ACTC_HUMAN
ID ACTC_HUMAN Reviewed; 377 AA.
AC P68032; P04270;
DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-1987, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Actin, alpha cardiac muscle 1;
DE AltName: Full=Alpha-cardiac actin;
DE Contains:
DE RecName: Full=Actin, alpha cardiac muscle 1, intermediate form;
DE Flags: Precursor;
GN Name=ACTC1; Synonyms=ACTC;
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 [GENOMIC DNA].
RX PubMed=6310553; DOI=10.1073/pnas.79.19.5901;
RA Hamada H., Petrino M.G., Kakunaga T.;
RT "Molecular structure and evolutionary origin of human cardiac muscle actin
RT gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 79:5901-5905(1982).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [4]
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 [5]
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 [6]
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 [7]
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 [8]
RP VARIANTS CMD1R HIS-314 AND GLY-363.
RX PubMed=9563954; DOI=10.1126/science.280.5364.750;
RA Olson T.M., Michels V.V., Thibodeau S.N., Tai Y.-S., Keating M.T.;
RT "Actin mutations in dilated cardiomyopathy, a heritable form of heart
RT failure.";
RL Science 280:750-752(1998).
RN [9]
RP VARIANT CMH11 SER-297.
RX PubMed=10330430; DOI=10.1172/jci6460;
RA Mogensen J., Klausen I.C., Pedersen A.K., Egeblad H., Bross P., Kruse T.A.,
RA Gregersen N., Hansen P.S., Baandrup U., Boerglum A.D.;
RT "Alpha-cardiac actin is a novel disease gene in familial hypertrophic
RT cardiomyopathy.";
RL J. Clin. Invest. 103:R39-R43(1999).
RN [10]
RP VARIANTS CMH11 LYS-101; ALA-166 AND PRO-333.
RX PubMed=10966831; DOI=10.1006/jmcc.2000.1204;
RA Olson T.M., Doan T.P., Kishimoto N.Y., Whitby F.G., Ackerman M.J.,
RA Fananapazir L.;
RT "Inherited and de novo mutations in the cardiac actin gene cause
RT hypertrophic cardiomyopathy.";
RL J. Mol. Cell. Cardiol. 32:1687-1694(2000).
RN [11]
RP VARIANTS CMH11 CYS-168 AND LEU-307.
RX PubMed=14729850; DOI=10.1136/jmg.2003.010447;
RA Mogensen J., Perrot A., Andersen P.S., Havndrup O., Klausen I.C.,
RA Christiansen M., Bross P., Egeblad H., Bundgaard H., Osterziel K.J.,
RA Haltern G., Lapp H., Reinecke P., Gregersen N., Borglum A.D.;
RT "Clinical and genetic characteristics of alpha cardiac actin gene mutations
RT in hypertrophic cardiomyopathy.";
RL J. Med. Genet. 41:E10-E10(2004).
RN [12]
RP VARIANT ASD5 VAL-125, AND CHARACTERIZATION OF VARIANT ASD5 VAL-125.
RX PubMed=17947298; DOI=10.1093/hmg/ddm302;
RA Matsson H., Eason J., Bookwalter C.S., Klar J., Gustavsson P.,
RA Sunnegardh J., Enell H., Jonzon A., Vikkula M., Gutierrez I.,
RA Granados-Riveron J., Pope M., Bu'Lock F., Cox J., Robinson T.E., Song F.,
RA Brook D.J., Marston S., Trybus K.M., Dahl N.;
RT "Alpha-cardiac actin mutations produce atrial septal defects.";
RL Hum. Mol. Genet. 17:256-265(2008).
RN [13]
RP VARIANTS CMH11 TYR-90 AND CYS-97.
RX PubMed=18403758; DOI=10.1056/nejmoa075463;
RA Morita H., Rehm H.L., Menesses A., McDonough B., Roberts A.E.,
RA Kucherlapati R., Towbin J.A., Seidman J.G., Seidman C.E.;
RT "Shared genetic causes of cardiac hypertrophy in children and adults.";
RL N. Engl. J. Med. 358:1899-1908(2008).
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.
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:P68033}.
CC -!- PTM: Monomethylation at Lys-86 (K86me1) 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: Cardiomyopathy, dilated 1R (CMD1R) [MIM:613424]: A disorder
CC characterized by ventricular dilation and impaired systolic function,
CC resulting in congestive heart failure and arrhythmia. Patients are at
CC risk of premature death. {ECO:0000269|PubMed:9563954}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Cardiomyopathy, familial hypertrophic 11 (CMH11) [MIM:612098]:
CC A hereditary heart disorder characterized by ventricular hypertrophy,
CC which is usually asymmetric and often involves the interventricular
CC septum. The symptoms include dyspnea, syncope, collapse, palpitations,
CC and chest pain. They can be readily provoked by exercise. The disorder
CC has inter- and intrafamilial variability ranging from benign to
CC malignant forms with high risk of cardiac failure and sudden cardiac
CC death. {ECO:0000269|PubMed:10330430, ECO:0000269|PubMed:10966831,
CC ECO:0000269|PubMed:14729850, ECO:0000269|PubMed:18403758}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Atrial septal defect 5 (ASD5) [MIM:612794]: A congenital heart
CC malformation characterized by incomplete closure of the wall between
CC the atria resulting in blood flow from the left to the right atria.
CC {ECO:0000269|PubMed:17947298}. Note=The disease is caused by variants
CC affecting the gene represented in this 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}.
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DR EMBL; J00073; AAB59619.1; -; Genomic_DNA.
DR EMBL; J00070; AAB59619.1; JOINED; Genomic_DNA.
DR EMBL; J00071; AAB59619.1; JOINED; Genomic_DNA.
DR EMBL; J00072; AAB59619.1; JOINED; Genomic_DNA.
DR EMBL; CR541795; CAG46594.1; -; mRNA.
DR EMBL; BC009978; AAH09978.1; -; mRNA.
DR CCDS; CCDS10041.1; -.
DR PIR; A02998; ATHUC.
DR RefSeq; NP_005150.1; NM_005159.4.
DR AlphaFoldDB; P68032; -.
DR SMR; P68032; -.
DR BioGRID; 106585; 639.
DR IntAct; P68032; 78.
DR MINT; P68032; -.
DR STRING; 9606.ENSP00000290378; -.
DR GlyGen; P68032; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P68032; -.
DR PhosphoSitePlus; P68032; -.
DR SwissPalm; P68032; -.
DR BioMuta; ACTC1; -.
DR DMDM; 54036697; -.
DR REPRODUCTION-2DPAGE; P68032; -.
DR EPD; P68032; -.
DR jPOST; P68032; -.
DR MassIVE; P68032; -.
DR MaxQB; P68032; -.
DR PaxDb; P68032; -.
DR PeptideAtlas; P68032; -.
DR PRIDE; P68032; -.
DR ProteomicsDB; 57527; -.
DR TopDownProteomics; P68032; -.
DR Antibodypedia; 9782; 324 antibodies from 35 providers.
DR DNASU; 70; -.
DR Ensembl; ENST00000290378.6; ENSP00000290378.4; ENSG00000159251.8.
DR GeneID; 70; -.
DR KEGG; hsa:70; -.
DR MANE-Select; ENST00000290378.6; ENSP00000290378.4; NM_005159.5; NP_005150.1.
DR UCSC; uc001ziu.2; human.
DR CTD; 70; -.
DR DisGeNET; 70; -.
DR GeneCards; ACTC1; -.
DR GeneReviews; ACTC1; -.
DR HGNC; HGNC:143; ACTC1.
DR HPA; ENSG00000159251; Tissue enriched (heart).
DR MalaCards; ACTC1; -.
DR MIM; 102540; gene.
DR MIM; 612098; phenotype.
DR MIM; 612794; phenotype.
DR MIM; 613424; phenotype.
DR neXtProt; NX_P68032; -.
DR OpenTargets; ENSG00000159251; -.
DR Orphanet; 99103; Atrial septal defect, ostium secundum type.
DR Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR Orphanet; 54260; Left ventricular noncompaction.
DR Orphanet; 155; NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy.
DR PharmGKB; PA162375571; -.
DR VEuPathDB; HostDB:ENSG00000159251; -.
DR eggNOG; KOG0676; Eukaryota.
DR GeneTree; ENSGT00940000154710; -.
DR HOGENOM; CLU_027965_0_2_1; -.
DR InParanoid; P68032; -.
DR OMA; STFQQKE; -.
DR OrthoDB; 649708at2759; -.
DR PhylomeDB; P68032; -.
DR TreeFam; TF354237; -.
DR PathwayCommons; P68032; -.
DR Reactome; R-HSA-390522; Striated Muscle Contraction.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013026; RHOB GTPase cycle.
DR SignaLink; P68032; -.
DR SIGNOR; P68032; -.
DR BioGRID-ORCS; 70; 7 hits in 1068 CRISPR screens.
DR ChiTaRS; ACTC1; human.
DR GeneWiki; ACTC1; -.
DR GenomeRNAi; 70; -.
DR Pharos; P68032; Tbio.
DR PRO; PR:P68032; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P68032; protein.
DR Bgee; ENSG00000159251; Expressed in left ventricle myocardium and 154 other tissues.
DR Genevisible; P68032; HS.
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:0005737; C:cytoplasm; IDA:BHF-UCL.
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:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0031674; C:I band; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISS:AgBase.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0030017; C:sarcomere; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000146; F:microfilament motor activity; IDA:UniProtKB.
DR GO; GO:0017022; F:myosin binding; IDA:BHF-UCL.
DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central.
DR GO; GO:0030048; P:actin filament-based movement; IDA:UniProtKB.
DR GO; GO:0033275; P:actin-myosin filament sliding; IMP:BHF-UCL.
DR GO; GO:0031032; P:actomyosin structure organization; ISS:UniProtKB.
DR GO; GO:0055008; P:cardiac muscle tissue morphogenesis; ISS:UniProtKB.
DR GO; GO:0055003; P:cardiac myofibril assembly; ISS:UniProtKB.
DR GO; GO:0060047; P:heart contraction; IMP:UniProtKB.
DR GO; GO:0090131; P:mesenchyme migration; ISS:AgBase.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:AgBase.
DR GO; GO:0030240; P:skeletal muscle thin filament assembly; ISS: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; Atrial septal defect; Cardiomyopathy; Cytoplasm;
KW Cytoskeleton; Disease variant; Isopeptide bond; Methylation;
KW Muscle protein; Nucleotide-binding; Oxidation; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..377
FT /note="Actin, alpha cardiac muscle 1, intermediate form"
FT /evidence="ECO:0000250|UniProtKB:P62737"
FT /id="PRO_0000442998"
FT CHAIN 3..377
FT /note="Actin, alpha cardiac muscle 1"
FT /evidence="ECO:0000250|UniProtKB:P68135"
FT /id="PRO_0000000813"
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:P68033"
FT MOD_RES 49
FT /note="Methionine (R)-sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P68033"
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 90
FT /note="H -> Y (in CMH11; dbSNP:rs121912676)"
FT /evidence="ECO:0000269|PubMed:18403758"
FT /id="VAR_045924"
FT VARIANT 97
FT /note="R -> C (in CMH11; dbSNP:rs759495229)"
FT /evidence="ECO:0000269|PubMed:18403758"
FT /id="VAR_045925"
FT VARIANT 101
FT /note="E -> K (in CMH11; dbSNP:rs193922680)"
FT /evidence="ECO:0000269|PubMed:10966831"
FT /id="VAR_012857"
FT VARIANT 125
FT /note="M -> V (in ASD5; reduced affinity for myosin; normal
FT actin filament polymerization ability; normal actomyosin
FT motor function; dbSNP:rs121912677)"
FT /evidence="ECO:0000269|PubMed:17947298"
FT /id="VAR_046502"
FT VARIANT 166
FT /note="P -> A (in CMH11; dbSNP:rs267606628)"
FT /evidence="ECO:0000269|PubMed:10966831"
FT /id="VAR_012858"
FT VARIANT 168
FT /note="Y -> C (in CMH11)"
FT /evidence="ECO:0000269|PubMed:14729850"
FT /id="VAR_046503"
FT VARIANT 297
FT /note="A -> S (in CMH11; dbSNP:rs121912675)"
FT /evidence="ECO:0000269|PubMed:10330430"
FT /id="VAR_012859"
FT VARIANT 307
FT /note="M -> L (in CMH11)"
FT /evidence="ECO:0000269|PubMed:14729850"
FT /id="VAR_046504"
FT VARIANT 314
FT /note="R -> H (in CMD1R; dbSNP:rs121912673)"
FT /evidence="ECO:0000269|PubMed:9563954"
FT /id="VAR_012860"
FT VARIANT 333
FT /note="A -> P (in CMH11; dbSNP:rs267606629)"
FT /evidence="ECO:0000269|PubMed:10966831"
FT /id="VAR_012861"
FT VARIANT 363
FT /note="E -> G (in CMD1R; dbSNP:rs121912674)"
FT /evidence="ECO:0000269|PubMed:9563954"
FT /id="VAR_012862"
SQ SEQUENCE 377 AA; 42019 MW; E5C10FA19730CAD2 CRC64;
MCDDEETTAL 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
LSGGTTMYPG IADRMQKEIT ALAPSTMKIK IIAPPERKYS VWIGGSILAS LSTFQQMWIS
KQEYDEAGPS IVHRKCF
