Actinin alpha 4

Actinin, alpha 4

PDB rendering based on 1wlx.

Available structures
PDB	1WLX, 1YDI, 2R0O

Identifiers

Symbols

ACTN4; ACTININ-4; DKFZp686K23158; FSGS; FSGS1

External IDs

OMIM: 604638 MGI: 1890773 HomoloGene: 55857 GeneCards: ACTN4 Gene

Gene Ontology
Molecular function	• nucleoside binding • actin binding • integrin binding • calcium ion binding • protein binding • protein homodimerization activity • protein N-terminus binding • actin filament binding
Cellular component	• stress fiber • extracellular region • nucleus • nucleolus • cytoplasm • actin cytoskeleton • ribonucleoprotein complex • cortical cytoskeleton • platelet alpha granule lumen • pseudopodium • protein complex • perinuclear region of cytoplasm
Biological process	• response to hypoxia • platelet degranulation • blood coagulation • protein transport • platelet activation • positive regulation of sodium:hydrogen antiporter activity • regulation of apoptosis • positive regulation of pinocytosis • actin filament bundle assembly • negative regulation of cellular component movement • positive regulation of cellular component movement • positive regulation of cellular component movement
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 19:
39.14 – 39.22 Mb

Chr 7:
29.68 – 29.75 Mb

PubMed search

[1]

[2]

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.^[1]

1 Interactions
2 See also
3 References
4 Further reading

Interactions

Actinin alpha 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]

References

^ ^a ^b "Entrez Gene: ACTN4 actinin, alpha 4". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=81.
^ 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. doi:10.1038/nature04209. PMID 16189514.
^ 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.
^ 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.
^ 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.
^ ^a ^b 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. PMID 11160423.
^ 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.
^ 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.

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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2116186.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132673.
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. 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. 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2150882.
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.

PDB gallery

1wlx: Solution structure of the third spectrin repeat of alpha-actinin-4

2eyi: Crystal structure of the actin-binding domain of human alpha-actinin 1 at 1.7 Angstrom resolution

2eyn: Crystal structure of the actin-binding domain of human alpha-actinin 1 at 1.8 Angstrom resolution

Proteins of the cytoskeleton

Human

Microfilaments
(ABPs)

Myofilament

Actins	A1, A2, B, C1, G1, G2

Myosins	I (MYO1A, MYO1B, MYO1C, MYO1D, MYO1E, MYO1F, MYO1G, MYO1H) · II (MYH1, MYH2, MYH3, MYH4, MYH6, MYH7, MYH7B, MYH8, MYH9, MYH10, MYH11, MYH13, MYH14, MYH15, MYH16) · III (MYO3A, MYO3B) · V (MYO5A, MYO5B, MYO5C) · VI (MYO6) · VII (MYO7A, MYO7B) · IX (MYO9A, MYO9B) · X (MYO10) · XV (MYO15A) · XVIII (MYO18A, MYO18B) · LC (MYL1, MYL2, MYL3, MYL4, MYL5, MYL6, MYL6B, MYL7, MYL9, MYLIP, MYLK, MYLK2, MYLL1)

Other	Tropomodulin (1, 2, 3, 4) · Troponin (T 1 2 3, C 1 2, I 1 2 3) · Tropomyosin (1, 2, 3, 4) Actinin (1, 2, 3, 4) · Arp2/3 complex · actin depolymerizing factors (Cofilin (1, 2) · Destrin) · Gelsolin · Profilin (1, 2) · Titin

Other

Wiskott-Aldrich syndrome protein · Fibrillin · Filamin (FLNA, FLNB, FLNC) · Espin · TRIOBP

IFs

Type 1/2
(Keratin,
Cytokeratin)

Epithelial keratins (soft alpha-keratins)	type I/chromosome 17 (10, 12, 13, 14, 15, 16, 17, 19, 20) · chromosome 12 (18) · none (21) type II/chromosome 12 (1, 2A, 3, 4, 5, 6A, 6B, 7, 8, 9)

Hair keratins (hard alpha-keratins)	type I/chromosome 17 (31, 32, 33A, 33B, 34, 35, 36, 37, 38) type II/chromosome 12 (81, 82, 83, 84, 85, 86)

Ungrouped alpha	chromosome 17 (23, 24, 25, 26, 27, 28, 39, 40) chromosome 12 (71, 72, 73, 74, 75, 76, 77, 78, 79, 80)

Not alpha	Beta-keratin

Type 3

Desmin, GFAP, Peripherin, Vimentin

Type 4

Internexin, Nestin, Neurofilament (NEFL, NEFM, NEFH), Synemin, Syncoilin

Type 5

Lamin A, B

Microtubules/
MAPs

Kinesins	KIF1A, KIF1B, KIF2A, KIF2C, KIF3B, KIF3C, KIF4A, KIF4B, KIF5A, KIF5B, KIF5C, KIF6, KIF7, KIF9, KIF11, KIF12, KIF13A, KIF13B, KIF14, KIF15, KIF16B, KIF17, KIF18A, KIF18B, KIF19, KIF20A, KIF20B, KIF21A, KIF21B, KIF22, KIF23, KIF24, KIF25, KIF26A, KIF26B, KIF27, KIFC1, KIFC2, KIFC3

Dyneins	axonemal: DNAH1, DNAH2, DNAH3, DNAH5, DNAH6, DNAH7, DNAH8, DNAH9, DNAH10, DNAH11, DNAH12, DNAH13, DNAH14, DNAH17, DNAI1, DNAI2, DNALI1, DNAL1, DNAL4 cytoplasmic: DYNC1H1, DYNC2H1, DYNC1I1, DYNC1I2, DYNC1LI1, DYNC1LI2, DYNC2LI1, DYNLL1, DYNLL2, DYNLRB1, DYNLRB2, DYNLT1, DYNLT3

Other	Tau protein · Dynactin (DCTN1) · Tubulins (TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8) · Stathmin · Tektin (TEKT1, TEKT2, TEKT3, TEKT4, TEKT5) · Dynamin (DNM1, DNM2, DNM3)

Catenins

Alpha catenin · Beta catenin (APC) · Plakoglobin (gamma catenin) · Delta catenin · GAN

Membrane

Dystrophin (Dystroglycan) · Utrophin · Ankyrin (ANK1, ANK2, ANK3) · Spectrin (SPTA1, SPTAN1, SPTB, SPTBN1, SPTBN2, SPTBN4, SPTBN5)

Other

plakin (Desmoplakin, Plectin) · Talin (TLN1) · Vinculin · Plakophilin (PKP1, PKP2)

Nonhuman

Major sperm proteins · Prokaryotic cytoskeleton (Crescentin, FtsZ, MreB)

see also cytoskeletal defects
B strc: edmb (perx), skel (ctrs), epit, cili, mito, nucl (chro)

Actinin alpha 4

Contents

Interactions

See also

References

Further reading