The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CLIC4  -  chloride intracellular channel 4

Homo sapiens

Synonyms: CLIC4L, Chloride intracellular channel protein 4, DKFZP566G223, H1, Intracellular chloride ion channel protein p64H1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of CLIC4


High impact information on CLIC4

  • Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors [6].
  • Further work will continue toward enhancing our understanding of the control by histamine of intracellular signaling via H1- and H2-receptors, and the rapid explosion of work on the H3-receptor should begin to unravel the mechanisms underlying its actions, perhaps via effects on ionic channels [7].
  • Chlorpheniramine, an H1 antihistamine, did not block the histamine inhibition of granulocyte lysosomal enzyme release [8].
  • In line with this, we found that PLCbeta3(-/-) mice showed significant defects in scratching behavior induced by histamine; histamine-trifluoromethyl-toluidine (HTMT), a selective H1 agonist; and compound 48/80, a mast cell activator [9].
  • It is known that histone H1 and HMG proteins compete for a common binding site, the linker DNA [10].

Chemical compound and disease context of CLIC4


Biological context of CLIC4

  • In a migration assay, we found that CLIC4 inhibited cell motility by 27% [1].
  • These results suggest that CLIC4 is differentially regulated in fibroblasts and that its expression contributes to a collective stationary myofibroblast phenotype [1].
  • Antisense- and small interfering RNA-mediated suppression of CLIC4 expression led to arrest in tubular morphogenesis [2].
  • The localization of CLIC4 to the cortical actin cytoskeleton and its association with AKAP350 at the centrosome and midbody suggests that CLIC4 may be important for regulating cytoskeletal organization during the cell cycle [15].
  • Quantitative proteomic analysis of myc-induced apoptosis: a direct role for Myc induction of the mitochondrial chloride ion channel, mtCLIC/CLIC4 [16].

Anatomical context of CLIC4


Associations of CLIC4 with chemical compounds


Regulatory relationships of CLIC4


Other interactions of CLIC4

  • Differential expression of a chloride intracellular channel gene, CLIC4, in transforming growth factor-beta1-mediated conversion of fibroblasts to myofibroblasts [1].
  • It has been previously shown that a 14-amino acid (aa) modified peptide (H1-S6A,F8A) derived from the helix 1 (H1) carboxylic region of c-Myc can interfere in vitro with specific c-Myc DNA binding [22].
  • We used a polymerase chain reaction-based approach to identify candidate genes in mammalian brain and cloned the cDNA corresponding to rat brain p64H1 [23].
  • We considered that the histamine-1 (H1) receptor antagonist hydroxyzine, which also partially inhibits brain mast cells and has anxiolytic properties, may reduce MS symptoms [24].
  • In huH-1 and HuH-7, both ATBF1 isoforms suppressed strongly enhancer activity and slightly promoter activity [21].

Analytical, diagnostic and therapeutic context of CLIC4


  1. Differential expression of a chloride intracellular channel gene, CLIC4, in transforming growth factor-beta1-mediated conversion of fibroblasts to myofibroblasts. Rønnov-Jessen, L., Villadsen, R., Edwards, J.C., Petersen, O.W. Am. J. Pathol. (2002) [Pubmed]
  2. Proteomic analysis of vascular endothelial growth factor-induced endothelial cell differentiation reveals a role for chloride intracellular channel 4 (CLIC4) in tubular morphogenesis. Bohman, S., Matsumoto, T., Suh, K., Dimberg, A., Jakobsson, L., Yuspa, S., Claesson-Welsh, L. J. Biol. Chem. (2005) [Pubmed]
  3. Reciprocal Modifications of CLIC4 in Tumor Epithelium and Stroma Mark Malignant Progression of Multiple Human Cancers. Suh, K.S., Crutchley, J.M., Koochek, A., Ryscavage, A., Bhat, K., Tanaka, T., Oshima, A., Fitzgerald, P., Yuspa, S.H. Clin. Cancer Res. (2007) [Pubmed]
  4. Histamine as a growth factor and chemoattractant for human carcinoma and melanoma cells: action through Ca2(+)-mobilizing H1 receptors. Tilly, B.C., Tertoolen, L.G., Remorie, R., Ladoux, A., Verlaan, I., de Laat, S.W., Moolenaar, W.H. J. Cell Biol. (1990) [Pubmed]
  5. Cardiac Na(+) channel dysfunction in Brugada syndrome is aggravated by beta(1)-subunit. Makita, N., Shirai, N., Wang, D.W., Sasaki, K., George, A.L., Kanno, M., Kitabatake, A. Circulation (2000) [Pubmed]
  6. Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Jutel, M., Watanabe, T., Klunker, S., Akdis, M., Thomet, O.A., Malolepszy, J., Zak-Nejmark, T., Koga, R., Kobayashi, T., Blaser, K., Akdis, C.A. Nature (2001) [Pubmed]
  7. Distribution, properties, and functional characteristics of three classes of histamine receptor. Hill, S.J. Pharmacol. Rev. (1990) [Pubmed]
  8. Histamine inhibition of neutrophil lysosomal enzyme release: an H2 histamine receptor response. Busse, W.W., Sosman, J. Science (1976) [Pubmed]
  9. Phospholipase cbeta 3 mediates the scratching response activated by the histamine h1 receptor on C-fiber nociceptive neurons. Han, S.K., Mancino, V., Simon, M.I. Neuron (2006) [Pubmed]
  10. Loss of linker histone H1 in cellular senescence. Funayama, R., Saito, M., Tanobe, H., Ishikawa, F. J. Cell Biol. (2006) [Pubmed]
  11. Topical ocular levocabastine reduces ICAM-1 expression on epithelial cells both in vivo and in vitro. Buscaglia, S., Paolieri, F., Catrullo, A., Fiorino, N., Riccio, A.M., Pesce, G., Montagna, P., Bagnasco, M., Ciprandi, G., Canonica, G.W. Clin. Exp. Allergy (1996) [Pubmed]
  12. Histamine activates phospholipase C in human airway epithelial cells via a phorbol ester-sensitive pathway. Rugolo, M., Barzanti, F., Gruenert, D.C., Hrelia, S. Am. J. Physiol. (1996) [Pubmed]
  13. Mechanism underlying histamine-induced intracellular Ca2+ movement in PC3 human prostate cancer cells. Lee, K.C., Chang, H.T., Chou, K.J., Tang, K.Y., Wang, J.L., Lo, Y.K., Huang, J.K., Chen, W.C., Su, W., Law, Y.P., Jan, C.R. Pharmacol. Res. (2001) [Pubmed]
  14. Mechanisms of pHi recovery from NH4Cl-induced acidosis in anoxic isolated turtle heart: a 31P-NMR study. Shi, H., Hamm, P.H., Meyers, R.S., Lawler, R.G., Jackson, D.C. Am. J. Physiol. (1997) [Pubmed]
  15. CLIC4 is enriched at cell-cell junctions and colocalizes with AKAP350 at the centrosome and midbody of cultured mammalian cells. Berryman, M.A., Goldenring, J.R. Cell Motil. Cytoskeleton (2003) [Pubmed]
  16. Quantitative proteomic analysis of myc-induced apoptosis: a direct role for Myc induction of the mitochondrial chloride ion channel, mtCLIC/CLIC4. Shiio, Y., Suh, K.S., Lee, H., Yuspa, S.H., Eisenman, R.N., Aebersold, R. J. Biol. Chem. (2006) [Pubmed]
  17. Identification of a novel member of the chloride intracellular channel gene family (CLIC5) that associates with the actin cytoskeleton of placental microvilli. Berryman, M., Bretscher, A. Mol. Biol. Cell (2000) [Pubmed]
  18. CLIC4, an intracellular chloride channel protein, is a novel molecular target for cancer therapy. Suh, K.S., Mutoh, M., Gerdes, M., Yuspa, S.H. J. Investig. Dermatol. Symp. Proc. (2005) [Pubmed]
  19. Regulation of M-phase progression in Chaetopterus oocytes by protein kinase C. Eckberg, W.R., Palazzo, R.E. Dev. Biol. (1992) [Pubmed]
  20. Histamine reduces gap junctional communication of human tonsil high endothelial cells in culture. Figueroa, X.F., Alviña, K., Martínez, A.D., Garcés, G., Rosemblatt, M., Boric, M.P., Sáez, J.C. Microvasc. Res. (2004) [Pubmed]
  21. Regulation of the alpha-fetoprotein gene by the isoforms of ATBF1 transcription factor in human hepatoma. Ninomiya, T., Mihara, K., Fushimi, K., Hayashi, Y., Hashimoto-Tamaoki, T., Tamaoki, T. Hepatology (2002) [Pubmed]
  22. Inhibition of cancer cell growth and c-Myc transcriptional activity by a c-Myc helix 1-type peptide fused to an internalization sequence. Giorello, L., Clerico, L., Pescarolo, M.P., Vikhanskaya, F., Salmona, M., Colella, G., Bruno, S., Mancuso, T., Bagnasco, L., Russo, P., Parodi, S. Cancer Res. (1998) [Pubmed]
  23. Rat brain p64H1, expression of a new member of the p64 chloride channel protein family in endoplasmic reticulum. Duncan, R.R., Westwood, P.K., Boyd, A., Ashley, R.H. J. Biol. Chem. (1997) [Pubmed]
  24. A pilot, open label, clinical trial using hydroxyzine in multiple sclerosis. Logothetis, L., Mylonas, I.A., Baloyannis, S., Pashalidou, M., Orologas, A., Zafeiropoulos, A., Kosta, V., Theoharides, T.C. International journal of immunopathology and pharmacology. (2005) [Pubmed]
  25. The organellular chloride channel protein CLIC4/mtCLIC translocates to the nucleus in response to cellular stress and accelerates apoptosis. Suh, K.S., Mutoh, M., Nagashima, K., Fernandez-Salas, E., Edwards, L.E., Hayes, D.D., Crutchley, J.M., Marin, K.G., Dumont, R.A., Levy, J.M., Cheng, C., Garfield, S., Yuspa, S.H. J. Biol. Chem. (2004) [Pubmed]
WikiGenes - Universities