




Gene Review

CLC  -  Charcot-Leyden crystal galectin

Homo sapiens

Synonyms: Charcot-Leyden crystal protein, Eosinophil lysophospholipase, GAL10, Gal-10, Galectin-10, ...

Disease relevance of CLC


High impact information on CLC


Chemical compound and disease context of CLC


Biological context of CLC

  • However, A23187 at a concentration (1 microgram/ml) that caused 15% EDN release and 30% CLC protein release also produced release of the cytoplasmic enzyme lactic dehydrogenase (LDH) and loss of cell viability, both of which were calcium dependent [12].
  • One of the genes, CLC, was reduced in gene expression and its four exons were sequenced [13].
  • Two SNPs (rs374185 and rs384138) were observed in the CLC gene, each with an allele frequency of 68% [13].
  • Despite considerable similarity in their amino acid sequences and structural features, the mammalian members of the CLC chloride channel/transporter family have different subcellular locations [14].
  • The gene encoding CLC protein was cloned from a chromosome 19-specific library and a fragment overlapping the transcriptional start site was isolated and sequenced [15].

Anatomical context of CLC


Associations of CLC with chemical compounds

  • Mixtures of the MBP and the CLC protein yielded two bands in polyacrylamide gel electrophoresis [18].
  • The CLC promoter sequence contains two consensus GATA binding sites, a purine-rich sequence that presents potential binding sites for PU.1, a member of the ets family of genes, as well as sequences described in other myeloid-specific promoters [15].
  • Interestingly, the CLC protein demonstrates no affinity for beta-galactosides and binds mannose in a manner very different from those of other related galectins that have been shown to bind lactosamine [19].
  • The extracellular release of CLC protein was studied during the degranulation of basophils stimulated by anti-immunoglobulin E (anti-IgE), N-formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol myristate acetate, eosinophil major basic protein (MBP), and calcium ionophore A23187 [20].
  • The overall structural fold of CLC protein is highly similar to that of galectins -1 and -2, members of an animal lectin family formerly classified as S-type or S-Lac (soluble lactose-binding) lectins [21].

Other interactions of CLC

  • Reverse transcriptase-polymerase chain reaction analyses revealed that undifferentiated HL-60 cells expressed galectin-1, -3, -8, -9, and -10 (identical to Charcot Leyden crystal) mRNAs, and galectin-2, -4, and -7 were negligible before and after the differentiations [22].
  • In basophils both the CLC protein positive and the negative granules showed the same characteristic particulate-like structure of the granular matrix and both share the same membrane marker CD63 [23].
  • ClC-3, a member of the CLC family of chloride channels and transporters, is expressed in intracellular compartments of neuronal cells and involved in vesicular acidification [24].
  • Double-labeling experiments showed, in eosinophils, that CLC protein-containing granules contain also eosinophil peroxidase, a characteristic specific granule protein [23].
  • Despite CLC protein having no significant sequence or structural similarities to other lysophospholipase catalytic triad has also been identified within the CLC structure, making it a unique dual-function polypeptide [21].

Analytical, diagnostic and therapeutic context of CLC


  1. Ultrastructural localization of Charcot-Leyden crystal protein (lysophospholipase) to intracytoplasmic crystals in tumor cells of primary solid and papillary epithelial neoplasm of the pancreas. Dvorak, A.M., Letourneau, L., Weller, P.F., Ackerman, S.J. Lab. Invest. (1990) [Pubmed]
  2. Ultrastructural localization of Charcot-Leyden crystal protein (lysophospholipase) and peroxidase in macrophages, eosinophils, and extracellular matrix of the skin in the hypereosinophilic syndrome. Dvorak, A.M., Weller, P.F., Monahan-Earley, R.A., Letourneau, L., Ackerman, S.J. Lab. Invest. (1990) [Pubmed]
  3. Genetic diseases of acid-base transporters. Alper, S.L. Annu. Rev. Physiol. (2002) [Pubmed]
  4. Chloride channels: an emerging molecular picture. Jentsch, T.J., Günther, W. Bioessays (1997) [Pubmed]
  5. Clinically-occult mixed cellularity Hodgkin's disease with Charcot-Leyden crystals. Carson, H.J., Pellettiere, E.V. Leuk. Lymphoma (1996) [Pubmed]
  6. Molecular physiology of anion channels. Jentsch, T.J. Curr. Opin. Cell Biol. (1994) [Pubmed]
  7. A decade of CLC chloride channels: structure, mechanism, and many unsettled questions. Maduke, M., Miller, C., Mindell, J.A. Annual review of biophysics and biomolecular structure. (2000) [Pubmed]
  8. Localization of eosinophil granule major basic protein in human basophils. Ackerman, S.J., Kephart, G.M., Habermann, T.M., Greipp, P.R., Gleich, G.J. J. Exp. Med. (1983) [Pubmed]
  9. Formation of Charcot-Leyden crystals by human basophils. Ackerman, S.J., Weil, G.J., Gleich, G.J. J. Exp. Med. (1982) [Pubmed]
  10. Charcot-Leyden crystals in fine needle aspiration cytology. Arora, V.K., Singh, N., Bhatia, A. Acta Cytol. (1997) [Pubmed]
  11. Increased plasma levels of substance P and disturbed water excretion in patients with liver cirrhosis. Uemura, M., Tsujii, T., Kikuchi, E., Fukui, H., Tsukamoto, N., Matsumura, M., Fujimoto, M., Koizumi, M., Takaya, A., Kojima, H., Ishii, Y., Okamoto, S. Scand. J. Gastroenterol. (1998) [Pubmed]
  12. Calcium ionophore A23187 calcium-dependent cytolytic degranulation in human eosinophils. Fukuda, T., Ackerman, S.J., Reed, C.E., Peters, M.S., Dunnette, S.L., Gleich, G.J. J. Immunol. (1985) [Pubmed]
  13. Altered expression of CLC, DSG3, EMP3, S100A2, and SLPI in corneal epithelium from keratoconus patients. Nielsen, K., Heegaard, S., Vorum, H., Birkenkamp-Demtröder, K., Ehlers, N., Orntoft, T.F. Cornea (2005) [Pubmed]
  14. The human ClC-4 protein, a member of the CLC chloride channel/transporter family, is localized to the endoplasmic reticulum by its N-terminus. Okkenhaug, H., Weylandt, K.H., Carmena, D., Wells, D.J., Higgins, C.F., Sardini, A. FASEB J. (2006) [Pubmed]
  15. Human eosinophil Charcot-Leyden crystal protein: cloning and characterization of a lysophospholipase gene promoter. Gomolin, H.I., Yamaguchi, Y., Paulpillai, A.V., Dvorak, L.A., Ackerman, S.J., Tenen, D.G. Blood (1993) [Pubmed]
  16. Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6. Poët, M., Kornak, U., Schweizer, M., Zdebik, A.A., Scheel, O., Hoelter, S., Wurst, W., Schmitt, A., Fuhrmann, J.C., Planells-Cases, R., Mole, S.E., Hübner, C.A., Jentsch, T.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  17. Human eosinophil lysophospholipase: the sole protein component of Charcot-Leyden crystals. Weller, P.F., Bach, D., Austen, K.F. J. Immunol. (1982) [Pubmed]
  18. Comparative properties of the Charcot-Leyden crystal protein and the major basic protein from human eosinophils. Gleich, G.J., Loegering, D.A., Mann, K.G., Maldonado, J.E. J. Clin. Invest. (1976) [Pubmed]
  19. Selective recognition of mannose by the human eosinophil Charcot-Leyden crystal protein (galectin-10): a crystallographic study at 1.8 A resolution. Swaminathan, G.J., Leonidas, D.D., Savage, M.P., Ackerman, S.J., Acharya, K.R. Biochemistry (1999) [Pubmed]
  20. Charcot-Leyden crystal protein in the degranulation and recovery of activated basophils. Golightly, L.M., Thomas, L.L., Dvorak, A.M., Ackerman, S.J. J. Leukoc. Biol. (1992) [Pubmed]
  21. Crystal structure of human Charcot-Leyden crystal protein, an eosinophil lysophospholipase, identifies it as a new member of the carbohydrate-binding family of galectins. Leonidas, D.D., Elbert, B.L., Zhou, Z., Leffler, H., Ackerman, S.J., Acharya, K.R. Structure (1995) [Pubmed]
  22. Potential roles of galectins in myeloid differentiation into three different lineages. Abedin, M.J., Kashio, Y., Seki, M., Nakamura, K., Hirashima, M. J. Leukoc. Biol. (2003) [Pubmed]
  23. Ultrastructural localization of Charcot-Leyden crystal protein in human eosinophils and basophils. Calafat, J., Janssen, H., Knol, E.F., Weller, P.F., Egesten, A. Eur. J. Haematol. (1997) [Pubmed]
  24. ClC-3 expression enhances etoposide resistance by increasing acidification of the late endocytic compartment. Weylandt, K.H., Nebrig, M., Jansen-Rosseck, N., Amey, J.S., Carmena, D., Wiedenmann, B., Higgins, C.F., Sardini, A. Mol. Cancer Ther. (2007) [Pubmed]
  25. Molecular cloning and characterization of human eosinophil Charcot-Leyden crystal protein (lysophospholipase). Similarities to IgE binding proteins and the S-type animal lectin superfamily. Ackerman, S.J., Corrette, S.E., Rosenberg, H.F., Bennett, J.C., Mastrianni, D.M., Nicholson-Weller, A., Weller, P.F., Chin, D.T., Tenen, D.G. J. Immunol. (1993) [Pubmed]
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