Actinin alpha 4

Alpha-actinin-4 is a protein that in humans is encoded by the ACTN4 gene.[5]

ACTN4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1WLX, 1YDI, 2R0O
Identifiers
Aliases	ACTN4, ACTININ-4, FSGS, FSGS1, Actinin alpha 4
External IDs	OMIM: 604638 MGI: 1890773 HomoloGene: 55857 GeneCards: ACTN4
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.2 Start 38,647,649 bp[1] End 38,731,589 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 B1 Start 28,893,248 bp[2] End 28,962,340 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • metal ion binding • calcium ion binding • actin binding • GO:0032403 macromolecular complex binding • RNA polymerase II regulatory region sequence-specific DNA binding • nuclear hormone receptor binding • protein homodimerization activity • protein N-terminus binding • nucleoside binding • ion channel binding • ligand-dependent nuclear receptor transcription coactivator activity • integrin binding • retinoic acid receptor binding • chromatin DNA binding • GO:0001948 protein binding • actin filament binding • RNA binding • GO:0001105 transcription coactivator activity Cellular component • extracellular exosome • extracellular region • brush border • pseudopodia • cytoplasm • actin cytoskeleton • cell junction • cell nucleus • stress fiber • intercellular junction • neuron projection • focal adhesion • platelet alpha granule lumen • intracellular • Z disc • perinuclear region of cytoplasm • cortical cytoskeleton • extracellular • cytosol • nuclear body • cytoskeleton • macromolecular complex • ribonucleoprotein Biological process • response to hypoxia • vesicle transport along actin filament • actin filament bundle assembly • positive regulation of NIK/NF-kappaB signaling • regulation of apoptotic process • positive regulation of cell migration • negative regulation of cellular component movement • bicellular tight junction assembly • positive regulation of sodium:proton antiporter activity • protein localization to bicellular tight junction • platelet degranulation • positive regulation of pinocytosis • retinoic acid receptor signaling pathway • regulation of nucleic acid-templated transcription • protein transport • peroxisome proliferator activated receptor signaling pathway • negative regulation of substrate adhesion-dependent cell spreading • positive regulation of cellular component movement • transport • tumor necrosis factor-mediated signaling pathway • positive regulation of nucleic acid-templated transcription Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	81	60595
Ensembl	ENSG00000130402 ENSG00000282844	ENSMUSG00000054808
UniProt	O43707	P57780
RefSeq (mRNA)	NM_004924 NM_001322033	NM_021895 NM_001360548 NM_001360549 NM_001360550
RefSeq (protein)	NP_001308962 NP_004915	NP_068695 NP_001347477 NP_001347478 NP_001347479
Location (UCSC)	Chr 19: 38.65 – 38.73 Mb	Chr 7: 28.89 – 28.96 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[5]

Interactions

Actinin alpha 4 has been shown to interact with PDLIM1,[6][7] Sodium-hydrogen exchange regulatory cofactor 2,[8] Collagen, type XVII, alpha 1,[9] CAMK2A,[10] CAMK2B,[10] MAGI1[11] and TRIM3.[12]

See also

• Focal segmental glomerulosclerosis

References

1. ENSG00000282844 GRCh38: Ensembl release 89: ENSG00000130402, ENSG00000282844 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000054808 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: ACTN4 actinin, alpha 4".
6. 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". Nature. England. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514.
7. 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. UNITED STATES. 275 (15): 11100–5. doi:10.1074/jbc.275.15.11100. ISSN 0021-9258. PMID 10753915.
8. 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. United States. 277 (26): 23714–24. doi:10.1074/jbc.M200835200. ISSN 0021-9258. PMID 11948184.
9. Gonzalez, A M; Otey C; Edlund M; Jones J C (Dec 2001). "Interactions of a hemidesmosome component and actinin family members". J. Cell Sci. England. 114 (Pt 23): 4197–206. ISSN 0021-9533. PMID 11739652.
10. 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. United States. 21 (2): 423–33. doi:10.1523/JNEUROSCI.21-02-00423.2001. PMID 11160423.
11. 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. United States. 277 (33): 30183–90. doi:10.1074/jbc.M203072200. ISSN 0021-9258. PMID 12042308.
12. 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. UNITED STATES. 267 (3): 906–11. doi:10.1006/bbrc.1999.2045. ISSN 0006-291X. PMID 10673389.

Further reading

• Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". J. Infect. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151.
• Yürüker B, Niggli V (1992). "Alpha-actinin and vinculin in human neutrophils: reorganization during adhesion and relation to the actin network". J. Cell Sci. 101. ( Pt 2): 403–14. PMID 1629252.
• Otey CA, Pavalko FM, Burridge K (1990). "An interaction between alpha-actinin and the beta 1 integrin subunit in vitro". J. Cell Biol. 111 (2): 721–9. doi:10.1083/jcb.111.2.721. PMC 2116186. PMID 2116421.
• Pavalko FM, LaRoche SM (1993). "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. PMID 8104223.
• Mathis BJ, Kim SH, Calabrese K, et al. (1998). "A locus for inherited focal segmental glomerulosclerosis maps to chromosome 19q13". Kidney Int. 53 (2): 282–6. doi:10.1046/j.1523-1755.1998.00828.x. PMID 9461087.
• Honda K, Yamada T, Endo R, et al. (1998). "Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion". J. Cell Biol. 140 (6): 1383–93. doi:10.1083/jcb.140.6.1383. PMC 2132673. PMID 9508771.
• Zhang H, Wang L, Kao S, et al. (1999). "Functional interaction between the cytoplasmic leucine-zipper domain of HIV-1 gp41 and p115-RhoGEF". Curr. Biol. 9 (21): 1271–4. doi:10.1016/S0960-9822(99)80511-9. PMC 4513661. PMID 10556093.
• Nikolopoulos SN, Spengler BA, Kisselbach K, et al. (2000). "The human non-muscle alpha-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells". Oncogene. 19 (3): 380–6. doi:10.1038/sj.onc.1203310. PMID 10656685.
• El-Husseini AE, Kwasnicka D, Yamada T, et al. (2000). "BERP, a novel ring finger protein, binds to alpha-actinin-4". Biochem. Biophys. Res. Commun. 267 (3): 906–11. doi:10.1006/bbrc.1999.2045. PMID 10673389.
• Kaplan JM, Kim SH, North KN, et al. (2000). "Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis". Nat. Genet. 24 (3): 251–6. doi:10.1038/73456. PMID 10700177.
• Vallenius T, Luukko K, Mäkelä TP (2000). "CLP-36 PDZ-LIM protein associates with nonmuscle alpha-actinin-1 and alpha-actinin-4". J. Biol. Chem. 275 (15): 11100–5. doi:10.1074/jbc.275.15.11100. PMID 10753915.
• Holliday LS, Lu M, Lee BS, et al. (2000). "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. doi:10.1074/jbc.M004795200. PMID 10915794.
• Walikonis RS, Oguni A, Khorosheva EM, et al. (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. doi:10.1523/JNEUROSCI.21-02-00423.2001. PMID 11160423.
• Echchakir H, Mami-Chouaib F, Vergnon I, et al. (2001). "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. PMID 11358829.
• Xu F, Zhao R, Peng Y, et al. (2001). "Association of tyrosine phosphatase SHP-2 with F-actin at low cell densities". J. Biol. Chem. 276 (31): 29479–84. doi:10.1074/jbc.M104428200. PMID 11382784.
• Hüttelmaier S, Illenberger S, Grosheva I, et al. (2002). "Raver1, a dual compartment protein, is a ligand for PTB/hnRNPI and microfilament attachment proteins". J. Cell Biol. 155 (5): 775–86. doi:10.1083/jcb.200105044. PMC 2150882. PMID 11724819.
• Renoult C, Blondin L, Fattoum A, et al. (2002). "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. doi:10.1046/j.0014-2956.2001.02574.x. PMID 11733011.
• Gonzalez AM, Otey C, Edlund M, Jones JC (2002). "Interactions of a hemidesmosome component and actinin family members". J. Cell Sci. 114 (Pt 23): 4197–206. PMID 11739652.
• Lukoyanova N, VanLoock MS, Orlova A, et al. (2002). "Each actin subunit has three nebulin binding sites: implications for steric blocking". Curr. Biol. 12 (5): 383–8. doi:10.1016/S0960-9822(02)00678-4. PMID 11882289.
• Kim JH, Lee-Kwon W, Park JB, et al. (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. doi:10.1074/jbc.M200835200. PMID 11948184.

External links

• Human ACTN4 genome location and ACTN4 gene details page in the UCSC Genome Browser.