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P68032 (ACTC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Actin, alpha cardiac muscle 1
Alternative name(s):
Alpha-cardiac actin
Gene names
Name:ACTC1
Synonyms:ACTC
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length377 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Subunit structure

Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others.

Subcellular location

Cytoplasmcytoskeleton.

Post-translational modification

Oxidation of Met-46 and Met-49 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization By similarity.

Monomethylation at Lys-86 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.

Involvement in disease

Cardiomyopathy, dilated 1R (CMD1R) [MIM:613424]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5

Cardiomyopathy, familial hypertrophic 11 (CMH11) [MIM:612098]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7 Ref.8 Ref.10

Atrial septal defect 5 (ASD5) [MIM:612794]: A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

Miscellaneous

In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.

Sequence similarities

Belongs to the actin family.

Ontologies

Keywords
   Cellular componentCytoplasm
Cytoskeleton
   DiseaseAtrial septal defect
Cardiomyopathy
Disease mutation
   LigandATP-binding
Nucleotide-binding
   Molecular functionMuscle protein
   PTMAcetylation
Methylation
Oxidation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP catabolic process

Inferred from direct assay PubMed 16611632PubMed 17765196. Source: GOC

actin filament-based movement

Inferred from direct assay PubMed 16611632. Source: UniProtKB

actin-myosin filament sliding

Inferred from mutant phenotype PubMed 19799913. Source: BHF-UCL

actomyosin structure organization

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

cardiac muscle contraction

Inferred from electronic annotation. Source: Ensembl

cardiac muscle tissue morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cardiac myofibril assembly

Inferred from sequence or structural similarity. Source: UniProtKB

heart contraction

Inferred from mutant phenotype PubMed 17611253Ref.9Ref.5. Source: UniProtKB

muscle filament sliding

Traceable author statement. Source: Reactome

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

skeletal muscle thin filament assembly

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentI band

Inferred from sequence or structural similarity. Source: UniProtKB

actin filament

Inferred from direct assay PubMed 16611632. Source: UniProtKB

actomyosin, actin portion

Inferred from direct assay PubMed 16611632. Source: UniProtKB

blood microparticle

Inferred from direct assay PubMed 22516433. Source: UniProt

cytoplasm

Inferred from direct assay PubMed 20962418. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 22664934PubMed 23580065. Source: UniProt

extracellular vesicular exosome

Inferred from direct assay PubMed 21362503. Source: UniProtKB

sarcomere

Inferred from direct assay PubMed 16288873. Source: UniProtKB

   Molecular_functionATP binding

Inferred from direct assay PubMed 16611632. Source: UniProtKB

ATPase activity

Inferred from direct assay PubMed 16611632PubMed 17765196. Source: UniProtKB

myosin binding

Inferred from physical interaction PubMed 16611632. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 22Removed in mature form By similarity
PRO_0000000812
Chain3 – 377375Actin, alpha cardiac muscle 1
PRO_0000000813

Amino acid modifications

Modified residue31N-acetylaspartate By similarity
Modified residue461Methionine (R)-sulfoxide By similarity
Modified residue491Methionine (R)-sulfoxide By similarity
Modified residue751Tele-methylhistidine By similarity
Modified residue861N6-methyllysine Ref.4

Natural variations

Natural variant901H → Y in CMH11. Ref.10
VAR_045924
Natural variant971R → C in CMH11. Ref.10
VAR_045925
Natural variant1011E → K in CMH11. Ref.7
VAR_012857
Natural variant1251M → V in ASD5; reduced affinity for myosin; normal actin filament polymerization ability; normal actomyosin motor function. Ref.9
VAR_046502
Natural variant1661P → A in CMH11. Ref.7
VAR_012858
Natural variant1681Y → C in CMH11. Ref.8
VAR_046503
Natural variant2971A → S in CMH11. Ref.6
VAR_012859
Natural variant3071M → L in CMH11. Ref.8
VAR_046504
Natural variant3141R → H in CMD1R. Ref.5
VAR_012860
Natural variant3331A → P in CMH11. Ref.7
VAR_012861
Natural variant3631E → G in CMD1R. Ref.5
VAR_012862

Sequences

Sequence LengthMass (Da)Tools
P68032 [UniParc].

Last modified March 20, 1987. Version 1.
Checksum: E5C10FA19730CAD2

FASTA37742,019
        10         20         30         40         50         60 
MCDDEETTAL VCDNGSGLVK AGFAGDDAPR AVFPSIVGRP RHQGVMVGMG QKDSYVGDEA 

        70         80         90        100        110        120 
QSKRGILTLK YPIEHGIITN WDDMEKIWHH TFYNELRVAP EEHPTLLTEA PLNPKANREK 

       130        140        150        160        170        180 
MTQIMFETFN VPAMYVAIQA VLSLYASGRT TGIVLDSGDG VTHNVPIYEG YALPHAIMRL 

       190        200        210        220        230        240 
DLAGRDLTDY LMKILTERGY SFVTTAEREI VRDIKEKLCY VALDFENEMA TAASSSSLEK 

       250        260        270        280        290        300 
SYELPDGQVI TIGNERFRCP ETLFQPSFIG MESAGIHETT YNSIMKCDID IRKDLYANNV 

       310        320        330        340        350        360 
LSGGTTMYPG IADRMQKEIT ALAPSTMKIK IIAPPERKYS VWIGGSILAS LSTFQQMWIS 

       370 
KQEYDEAGPS IVHRKCF 

« Hide

References

« Hide 'large scale' references
[1]"Molecular structure and evolutionary origin of human cardiac muscle actin gene."
Hamada H., Petrino M.G., Kakunaga T.
Proc. Natl. Acad. Sci. U.S.A. 79:5901-5905(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Muscle.
[4]"ALKBH4-dependent demethylation of actin regulates actomyosin dynamics."
Li M.M., Nilsen A., Shi Y., Fusser M., Ding Y.H., Fu Y., Liu B., Niu Y., Wu Y.S., Huang C.M., Olofsson M., Jin K.X., Lv Y., Xu X.Z., He C., Dong M.Q., Rendtlew Danielsen J.M., Klungland A., Yang Y.G.
Nat. Commun. 4:1832-1832(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: METHYLATION AT LYS-86, DEMETHYLATION BY ALKBH4.
[5]"Actin mutations in dilated cardiomyopathy, a heritable form of heart failure."
Olson T.M., Michels V.V., Thibodeau S.N., Tai Y.-S., Keating M.T.
Science 280:750-752(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMD1R HIS-314 AND GLY-363.
[6]"Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy."
Mogensen J., Klausen I.C., Pedersen A.K., Egeblad H., Bross P., Kruse T.A., Gregersen N., Hansen P.S., Baandrup U., Boerglum A.D.
J. Clin. Invest. 103:R39-R43(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMH11 SER-297.
[7]"Inherited and de novo mutations in the cardiac actin gene cause hypertrophic cardiomyopathy."
Olson T.M., Doan T.P., Kishimoto N.Y., Whitby F.G., Ackerman M.J., Fananapazir L.
J. Mol. Cell. Cardiol. 32:1687-1694(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMH11 LYS-101; ALA-166 AND PRO-333.
[8]"Clinical and genetic characteristics of alpha cardiac actin gene mutations in hypertrophic cardiomyopathy."
Mogensen J., Perrot A., Andersen P.S., Havndrup O., Klausen I.C., Christiansen M., Bross P., Egeblad H., Bundgaard H., Osterziel K.J., Haltern G., Lapp H., Reinecke P., Gregersen N., Borglum A.D.
J. Med. Genet. 41:E10-E10(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMH11 CYS-168 AND LEU-307.
[9]"Alpha-cardiac actin mutations produce atrial septal defects."
Matsson H., Eason J., Bookwalter C.S., Klar J., Gustavsson P., Sunnegardh J., Enell H., Jonzon A., Vikkula M., Gutierrez I., Granados-Riveron J., Pope M., Bu'Lock F., Cox J., Robinson T.E., Song F., Brook D.J., Marston S., Trybus K.M., Dahl N.
Hum. Mol. Genet. 17:256-265(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASD5 VAL-125, CHARACTERIZATION OF VARIANT ASD5 VAL-125.
[10]"Shared genetic causes of cardiac hypertrophy in children and adults."
Morita H., Rehm H.L., Menesses A., McDonough B., Roberts A.E., Kucherlapati R., Towbin J.A., Seidman J.G., Seidman C.E.
N. Engl. J. Med. 358:1899-1908(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMH11 TYR-90 AND CYS-97.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J00073 expand/collapse EMBL AC list , J00070, J00071, J00072 Genomic DNA. Translation: AAB59619.1.
CR541795 mRNA. Translation: CAG46594.1.
BC009978 mRNA. Translation: AAH09978.1.
CCDSCCDS10041.1.
PIRATHUC. A02998.
RefSeqNP_005150.1. NM_005159.4.
UniGeneHs.118127.

3D structure databases

ProteinModelPortalP68032.
SMRP68032. Positions 6-377.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106585. 30 interactions.
IntActP68032. 14 interactions.
MINTMINT-1425728.
STRING9606.ENSP00000290378.

PTM databases

PhosphoSiteP68032.

Polymorphism databases

DMDM54036697.

2D gel databases

REPRODUCTION-2DPAGEP68032.

Proteomic databases

MaxQBP68032.
PaxDbP68032.
PRIDEP68032.

Protocols and materials databases

DNASU70.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000290378; ENSP00000290378; ENSG00000159251.
GeneID70.
KEGGhsa:70.
UCSCuc001ziu.1. human.

Organism-specific databases

CTD70.
GeneCardsGC15M035080.
GeneReviewsACTC1.
HGNCHGNC:143. ACTC1.
HPACAB037330.
HPA041271.
MIM102540. gene.
612098. phenotype.
612794. phenotype.
613424. phenotype.
neXtProtNX_P68032.
Orphanet99103. Atrial septal defect, ostium secundum type.
154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
54260. Left ventricular noncompaction.
PharmGKBPA162375571.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5277.
HOGENOMHOG000233340.
HOVERGENHBG003771.
InParanoidP68032.
KOK12314.
OMAGGERFRC.
OrthoDBEOG72RMZ1.
PhylomeDBP68032.
TreeFamTF354237.

Enzyme and pathway databases

ReactomeREACT_17044. Muscle contraction.
SignaLinkP68032.

Gene expression databases

ArrayExpressP68032.
BgeeP68032.
CleanExHS_ACTC1.
GenevestigatorP68032.

Family and domain databases

InterProIPR004000. Actin-related.
IPR020902. Actin/actin-like_CS.
IPR004001. Actin_CS.
[Graphical view]
PANTHERPTHR11937. PTHR11937. 1 hit.
PfamPF00022. Actin. 1 hit.
[Graphical view]
PRINTSPR00190. ACTIN.
SMARTSM00268. ACTIN. 1 hit.
[Graphical view]
PROSITEPS00406. ACTINS_1. 1 hit.
PS00432. ACTINS_2. 1 hit.
PS01132. ACTINS_ACT_LIKE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiACTC1.
GenomeRNAi70.
NextBio275.
PROP68032.
SOURCESearch...

Entry information

Entry nameACTC_HUMAN
AccessionPrimary (citable) accession number: P68032
Secondary accession number(s): P04270
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: March 20, 1987
Last modified: July 9, 2014
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM