG IADRMQKEIT ALAPSTMKIK IIAPPERKYS VWIGGSILAS LSTFQQMWIT KQEYDEAGPS IVHRKCF //