Reviewed, UniProtKB/Swiss-Prot P68133 (ACTS_HUMAN)

Names and origin

Protein names

Recommended name:
    Actin, alpha skeletal muscle
Alternative name(s):
    Alpha-actin-1

Gene names

Name:	ACTA1
Synonyms:	ACTA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	377 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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. Interacts with TTID.
Subcellular location	Cytoplasm › cytoskeleton.
Involvement in disease	Defects in ACTA1 are the cause of nemaline myopathy type 3 (NEM3) [MIM:161800]. Nemaline myopathy (NEM) is a form of congenital myopathy characterized by abnormal thread- or rod-like structures in muscle fibers on histologic examination. The clinical phenotype is highly variable, with differing age at onset and severity. Defects in ACTA1 are a cause of congenital myopathy with excess of thin myofilaments (CM) [MIM:102610]. Defects in ACTA1 are a cause of congenital myopathy with fiber-type disproportion (CFTD) [MIM:255310]; also known as congenital fiber-type disproportion myopathy (CFTDM). CFTD is a genetically heterogeneous disorder in which there is relative hypotrophy of type 1 muscle fibers compared to type 2 fibers on skeletal muscle biopsy. However, these findings are not specific and can be found in many different myopathic and neuropathic conditions.
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	Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Muscle protein Structural protein
PTM	Acetylation Methylation Phosphoprotein
Gene Ontology (GO)
Biological process	muscle contraction Ref.3 Traceable author statement. Source: UniProtKB muscle thin filament assembly Ref.9 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	actin filament Inferred from direct assay. Source: UniProtKB stress fiber Inferred from direct assay. Source: UniProtKB striated muscle thin filament Inferred from direct assay. Source: UniProtKB
Molecular function	ADP binding Ref.3 Traceable author statement. Source: UniProtKB ATP binding Ref.3 Traceable author statement. Source: UniProtKB myosin binding Ref.3 Traceable author statement. Source: UniProtKB structural constituent of cytoskeleton Ref.3 Traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Propeptide	1 – 2	2	Removed in mature form By similarity
	Chain	3 – 377	375	Actin, alpha skeletal muscle
Amino acid modifications
	Modified residue	3	1	N-acetylaspartate By similarity
	Modified residue	55	1	Phosphotyrosine
	Modified residue	63	1	N6-acetyllysine
	Modified residue	75	1	Tele-methylhistidine By similarity
	Modified residue	93	1	Phosphotyrosine
	Modified residue	242	1	Phosphotyrosine By similarity
Natural variations
	Natural variant	17	1	G → R in CM.
	Natural variant	42	1	H → Y in NEM3; severe.
	Natural variant	96	1	L → P in NEM3; autosomal recessive.
	Natural variant	117	1	N → S in NEM3; autosomal dominant.
	Natural variant	134	1	M → V in NEM3; autosomal dominant.
	Natural variant	138	1	I → M in NEM3; autosomal recessive.
	Natural variant	165	1	V → L in CM.
	Natural variant	184	1	G → D in NEM3; mild.
	Natural variant	185	1	R → C in NEM3; severe.
	Natural variant	185	1	R → G in NEM3; autosomal dominant; severe.
	Natural variant	223	1	L → P in CFTD.
	Natural variant	258	1	R → H in NEM3; severe.
	Natural variant	261	1	E → V in NEM3; autosomal recessive.
	Natural variant	265	1	Q → L in NEM3; severe.
	Natural variant	270	1	G → C in NEM3; autosomal dominant.
	Natural variant	271	1	M → R in NEM3; autosomal dominant.
	Natural variant	282	1	N → K in NEM3; severe.
	Natural variant	288	1	D → G in NEM3; severe.
	Natural variant	294	1	D → V in CFTD.
	Natural variant	334	1	P → S in CFTD.
	Natural variant	359	1	I → L in NEM3; autosomal dominant; severe.
	Natural variant	372	1	V → F in NEM3; severe.

Sequences

	Sequence		Length	Mass (Da)
	P68133-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: DF2A3A046346A179	FASTA	377	42,051
	10 20 30 40 50 60 MCDEDETTAL 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 MSGGTTMYPG IADRMQKEIT ALAPSTMKIK IIAPPERKYS VWIGGSILAS LSTFQQMWIT 370 KQEYDEAGPS IVHRKCF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of cDNA clones for human skeletal muscle alpha actin." Hanauer A., Levin M., Heilig R., Daegelen D., Kahn A., Mandel J.-L. Nucleic Acids Res. 11:3503-3516(1983) [PubMed: 6190133] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Skeletal muscle.
[2]	"Nucleotide sequence and expression of the human skeletal alpha-actin gene: evolution of functional regulatory domains." Taylor A., Erba H.P., Muscat G.E.O., Kedes L. Genomics 3:323-336(1988) [PubMed: 2907503] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy." Nowak K.J., Wattanasirichaigoon D., Goebel H.H., Wilce M., Pelin K., Donner K., Jacob R.L., Hubner C., Oexle K., Anderson J.R., Verity C.M., North K.N. Nat. Genet. 23:208-212(1999) [PubMed: 10508519] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS NEM3 TYR-42; PRO-96; SER-117; VAL-134; ASP-184; CYS-185; HIS-258; VAL-261; LEU-265; LYS-282; GLY-288 AND PHE-372, VARIANTS CM ARG-17 AND LEU-165.
[4]	"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].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skeletal muscle.
[6]	"Myotilin is mutated in limb girdle muscular dystrophy 1A." Hauser M.A., Horrigan S.K., Salmikangas P., Torian U.M., Viles K.D., Dancel R., Tim R.W., Taivainen A., Bartoloni L., Gilchrist J.M., Stajich J.M., Gaskell P.C., Gilbert J.R., Vance J.M., Pericak-Vance M.A., Carpen O., Westbrook C.A., Speer M.C. Hum. Mol. Genet. 9:2141-2147(2000) [PubMed: 10958653] [Abstract] Cited for: INTERACTION WITH TTID.
[7]	"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey." Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y. Mol. Cell 23:607-618(2006) [PubMed: 16916647] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-63, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-55 AND TYR-93, MASS SPECTROMETRY.
[9]	"Nemaline myopathy caused by mutations in the muscle alpha-skeletal-actin gene." Ilkovski B., Cooper S.T., Nowak K., Ryan M.M., Yang N., Schnell C., Durling H.J., Roddick L.G., Wilkinson I., Kornberg A.J., Collins K.J., Wallace G., Gunning P., Hardeman E.C., Laing N.G., North K.N. Am. J. Hum. Genet. 68:1333-1343(2001) [PubMed: 11333380] [Abstract] Cited for: VARIANTS NEM3 SER-117; MET-138; GLY-185; CYS-270 AND LEU-359.
[10]	"Mild phenotype of nemaline myopathy with sleep hypoventilation due to a mutation in the skeletal muscle alpha-actin (ACTA1) gene." Jungbluth H., Sewry C.A., Brown S.C., Nowak K.J., Laing N.G., Wallgren-Pettersson C., Pelin K., Manzur A.Y., Mercuri E., Dubowitz V., Muntoni F. Neuromuscul. Disord. 11:35-40(2001) [PubMed: 11166164] [Abstract] Cited for: VARIANTS NEM3 VAL-134 AND ARG-271.
[11]	"Actin mutations are one cause of congenital fibre type disproportion." Laing N.G., Clarke N.F., Dye D.E., Liyanage K., Walker K.R., Kobayashi Y., Shimakawa S., Hagiwara T., Ouvrier R., Sparrow J.C., Nishino I., North K.N., Nonaka I. Ann. Neurol. 56:689-694(2004) [PubMed: 15468086] [Abstract] Cited for: VARIANTS CFTD PRO-223; VAL-294 AND SER-334.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	J00068 mRNA. Translation: AAB59376.1. M20543 Genomic DNA. Translation: AAA60296.1. AF182035 Genomic DNA. Translation: AAF02694.1. CR536516 mRNA. Translation: CAG38754.1. CR541796 mRNA. Translation: CAG46595.1. BC012597 mRNA. Translation: AAH12597.1.
PIR	ATHU. A31251.
RefSeq	NP_001091.1.
UniGene	Hs.1288
3D structure databases
SMR	P68133. Positions 6-373.
ModBase	Search...
Protein-protein interaction databases
IntAct	P68133.
PTM databases
PhosphoSite	P68133.
Genome annotation databases
Ensembl	ENSG00000143632. Homo sapiens. [Contig view]
GeneID	58.
KEGG	hsa:58.
Organism-specific databases
H-InvDB	HIX0001679.
HGNC	HGNC:129. ACTA1.
HPA	CAB000045.
MIM	102610. gene+phenotype. 161800. phenotype. 255310. phenotype.
Orphanet	2020. Congenital fiber type disproportion. 607. Nemaline myopathy.
PharmGKB	PA24455.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P68133.
HOVERGEN	P68133.
Gene expression databases
ArrayExpress	P68133.
CleanEx	HS_ACTA1.
GermOnline	ENSG00000143632. Homo sapiens.
Family and domain databases
InterPro	IPR004001. Actin_CS. IPR004000. Actin_like. [Graphical view]
PANTHER	PTHR11937. Actin_like. 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]
ProDom	P68133. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
DrugBank	DB00003. Dornase Alfa.
LinkHub	P68133.
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

ACTS_HUMAN

Accession

Primary (citable) accession number: P68133
Secondary accession number(s): P02568, P99020

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	September 2, 2008
This is version 52 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)