P68133 (ACTS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [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. 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 USP25m in muscle differentiating cells. Ref.8 Ref.9
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	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-or rod-like structures in muscle fibers on histologic examination. Some patients present areas devoid of oxidative activity containg (cores) within myofibers. Core lesions are unstructured and poorly circumscribed. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.11 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.22 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 Congenital myopathy with fiber-type disproportion (CFTD) [MIM:255310]: 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.15 Ref.21
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 Nemaline myopathy
Ligand	ATP-binding Nucleotide-binding
Molecular function	Muscle protein
PTM	Acetylation Methylation Oxidation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell growth Inferred from electronic annotation. Source: Compara muscle filament sliding Traceable author statement. Source: Reactome response to extracellular stimulus Inferred from electronic annotation. Source: Compara response to lithium ion Inferred from electronic annotation. Source: Compara response to mechanical stimulus Inferred from electronic annotation. Source: Compara response to steroid hormone stimulus Inferred from electronic annotation. Source: Compara skeletal muscle fiber adaptation Inferred from electronic annotation. Source: Compara skeletal muscle fiber development Inferred from sequence or structural similarity. Source: UniProtKB skeletal muscle thin filament assembly Inferred from mutant phenotype Ref.11. Source: UniProtKB
Cellular_component	actin filament Inferred from direct assay PubMed 12849983. Source: UniProtKB cytosol Traceable author statement. Source: Reactome extracellular vesicular exosome Inferred from direct assay PubMed 21362503. Source: UniProtKB stress fiber Inferred from direct assay Ref.16. Source: UniProtKB striated muscle thin filament Inferred from direct assay Ref.16. Source: UniProtKB
Molecular_function	ADP 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 structural constituent of cytoskeleton Traceable author statement Ref.3. Source: UniProtKB
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_0000000844

Chain

3 – 377

375

Actin, alpha skeletal muscle

PRO_0000000845

Amino acid modifications

Modified residue

3

1

N-acetylaspartate By similarity

Modified residue

46

1

Methionine sulfoxide By similarity

Modified residue

55

1

Phosphotyrosine By similarity

Modified residue

63

1

N6-malonyllysine Ref.10

Modified residue

75

1

Tele-methylhistidine By similarity

Modified residue

93

1

Phosphotyrosine By similarity

Modified residue

242

1

Phosphotyrosine By similarity

Natural variations

Natural variant

3

1

D → Y in NEM3; some patients have core lesions on muscle biopsy. Ref.17

VAR_062424

Natural variant

17

1

G → R in MPCETM. Ref.3

VAR_011680

Natural variant

27

1

D → N in NEM3.

VAR_062425

Natural variant

37

1

V → L in NEM3. Ref.14

VAR_062426

Natural variant

40

1

P → L in NEM3. Ref.14

VAR_062427

Natural variant

42

1

H → Y in NEM3; severe. Ref.3 Ref.14

VAR_015579

Natural variant

43

1

Q → R in NEM3. Ref.14

VAR_062428

Natural variant

44

1

G → V in NEM3.

VAR_062429

Natural variant

45

1

V → F in NEM3.

VAR_062430

Natural variant

66

1

I → N in NEM3. Ref.14

VAR_062431

Natural variant

68

1

T → I in NEM3. Ref.16

VAR_062432

Natural variant

74

1

E → K in NEM3. Ref.16

VAR_062433

Natural variant

75

1

H → L in NEM3. Ref.14

VAR_062434

Natural variant

75

1

H → R in NEM3. Ref.14

VAR_062435

Natural variant

77

1

I → L in NEM3. Ref.14

VAR_062436

Natural variant

79

1

T → A in NEM3. Ref.14

VAR_062437

Natural variant

85

1

E → K in NEM3. Ref.14

VAR_062438

Natural variant

96

1

L → P in NEM3; autosomal recessive. Ref.3

VAR_011681

Natural variant

116

1

A → T in NEM3.

VAR_062439

Natural variant

117

1

N → S in NEM3; autosomal dominant. Ref.3 Ref.11 Ref.16

VAR_011682

Natural variant

117

1

N → T in NEM3.

VAR_062440

Natural variant

118

1

R → H in NEM3.

VAR_062441

Natural variant

134

1

M → V in NEM3; autosomal dominant. Ref.3 Ref.13

VAR_013470

Natural variant

136

1

V → A in NEM3. Ref.14

VAR_062442

Natural variant

138

1

I → M in NEM3; autosomal recessive. Ref.11 Ref.16

VAR_011683

Natural variant

140

1

A → P in NEM3.

VAR_062443

Natural variant

142

1

L → P in NEM3.

VAR_062444

Natural variant

148

1

G → D in NEM3. Ref.14

VAR_062445

Natural variant

150

1

T → N in NEM3.

VAR_062446

Natural variant

156

1

D → N in NEM3.

VAR_062447

Natural variant

165

1

V → L in MPCETM. Ref.3 Ref.16

VAR_011684

Natural variant

165

1

V → 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.16 Ref.19 Ref.22

VAR_062448

Natural variant

172

1

A → G in NEM3.

VAR_062449

Natural variant

181

1

D → G in NEM3. Ref.14

VAR_062450

Natural variant

181

1

D → H in NEM3.

VAR_062451

Natural variant

181

1

D → N in NEM3.

VAR_062452

Natural variant

184

1

G → D in NEM3; mild. Ref.3 Ref.14

VAR_015580

Natural variant

185

1

R → C in NEM3; severe. Ref.3

VAR_015582

Natural variant

185

1

R → D in NEM3; requires 2 nucleotide substitutions.

VAR_062453

Natural variant

185

1

R → G in NEM3; autosomal dominant; severe. Ref.11 Ref.14 Ref.16

VAR_015581

Natural variant

185

1

R → S in NEM3.

VAR_062454

Natural variant

198

1

R → L in NEM3.

VAR_062455

Natural variant

199

1

G → S in NEM3. Ref.14

VAR_062456

Natural variant

223

1

L → P in CFTD. Ref.15

VAR_032917

Natural variant

226

1

E → G in NEM3. Ref.14

VAR_062457

Natural variant

226

1

E → Q in NEM3.

VAR_062458

Natural variant

227

1

N → V in NEM3; requires 2 nucleotide substitutions.

VAR_062459

Natural variant

229

1

M → I in NEM3. Ref.14

VAR_062460

Natural variant

229

1

M → T in NEM3.

VAR_062461

Natural variant

229

1

M → V in NEM3. Ref.14

VAR_062462

Natural variant

243

1

E → K in NEM3.

VAR_062463

Natural variant

248

1

Q → K in NEM3.

VAR_062464

Natural variant

248

1

Q → R in NEM3. Ref.14

VAR_062465

Natural variant

253

1

G → D in NEM3. Ref.14

VAR_062466

Natural variant

258

1

R → H in NEM3; severe. Ref.3

VAR_015583

Natural variant

258

1

R → L in NEM3.

VAR_062467

Natural variant

261

1

E → V in NEM3; autosomal recessive. Ref.3

VAR_011685

Natural variant

265

1

Q → L in NEM3; severe. Ref.3

VAR_015584

Natural variant

270

1

G → C in NEM3; autosomal dominant. Ref.11 Ref.14 Ref.16

VAR_011686

Natural variant

270

1

G → D in NEM3. Ref.18

VAR_062468

Natural variant

270

1

G → R in NEM3.

VAR_062469

Natural variant

271

1

M → R in NEM3; autosomal dominant. Ref.13

VAR_013471

Natural variant

274

1

A → E in NEM3.

VAR_062470

Natural variant

281

1

Y → H in NEM3. Ref.14

VAR_062471

Natural variant

282

1

N → K in NEM3; severe. Ref.3 Ref.14

VAR_015585

Natural variant

285

1

M → K in NEM3.

VAR_062472

Natural variant

288

1

D → G in NEM3; severe. Ref.3 Ref.14

VAR_015586

Natural variant

294

1

D → 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.15 Ref.21

VAR_032918

Natural variant

334

1

P → S in CFTD. Ref.15

VAR_032919

Natural variant

336

1

E → A in NEM3. Ref.17

VAR_062473

Natural variant

338

1

K → E in NEM3. Ref.20

VAR_062474

Natural variant

338

1

K → I in NEM3.

VAR_062475

Natural variant

350

1

S → L in NEM3.

VAR_062476

Natural variant

359

1

I → L in NEM3; autosomal dominant; severe. Ref.11 Ref.16

VAR_015587

Natural variant

372

1

V → F in NEM3; severe. Ref.3

VAR_011687

Natural variant

374

1

R → S in NEM3.

VAR_062477

Natural variant

375

1

K → E in NEM3. Ref.18

VAR_062478

Natural variant

375

1

K → Q in NEM3. Ref.14

VAR_062479

Secondary structure

1

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377

Helix Strand Turn

Details...

Beta strand

10 – 13

4

Beta strand

19 – 21

3

Beta strand

30 – 33

4

Turn

59 – 61

3

Helix

81 – 93

13

Helix

100 – 102

3

Beta strand

105 – 109

5

Helix

115 – 127

13

Beta strand

132 – 138

7

Helix

139 – 146

8

Beta strand

154 – 157

4

Beta strand

162 – 165

4

Helix

174 – 176

3

Beta strand

178 – 180

3

Helix

186 – 197

12

Helix

205 – 218

14

Helix

225 – 234

10

Beta strand

240 – 243

4

Beta strand

249 – 252

4

Helix

255 – 264

10

Helix

266 – 268

3

Helix

277 – 284

8

Turn

289 – 291

3

Helix

292 – 297

6

Beta strand

299 – 302

4

Helix

312 – 320

9

Turn

335 – 338

4

Turn

340 – 342

3

Helix

347 – 350

4

Helix

354 – 357

4

Beta strand

358 – 360

3

Helix

361 – 366

6

Helix

371 – 375

5

Sequences

	Sequence		Length	Mass (Da)
	P68133 [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] [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. , 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. , 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]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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.
[18]	"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.
[19]	"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.
[20]	"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.
[21]	"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.
[22]	"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.

Web resources

GeneReviews

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.

IPI

IPI00021428.

PIR

ATHU. A31251.

RefSeq

NP_001091.1. NM_001100.3.

UniGene

Hs.1288.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1T44	X-ray	2.00	A	8-377	[»]

ProteinModelPortal

P68133.

ModBase

Search...

Protein-protein interaction databases

IntAct

P68133. 7 interactions.

MINT

MINT-135471.

STRING

9606.ENSP00000355645.

PTM databases

PhosphoSite

P68133.

Polymorphism databases

DMDM

61218043.

Proteomic databases

PRIDE

P68133.

Protocols and materials databases

DNASU

58.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000366684; ENSP00000355645; ENSG00000143632.

GeneID

58.

KEGG

hsa:58.

UCSC

uc001htm.3. human.

Organism-specific databases

CTD

58.

GeneCards

GC01M229567.

HGNC

HGNC:129. ACTA1.

HPA

CAB000045.
HPA041271.

MIM

102610. gene.
161800. phenotype.
255310. phenotype.

neXtProt

NX_P68133.

Orphanet

2020. Congenital fiber-type disproportion myopathy.
171433. Intermediate nemaline myopathy.
171439. Mild nemaline myopathy.
171430. Severe congenital nemaline myopathy.
171436. Typical nemaline myopathy.

PharmGKB

PA24455.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HOG000233340.

HOVERGEN

HBG003771.

InParanoid

P68133.

KO

K10354.

OMA

FEEEMAT.

OrthoDB

EOG4W9J40.

PhylomeDB

P68133.

Enzyme and pathway databases

Pathway_Interaction_DB

caspase_pathway. Caspase cascade in apoptosis.

Reactome

REACT_17044. Muscle contraction.

Gene expression databases

ArrayExpress

P68133.

Bgee

P68133.

CleanEx

HS_ACTA1.

Genevestigator

P68133.

GermOnline

ENSG00000143632. 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

ChiTaRS

ACTA1. human.

DrugBank

DB00003. Dornase Alfa.

EvolutionaryTrace

P68133.

GenomeRNAi

58.

NextBio

245.

SOURCE

Search...

Entry information

Entry name

ACTS_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 102 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.