Alpha-actinin-4

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

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; OMA:ACTN4 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) Band 19q13.2 Start 38,647,649 bp End 38,731,589 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7|7 B1 Start 28,592,673 bp End 28,661,765 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in popliteal artery tibial arteries smooth muscle tissue right coronary artery stromal cell of endometrium ascending aorta placenta body of uterus islet of Langerhans myometrium Top expressed in corneal stroma vestibular membrane of cochlear duct tunica media of zone of aorta pyloric antrum lip neural layer of retina internal carotid artery conjunctival fornix external carotid artery genital tubercle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function metal ion binding calcium ion binding actin binding protein-containing complex binding RNA polymerase II transcription regulatory region sequence-specific DNA binding protein homodimerization activity protein N-terminus binding nucleoside binding transmembrane transporter binding nuclear receptor coactivator activity integrin binding retinoic acid receptor binding chromatin DNA binding protein binding actin filament binding RNA binding transcription coactivator activity Cellular component extracellular exosome extracellular region brush border pseudopodium cytoplasm actin cytoskeleton cell junction nucleus stress fiber cell-cell junction neuron projection focal adhesion platelet alpha granule lumen intracellular anatomical structure Z discdkac perinuclear region of cytoplasm cortical cytoskeleton extracellular space cytosol nuclear body cytoskeleton protein-containing complex ribonucleoprotein complex 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 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 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: 28.59 – 28.66 Mb PubMed search
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.

Interactions

Alpha-actinin-4 has been shown to interact with PDLIM1, Sodium-hydrogen exchange regulatory cofactor 2, Collagen, type XVII, alpha 1, CAMK2A, CAMK2B, MAGI1 and TRIM3.

See also

• Focal segmental glomerulosclerosis

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) (2): 403–14. doi:10.1242/jcs.101.2.403. 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. doi:10.4049/jimmunol.151.7.3795. PMID 8104223. S2CID 32574143.
• 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. Bibcode:1999CBio....9.1271Z. 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. S2CID 36426082.
• 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. PMC 6763799. 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. doi:10.1242/jcs.114.23.4197. 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. Bibcode:2002CBio...12..383L. doi:10.1016/S0960-9822(02)00678-4. PMID 11882289. S2CID 15397046.
• 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.