Alpha-actinin-4 explained

Alpha-actinin-4 is a protein that in humans is encoded by the ACTN4 gene.^[1]

Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. This gene encodes a nonmuscle, alpha actinin isoform which is concentrated in the cytoplasm, and thought to be involved in metastatic processes. Mutations in this gene have been associated with focal and segmental glomerulosclerosis.

Interactions

Alpha-actinin-4 has been shown to interact with PDLIM1,^{[2] [3]} Sodium-hydrogen exchange regulatory cofactor 2,^[4] Collagen, type XVII, alpha 1,^[5] CAMK2A,^[6] CAMK2B,^[6] MAGI1^[7] and TRIM3.^[8]

See also

• Focal segmental glomerulosclerosis

Further reading

• Dawson SJ, White LA . Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin. . J. Infect. . 24 . 3 . 317–20 . 1992 . 1602151 . 10.1016/S0163-4453(05)80037-4 .
• Yürüker B, Niggli V . Alpha-actinin and vinculin in human neutrophils: reorganization during adhesion and relation to the actin network. . 101 . J. Cell Sci. . (Pt 2) . 403–14 . 1992 . 2 . 10.1242/jcs.101.2.403 . 1629252 .
• Otey CA, Pavalko FM, Burridge K . An interaction between alpha-actinin and the beta 1 integrin subunit in vitro. . J. Cell Biol. . 111 . 2 . 721–9 . 1990 . 2116421 . 10.1083/jcb.111.2.721 . 2116186 .
• Pavalko FM, LaRoche SM . Activation of human neutrophils induces an interaction between the integrin beta 2-subunit (CD18) and the actin binding protein alpha-actinin. . J. Immunol. . 151 . 7 . 3795–807 . 1993 . 10.4049/jimmunol.151.7.3795 . 8104223 . 32574143 . free .
• Mathis BJ, Kim SH, Calabrese K . A locus for inherited focal segmental glomerulosclerosis maps to chromosome 19q13. . Kidney Int. . 53 . 2 . 282–6 . 1998 . 9461087 . 10.1046/j.1523-1755.1998.00828.x . etal. free .
• Honda K, Yamada T, Endo R . Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion. . J. Cell Biol. . 140 . 6 . 1383–93 . 1998 . 9508771 . 10.1083/jcb.140.6.1383 . 2132673 . etal.
• Zhang H, Wang L, Kao S . Functional interaction between the cytoplasmic leucine-zipper domain of HIV-1 gp41 and p115-RhoGEF. . Curr. Biol. . 9 . 21 . 1271–4 . 1999 . 10556093 . 10.1016/S0960-9822(99)80511-9 . etal. 4513661 . 1999CBio....9.1271Z .
• Nikolopoulos SN, Spengler BA, Kisselbach K . The human non-muscle alpha-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells. . Oncogene . 19 . 3 . 380–6 . 2000 . 10656685 . 10.1038/sj.onc.1203310 . etal. free .
• El-Husseini AE, Kwasnicka D, Yamada T . BERP, a novel ring finger protein, binds to alpha-actinin-4. . Biochem. Biophys. Res. Commun. . 267 . 3 . 906–11 . 2000 . 10673389 . 10.1006/bbrc.1999.2045 . etal.
• Kaplan JM, Kim SH, North KN . Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. . Nat. Genet. . 24 . 3 . 251–6 . 2000 . 10700177 . 10.1038/73456 . 36426082 . etal.
• Vallenius T, Luukko K, Mäkelä TP . CLP-36 PDZ-LIM protein associates with nonmuscle alpha-actinin-1 and alpha-actinin-4. . J. Biol. Chem. . 275 . 15 . 11100–5 . 2000 . 10753915 . 10.1074/jbc.275.15.11100 . free .
• Holliday LS, Lu M, Lee BS . The amino-terminal domain of the B subunit of vacuolar H+-ATPase contains a filamentous actin binding site. . J. Biol. Chem. . 275 . 41 . 32331–7 . 2000 . 10915794 . 10.1074/jbc.M004795200 . etal. free .
• Walikonis RS, Oguni A, Khorosheva EM . Densin-180 forms a ternary complex with the (alpha)-subunit of Ca2+/calmodulin-dependent protein kinase II and (alpha)-actinin. . J. Neurosci. . 21 . 2 . 423–33 . 2001 . 11160423 . 10.1523/JNEUROSCI.21-02-00423.2001. 6763799 . etal. free .
• Echchakir H, Mami-Chouaib F, Vergnon I . A point mutation in the alpha-actinin-4 gene generates an antigenic peptide recognized by autologous cytolytic T lymphocytes on a human lung carcinoma. . Cancer Res. . 61 . 10 . 4078–83 . 2001 . 11358829 . etal.
• Xu F, Zhao R, Peng Y . Association of tyrosine phosphatase SHP-2 with F-actin at low cell densities. . J. Biol. Chem. . 276 . 31 . 29479–84 . 2001 . 11382784 . 10.1074/jbc.M104428200 . etal. free .
• Hüttelmaier S, Illenberger S, Grosheva I . Raver1, a dual compartment protein, is a ligand for PTB/hnRNPI and microfilament attachment proteins. . J. Cell Biol. . 155 . 5 . 775–86 . 2002 . 11724819 . 10.1083/jcb.200105044 . 2150882 . etal.
• Renoult C, Blondin L, Fattoum A . Binding of gelsolin domain 2 to actin. An actin interface distinct from that of gelsolin domain 1 and from ADF/cofilin. . Eur. J. Biochem. . 268 . 23 . 6165–75 . 2002 . 11733011 . 10.1046/j.0014-2956.2001.02574.x . etal. free .
• Gonzalez AM, Otey C, Edlund M, Jones JC . Interactions of a hemidesmosome component and actinin family members. . J. Cell Sci. . 114 . Pt 23 . 4197–206 . 2002 . 10.1242/jcs.114.23.4197 . 11739652 .
• Lukoyanova N, VanLoock MS, Orlova A . Each actin subunit has three nebulin binding sites: implications for steric blocking. . Curr. Biol. . 12 . 5 . 383–8 . 2002 . 11882289 . 10.1016/S0960-9822(02)00678-4 . 15397046 . etal. free . 2002CBio...12..383L .
• Kim JH, Lee-Kwon W, Park JB . Ca(2+)-dependent inhibition of Na+/H+ exchanger 3 (NHE3) requires an NHE3-E3KARP-alpha-actinin-4 complex for oligomerization and endocytosis. . J. Biol. Chem. . 277 . 26 . 23714–24 . 2002 . 11948184 . 10.1074/jbc.M200835200 . etal. free .

Notes and References

1. Web site: Entrez Gene: ACTN4 actinin, alpha 4.
2. Rual . Jean-François . Venkatesan Kavitha . Hao Tong . Hirozane-Kishikawa Tomoko . Dricot Amélie . Li Ning . Berriz Gabriel F . Gibbons Francis D . Dreze Matija . Ayivi-Guedehoussou Nono . Klitgord Niels . Simon Christophe . Boxem Mike . Milstein Stuart . Rosenberg Jennifer . Goldberg Debra S . Zhang Lan V . Wong Sharyl L . Franklin Giovanni . Li Siming . Albala Joanna S . Lim Janghoo . Fraughton Carlene . Llamosas Estelle . Cevik Sebiha . Bex Camille . Lamesch Philippe . Sikorski Robert S . Vandenhaute Jean . Zoghbi Huda Y . Smolyar Alex . Bosak Stephanie . Sequerra Reynaldo . Doucette-Stamm Lynn . Cusick Michael E . Hill David E . Roth Frederick P . Vidal Marc . Oct 2005 . Towards a proteome-scale map of the human protein-protein interaction network . . 437 . 7062 . 1173–8 . England. 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
3. 10.1074/jbc.275.15.11100 . Vallenius . T . Luukko K. Mäkelä T P . Apr 2000 . CLP-36 PDZ-LIM protein associates with nonmuscle alpha-actinin-1 and alpha-actinin-4 . J. Biol. Chem. . 275 . 15 . 11100–5 . UNITED STATES. 0021-9258. 10753915 . free .
4. Kim . Jae Ho . Lee-Kwon Whaseon . Park Jong Bae . Ryu Sung Ho. Yun C H Chris . Donowitz Mark . Jun 2002 . Ca(2+)-dependent inhibition of Na+/H+ exchanger 3 (NHE3) requires an NHE3-E3KARP-alpha-actinin-4 complex for oligomerization and endocytosis . J. Biol. Chem. . 277 . 26 . 23714–24 . United States. 0021-9258. 11948184 . 10.1074/jbc.M200835200 . free .
5. Gonzalez . A M . Otey C. Edlund M. Jones J C . Dec 2001 . Interactions of a hemidesmosome component and actinin family members . J. Cell Sci. . 114 . Pt 23 . 4197–206 . England. 10.1242/jcs.114.23.4197 . 0021-9533. 11739652 .
6. Walikonis . R S . Oguni A . Khorosheva E M . Jeng C J . Asuncion F J . Kennedy M B . Jan 2001 . Densin-180 forms a ternary complex with the (alpha)-subunit of Ca2+/calmodulin-dependent protein kinase II and (alpha)-actinin . J. Neurosci. . 21 . 2 . 423–33 . United States. 10.1523/JNEUROSCI.21-02-00423.2001 . 11160423 . 6763799 . free .
7. Patrie . Kevin M . Drescher Andrew J. Welihinda Ajith. Mundel Peter. Margolis Ben . Aug 2002 . Interaction of two actin-binding proteins, synaptopodin and alpha-actinin-4, with the tight junction protein MAGI-1 . J. Biol. Chem. . 277 . 33 . 30183–90 . United States. 0021-9258. 12042308 . 10.1074/jbc.M203072200 . free.
8. El-Husseini . A E . Kwasnicka D . Yamada T . Hirohashi S . Vincent S R . Jan 2000 . BERP, a novel ring finger protein, binds to alpha-actinin-4 . Biochem. Biophys. Res. Commun. . 267 . 3 . 906–11 . UNITED STATES. 0006-291X. 10673389 . 10.1006/bbrc.1999.2045 .