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P68133 (ACTS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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 skeletal muscle
Alternative name(s):
Alpha-actin-1
Gene names
Name:ACTA1
Synonyms:ACTA
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. Identified in a complex composed of ACTA1, COBL, GSN AND TMSB4X By similarity. Interacts with TTID. Interacts (via its C-terminus) with USP25; the interaction occurs for all USP25 isoforms but is strongest for isoform USP25min muscle differentiating cells. Ref.8 Ref.9

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

Nemaline myopathy 3 (NEM3) [MIM:161800]: A form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.12 Ref.14 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23

Myopathy, actin, congenital, with excess of thin myofilaments (MPCETM) [MIM:161800]: A congenital muscular disorder characterized at histological level by areas of sarcoplasm devoid of normal myofibrils and mitochondria, and replaced with dense masses of thin filaments. Central cores, rods, ragged red fibers, and necrosis are absent.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3

Myopathy, congenital, with fiber-type disproportion (CFTD) [MIM:255310]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16 Ref.22

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
   DiseaseDisease mutation
Nemaline myopathy
   LigandATP-binding
Nucleotide-binding
   Molecular functionMuscle protein
   PTMAcetylation
Methylation
Oxidation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell growth

Inferred from electronic annotation. Source: Ensembl

muscle contraction

Traceable author statement Ref.3. Source: UniProtKB

muscle filament sliding

Traceable author statement. Source: Reactome

response to extracellular stimulus

Inferred from electronic annotation. Source: Ensembl

response to lithium ion

Inferred from electronic annotation. Source: Ensembl

response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

response to steroid hormone

Inferred from electronic annotation. Source: Ensembl

skeletal muscle fiber adaptation

Inferred from electronic annotation. Source: Ensembl

skeletal muscle fiber development

Inferred from sequence or structural similarity. Source: UniProtKB

skeletal muscle thin filament assembly

Inferred from mutant phenotype Ref.12. Source: UniProtKB

   Cellular_componentactin cytoskeleton

Inferred from mutant phenotype Ref.17. Source: UniProtKB

actin filament

Inferred from direct assay PubMed 12849983. Source: UniProtKB

blood microparticle

Inferred from direct assay PubMed 22516433. Source: UniProt

cytosol

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 23580065. Source: UniProt

extracellular vesicular exosome

Inferred from direct assay PubMed 21362503. Source: UniProtKB

sarcomere

Inferred from direct assay PubMed 1423520. Source: UniProtKB

stress fiber

Inferred from direct assay Ref.17. Source: UniProtKB

striated muscle thin filament

Inferred from direct assay Ref.17. Source: UniProtKB

   Molecular_functionADP binding

Traceable author statement Ref.3. Source: UniProtKB

ATP binding

Traceable author statement Ref.3. Source: UniProtKB

myosin binding

Traceable author statement Ref.3. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 12849983. Source: UniProtKB

structural constituent of cytoskeleton

Traceable author statement Ref.3. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 22Removed in mature form By similarity
PRO_0000000844
Chain3 – 377375Actin, alpha skeletal muscle
PRO_0000000845

Amino acid modifications

Modified residue31N-acetylaspartate By similarity
Modified residue461Methionine (R)-sulfoxide By similarity
Modified residue491Methionine (R)-sulfoxide By similarity
Modified residue631N6-malonyllysine Ref.10
Modified residue751Tele-methylhistidine By similarity
Modified residue861N6-methyllysine Ref.11

Natural variations

Natural variant31D → Y in NEM3; some patients have core lesions on muscle biopsy. Ref.18
VAR_062424
Natural variant171G → R in MPCETM. Ref.3
VAR_011680
Natural variant271D → N in NEM3.
VAR_062425
Natural variant371V → L in NEM3. Ref.15
VAR_062426
Natural variant401P → L in NEM3. Ref.15
VAR_062427
Natural variant421H → Y in NEM3; severe. Ref.3 Ref.15
VAR_015579
Natural variant431Q → R in NEM3. Ref.15
VAR_062428
Natural variant441G → V in NEM3.
VAR_062429
Natural variant451V → F in NEM3.
VAR_062430
Natural variant661I → N in NEM3. Ref.15
VAR_062431
Natural variant681T → I in NEM3. Ref.17
VAR_062432
Natural variant741E → K in NEM3. Ref.17
VAR_062433
Natural variant751H → L in NEM3. Ref.15
VAR_062434
Natural variant751H → R in NEM3. Ref.15
VAR_062435
Natural variant771I → L in NEM3. Ref.15
VAR_062436
Natural variant791T → A in NEM3. Ref.15
VAR_062437
Natural variant851E → K in NEM3. Ref.15
VAR_062438
Natural variant961L → P in NEM3; autosomal recessive. Ref.3
VAR_011681
Natural variant1161A → T in NEM3.
VAR_062439
Natural variant1171N → S in NEM3; autosomal dominant. Ref.3 Ref.12 Ref.17
VAR_011682
Natural variant1171N → T in NEM3.
VAR_062440
Natural variant1181R → H in NEM3.
VAR_062441
Natural variant1341M → V in NEM3; autosomal dominant. Ref.3 Ref.14
VAR_013470
Natural variant1361V → A in NEM3. Ref.15
VAR_062442
Natural variant1381I → M in NEM3; autosomal recessive. Ref.12 Ref.17
VAR_011683
Natural variant1401A → P in NEM3.
VAR_062443
Natural variant1421L → P in NEM3.
VAR_062444
Natural variant1481G → D in NEM3. Ref.15
VAR_062445
Natural variant1501T → N in NEM3.
VAR_062446
Natural variant1561D → N in NEM3.
VAR_062447
Natural variant1651V → L in MPCETM. Ref.3 Ref.17
VAR_011684
Natural variant1651V → M in NEM3; results in sequestration of sarcomeric and Z line proteins into intranuclear aggregates; there is some evidence of muscle regeneration suggesting a compensatory effect. Ref.17 Ref.20 Ref.23
VAR_062448
Natural variant1721A → G in NEM3.
VAR_062449
Natural variant1811D → G in NEM3. Ref.15
VAR_062450
Natural variant1811D → H in NEM3.
VAR_062451
Natural variant1811D → N in NEM3.
VAR_062452
Natural variant1841G → D in NEM3; mild. Ref.3 Ref.15
VAR_015580
Natural variant1851R → C in NEM3; severe. Ref.3
VAR_015582
Natural variant1851R → D in NEM3; requires 2 nucleotide substitutions.
VAR_062453
Natural variant1851R → G in NEM3; autosomal dominant; severe. Ref.12 Ref.15 Ref.17
VAR_015581
Natural variant1851R → S in NEM3.
VAR_062454
Natural variant1981R → L in NEM3.
VAR_062455
Natural variant1991G → S in NEM3. Ref.15
VAR_062456
Natural variant2231L → P in CFTD. Ref.16
VAR_032917
Natural variant2261E → G in NEM3. Ref.15
VAR_062457
Natural variant2261E → Q in NEM3.
VAR_062458
Natural variant2271N → V in NEM3; requires 2 nucleotide substitutions.
VAR_062459
Natural variant2291M → I in NEM3. Ref.15
VAR_062460
Natural variant2291M → T in NEM3.
VAR_062461
Natural variant2291M → V in NEM3. Ref.15
VAR_062462
Natural variant2431E → K in NEM3.
VAR_062463
Natural variant2481Q → K in NEM3.
VAR_062464
Natural variant2481Q → R in NEM3. Ref.15
VAR_062465
Natural variant2531G → D in NEM3. Ref.15
VAR_062466
Natural variant2581R → H in NEM3; severe. Ref.3
VAR_015583
Natural variant2581R → L in NEM3.
VAR_062467
Natural variant2611E → V in NEM3; autosomal recessive. Ref.3
VAR_011685
Natural variant2651Q → L in NEM3; severe. Ref.3
VAR_015584
Natural variant2701G → C in NEM3; autosomal dominant. Ref.12 Ref.15 Ref.17
VAR_011686
Natural variant2701G → D in NEM3. Ref.19
VAR_062468
Natural variant2701G → R in NEM3.
VAR_062469
Natural variant2711M → R in NEM3; autosomal dominant. Ref.14
VAR_013471
Natural variant2741A → E in NEM3.
VAR_062470
Natural variant2811Y → H in NEM3. Ref.15
VAR_062471
Natural variant2821N → K in NEM3; severe. Ref.3 Ref.15
VAR_015585
Natural variant2851M → K in NEM3.
VAR_062472
Natural variant2881D → G in NEM3; severe. Ref.3 Ref.15
VAR_015586
Natural variant2941D → V in CFTD; results in decreased motility due to abnormal interactions between actin and tropomyosin with tropomyosin stabilized in the 'off' position; the mutant protein incorporates into actin filaments and does not result in increased actin aggregation or disruption of the sarcomere. Ref.16 Ref.22
VAR_032918
Natural variant3341P → S in CFTD. Ref.16
VAR_032919
Natural variant3361E → A in NEM3. Ref.18
VAR_062473
Natural variant3381K → E in NEM3. Ref.21
VAR_062474
Natural variant3381K → I in NEM3.
VAR_062475
Natural variant3501S → L in NEM3.
VAR_062476
Natural variant3591I → L in NEM3; autosomal dominant; severe. Ref.12 Ref.17
VAR_015587
Natural variant3721V → F in NEM3; severe. Ref.3
VAR_011687
Natural variant3741R → S in NEM3.
VAR_062477
Natural variant3751K → E in NEM3. Ref.19
VAR_062478
Natural variant3751K → Q in NEM3. Ref.15
VAR_062479

Secondary structure

............................................................... 377
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P68133 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: DF2A3A046346A179

FASTA37742,051
        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 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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 MPCETM 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 DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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: Skeletal muscle.
[8]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TTID.
[9]"The ubiquitin-specific protease USP25 interacts with three sarcomeric proteins."
Bosch-Comas A., Lindsten K., Gonzalez-Duarte R., Masucci M.G., Marfany G.
Cell. Mol. Life Sci. 63:723-734(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH USP25.
[10]"The first identification of lysine malonylation substrates and its regulatory enzyme."
Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y., He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C., Dai J., Verdin E., Ye Y., Zhao Y.
Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: MALONYLATION AT LYS-63.
[11]"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.
[12]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS NEM3 SER-117; MET-138; GLY-185; CYS-270 AND LEU-359.
[13]"Muscle disease caused by mutations in the skeletal muscle alpha-actin gene (ACTA1)."
Sparrow J.C., Nowak K.J., Durling H.J., Beggs A.H., Wallgren-Pettersson C., Romero N., Nonaka I., Laing N.G.
Neuromuscul. Disord. 13:519-531(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[14]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS NEM3 VAL-134 AND ARG-271.
[15]"Heterogeneity of nemaline myopathy cases with skeletal muscle alpha-actin gene mutations."
Agrawal P.B., Strickland C.D., Midgett C., Morales A., Newburger D.E., Poulos M.A., Tomczak K.K., Ryan M.M., Iannaccone S.T., Crawford T.O., Laing N.G., Beggs A.H.
Ann. Neurol. 56:86-96(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NEM3 LEU-37; LEU-40; TYR-42; ARG-43; ASN-66; LEU-75; ARG-75; LEU-77; ALA-79; LYS-85; ALA-136; ASP-148; GLY-181; ASP-184; GLY-185; SER-199; GLY-226; VAL-229; ILE-229; ARG-248; ASP-253; CYS-270; HIS-281; LYS-282; GLY-288 AND GLN-375.
[16]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS CFTD PRO-223; VAL-294 AND SER-334.
[17]"Evidence for a dominant-negative effect in ACTA1 nemaline myopathy caused by abnormal folding, aggregation and altered polymerization of mutant actin isoforms."
Ilkovski B., Nowak K.J., Domazetovska A., Maxwell A.L., Clement S., Davies K.E., Laing N.G., North K.N., Cooper S.T.
Hum. Mol. Genet. 13:1727-1743(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NEM3 ILE-68; LYS-74; SER-117; MET-138; LEU-165; MET-165; GLY-185; CYS-270 AND LEU-359.
[18]"Missense mutations of ACTA1 cause dominant congenital myopathy with cores."
Kaindl A.M., Rueschendorf F., Krause S., Goebel H.-H., Koehler K., Becker C., Pongratz D., Mueller-Hoecker J., Nuernberg P., Stoltenburg-Didinger G., Lochmueller H., Huebner A.
J. Med. Genet. 41:842-848(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NEM3 TYR-3 AND ALA-336.
[19]"Follow-up of nemaline myopathy in two patients with novel mutations in the skeletal muscle alpha-actin gene (ACTA1)."
Ohlsson M., Tajsharghi H., Darin N., Kyllerman M., Oldfors A.
Neuromuscul. Disord. 14:471-475(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NEM3 ASP-270 AND GLU-375.
[20]"Autosomal dominant nemaline myopathy with intranuclear rods due to mutation of the skeletal muscle ACTA1 gene: clinical and pathological variability within a kindred."
Hutchinson D.O., Charlton A., Laing N.G., Ilkovski B., North K.N.
Neuromuscul. Disord. 16:113-121(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NEM3 MET-165.
[21]"Fatal hypertrophic cardiomyopathy and nemaline myopathy associated with ACTA1 K336E mutation."
D'Amico A., Graziano C., Pacileo G., Petrini S., Nowak K.J., Boldrini R., Jacques A., Feng J.-J., Porfirio B., Sewry C.A., Santorelli F.M., Limongelli G., Bertini E., Laing N., Marston S.B.
Neuromuscul. Disord. 16:548-552(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NEM3 GLU-338.
[22]"The pathogenesis of ACTA1-related congenital fiber type disproportion."
Clarke N.F., Ilkovski B., Cooper S., Valova V.A., Robinson P.J., Nonaka I., Feng J.-J., Marston S., North K.
Ann. Neurol. 61:552-561(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT CFTD VAL-294.
[23]"Intranuclear rod myopathy: molecular pathogenesis and mechanisms of weakness."
Domazetovska A., Ilkovski B., Kumar V., Valova V.A., Vandebrouck A., Hutchinson D.O., Robinson P.J., Cooper S.T., Sparrow J.C., Peckham M., North K.N.
Ann. Neurol. 62:597-608(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT NEM3 MET-165.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
AL160004 Genomic DNA. Translation: CAI19050.1.
CH471098 Genomic DNA. Translation: EAW69898.1.
BC012597 mRNA. Translation: AAH12597.1.
CCDSCCDS1578.1.
PIRATHU. A31251.
RefSeqNP_001091.1. NM_001100.3.
UniGeneHs.1288.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1T44X-ray2.00A8-377[»]
ProteinModelPortalP68133.
SMRP68133. Positions 6-377.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106573. 95 interactions.
IntActP68133. 13 interactions.
MINTMINT-135471.
STRING9606.ENSP00000355645.

Chemistry

DrugBankDB00003. Dornase Alfa.

PTM databases

PhosphoSiteP68133.

Polymorphism databases

DMDM61218043.

Proteomic databases

MaxQBP68133.
PRIDEP68133.

Protocols and materials databases

DNASU58.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000366684; ENSP00000355645; ENSG00000143632.
GeneID58.
KEGGhsa:58.
UCSCuc001htm.3. human.

Organism-specific databases

CTD58.
GeneCardsGC01M229567.
GeneReviewsACTA1.
HGNCHGNC:129. ACTA1.
HPACAB000045.
HPA041271.
MIM102610. gene.
161800. phenotype.
255310. phenotype.
neXtProtNX_P68133.
Orphanet171439. Childhood-onset nemaline myopathy.
2020. Congenital fiber-type disproportion myopathy.
98904. Congenital myopathy with excess of thin filaments.
171433. Intermediate nemaline myopathy.
171430. Severe congenital nemaline myopathy.
171436. Typical nemaline myopathy.
PharmGKBPA24455.
GenAtlasSearch...

Phylogenomic databases

HOGENOMHOG000233340.
HOVERGENHBG003771.
InParanoidP68133.
KOK10354.
OMAILMETGM.
OrthoDBEOG72RMZ1.
PhylomeDBP68133.
TreeFamTF354237.

Enzyme and pathway databases

ReactomeREACT_17044. Muscle contraction.
SignaLinkP68133.

Gene expression databases

ArrayExpressP68133.
BgeeP68133.
CleanExHS_ACTA1.
GenevestigatorP68133.

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

ChiTaRSACTA1. human.
EvolutionaryTraceP68133.
GeneWikiActin,_alpha_1.
GenomeRNAi58.
NextBio245.
PROP68133.
SOURCESearch...

Entry information

Entry nameACTS_HUMAN
AccessionPrimary (citable) accession number: P68133
Secondary accession number(s): P02568, P99020, Q5T8M9
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 9, 2014
This is version 116 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 1

Human chromosome 1: entries, gene names and cross-references to MIM