ACTL6A explained

Actin-like protein 6A is a protein that in humans is encoded by the ACTL6A gene.^{[1] [2] [3]}

Function

This gene encodes a family member of actin-related proteins (ARPs), which share significant amino acid sequence identity to conventional actins. Both actins and ARPs have an actin fold, which is an ATP-binding cleft, as a common feature. The ARPs are involved in diverse cellular processes, including vesicular transport, spindle orientation, nuclear migration and chromatin remodeling. This gene encodes a 53 kDa subunit protein of the BAF (BRG1/brm-associated factor) complex in mammals, which is functionally related to SWI/SNF complex in S. cerevisiae and Drosophila; the latter is thought to facilitate transcriptional activation of specific genes by antagonizing chromatin-mediated transcriptional repression. Together with beta-actin, it is required for maximal ATPase activity of BRG1, and for the association of the BAF complex with chromatin/matrix. Three transcript variants that encode two different protein isoforms have been described.^[3]

Clinical significance

ACTL6A is amplified in head and squamous cancers and confers poor prognosis in patients. This is also the first report of amplification of an epigenetic factor by Saladi SV.^[4] In hepatocellular carcinomas, it promotes metastasis.^[5]

Interactions

ACTL6A has been shown to interact with SMARCA2,^{[6] [7] [8]} Myc,^[7] Transformation/transcription domain-associated protein,^[7] RuvB-like 1^[7] and SMARCA4.^[6]

Further reading

• Schafer DA, Schroer TA . Actin-related proteins. . Annu. Rev. Cell Dev. Biol. . 15 . 341–63 . 2000 . 10611965 . 10.1146/annurev.cellbio.15.1.341 .
• Doyon Y, Côté J . The highly conserved and multifunctional NuA4 HAT complex. . Curr. Opin. Genet. Dev. . 14 . 2 . 147–54 . 2004 . 15196461 . 10.1016/j.gde.2004.02.009 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Cho H, Orphanides G, Sun X, Yang XJ, Ogryzko V, Lees E, Nakatani Y, Reinberg D . A human RNA polymerase II complex containing factors that modify chromatin structure . Mol. Cell. Biol. . 18 . 9 . 5355–63 . 1998 . 9710619 . 109120 . 10.1128/MCB.18.9.5355.
• Phelan ML, Sif S, Narlikar GJ, Kingston RE . Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits . Mol. Cell . 3 . 2 . 247–53 . 1999 . 10078207 . 10.1016/S1097-2765(00)80315-9 . free .
• Ikura T, Ogryzko VV, Grigoriev M, Groisman R, Wang J, Horikoshi M, Scully R, Qin J, Nakatani Y . Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis . Cell . 102 . 4 . 463–73 . 2000 . 10966108 . 10.1016/S0092-8674(00)00051-9 . 18047169 . free .
• Xue Y, Canman JC, Lee CS, Nie Z, Yang D, Moreno GT, Young MK, Salmon ED, Wang W . The human SWI/SNF-B chromatin-remodeling complex is related to yeast rsc and localizes at kinetochores of mitotic chromosomes . Proc. Natl. Acad. Sci. U.S.A. . 97 . 24 . 13015–20 . 2001 . 11078522 . 27170 . 10.1073/pnas.240208597 . 2000PNAS...9713015X . free .
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs . Genome Res. . 11 . 3 . 422–35 . 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R .
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S . Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing . EMBO Rep. . 1 . 3 . 287–92 . 2001 . 11256614 . 1083732 . 10.1093/embo-reports/kvd058 .
• Sung YH, Choi EY, Kwon H . Identification of a nuclear protein ArpN as a component of human SWI/SNF complex and its selective association with a subset of active genes . Mol. Cells . 11 . 1 . 75–81 . 2001 . 10.1016/S1016-8478(23)17006-3 . 11266125 . free .
• Lai CH, Chiu JY, Lin W . Identification of the human crooked neck gene by comparative gene identification . Biochim. Biophys. Acta . 1517 . 3 . 449–54 . 2001 . 11342225 . 10.1016/s0167-4781(00)00295-5 .
• Fuchs M, Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V, Lane WS, Nakatani Y, Livingston DM . The p400 complex is an essential E1A transformation target . Cell . 106 . 3 . 297–307 . 2001 . 11509179 . 10.1016/S0092-8674(01)00450-0 . 15634637 . free .
• Kato H, Tjernberg A, Zhang W, Krutchinsky AN, An W, Takeuchi T, Ohtsuki Y, Sugano S, de Bruijn DR, Chait BT, Roeder RG . SYT associates with human SNF/SWI complexes and the C-terminal region of its fusion partner SSX1 targets histones . J. Biol. Chem. . 277 . 7 . 5498–505 . 2002 . 11734557 . 10.1074/jbc.M108702200 . free . 2066/170683 . free .
• Park J, Wood MA, Cole MD . BAF53 forms distinct nuclear complexes and functions as a critical c-Myc-interacting nuclear cofactor for oncogenic transformation . Mol. Cell. Biol. . 22 . 5 . 1307–16 . 2002 . 11839798 . 134713 . 10.1128/MCB.22.5.1307-1316.2002 .
• Ohfuchi E, Nishimori K, Harata M . Alternative splicing products of the gene for a human nuclear actin-related protein, hArpNbeta/Baf53, that encode a protein isoform, hArpNbetaS, in the cytoplasm . Biosci. Biotechnol. Biochem. . 66 . 8 . 1740–3 . 2003 . 12353638 . 10.1271/bbb.66.1740 . 35246242 . free .
• Kuroda Y, Oma Y, Nishimori K, Ohta T, Harata M . Brain-specific expression of the nuclear actin-related protein ArpNalpha and its involvement in mammalian SWI/SNF chromatin remodeling complex . Biochem. Biophys. Res. Commun. . 299 . 2 . 328–34 . 2003 . 12437990 . 10.1016/S0006-291X(02)02637-2 .

Notes and References

1. Zhao K, Wang W, Rando OJ, Xue Y, Swiderek K, Kuo A, Crabtree GR . Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling . Cell . 95 . 5 . 625–36 . December 1998 . 9845365 . 10.1016/S0092-8674(00)81633-5 . 3184211 . free .
2. Harata M, Mochizuki R, Mizuno S . Two isoforms of a human actin-related protein show nuclear localization and mutually selective expression between brain and other tissues . Biosci Biotechnol Biochem . 63 . 5 . 917–23 . July 1999 . 10380635 . 10.1271/bbb.63.917 . free .
3. Web site: Entrez Gene: ACTL6A actin-like 6A.
4. Saladi SV, Ross K, Karaayvaz M, Tata PR, Mou H, Rajagopal J, Ramaswamy S, Ellisen LW . ACTL6A Is Co-Amplified with p63 in Squamous Cell Carcinoma to Drive YAP Activation, Regenerative Proliferation, and Poor Prognosis . Cancer Cell . 31 . 1 . 35–49 . 2017 . 28041841 . 10.1016/j.ccell.2016.12.001 . 5225026.
5. Xiao S, Chang RM, Yang MY, Lei X, Liu X, Gao WB, Xiao JL, Yang LY . Actin-like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial-mesenchymal transition . Hepatology . 63 . 4 . 1256–71 . 2016 . 26698646 . 4834727 . 10.1002/hep.28417 .
6. Wang W, Côté J, Xue Y, Zhou S, Khavari PA, Biggar SR, Muchardt C, Kalpana GV, Goff SP, Yaniv M, Workman JL, Crabtree GR . Purification and biochemical heterogeneity of the mammalian SWI-SNF complex . EMBO J. . 15 . 19 . 5370–82 . October 1996 . 8895581 . 452280 . 10.1002/j.1460-2075.1996.tb00921.x.
7. Park J, Wood MA, Cole MD . BAF53 forms distinct nuclear complexes and functions as a critical c-Myc-interacting nuclear cofactor for oncogenic transformation . Mol. Cell. Biol. . 22 . 5 . 1307–16 . March 2002 . 11839798 . 134713 . 10.1128/MCB.22.5.1307-1316.2002 .
8. Kuroda Y, Oma Y, Nishimori K, Ohta T, Harata M . Brain-specific expression of the nuclear actin-related protein ArpNalpha and its involvement in mammalian SWI/SNF chromatin remodeling complex . Biochem. Biophys. Res. Commun. . 299 . 2 . 328–34 . November 2002 . 12437990 . 10.1016/S0006-291X(02)02637-2 .