P68032 (ACTC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Actin, alpha cardiac muscle 1

Alternative name(s):
Alpha-cardiac actin

Gene names

Name:	ACTC1
Synonyms:	ACTC

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	377 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Cytoplasm › cytoskeleton.
Post-translational modification	Oxidation of Met-46 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. Methionine sulfoxide is produced stereospecifically, but it is not known whether the (S)-S-oxide or the (R)-S-oxide is produced By similarity.
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.4 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.5 Ref.6 Ref.7 Ref.9 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.8
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 component	Cytoplasm Cytoskeleton
Disease	Atrial septal defect Cardiomyopathy Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Muscle protein
PTM	Oxidation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB cardiac muscle contraction Inferred from electronic annotation. Source: Compara 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.8Ref.4. Source: UniProtKB muscle filament sliding Traceable author statement. Source: Reactome response to drug Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara skeletal muscle thin filament assembly Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	I band Inferred from sequence or structural similarity. Source: UniProtKB actomyosin, actin part Inferred from direct assay PubMed 16611632. Source: UniProtKB cytosol Traceable author statement. Source: Reactome extracellular vesicular exosome Inferred from direct assay PubMed 21362503. Source: UniProtKB
Molecular_function	ATP binding Inferred from direct assay PubMed 16611632. Source: UniProtKB ATPase activity Inferred from direct assay PubMed 16611632PubMed 17765196. Source: UniProtKB myosin binding Inferred from direct assay PubMed 19799913. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Propeptide	1 – 2	2	Removed in mature form By similarity		PRO_0000000812
	Chain	3 – 377	375	Actin, alpha cardiac muscle 1		PRO_0000000813
Amino acid modifications
	Modified residue	46	1	Methionine sulfoxide By similarity
Natural variations
	Natural variant	90	1	H → Y in CMH11. Ref.9		VAR_045924
	Natural variant	97	1	R → C in CMH11. Ref.9		VAR_045925
	Natural variant	101	1	E → K in CMH11. Ref.6		VAR_012857
	Natural variant	125	1	M → V in ASD5; reduced affinity for myosin; normal actin filament polymerization ability; normal actomyosin motor function. Ref.8		VAR_046502
	Natural variant	166	1	P → A in CMH11. Ref.6		VAR_012858
	Natural variant	168	1	Y → C in CMH11. Ref.7		VAR_046503
	Natural variant	297	1	A → S in CMH11. Ref.5		VAR_012859
	Natural variant	307	1	M → L in CMH11. Ref.7		VAR_046504
	Natural variant	314	1	R → H in CMD1R. Ref.4		VAR_012860
	Natural variant	333	1	A → P in CMH11. Ref.6		VAR_012861
	Natural variant	363	1	E → G in CMD1R. Ref.4		VAR_012862

Sequences

	Sequence		Length	Mass (Da)
	P68032 [UniParc]. Last modified March 20, 1987. Version 1. Checksum: E5C10FA19730CAD2	FASTA	377	42,019
	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

References

	« Hide 'large scale' referencesShow '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]	"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.
[5]	"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.
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	J00073 , J00070, J00071, J00072 Genomic DNA. Translation: AAB59619.1. CR541795 mRNA. Translation: CAG46594.1. BC009978 mRNA. Translation: AAH09978.1.
IPI	IPI00023006.
PIR	ATHUC. A02998.
RefSeq	NP_005150.1. NM_005159.4.
UniGene	Hs.118127.
3D structure databases
ProteinModelPortal	P68032.
ModBase	Search...
Protein-protein interaction databases
IntAct	P68032. 11 interactions.
MINT	MINT-1425728.
STRING	9606.ENSP00000290378.
PTM databases
PhosphoSite	P68032.
Polymorphism databases
DMDM	54036697.
2D gel databases
REPRODUCTION-2DPAGE	P68032.
Proteomic databases
PaxDb	P68032.
PRIDE	P68032.
Protocols and materials databases
DNASU	70.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000290378; ENSP00000290378; ENSG00000159251.
GeneID	70.
KEGG	hsa:70.
UCSC	uc001ziu.1. human.
Organism-specific databases
CTD	70.
GeneCards	GC15M035080.
HGNC	HGNC:143. ACTC1.
HPA	CAB037330. HPA041271.
MIM	102540. gene. 612098. phenotype. 612794. phenotype. 613424. phenotype.
neXtProt	NX_P68032.
Orphanet	99103. Atrial septal defect, ostium secundum type. 154. Familial isolated dilated cardiomyopathy. 155. Familial isolated hypertrophic cardiomyopathy. 54260. Left ventricular noncompaction.
PharmGKB	PA162375571.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5277.
HOGENOM	HOG000233340.
HOVERGEN	HBG003771.
InParanoid	P68032.
KO	K12314.
OMA	MGSANKT.
OrthoDB	EOG4W9J40.
PhylomeDB	P68032.
Enzyme and pathway databases
Reactome	REACT_17044. Muscle contraction.
Gene expression databases
ArrayExpress	P68032.
Bgee	P68032.
CleanEx	HS_ACTC1.
Genevestigator	P68032.
GermOnline	ENSG00000159251. Homo sapiens.
Family and domain databases
InterPro	IPR004000. Actin-related. IPR020902. Actin/actin-like_CS. IPR004001. Actin_CS. [Graphical view]
PANTHER	PTHR11937. PTHR11937. 1 hit.
Pfam	PF00022. Actin. 1 hit. [Graphical view]
PRINTS	PR00190. ACTIN.
SMART	SM00268. ACTIN. 1 hit. [Graphical view]
PROSITE	PS00406. ACTINS_1. 1 hit. PS00432. ACTINS_2. 1 hit. PS01132. ACTINS_ACT_LIKE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	70.
NextBio	275.
SOURCE	Search...

Entry information

Entry name

ACTC_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.