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 27-MAR-2024, entry version 183. DE RecName: Full=Actin, aortic smooth muscle; DE EC=3.6.4.- {ECO:0000250|UniProtKB:P68137}; 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 -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; CC Evidence={ECO:0000250|UniProtKB:P68137}; 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: [Actin, aortic smooth muscle, intermediate form]: N-terminal CC cleavage of acetylated cysteine of intermediate muscle actin by ACTMAP. CC {ECO:0000250|UniProtKB:P62737}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 EMDB; EMD-35888; -. DR SMR; P62736; -. DR BioGRID; 106574; 516. DR CORUM; P62736; -. DR ELM; P62736; -. DR IntAct; P62736; 103. DR MINT; P62736; -. DR STRING; 9606.ENSP00000224784; -. DR DrugBank; DB12695; Phenethyl Isothiocyanate. DR GlyCosmos; P62736; 1 site, 2 glycans. DR GlyGen; P62736; 3 sites, 2 O-linked glycans (3 sites). DR iPTMnet; P62736; -. DR MetOSite; P62736; -. DR PhosphoSitePlus; P62736; -. DR SwissPalm; P62736; -. DR BioMuta; ACTA2; -. DR DMDM; 51316972; -. DR REPRODUCTION-2DPAGE; IPI00008603; -. DR EPD; P62736; -. DR jPOST; P62736; -. DR MassIVE; P62736; -. DR MaxQB; P62736; -. DR PaxDb; 9606-ENSP00000402373; -. DR PeptideAtlas; P62736; -. DR PRIDE; P62736; -. DR ProteomicsDB; 57419; -. DR Pumba; P62736; -. DR TopDownProteomics; P62736; -. DR Antibodypedia; 30207; 1807 antibodies from 51 providers. DR DNASU; 59; -. DR Ensembl; ENST00000224784.10; ENSP00000224784.6; ENSG00000107796.13. DR Ensembl; ENST00000415557.2; ENSP00000396730.2; ENSG00000107796.13. DR Ensembl; ENST00000458159.6; ENSP00000398239.2; 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 AGR; HGNC:130; -. 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; FTTSAEF; -. DR OrthoDB; 4646155at2759; -. 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; 15 hits in 1146 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 213 other cell types or tissues. DR ExpressionAtlas; P62736; baseline and differential. DR GO; GO:0005604; C:basement membrane; IEA:Ensembl. 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: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:0031514; C:motile cilium; IEA:Ensembl. 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:0016787; F:hydrolase activity; IEA:UniProtKB-KW. DR GO; GO:0019901; F:protein kinase binding; ISS:ParkinsonsUK-UCL. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl. DR GO; GO:0072144; P:glomerular mesangial cell development; IEP:UniProtKB. DR GO; GO:0072051; P:juxtaglomerular apparatus development; IEA:Ensembl. 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:0009615; P:response to virus; IEP:UniProtKB. DR GO; GO:0014829; P:vascular associated smooth muscle contraction; IEA:Ensembl. DR CDD; cd00012; NBD_sugar-kinase_HSP70_actin; 1. DR Gene3D; 3.30.420.40; -; 2. DR InterPro; IPR004000; Actin. DR InterPro; IPR020902; Actin/actin-like_CS. DR InterPro; IPR004001; Actin_CS. DR InterPro; IPR043129; ATPase_NBD. DR PANTHER; PTHR11937; ACTIN; 1. DR PANTHER; PTHR11937:SF445; ACTIN, AORTIC SMOOTH MUSCLE; 1. DR Pfam; PF00022; Actin; 1. DR PRINTS; PR00190; ACTIN. DR SMART; SM00268; ACTIN; 1. DR SUPFAM; SSF53067; Actin-like ATPase domain; 2. DR PROSITE; PS00406; ACTINS_1; 1. DR PROSITE; PS00432; ACTINS_2; 1. DR PROSITE; PS01132; ACTINS_ACT_LIKE; 1. DR UCD-2DPAGE; P62736; -. DR Genevisible; P62736; HS. PE 1: Evidence at protein level; KW Acetylation; Aortic aneurysm; ATP-binding; Cytoplasm; Cytoskeleton; KW Disease variant; Hydrolase; 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; dbSNP:rs886039303)" 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 //