CLIC4 explained

Chloride intracellular channel 4, also known as CLIC4,p644H1,HuH1, is a eukaryotic gene.

Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. Chloride intracellular channel 4 (CLIC4) protein, encoded by the clic4 gene, is a member of the p64 family; the gene is expressed in many tissues. These channels are implicated in angiogenesis, pulmonary hypertension, cancer, and cardioprotection from ischemia-reperfusion injury. They exhibit an intracellular vesicular pattern in PANC-1 cells (pancreatic cancer cells).^[1]

Binding partners

CLIC4 binds to dynamin I, α-tubulin, β-actin, creatine kinase and two 14-3-3 isoforms.^[2]

See also

• Chloride channel

Further reading

• Berryman M, Bretscher A . Identification of a Novel Member of the Chloride Intracellular Channel Gene Family (CLIC5) That Associates with the Actin Cytoskeleton of Placental Microvilli . Mol. Biol. Cell . 11 . 5 . 1509–21 . 2000 . 10793131 . 10.1091/mbc.11.5.1509. 14863 .
• Ponnalagu D, Hamilton S, Sanghvi S, Antelo D, Schwieterman N, Hansra I, Xu X, Gao E, Edwards JC, Bansal SS, Wold LE, Terentyev, D, Janssen PM, Hund TJ, Khan M, Kohut AR, Koch WJ, Singh H . CLIC4 localizes to mitochondrial-associated membranes and mediates cardioprotection. Science Advances . 8 . 42 . eabo1244 . 2022 . 36269835 . 10.1126/sciadv.abo1244 . 9586484 . 2022SciA....8O1244P .
• Berryman MA, Goldenring JR . CLIC4 is enriched at cell-cell junctions and colocalizes with AKAP350 at the centrosome and midbody of cultured mammalian cells . Cell Motil. Cytoskeleton . 56 . 3 . 159–72 . 2004 . 14569596 . 10.1002/cm.10141 .
• Bohman S, Matsumoto T, Suh K . Proteomic analysis of vascular endothelial growth factor-induced endothelial cell differentiation reveals a role for chloride intracellular channel 4 (CLIC4) in tubular morphogenesis . J. Biol. Chem. . 280 . 51 . 42397–404 . 2006 . 16239224 . 10.1074/jbc.M506724200 . etal. free .
• Chuang JZ, Milner TA, Zhu M, Sung CH . A 29 kDa intracellular chloride channel p64H1 is associated with large dense-core vesicles in rat hippocampal neurons . J. Neurosci. . 19 . 8 . 2919–28 . 1999 . 10191309 . 10.1523/JNEUROSCI.19-08-02919.1999. 6782274 . free .
• Duncan RR, Westwood PK, Boyd A, Ashley RH . Rat brain p64H1, expression of a new member of the p64 chloride channel protein family in endoplasmic reticulum . J. Biol. Chem. . 272 . 38 . 23880–6 . 1997 . 9295337 . 10.1074/jbc.272.38.23880 . free .
• Edwards JC . A novel p64-related Cl⁻ channel: subcellular distribution and nephron segment-specific expression . Am. J. Physiol. . 276 . 3 Pt 2 . F398–408 . 1999 . 10070163 . 10.1152/ajprenal.1999.276.3.F398. 19105320 .
• Qian Z, Okuhara D, Abe MK, Rosner MR . Molecular cloning and characterization of a mitogen-activated protein kinase-associated intracellular chloride channel . J. Biol. Chem. . 274 . 3 . 1621–7 . 1999 . 9880541 . 10.1074/jbc.274.3.1621 . free .
• Gerhard DS, Wagner L, Feingold EA . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Hartley JL, Temple GF, Brasch MA . DNA Cloning Using In Vitro Site-Specific Recombination . Genome Res. . 10 . 11 . 1788–95 . 2001 . 11076863 . 10.1101/gr.143000 . 310948 .
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Rønnov-Jessen L, Villadsen R, Edwards JC, Petersen OW . Differential Expression of a Chloride Intracellular Channel Gene, CLIC4, in Transforming Growth Factor-β1-Mediated Conversion of Fibroblasts to Myofibroblasts . Am. J. Pathol. . 161 . 2 . 471–80 . 2002 . 12163372 . 10.1016/S0002-9440(10)64203-4. 1850723 .
• Rual JF, Venkatesan K, Hao T . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . etal. 2005Natur.437.1173R . 4427026 .
• Shiio Y, Suh KS, Lee H . Quantitative proteomic analysis of myc-induced apoptosis: a direct role for Myc induction of the mitochondrial chloride ion channel, mtCLIC/CLIC4 . J. Biol. Chem. . 281 . 5 . 2750–6 . 2006 . 16316993 . 10.1074/jbc.M509349200 . etal. free .
• Simpson JC, Wellenreuther R, Poustka A . Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing . EMBO Rep. . 1 . 3 . 287–92 . 2001 . 11256614 . 10.1093/embo-reports/kvd058 . 1083732 . etal.
• Singh H, Ashley RH . CLIC4 (p64H1) and its putative transmembrane domain form poorly selective, redox-regulated ion channels . Mol. Membr. Biol. . 24 . 1 . 41–52 . 2007 . 17453412 . 10.1080/09687860600927907 . 9986497 .
• Singh H, Cousin MA, Ashley RH . Functional reconstitution of mammalian 'chloride intracellular channels' CLIC1, CLIC4 and CLIC5 reveals differential regulation by cytoskeletal actin . FEBS J.. 274 . 24 . 6306–6316 . 2007 . 18028448 . 10.1111/j.1742-4658.2007.06145.x . 22494250 .
• Singh H . Two decades with dimorphic Chloride Intracellular Channels (CLICs) . FEBS Letters. 584. 10. 2112–21. 2010 . 20226783 . 10.1016/j.febslet.2010.03.013 . free . 2010FEBSL.584.2112S .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . etal . 2002PNAS...9916899M. free .
• Suginta W, Karoulias N, Aitken A, Ashley RH . Chloride intracellular channel protein CLIC4 (p64H1) binds directly to brain dynamin I in a complex containing actin, tubulin and 14-3-3 isoforms . Biochem. J. . 359 . Pt 1 . 55–64 . 2003 . 11563969 . 10.1042/0264-6021:3590055 . 1222121 .
• Valenzuela SM, Martin DK, Por SB . Molecular cloning and expression of a chloride ion channel of cell nuclei . J. Biol. Chem. . 272 . 19 . 12575–82 . 1997 . 9139710 . 10.1074/jbc.272.19.12575 . etal. free .
• Wick M, Bürger C, Brüsselbach S . Identification of serum-inducible genes: different patterns of gene regulation during G0-->S and G1-->S progression . J. Cell Sci. . 107 . 1. 227–39 . 1994 . 10.1242/jcs.107.1.227 . 8175911 . etal.
• Wiemann S, Arlt D, Huber W . From ORFeome to Biology: A Functional Genomics Pipeline . Genome Res. . 14 . 10B . 2136–44 . 2004 . 15489336 . 10.1101/gr.2576704 . 528930 . etal.
• Wiemann S, Weil B, Wellenreuther R . 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 . 10.1101/gr.GR1547R . 311072 . etal.

Notes and References

1. Web site: Entrez Gene: CLIC4 chloride intracellular channel 4.
2. Suginta W, Karoulias N, Aitken A, Ashley RH . Chloride intracellular channel protein CLIC4 (p64H1) binds directly to brain dynamin I in a complex containing actin, tubulin and 14-3-3 isoforms . Biochem. J. . 359 . Pt1 . 55–64. October 2001 . 11563969 . 10.1042/0264-6021:3590055. 1222121 .