ACTA_HUMAN
ID ACTA_HUMAN Reviewed; 377 AA.
AC P62736; B2R8A4; P03996; P04108; Q6FI19;
DT 23-OCT-1986, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Actin, aortic smooth muscle;
DE AltName: Full=Alpha-actin-2;
DE AltName: Full=Cell growth-inhibiting gene 46 protein;
DE Contains:
DE RecName: Full=Actin, aortic smooth muscle, intermediate form;
DE Flags: Precursor;
GN Name=ACTA2; Synonyms=ACTSA, ACTVS; ORFNames=GIG46;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2701935; DOI=10.1093/nar/17.4.1767;
RA Kamada S., Kakunaga T.;
RT "The nucleotide sequence of a human smooth muscle alpha-actin (aortic type)
RT cDNA.";
RL Nucleic Acids Res. 17:1767-1767(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2295650; DOI=10.1016/s0021-9258(19)40070-7;
RA Reddy S., Ozgur K., Lu M., Chang W., Mohan S.R., Kumar C.C., Ruley H.E.;
RT "Structure of the human smooth muscle alpha-actin gene. Analysis of a cDNA
RT and 5' upstream region.";
RL J. Biol. Chem. 265:1683-1687(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a human cell growth inhibiting gene.";
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-330.
RX PubMed=6330528; DOI=10.1128/mcb.4.6.1073-1078.1984;
RA Ueyama H., Hamada H., Battula N., Kakunaga T.;
RT "Structure of a human smooth muscle actin gene (aortic type) with a unique
RT intron site.";
RL Mol. Cell. Biol. 4:1073-1078(1984).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 331-377.
RX PubMed=2612915; DOI=10.1016/0378-1119(89)90520-9;
RA Kamada S., Nakano Y., Kakunaga T.;
RT "Structure of 3'-downstream segment of the human smooth muscle (aortic-
RT type) alpha-actin-encoding gene and isolation of the specific DNA probe.";
RL Gene 84:455-462(1989).
RN [11]
RP INDUCTION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16548883; DOI=10.1111/j.1462-5822.2005.00644.x;
RA Leong W.F., Chow V.T.;
RT "Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal
RT differential cellular gene expression in response to enterovirus 71
RT infection.";
RL Cell. Microbiol. 8:565-580(2006).
RN [12]
RP CROSS-LINK BY V.CHOLERAE TOXIN RTXA (MICROBIAL INFECTION).
RX PubMed=19015515; DOI=10.1073/pnas.0808082105;
RA Kudryashov D.S., Durer Z.A., Ytterberg A.J., Sawaya M.R., Pashkov I.,
RA Prochazkova K., Yeates T.O., Loo R.R., Loo J.A., Satchell K.J., Reisler E.;
RT "Connecting actin monomers by iso-peptide bond is a toxicity mechanism of
RT the Vibrio cholerae MARTX toxin.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:18537-18542(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT GLU-3, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP CROSS-LINK BY V.CHOLERAE TOXIN RTXA (MICROBIAL INFECTION).
RX PubMed=26228148; DOI=10.1126/science.aab4090;
RA Heisler D.B., Kudryashova E., Grinevich D.O., Suarez C., Winkelman J.D.,
RA Birukov K.G., Kotha S.R., Parinandi N.L., Vavylonis D., Kovar D.R.,
RA Kudryashov D.S.;
RT "ACD toxin-produced actin oligomers poison formin-controlled actin
RT polymerization.";
RL Science 349:535-539(2015).
RN [16]
RP METHYLATION AT HIS-75.
RX PubMed=30626964; DOI=10.1038/s41586-018-0821-8;
RA Wilkinson A.W., Diep J., Dai S., Liu S., Ooi Y.S., Song D., Li T.M.,
RA Horton J.R., Zhang X., Liu C., Trivedi D.V., Ruppel K.M.,
RA Vilches-Moure J.G., Casey K.M., Mak J., Cowan T., Elias J.E.,
RA Nagamine C.M., Spudich J.A., Cheng X., Carette J.E., Gozani O.;
RT "SETD3 is an actin histidine methyltransferase that prevents primary
RT dystocia.";
RL Nature 565:372-376(2019).
RN [17]
RP VARIANTS AAT6 THR-117; GLN-118; HIS-135; CYS-149; ALA-154; CYS-258;
RP HIS-258; GLY-292 AND ASN-353.
RX PubMed=17994018; DOI=10.1038/ng.2007.6;
RA Guo D.-C., Pannu H., Tran-Fadulu V., Papke C.L., Yu R.K., Avidan N.,
RA Bourgeois S., Estrera A.L., Safi H.J., Sparks E., Amor D., Ades L.,
RA McConnell V., Willoughby C.E., Abuelo D., Willing M., Lewis R.A., Kim D.H.,
RA Scherer S., Tung P.P., Ahn C., Buja L.M., Raman C.S., Shete S.S.,
RA Milewicz D.M.;
RT "Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic
RT aneurysms and dissections.";
RL Nat. Genet. 39:1488-1493(2007).
RN [18]
RP VARIANTS AAT6 HIS-39; THR-117; GLN-118; CYS-149; ALA-154; GLN-185; GLN-212;
RP HIS-258; CYS-258; ASN-326 AND ASN-353.
RX PubMed=19409525; DOI=10.1016/j.ajhg.2009.04.007;
RA Guo D.-C., Papke C.L., Tran-Fadulu V., Regalado E.S., Avidan N.,
RA Johnson R.J., Kim D.H., Pannu H., Willing M.C., Sparks E., Pyeritz R.E.,
RA Singh M.N., Dalman R.L., Grotta J.C., Marian A.J., Boerwinkle E.A.,
RA Frazier L.Q., LeMaire S.A., Coselli J.S., Estrera A.L., Safi H.J.,
RA Veeraraghavan S., Muzny D.M., Wheeler D.A., Willerson J.T., Yu R.K.,
RA Shete S.S., Scherer S.E., Raman C.S., Buja L.M., Milewicz D.M.;
RT "Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery
RT disease, stroke, and Moyamoya disease, along with thoracic aortic
RT disease.";
RL Am. J. Hum. Genet. 84:617-627(2009).
RN [19]
RP VARIANTS AAT6 CYS-145; CYS-149 AND GLN-212, AND PREDISPOSITION TO A VARIETY
RP OF VASCULAR DISEASES.
RX PubMed=19639654; DOI=10.1002/humu.21081;
RA Morisaki H., Akutsu K., Ogino H., Kondo N., Yamanaka I., Tsutsumi Y.,
RA Yoshimuta T., Okajima T., Matsuda H., Minatoya K., Sasaki H., Tanaka H.,
RA Ishibashi-Ueda H., Morisaki T.;
RT "Mutation of ACTA2 gene as an important cause of familial and nonfamilial
RT nonsyndromatic thoracic aortic aneurysm and/or dissection (TAAD).";
RL Hum. Mutat. 30:1406-1411(2009).
RN [20]
RP VARIANT MSMDS HIS-179.
RX PubMed=20734336; DOI=10.1002/ajmg.a.33657;
RA Milewicz D.M., Ostergaard J.R., Ala-Kokko L.M., Khan N., Grange D.K.,
RA Mendoza-Londono R., Bradley T.J., Olney A.H., Ades L., Maher J.F., Guo D.,
RA Buja L.M., Kim D., Hyland J.C., Regalado E.S.;
RT "De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth
RT muscle dysfunction.";
RL Am. J. Med. Genet. A 152:2437-2443(2010).
RN [21]
RP VARIANT MYMY5 HIS-179.
RX PubMed=20970362; DOI=10.1016/j.ejpn.2010.09.002;
RA Roder C., Peters V., Kasuya H., Nishizawa T., Wakita S., Berg D.,
RA Schulte C., Khan N., Tatagiba M., Krischek B.;
RT "Analysis of ACTA2 in European Moyamoya disease patients.";
RL Eur. J. Paediatr. Neurol. 15:117-122(2011).
RN [22]
RP VARIANT MSMDS CYS-179.
RX PubMed=27481187; DOI=10.1002/ajmg.a.37857;
RA Moreno C.A., Metze K., Lomazi E.A., Bertola D.R., Barbosa R.H.,
RA Cosentino V., Sobreira N., Cavalcanti D.P.;
RT "Visceral myopathy: Clinical and molecular survey of a cohort of seven new
RT patients and state of the art of overlapping phenotypes.";
RL Am. J. Med. Genet. A 170:2965-2974(2016).
CC -!- FUNCTION: Actins are highly conserved proteins that are involved in
CC various types of cell motility and are ubiquitously expressed in all
CC eukaryotic cells.
CC -!- SUBUNIT: Polymerization of globular actin (G-actin) leads to a
CC structural filament (F-actin) in the form of a two-stranded helix. Each
CC actin can bind to 4 others.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
CC -!- INDUCTION: Up-regulated in response to enterovirus 71 (EV71) infection.
CC {ECO:0000269|PubMed:16548883}.
CC -!- PTM: Oxidation of Met-46 and Met-49 by MICALs (MICAL1, MICAL2 or
CC MICAL3) to form methionine sulfoxide promotes actin filament
CC depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The
CC (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promotes actin
CC repolymerization. {ECO:0000250|UniProtKB:P62737}.
CC -!- PTM: Monomethylation at Lys-86 (K84me1) regulates actin-myosin
CC interaction and actomyosin-dependent processes. Demethylation by ALKBH4
CC is required for maintaining actomyosin dynamics supporting normal
CC cleavage furrow ingression during cytokinesis and cell migration.
CC {ECO:0000250|UniProtKB:P68032}.
CC -!- PTM: Methylated at His-75 by SETD3. {ECO:0000269|PubMed:30626964}.
CC -!- PTM: (Microbial infection) Monomeric actin is cross-linked by
CC V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins
CC mediate the cross-link between Lys-52 of one monomer and Glu-272 of
CC another actin monomer, resulting in formation of highly toxic actin
CC oligomers that cause cell rounding (PubMed:19015515). The toxin can be
CC highly efficient at very low concentrations by acting on formin
CC homology family proteins: toxic actin oligomers bind with high affinity
CC to formins and adversely affect both nucleation and elongation
CC abilities of formins, causing their potent inhibition in both profilin-
CC dependent and independent manners (PubMed:26228148).
CC {ECO:0000305|PubMed:19015515, ECO:0000305|PubMed:26228148}.
CC -!- DISEASE: Note=ACTA2 mutations predispose patients to a variety of
CC diffuse and diverse vascular diseases, premature onset coronary artery
CC disease (CAD), premature ischemic strokes and Moyamoya disease.
CC {ECO:0000269|PubMed:19409525}.
CC -!- DISEASE: Aortic aneurysm, familial thoracic 6 (AAT6) [MIM:611788]: A
CC disease characterized by permanent dilation of the thoracic aorta
CC usually due to degenerative changes in the aortic wall. It is primarily
CC associated with a characteristic histologic appearance known as 'medial
CC necrosis' or 'Erdheim cystic medial necrosis' in which there is
CC degeneration and fragmentation of elastic fibers, loss of smooth muscle
CC cells, and an accumulation of basophilic ground substance.
CC {ECO:0000269|PubMed:17994018, ECO:0000269|PubMed:19409525,
CC ECO:0000269|PubMed:19639654}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Moyamoya disease 5 (MYMY5) [MIM:614042]: A progressive
CC cerebral angiopathy characterized by bilateral intracranial carotid
CC artery stenosis and telangiectatic vessels in the region of the basal
CC ganglia. The abnormal vessels resemble a 'puff of smoke' (moyamoya) on
CC cerebral angiogram. Affected individuals can develop transient ischemic
CC attacks and/or cerebral infarction, and rupture of the collateral
CC vessels can cause intracranial hemorrhage. Hemiplegia of sudden onset
CC and epileptic seizures constitute the prevailing presentation in
CC childhood, while subarachnoid bleeding occurs more frequently in
CC adults. {ECO:0000269|PubMed:20970362}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Multisystemic smooth muscle dysfunction syndrome (MSMDS)
CC [MIM:613834]: A syndrome characterized by dysfunction of smooth muscle
CC cells throughout the body, leading to aortic and cerebrovascular
CC disease, fixed dilated pupils, hypotonic bladder, malrotation, and
CC hypoperistalsis of the gut and pulmonary hypertension.
CC {ECO:0000269|PubMed:20734336, ECO:0000269|PubMed:27481187}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: In vertebrates 3 main groups of actin isoforms, alpha,
CC beta and gamma have been identified. The alpha actins are found in
CC muscle tissues and are a major constituent of the contractile
CC apparatus. The beta and gamma actins coexist in most cell types as
CC components of the cytoskeleton and as mediators of internal cell
CC motility.
CC -!- SIMILARITY: Belongs to the actin family. {ECO:0000305}.
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DR EMBL; X13839; CAA32064.1; -; mRNA.
DR EMBL; J05192; AAA51577.1; -; mRNA.
DR EMBL; AY692464; AAW29811.1; -; mRNA.
DR EMBL; CR536518; CAG38756.1; -; mRNA.
DR EMBL; AK313294; BAG36101.1; -; mRNA.
DR EMBL; AL157394; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW50153.1; -; Genomic_DNA.
DR EMBL; BC017554; AAH17554.1; -; mRNA.
DR EMBL; BC093052; AAH93052.1; -; mRNA.
DR EMBL; K01741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; K01742; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; K01743; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M33216; AAA60560.1; -; Genomic_DNA.
DR CCDS; CCDS7392.1; -.
DR PIR; A35020; ATHUSM.
DR RefSeq; NP_001135417.1; NM_001141945.2.
DR RefSeq; NP_001307784.1; NM_001320855.1.
DR RefSeq; NP_001604.1; NM_001613.2.
DR AlphaFoldDB; P62736; -.
DR SMR; P62736; -.
DR BioGRID; 106574; 506.
DR CORUM; P62736; -.
DR ELM; P62736; -.
DR IntAct; P62736; 102.
DR MINT; P62736; -.
DR STRING; 9606.ENSP00000402373; -.
DR DrugBank; DB12695; Phenethyl Isothiocyanate.
DR GlyGen; P62736; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; P62736; -.
DR MetOSite; P62736; -.
DR PhosphoSitePlus; P62736; -.
DR SwissPalm; P62736; -.
DR BioMuta; ACTA2; -.
DR DMDM; 51316972; -.
DR REPRODUCTION-2DPAGE; IPI00008603; -.
DR UCD-2DPAGE; P62736; -.
DR EPD; P62736; -.
DR jPOST; P62736; -.
DR MassIVE; P62736; -.
DR MaxQB; P62736; -.
DR PaxDb; P62736; -.
DR PeptideAtlas; P62736; -.
DR PRIDE; P62736; -.
DR ProteomicsDB; 57419; -.
DR TopDownProteomics; P62736; -.
DR Antibodypedia; 30207; 1525 antibodies from 51 providers.
DR DNASU; 59; -.
DR Ensembl; ENST00000224784.10; ENSP00000224784.6; ENSG00000107796.13.
DR GeneID; 59; -.
DR KEGG; hsa:59; -.
DR MANE-Select; ENST00000224784.10; ENSP00000224784.6; NM_001613.4; NP_001604.1.
DR UCSC; uc001kfp.4; human.
DR CTD; 59; -.
DR DisGeNET; 59; -.
DR GeneCards; ACTA2; -.
DR GeneReviews; ACTA2; -.
DR HGNC; HGNC:130; ACTA2.
DR HPA; ENSG00000107796; Tissue enhanced (endometrium, seminal vesicle, smooth muscle).
DR MalaCards; ACTA2; -.
DR MIM; 102620; gene.
DR MIM; 611788; phenotype.
DR MIM; 613834; phenotype.
DR MIM; 614042; phenotype.
DR neXtProt; NX_P62736; -.
DR OpenTargets; ENSG00000107796; -.
DR Orphanet; 91387; Familial thoracic aortic aneurysm and aortic dissection.
DR Orphanet; 2573; Moyamoya disease.
DR Orphanet; 404463; Multisystemic smooth muscle dysfunction syndrome.
DR PharmGKB; PA24456; -.
DR VEuPathDB; HostDB:ENSG00000107796; -.
DR eggNOG; KOG0676; Eukaryota.
DR GeneTree; ENSGT00940000154148; -.
DR HOGENOM; CLU_027965_0_2_1; -.
DR InParanoid; P62736; -.
DR OMA; PNIMVGM; -.
DR OrthoDB; 649708at2759; -.
DR PhylomeDB; P62736; -.
DR TreeFam; TF354237; -.
DR PathwayCommons; P62736; -.
DR Reactome; R-HSA-445355; Smooth Muscle Contraction.
DR Reactome; R-HSA-9013695; NOTCH4 Intracellular Domain Regulates Transcription.
DR SignaLink; P62736; -.
DR SIGNOR; P62736; -.
DR BioGRID-ORCS; 59; 13 hits in 1068 CRISPR screens.
DR ChiTaRS; ACTA2; human.
DR GeneWiki; ACTA2; -.
DR GenomeRNAi; 59; -.
DR Pharos; P62736; Tbio.
DR PRO; PR:P62736; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P62736; protein.
DR Bgee; ENSG00000107796; Expressed in saphenous vein and 211 other tissues.
DR ExpressionAtlas; P62736; baseline and differential.
DR Genevisible; P62736; HS.
DR GO; GO:0044297; C:cell body; ISS:AgBase.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005869; C:dynactin complex; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0030175; C:filopodium; ISS:AgBase.
DR GO; GO:0030027; C:lamellipodium; ISS:AgBase.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0030485; C:smooth muscle contractile fiber; IEA:Ensembl.
DR GO; GO:0001725; C:stress fiber; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0072144; P:glomerular mesangial cell development; IEP:UniProtKB.
DR GO; GO:0090131; P:mesenchyme migration; ISS:AgBase.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:AgBase.
DR GO; GO:2000491; P:positive regulation of hepatic stellate cell activation; IEA:Ensembl.
DR GO; GO:0061874; P:positive regulation of hepatic stellate cell contraction; IEA:Ensembl.
DR GO; GO:0061870; P:positive regulation of hepatic stellate cell migration; IEA:Ensembl.
DR GO; GO:0008217; P:regulation of blood pressure; IEA:Ensembl.
DR GO; GO:0061041; P:regulation of wound healing; IEA:Ensembl.
DR GO; GO:0009615; P:response to virus; IEP:UniProtKB.
DR GO; GO:0014829; P:vascular associated smooth muscle contraction; IBA:GO_Central.
DR InterPro; IPR004000; Actin.
DR InterPro; IPR020902; Actin/actin-like_CS.
DR InterPro; IPR004001; Actin_CS.
DR InterPro; IPR043129; ATPase_NBD.
DR PANTHER; PTHR11937; PTHR11937; 1.
DR Pfam; PF00022; Actin; 1.
DR PRINTS; PR00190; ACTIN.
DR SMART; SM00268; ACTIN; 1.
DR SUPFAM; SSF53067; SSF53067; 2.
DR PROSITE; PS00406; ACTINS_1; 1.
DR PROSITE; PS00432; ACTINS_2; 1.
DR PROSITE; PS01132; ACTINS_ACT_LIKE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Aortic aneurysm; ATP-binding; Cytoplasm; Cytoskeleton;
KW Disease variant; Isopeptide bond; Methylation; Muscle protein;
KW Nucleotide-binding; Oxidation; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..377
FT /note="Actin, aortic smooth muscle, intermediate form"
FT /evidence="ECO:0000250|UniProtKB:P62737"
FT /id="PRO_0000442603"
FT CHAIN 3..377
FT /note="Actin, aortic smooth muscle"
FT /id="PRO_0000442604"
FT MOD_RES 2
FT /note="N-acetylcysteine; in intermediate form"
FT /evidence="ECO:0000250|UniProtKB:P62737"
FT MOD_RES 3
FT /note="N-acetylglutamate; in Actin, aortic smooth muscle"
FT /evidence="ECO:0007744|PubMed:22223895"
FT MOD_RES 46
FT /note="Methionine (R)-sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P62737"
FT MOD_RES 49
FT /note="Methionine (R)-sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P62737"
FT MOD_RES 75
FT /note="Tele-methylhistidine"
FT /evidence="ECO:0000269|PubMed:30626964"
FT MOD_RES 86
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:P68032"
FT CROSSLNK 52
FT /note="Isoglutamyl lysine isopeptide (Lys-Glu) (interchain
FT with E-272); by Vibrio toxins RtxA and VgrG1"
FT /evidence="ECO:0000250|UniProtKB:P60709"
FT CROSSLNK 272
FT /note="Isoglutamyl lysine isopeptide (Glu-Lys) (interchain
FT with K-52); by Vibrio toxins RtxA and VgrG1"
FT /evidence="ECO:0000250|UniProtKB:P60709"
FT VARIANT 39
FT /note="R -> H (in AAT6; dbSNP:rs794728021)"
FT /evidence="ECO:0000269|PubMed:19409525"
FT /id="VAR_062577"
FT VARIANT 117
FT /note="N -> T (in AAT6)"
FT /evidence="ECO:0000269|PubMed:17994018,
FT ECO:0000269|PubMed:19409525"
FT /id="VAR_045915"
FT VARIANT 118
FT /note="R -> Q (in AAT6; dbSNP:rs112602953)"
FT /evidence="ECO:0000269|PubMed:17994018,
FT ECO:0000269|PubMed:19409525"
FT /id="VAR_045916"
FT VARIANT 135
FT /note="Y -> H (in AAT6; dbSNP:rs751300489)"
FT /evidence="ECO:0000269|PubMed:17994018"
FT /id="VAR_045917"
FT VARIANT 145
FT /note="Y -> C (in AAT6)"
FT /evidence="ECO:0000269|PubMed:19639654"
FT /id="VAR_062578"
FT VARIANT 149
FT /note="R -> C (in AAT6; dbSNP:rs121434526)"
FT /evidence="ECO:0000269|PubMed:17994018,
FT ECO:0000269|PubMed:19409525, ECO:0000269|PubMed:19639654"
FT /id="VAR_045918"
FT VARIANT 154
FT /note="V -> A (in AAT6; dbSNP:rs1554841298)"
FT /evidence="ECO:0000269|PubMed:17994018,
FT ECO:0000269|PubMed:19409525"
FT /id="VAR_045919"
FT VARIANT 179
FT /note="R -> C (in MSMDS)"
FT /evidence="ECO:0000269|PubMed:27481187"
FT /id="VAR_085865"
FT VARIANT 179
FT /note="R -> H (in MYMY5 and MSMDS; disease phenotype
FT include smooth muscle cells dysfunction in organs
FT throughout the body with decreased contractile function in
FT the iris, bladder and gastrointestinal tract;
FT dbSNP:rs387906592)"
FT /evidence="ECO:0000269|PubMed:20734336,
FT ECO:0000269|PubMed:20970362"
FT /id="VAR_064516"
FT VARIANT 185
FT /note="R -> Q (in AAT6; dbSNP:rs1057521105)"
FT /evidence="ECO:0000269|PubMed:19409525"
FT /id="VAR_062579"
FT VARIANT 196
FT /note="T -> S (in dbSNP:rs1803028)"
FT /id="VAR_011944"
FT VARIANT 212
FT /note="R -> Q (in AAT6; dbSNP:rs397516685)"
FT /evidence="ECO:0000269|PubMed:19409525,
FT ECO:0000269|PubMed:19639654"
FT /id="VAR_062580"
FT VARIANT 258
FT /note="R -> C (in AAT6; dbSNP:rs121434528)"
FT /evidence="ECO:0000269|PubMed:17994018,
FT ECO:0000269|PubMed:19409525"
FT /id="VAR_045920"
FT VARIANT 258
FT /note="R -> H (in AAT6; dbSNP:rs121434527)"
FT /evidence="ECO:0000269|PubMed:17994018,
FT ECO:0000269|PubMed:19409525"
FT /id="VAR_045921"
FT VARIANT 292
FT /note="R -> G (in AAT6)"
FT /evidence="ECO:0000269|PubMed:17994018"
FT /id="VAR_045922"
FT VARIANT 320
FT /note="T -> A (in dbSNP:rs1803027)"
FT /id="VAR_011945"
FT VARIANT 326
FT /note="T -> N (in AAT6; dbSNP:rs777832794)"
FT /evidence="ECO:0000269|PubMed:19409525"
FT /id="VAR_062581"
FT VARIANT 353
FT /note="T -> N (in AAT6)"
FT /evidence="ECO:0000269|PubMed:17994018,
FT ECO:0000269|PubMed:19409525"
FT /id="VAR_045923"
FT VARIANT 373
FT /note="H -> P (in dbSNP:rs1062398)"
FT /id="VAR_011946"
FT CONFLICT 234
FT /note="S -> W (in Ref. 2; AAA51577)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 377 AA; 42009 MW; 2D0543262DB35CA5 CRC64;
MCEEEDSTAL VCDNGSGLCK AGFAGDDAPR AVFPSIVGRP RHQGVMVGMG QKDSYVGDEA
QSKRGILTLK YPIEHGIITN WDDMEKIWHH SFYNELRVAP EEHPTLLTEA PLNPKANREK
MTQIMFETFN VPAMYVAIQA VLSLYASGRT TGIVLDSGDG VTHNVPIYEG YALPHAIMRL
DLAGRDLTDY LMKILTERGY SFVTTAEREI VRDIKEKLCY VALDFENEMA TAASSSSLEK
SYELPDGQVI TIGNERFRCP ETLFQPSFIG MESAGIHETT YNSIMKCDID IRKDLYANNV
LSGGTTMYPG IADRMQKEIT ALAPSTMKIK IIAPPERKYS VWIGGSILAS LSTFQQMWIS
KQEYDEAGPS IVHRKCF
