GenomeNet

Database: UniProt
Entry: P68133
LinkDB: P68133
Original site: P68133 
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   10-FEB-2021, entry version 175.
DE   RecName: Full=Actin, alpha skeletal muscle;
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 NEM3 TYR-42; PRO-96; SER-117;
RP   VAL-134; ASP-184; CYS-185; HIS-258; VAL-261; LEU-265; LYS-282; GLY-288 AND
RP   PHE-372, AND VARIANTS MPCETM ARG-17 AND LEU-165.
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 NEM3 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.
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 NEM3 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 NEM3 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 CFTD 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 NEM3 ILE-68; LYS-74; SER-117; MET-138; LEU-165; MET-165; GLY-185;
RP   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 NEM3 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 NEM3 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 NEM3 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 NEM3 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 CFTD 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 NEM3 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 NEM3 ASN-328, AND CHARACTERIZATION OF VARIANT NEM3 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 NEM3 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 NEM3 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 NEM3 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).
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   -!- 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: 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: Nemaline myopathy 3 (NEM3) [MIM:161800]: A form of nemaline
CC       myopathy. Nemaline myopathies are muscular disorders characterized by
CC       muscle weakness of varying severity and onset, and abnormal thread-like
CC       or rod-shaped structures in muscle fibers on histologic examination.
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}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- DISEASE: Myopathy, actin, congenital, with excess of thin myofilaments
CC       (MPCETM) [MIM:161800]: A congenital muscular disorder characterized at
CC       histological level by areas of sarcoplasm devoid of normal myofibrils
CC       and mitochondria, and replaced with dense masses of thin filaments.
CC       Central cores, rods, ragged red fibers, and necrosis are absent.
CC       {ECO:0000269|PubMed:10508519}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Myopathy, congenital, with fiber-type disproportion (CFTD)
CC       [MIM:255310]: A genetically heterogeneous disorder in which there is
CC       relative hypotrophy of type 1 muscle fibers compared to type 2 fibers
CC       on skeletal muscle biopsy. However, these findings are not specific and
CC       can be found in many different myopathic and neuropathic conditions.
CC       {ECO:0000269|PubMed:15468086, ECO:0000269|PubMed:17387733}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       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   SMR; P68133; -.
DR   BioGRID; 106573; 177.
DR   IntAct; P68133; 41.
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   iPTMnet; P68133; -.
DR   PhosphoSitePlus; P68133; -.
DR   SwissPalm; P68133; -.
DR   BioMuta; ACTA1; -.
DR   DMDM; 61218043; -.
DR   EPD; P68133; -.
DR   jPOST; P68133; -.
DR   MassIVE; P68133; -.
DR   MaxQB; P68133; -.
DR   PaxDb; P68133; -.
DR   PeptideAtlas; P68133; -.
DR   PRIDE; P68133; -.
DR   ProteomicsDB; 57532; -.
DR   Antibodypedia; 3508; 1291 antibodies.
DR   DNASU; 58; -.
DR   Ensembl; ENST00000366684; ENSP00000355645; ENSG00000143632.
DR   GeneID; 58; -.
DR   KEGG; hsa:58; -.
DR   UCSC; uc001htm.4; human.
DR   CTD; 58; -.
DR   DisGeNET; 58; -.
DR   GeneCards; ACTA1; -.
DR   GeneReviews; ACTA1; -.
DR   HGNC; HGNC:129; ACTA1.
DR   HPA; ENSG00000143632; Group enriched (skeletal muscle, tongue).
DR   MalaCards; ACTA1; -.
DR   MIM; 102610; gene.
DR   MIM; 161800; phenotype.
DR   MIM; 255310; phenotype.
DR   MIM; 616852; 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:ENSG00000143632.14; -.
DR   eggNOG; KOG0676; Eukaryota.
DR   GeneTree; ENSGT00940000156048; -.
DR   InParanoid; P68133; -.
DR   OMA; WIGKSEY; -.
DR   OrthoDB; 649708at2759; -.
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; 8 hits in 880 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 biceps brachii and 167 other tissues.
DR   ExpressionAtlas; P68133; baseline and differential.
DR   Genevisible; P68133; HS.
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:0005869; C:dynactin complex; IBA:GO_Central.
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: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:0030049; P:muscle filament sliding; TAS:Reactome.
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:0010226; P:response to lithium ion; 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   InterPro; IPR004000; Actin.
DR   InterPro; IPR020902; Actin/actin-like_CS.
DR   InterPro; IPR004001; Actin_CS.
DR   InterPro; IPR043129; ATPase_NBD.
DR   PANTHER; PTHR11937; PTHR11937; 1.
DR   Pfam; PF00022; Actin; 1.
DR   PRINTS; PR00190; ACTIN.
DR   SMART; SM00268; ACTIN; 1.
DR   SUPFAM; SSF53067; SSF53067; 2.
DR   PROSITE; PS00406; ACTINS_1; 1.
DR   PROSITE; PS00432; ACTINS_2; 1.
DR   PROSITE; PS01132; ACTINS_ACT_LIKE; 1.
PE   1: Evidence at protein level;
KW   Acetylation; ATP-binding; Cytoplasm; Cytoskeleton; Disease variant;
KW   Isopeptide bond; Methylation; Muscle protein; Nemaline myopathy;
KW   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:P62737"
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 NEM3; some patients have core lesions on
FT                   muscle biopsy; dbSNP:rs121909527)"
FT                   /evidence="ECO:0000269|PubMed:15520409"
FT                   /id="VAR_062424"
FT   VARIANT         17
FT                   /note="G -> R (in MPCETM; dbSNP:rs121909521)"
FT                   /evidence="ECO:0000269|PubMed:10508519"
FT                   /id="VAR_011680"
FT   VARIANT         27
FT                   /note="D -> N (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062425"
FT   VARIANT         37
FT                   /note="V -> L (in NEM3; 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 NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789,
FT                   ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062427"
FT   VARIANT         42
FT                   /note="H -> Y (in NEM3; severe)"
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 NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789,
FT                   ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062428"
FT   VARIANT         44
FT                   /note="G -> V (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062429"
FT   VARIANT         45
FT                   /note="V -> F (in NEM3; dbSNP:rs398123562)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062430"
FT   VARIANT         66
FT                   /note="I -> N (in NEM3; 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 NEM3)"
FT                   /evidence="ECO:0000269|PubMed:15198992"
FT                   /id="VAR_062432"
FT   VARIANT         72
FT                   /note="P -> R (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:25635128"
FT                   /id="VAR_083589"
FT   VARIANT         74
FT                   /note="E -> K (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:15198992"
FT                   /id="VAR_062433"
FT   VARIANT         75
FT                   /note="H -> L (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789,
FT                   ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062434"
FT   VARIANT         75
FT                   /note="H -> R (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789,
FT                   ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062435"
FT   VARIANT         77
FT                   /note="I -> L (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062436"
FT   VARIANT         79
FT                   /note="T -> A (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789,
FT                   ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062437"
FT   VARIANT         85
FT                   /note="E -> K (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062438"
FT   VARIANT         96
FT                   /note="L -> P (in NEM3; autosomal recessive;
FT                   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 NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062439"
FT   VARIANT         116
FT                   /note="A -> V (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:25635128"
FT                   /id="VAR_083590"
FT   VARIANT         117
FT                   /note="N -> S (in NEM3; autosomal dominant;
FT                   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 NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062440"
FT   VARIANT         118
FT                   /note="R -> H (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062441"
FT   VARIANT         134
FT                   /note="M -> V (in NEM3; autosomal dominant)"
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 NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789,
FT                   ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062442"
FT   VARIANT         138
FT                   /note="I -> M (in NEM3; autosomal recessive;
FT                   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 NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062443"
FT   VARIANT         142
FT                   /note="L -> P (in NEM3; dbSNP:rs1553255482)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062444"
FT   VARIANT         148
FT                   /note="G -> D (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789,
FT                   ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062445"
FT   VARIANT         150
FT                   /note="T -> N (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062446"
FT   VARIANT         156
FT                   /note="D -> N (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062447"
FT   VARIANT         165
FT                   /note="V -> L (in MPCETM; 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 NEM3; 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 NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062449"
FT   VARIANT         181
FT                   /note="D -> G (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062450"
FT   VARIANT         181
FT                   /note="D -> H (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062451"
FT   VARIANT         181
FT                   /note="D -> N (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062452"
FT   VARIANT         184
FT                   /note="G -> D (in NEM3; mild)"
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 NEM3; severe; 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 NEM3; requires 2 nucleotide
FT                   substitutions)"
FT                   /id="VAR_062453"
FT   VARIANT         185
FT                   /note="R -> G (in NEM3; autosomal dominant; severe)"
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 NEM3; 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 NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062455"
FT   VARIANT         199
FT                   /note="G -> S (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062456"
FT   VARIANT         223
FT                   /note="L -> P (in CFTD; dbSNP:rs121909530)"
FT                   /evidence="ECO:0000269|PubMed:15468086"
FT                   /id="VAR_032917"
FT   VARIANT         226
FT                   /note="E -> G (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789,
FT                   ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062457"
FT   VARIANT         226
FT                   /note="E -> Q (in NEM3; dbSNP:rs1057521118)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062458"
FT   VARIANT         227
FT                   /note="N -> V (in NEM3; requires 2 nucleotide
FT                   substitutions)"
FT                   /id="VAR_062459"
FT   VARIANT         229
FT                   /note="M -> I (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789,
FT                   ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062460"
FT   VARIANT         229
FT                   /note="M -> T (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062461"
FT   VARIANT         229
FT                   /note="M -> V (in NEM3; 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 NEM3; dbSNP:rs367543051)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062463"
FT   VARIANT         248
FT                   /note="Q -> K (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062464"
FT   VARIANT         248
FT                   /note="Q -> R (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789,
FT                   ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062465"
FT   VARIANT         253
FT                   /note="G -> D (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789,
FT                   ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062466"
FT   VARIANT         258
FT                   /note="R -> H (in NEM3; severe)"
FT                   /evidence="ECO:0000269|PubMed:10508519,
FT                   ECO:0000269|PubMed:12921789"
FT                   /id="VAR_015583"
FT   VARIANT         258
FT                   /note="R -> L (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062467"
FT   VARIANT         261
FT                   /note="E -> V (in NEM3; autosomal recessive;
FT                   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 NEM3; severe)"
FT                   /evidence="ECO:0000269|PubMed:10508519,
FT                   ECO:0000269|PubMed:12921789"
FT                   /id="VAR_015584"
FT   VARIANT         270
FT                   /note="G -> C (in NEM3; autosomal dominant;
FT                   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 NEM3)"
FT                   /evidence="ECO:0000269|PubMed:15336687"
FT                   /id="VAR_062468"
FT   VARIANT         270
FT                   /note="G -> R (in NEM3; dbSNP:rs121909525)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062469"
FT   VARIANT         271
FT                   /note="M -> R (in NEM3; autosomal dominant;
FT                   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 NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062470"
FT   VARIANT         281
FT                   /note="Y -> H (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789,
FT                   ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062471"
FT   VARIANT         282
FT                   /note="N -> K (in NEM3; severe)"
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 NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062472"
FT   VARIANT         288
FT                   /note="D -> G (in NEM3; severe; formation of rod-like
FT                   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 CFTD; 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 NEM3; 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 CFTD; dbSNP:rs121909531)"
FT                   /evidence="ECO:0000269|PubMed:15468086"
FT                   /id="VAR_032919"
FT   VARIANT         336
FT                   /note="E -> A (in NEM3; dbSNP:rs121909528)"
FT                   /evidence="ECO:0000269|PubMed:15520409"
FT                   /id="VAR_062473"
FT   VARIANT         338
FT                   /note="K -> E (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:16945537"
FT                   /id="VAR_062474"
FT   VARIANT         338
FT                   /note="K -> I (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062475"
FT   VARIANT         350
FT                   /note="S -> L (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062476"
FT   VARIANT         358
FT                   /note="W -> C (in NEM3; found in a patient with a rare
FT                   combination of NEM3 and dilated cardiomyopathy;
FT                   dbSNP:rs587777354)"
FT                   /evidence="ECO:0000269|PubMed:23650303"
FT                   /id="VAR_076428"
FT   VARIANT         359
FT                   /note="I -> L (in NEM3; autosomal dominant; severe;
FT                   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 NEM3; severe)"
FT                   /evidence="ECO:0000269|PubMed:10508519,
FT                   ECO:0000269|PubMed:12921789"
FT                   /id="VAR_011687"
FT   VARIANT         374
FT                   /note="R -> S (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789"
FT                   /id="VAR_062477"
FT   VARIANT         375
FT                   /note="K -> E (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:15336687"
FT                   /id="VAR_062478"
FT   VARIANT         375
FT                   /note="K -> Q (in NEM3)"
FT                   /evidence="ECO:0000269|PubMed:12921789,
FT                   ECO:0000269|PubMed:15236405"
FT                   /id="VAR_062479"
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
//
DBGET integrated database retrieval system