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Gene Review

CALD1  -  caldesmon 1

Homo sapiens

Synonyms: CAD, CDM, Caldesmon, H-CAD, HCAD, ...
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Disease relevance of CALD1


Psychiatry related information on CALD1

  • Smooth muscle caldesmon is a thin-filament constituent which takes part in the Ca2+-dependent regulation of actomyosin motor activity which converts chemical energy of ATP into force [6].
  • Psychometric performance based on all 11 variables deteriorated under hypoxia by 49% after placebo, while after 5 mg CDM only by 26% [7].

High impact information on CALD1

  • A single protein (CAD) contains the first three enzymatic activities of de novo uridine biosynthesis [8].
  • The chromosomal location of CAD genes introduced into Chinese hamster ovary cells significantly affects the frequency and cytogenetic result of their amplification [8].
  • Rac and cell migration: CDM proteins integrate signals [9].
  • The content of caldesmon was significantly increased in myometrium of pregnant women, whereas that of calponin (a smooth muscle-specific protein associated with the thin filaments) was not different [10].
  • Methods: Ten readers trained in CT but without special expertise in colonography interpreted CT colonography images of 107 patients (60 with 142 polyps), first without CAD and then with CAD after temporal separation of 2 months [11].

Chemical compound and disease context of CALD1


Biological context of CALD1

  • The tyrosine phosphorylation of caldesmon, and its association with the Shc-Grb2-Sos signaling complex directly links tyrosine kinase oncogenic signaling events with cytoskeletal regulatory processes, and may define one mechanism regulating actin stress fiber disassembly in transformed cells [2].
  • Overlapping cDNA clones encoding a low M gamma human nonmuscle caldesmon isoform (HUM 1-CaD) span the entire coding region (538 amino acids) as well as 111 base pairs (bp) of 5'-noncoding and 1249 bp of 3'-noncoding region [17].
  • One such gene, caldesmon, lies on chromosome 7q35, a region linked to nephropathy in family studies, making it a candidate susceptibility gene for diabetic nephropathy [18].
  • Together, these results demonstrate that CaD plays a crucial role in mediating the effects of Ca(2+)-CaM on the dynamics of the actin cytoskeleton during cell migration [19].
  • Moreover, CaD39-AB-expressing cells exhibited motility defects in a wound-healing assay, in both velocity and the persistence of translocation, suggesting a role for CaD regulation by Ca(2+)-CaM in cell migration [19].

Anatomical context of CALD1


Associations of CALD1 with chemical compounds

  • A transformation-associated complex involving tyrosine kinase signal adapter proteins and caldesmon links v-erbB signaling to actin stress fiber disassembly [2].
  • To investigate this regulation, a mutant was generated of the C-terminal fragment of human fibroblast CaD, termed CaD39-AB, in which two crucial tryptophan residues involved in Ca(2+)-CaM binding were each replaced with alanine [19].
  • Tryptophan residues in caldesmon are major determinants for calmodulin binding [22].
  • Cysteine residues of caldesmon were labeled with the fluorescent reagent N-(1-pyrenyl)maleimide [23].
  • Acrylodan-labeled caldesmon, when excited at 375 nm, had an emission maximum at 504 nm [24].

Physical interactions of CALD1

  • The C-terminal part of caldesmon contains three peptides with a primary structure similar to that of the calmodulin- and phospholipid-binding site of neuromodulin [25].
  • Lys172-His187 inhibited the binding of calponin to F-actin in a concentration-dependent manner but not the binding of caldesmon [26].

Enzymatic interactions of CALD1


Regulatory relationships of CALD1


Other interactions of CALD1

  • Phosphorylation of caldesmon by extracellular signal-regulated kinase (ERK) reverses this inhibitory effect and weakens actin binding [21].
  • Here we demonstrate the transformation-specific interaction between two components of this complex: the adaptor protein Grb2 and the cytoskeletal regulatory protein caldesmon [32].
  • These results suggest that CaD is critically involved in the regulation of the actin cytoskeleton and migration in EC, and that p38 MAPK-mediated CaD phosphorylation may be involved in endothelial cytoskeletal remodeling [33].
  • The median amount both groups were willing to pay for a month of oral EGFR TKI therapy was $100 CAD (range $0-5000 per month) [34].
  • The yet unidentified cDNA of the human Rabex5 gene and the 3' untranslated region of the human caldesmon gene were cloned [35].

Analytical, diagnostic and therapeutic context of CALD1

  • To better understand this function, we have examined the phosphorylation-dependent contact sites of caldesmon on actin by low dose electron microscopy and three-dimensional reconstruction of actin filaments decorated with a C-terminal fragment, hH32K, of human caldesmon containing the principal actin-binding domains [21].
  • Titration of caltropin with labeled caldesmon indicated a strong affinity for this protein (Kd was in the order of 8 x 10(-8)-2 x 10(-7) M) [24].
  • Caldesmon from chicken gizzard muscle has been examined for its ability to interact with caltropin using affinity chromatography and the fluorescent probe acrylodan [24].
  • Seven highly conserved regions were found in caldesmon molecules from various sources using the multiple sequence alignment method [36].
  • Conclusions: CAD for CT colonography significantly increases per-patient and per-polyp detection and significantly reduces interpretation times but cannot substitute for adequate training [11].


  1. Differential expression of splicing variants of the human caldesmon gene (CALD1) in glioma neovascularization versus normal brain microvasculature. Zheng, P.P., Sieuwerts, A.M., Luider, T.M., van der Weiden, M., Sillevis-Smitt, P.A., Kros, J.M. Am. J. Pathol. (2004) [Pubmed]
  2. A transformation-associated complex involving tyrosine kinase signal adapter proteins and caldesmon links v-erbB signaling to actin stress fiber disassembly. McManus, M.J., Lingle, W.L., Salisbury, J.L., Maihle, N.J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  3. Over-expression of smooth muscle caldesmon in mouse fibroblasts. Surgucheva, I., Bryan, J. Cell Motil. Cytoskeleton (1995) [Pubmed]
  4. Pseudosarcomatous myofibroblastic tumor and myosarcoma of the urogenital tract. Watanabe, K., Baba, K., Saito, A., Hoshi, N., Suzuki, T. Arch. Pathol. Lab. Med. (2001) [Pubmed]
  5. Specific but variable expression of h-caldesmon in leiomyosarcomas: an immunohistochemical reassessment of a novel myogenic marker. Hisaoka, M., Wei-Qi, S., Jian, W., Morio, T., Hashimoto, H. Appl. Immunohistochem. Mol. Morphol. (2001) [Pubmed]
  6. Nonmuscle caldesmon: its distribution and involvement in various cellular processes. Review article. Dabrowska, R., Kulikova, N., Gagola, M. Protoplasma (2004) [Pubmed]
  7. On brain protection of co-dergocrine mesylate (Hydergine) against hypoxic hypoxidosis of different severity: double-blind placebo-controlled quantitative EEG and psychometric studies. Saletu, B., Grünberger, J., Anderer, R. International journal of clinical pharmacology, therapy, and toxicology. (1990) [Pubmed]
  8. Effect of chromosomal position on amplification of transfected genes in animal cells. Wahl, G.M., Robert de Saint Vincent, B., DeRose, M.L. Nature (1984) [Pubmed]
  9. Rac and cell migration: CDM proteins integrate signals. Bourne, H.R. Nat. Cell Biol. (2005) [Pubmed]
  10. Contractile elements and myosin light chain phosphorylation in myometrial tissue from nonpregnant and pregnant women. Word, R.A., Stull, J.T., Casey, M.L., Kamm, K.E. J. Clin. Invest. (1993) [Pubmed]
  11. Computed tomographic colonography: assessment of radiologist performance with and without computer-aided detection. Halligan, S., Altman, D.G., Mallett, S., Taylor, S.A., Burling, D., Roddie, M., Honeyfield, L., McQuillan, J., Amin, H., Dehmeshki, J. Gastroenterology (2006) [Pubmed]
  12. Molecular mechanism of inhibitory aryl hydrocarbon receptor-estrogen receptor/Sp1 cross talk in breast cancer cells. Khan, S., Barhoumi, R., Burghardt, R., Liu, S., Kim, K., Safe, S. Mol. Endocrinol. (2006) [Pubmed]
  13. Enhanced glomerular expression of caldesmon in IgA nephropathy and its suppression by glucocorticoid-heparin therapy. Ando, Y., Moriyama, T., Miyazaki, M., Akagi, Y., Kawada, N., Isaka, Y., Izumi, M., Yokoyama, K., Yamauchi, A., Horio, M., Ando, A., Ueda, N., Sobue, K., Imai, E., Hori, M. Nephrol. Dial. Transplant. (1998) [Pubmed]
  14. Role of ERK1/2 in uterine contractility and preterm labor in rats. Li, Y., Je, H.D., Malek, S., Morgan, K.G. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2004) [Pubmed]
  15. Hyperhomocysteinemia as a cardiovascular risk factor in Indian women: determinants and directionality. Pandey, S.N., Vaidya, A.D., Vaidya, R.A., Talwalkar, S. The Journal of the Association of Physicians of India (2006) [Pubmed]
  16. I.V. Labetalol during coronary artery surgery. Joucken, K. Acta anaesthesiologica Belgica. (1983) [Pubmed]
  17. Characterization of cDNA clones encoding a human fibroblast caldesmon isoform and analysis of caldesmon expression in normal and transformed cells. Novy, R.E., Lin, J.L., Lin, J.J. J. Biol. Chem. (1991) [Pubmed]
  18. Association between variation in the actin-binding gene caldesmon and diabetic nephropathy in type 1 diabetes. Conway, B.R., Maxwell, A.P., Savage, D.A., Patterson, C.C., Doran, P.P., Murphy, M., Brady, H.R., Fogarty, D.G. Diabetes (2004) [Pubmed]
  19. Caldesmon mutant defective in Ca(2+)-calmodulin binding interferes with assembly of stress fibers and affects cell morphology, growth and motility. Li, Y., Lin, J.L., Reiter, R.S., Daniels, K., Soll, D.R., Lin, J.J. J. Cell. Sci. (2004) [Pubmed]
  20. Genomic structure of the human caldesmon gene. Hayashi, K., Yano, H., Hashida, T., Takeuchi, R., Takeda, O., Asada, K., Takahashi, E., Kato, I., Sobue, K. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  21. Modes of caldesmon binding to actin: sites of caldesmon contact and modulation of interactions by phosphorylation. Foster, D.B., Huang, R., Hatch, V., Craig, R., Graceffa, P., Lehman, W., Wang, C.L. J. Biol. Chem. (2004) [Pubmed]
  22. Tryptophan residues in caldesmon are major determinants for calmodulin binding. Graether, S.P., Heinonen, T.Y., Raharjo, W.H., Jin, J.P., Mak, A.S. Biochemistry (1997) [Pubmed]
  23. Interaction between caldesmon and tropomyosin in the presence and absence of smooth muscle actin. Horiuchi, K.Y., Chacko, S. Biochemistry (1988) [Pubmed]
  24. Calcium-dependent regulation of caldesmon by an 11-kDa smooth muscle calcium-binding protein, caltropin. Mani, R.S., McCubbin, W.D., Kay, C.M. Biochemistry (1992) [Pubmed]
  25. Caldesmon-phospholipid interaction. Effect of protein kinase C phosphorylation and sequence similarity with other phospholipid-binding proteins. Vorotnikov, A.V., Bogatcheva, N.V., Gusev, N.B. Biochem. J. (1992) [Pubmed]
  26. Two distinct actin-binding sites of smooth muscle calponin. Mino, T., Yuasa, U., Nakamura, F., Naka, M., Tanaka, T. Eur. J. Biochem. (1998) [Pubmed]
  27. Purification and characterization of calmodulin-dependent multifunctional protein kinase from smooth muscle: isolation of caldesmon kinase. Ikebe, M., Reardon, S., Scott-Woo, G.C., Zhou, Z., Koda, Y. Biochemistry (1990) [Pubmed]
  28. Caldesmon effects on the actin cytoskeleton and cell adhesion in cultured HTM cells. Grosheva, I., Vittitow, J.L., Goichberg, P., Gabelt, B.T., Kaufman, P.L., Borrás, T., Geiger, B., Bershadsky, A.D. Exp. Eye Res. (2006) [Pubmed]
  29. Phosphorylated HSP27 modulates the association of phosphorylated caldesmon with tropomyosin in colonic smooth muscle. Somara, S., Bitar, K.N. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  30. Functional involvement of serum response factor in the transcriptional regulation of caldesmon gene. Momiyama, T., Hayashi, K., Obata, H., Chimori, Y., Nishida, T., Ito, T., Kamiike, W., Matsuda, H., Sobue, K. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  31. Gene profiling of polycystic kidneys. Schieren, G., Rumberger, B., Klein, M., Kreutz, C., Wilpert, J., Geyer, M., Faller, D., Timmer, J., Quack, I., Rump, L.C., Walz, G., Donauer, J. Nephrol. Dial. Transplant. (2006) [Pubmed]
  32. Grb2 regulation of the actin-based cytoskeleton is required for ligand-independent EGF receptor-mediated oncogenesis. Boerner, J.L., Danielsen, A.J., Lovejoy, C.A., Wang, Z., Juneja, S.C., Faupel-Badger, J.M., Darce, J.R., Maihle, N.J. Oncogene (2003) [Pubmed]
  33. The role of caldesmon in the regulation of endothelial cytoskeleton and migration. Mirzapoiazova, T., Kolosova, I.A., Romer, L., Garcia, J.G., Verin, A.D. J. Cell. Physiol. (2005) [Pubmed]
  34. A willingness-to-pay study of oral epidermal growth factor tyrosine kinase inhibitors in advanced non-small cell lung cancer. Leighl, N.B., Tsao, W.S., Zawisza, D.L., Nematollahi, M., Shepherd, F.A. Lung Cancer (2006) [Pubmed]
  35. Seven genes that are differentially transcribed in colorectal tumor cell lines. Nimmrich, I., Erdmann, S., Melchers, U., Finke, U., Hentsch, S., Moyer, M.P., Hoffmann, I., Müller, O. Cancer Lett. (2000) [Pubmed]
  36. Motifs of the caldesmon family. Czuryło, E.A. Acta Biochim. Pol. (2000) [Pubmed]
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