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Gene Review

CALML3  -  calmodulin-like 3

Homo sapiens

Synonyms: CLP, CaM-like protein, Calmodulin-like protein 3, Calmodulin-related protein NB-1
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Disease relevance of CALML3

  • Isolated or nonsyndromic cleft lip and palate (NS CLP) is a complex disorder resulting from multiple genetic and environmental factors [1].
  • In contrast to the CaMIII promoter, the CLP gene upstream region was driving hGH expression only in human teratoma, but not in monkey COS cells [2].
  • To test this we carried out studies in which we assessed the capacity of hemorrhage alone or hemorrhage followed by septic challenge (CLP) to induce ALI [3].
  • We studied the therapeutic potential of lipid/DNA complexes consisting of cationic liposomes and an endostatin-coding plasmid (Endo cDNA/CLP) in an orthotopic osteosarcoma model in rats [4].
  • METHODS: We examined the expression of TLR-9 in the liver and spleen in a murine peritonitis model (CLP mice) [5].

Psychiatry related information on CALML3

  • The results indicate that those with CLP have a normal or even a high self-concept, and no signs of introversion [6].
  • Aspects of social and psychological adjustment were investigated in a sample of 233 Norwegian adults 20-35 years old with repaired complete cleft of the lip and palate (CLP); in 126 the cleft was on the left, in 45 on the right, and in 62 it was bilateral [7].
  • Low doses of the selective kappa agonist (+/-)-trans-U-50-trans-3,4-dichloro-N-methyl-N[2-(1-pyrrodinyl)-cyclohexyl]benzene acetamide methasulphonate (U50, 488) and bremazocine-HCl increased motor activity leading to C-like position (CLP) and screw-like hyperkinesia (SLH) [8].
  • In addition to the influences of family dynamics, educational and vocational factors on the social development and rehabilitation of CLP patients, psychological problems, such as lowered self-esteem and difficulties during social interaction, are also experienced by CLP individuals [9].

High impact information on CALML3

  • This manuscript shows that CLP and CMP both can give rise to pDCs. pDCs derived from CMP express RAG gene products and show IgHD-J rearrangement, suggesting that pDC represent a unique lineage whose gene expression program shows substantial plasticity [10].
  • Thus, CLP access to the thymus is controlled by a tissue-specific and subset-selective multistep adhesion cascade [11].
  • Thus, CLP functions by increasing the stability of myosin-10, leading to enhanced myosin-10 function and a subsequent increase in filopodial dynamics and cell migration [12].
  • Fluorescence microscopy and Western blotting revealed that CLP expression results in up-regulation of its target protein, myosin-10 [12].
  • Using stably transfected and inducible HeLa cell lines, we found that CLP expression did not alter the proliferation rate and colony-forming potential of these cells [12].

Chemical compound and disease context of CALML3

  • Both sepsis models caused bradykinin-induced pulmonary vasoconstriction, with the CLP groups demonstrating a time dependency of this effect [13].
  • METHODS: Male NMRI-mice were subjected to sham operation or to sepsis (caecal ligation and puncture, CLP) following administration of either the non-selective beta-adrenergic antagonist propranolol (0.5mg/kg s.c. every 12h in 1ml vehicle) or saline 0.9% (1ml s.c. every 12h) [14].
  • Although the BCAA isoleucine and valine were taken up to a greater extent in sepsis, the overall BCAA uptake was not significantly greater in sepsis than in control (CON 6.92 +/- 2.15 mumol/g liver protein vs CLP 15.8 +/- 1.9 mumol/g liver protein) [15].
  • The greatest increase in uptake following sepsis was among the gluconeogenic precursor amino acids alanine, glycine, threonine, and serine (CON, 27.0 +/- 4.2 mumol/g liver protein, TRA, 38.8 +/- 8.9 mumol/g liver protein; CLP, 62.8 +/- 6.0 mumol/g liver protein).(ABSTRACT TRUNCATED AT 250 WORDS)[15]

Biological context of CALML3


Anatomical context of CALML3

  • CLP expression correlated with an agent's ability to promote terminal differentiation regardless of the agent's effect on keratinocyte proliferation [18].
  • CLP was expressed exclusively in the epithelium of the tissues surveyed and was most abundant in thyroid, breast, prostate, kidney, and skin [18].
  • CLP down-regulation may be a result of the poorly differentiated state of these cell lines and tumors, or CLP expression may be incompatible with the uncontrolled cell growth associated with tumorigenesis [18].
  • The Ca(2+)-binding parameters of recombinant human calmodulin-like protein (CLP), a protein specifically expressed in mammary epithelial cells, were studied by flow dialysis in the absence and presence of 2, 10, and 30 mM MgCl2 [19].
  • In contrast, the erythrocyte plasma membrane Ca(2+)-ATPase could only be stimulated to 62% of its maximal CaM-dependent activity by CLP [20].

Associations of CALML3 with chemical compounds

  • Data analyzed from subjects with various degrees of renal dysfunction who were given single oral doses of loracarbef indicated a linear relationship between creatinine clearance (CLCR) and plasma clearance [CLP (L/hr) = 0.106.CLCR (ml/min/1.73 m2)] [21].
  • The CLP of isepamicin and CLCR were significantly related [(COP = 0.391.[CLCR] + 1.83; r2 = 0.878)] [22].
  • Cefmetazole CLP correlated positively with CLCR (r = 0.951, P less than 0.001): CLP = (1.181 . CLCR) -- 0.287 [23].
  • Cefpodoxime apparent total body clearance (CLP/F) values in groups II, III, and IV (132 +/- 29, 112 +/- 41, and 55.7 +/- 9.9 ml/min, respectively) were significantly lower than that in group I (238 +/- 44 ml/min) [24].
  • The terminal elimination half-life (t1/2 beta) of tobramycin was markedly reduced (59.62 +/- 25.18 [mean +/- standard deviation] versus 24.71 +/- 5.41 h) and total body clearance (CLP) was significantly increased in the presence of piperacillin (3.45 +/- 1.61 versus 7.16 +/- 1.64 ml/min) [25].

Physical interactions of CALML3

  • Yeast two-hybrid screening yielded a CLP-interacting clone encoding the three light chain binding IQ motifs of human "unconventional" myosin X. Pull-down experiments showed CLP binding to the IQ domain to be direct and Ca(2+)-dependent [16].
  • Binding occurs via the HMG box and an SRY peptide of residues 57-80 binds CaM like the intact domain [26].

Co-localisations of CALML3

  • Epitope-tagged myosin X was localized preferentially at the cell periphery in MCF-7 cells, and CLP colocalized with myosin X in these cells [16].

Regulatory relationships of CALML3

  • Factors modulating the EGF receptor signaling pathway were particularly potent in regulating CLP expression [18].

Other interactions of CALML3


Analytical, diagnostic and therapeutic context of CALML3

  • CLP interacted strongly with IQ motif 3 (K(d) approximately 0.5 nm) as determined by surface plasmon resonance [16].
  • To learn more about CLP expression and regulation, we determined the distribution of CLP in various human tissues by immunohistochemistry [18].
  • Human calmodulin-like protein (CLP) is a calcium-binding protein down-regulated in a cell culture model of mammary tumorigenesis as well as in a majority of breast cancers in vivo [18].
  • Direct Mg2+ binding studies by equilibrium gel filtration indicate that 4-5 Mg2+ bind to CLP with a mean K'Mg of 250 M-1 [19].
  • The generation of a human CLP gene-specific sequence tag site specified by the two primers used for PCR should prove useful for future linkage studies [17].


  1. A genome-wide linkage scan for cleft lip and cleft palate identifies a novel locus on 8p11-23. Riley, B.M., Schultz, R.E., Cooper, M.E., Goldstein-McHenry, T., Daack-Hirsch, S., Lee, K.T., Dragan, E., Vieira, A.R., Lidral, A.C., Marazita, M.L., Murray, J.C. Am. J. Med. Genet. A (2007) [Pubmed]
  2. Functional analysis of the promoters of the human CaMIII calmodulin gene and of the intronless gene coding for a calmodulin-like protein. Koller, M., Strehler, E.E. Biochim. Biophys. Acta (1993) [Pubmed]
  3. Shock-induced neutrophil mediated priming for acute lung injury in mice: divergent effects of TLR-4 and TLR-4/FasL deficiency. Ayala, A., Chung, C.S., Lomas, J.L., Song, G.Y., Doughty, L.A., Gregory, S.H., Cioffi, W.G., LeBlanc, B.W., Reichner, J., Simms, H.H., Grutkoski, P.S. Am. J. Pathol. (2002) [Pubmed]
  4. Endostatin cDNA/cationic liposome complexes as a promising therapy to prevent lung metastases in osteosarcoma: study in a human-like rat orthotopic tumor. Dutour, A., Monteil, J., Paraf, F., Charissoux, J.L., Kaletta, C., Sauer, B., Naujoks, K., Rigaud, M. Mol. Ther. (2005) [Pubmed]
  5. A critical role of CpG motifs in a murine peritonitis model by their binding to highly expressed toll-like receptor-9 on liver NKT cells. Tsujimoto, H., Ono, S., Matsumoto, A., Kawabata, T., Kinoshita, M., Majima, T., Hiraki, S., Seki, S., Moldawer, L.L., Mochizuki, H. J. Hepatol. (2006) [Pubmed]
  6. Self-concept and introversion in adolescents with cleft lip and palate. Persson, M., Aniansson, G., Becker, M., Svensson, H. Scandinavian journal of plastic and reconstructive surgery and hand surgery / Nordisk plastikkirurgisk forening [and] Nordisk klubb for handkirurgi. (2002) [Pubmed]
  7. Psychosocial adjustment in Norwegian adults who had undergone standardised treatment of complete cleft lip and palate. I. Education, employment and marriage. Ramstad, T., Ottem, E., Shaw, W.C. Scandinavian journal of plastic and reconstructive surgery and hand surgery / Nordisk plastikkirurgisk forening [and] Nordisk klubb for handkirurgi. (1995) [Pubmed]
  8. Opioid-dopamine interaction in planaria: a behavioral study. Passarelli, F., Merante, A., Pontieri, F.E., Margotta, V., Venturini, G., Palladini, G. Comp. Biochem. Physiol. C, Pharmacol. Toxicol. Endocrinol. (1999) [Pubmed]
  9. Psychological aspects of cleft lip and palate. Turner, S.R., Rumsey, N., Sandy, J.R. European journal of orthodontics. (1998) [Pubmed]
  10. Mysterious origin of plasmacytoid dendritic cell precursors. Wang, Y.H., Liu, Y.J. Immunity (2004) [Pubmed]
  11. A multistep adhesion cascade for lymphoid progenitor cell homing to the thymus. Scimone, M.L., Aifantis, I., Apostolou, I., von Boehmer, H., von Andrian, U.H. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  12. Calmodulin-like Protein Increases Filopodia-dependent Cell Motility via Up-regulation of Myosin-10. Bennett, R.D., Mauer, A.S., Strehler, E.E. J. Biol. Chem. (2007) [Pubmed]
  13. Bradykinin-induced pulmonary vasoconstriction is time and inducible nitric oxide synthase dependent in a peritonitis sepsis model. Fischer, L.G., Hilpert, J.H., Freise, H., Wendholt, D., Van Aken, H., Sielenkämper, A.W. Anesth. Analg. (2004) [Pubmed]
  14. beta-Adrenergic blockade during systemic inflammation: Impact on cellular immune functions and survival in a murine model of sepsis. Schmitz, D., Wilsenack, K., Lendemanns, S., Schedlowski, M., Oberbeck, R. Resuscitation (2007) [Pubmed]
  15. Amino acid uptake in isolated, perfused liver: effect of trauma and sepsis. Sax, H.C., Hasselgren, P.O., Talamini, M.A., Edwards, L.L., Fischer, J.E. J. Surg. Res. (1988) [Pubmed]
  16. The tumor-sensitive calmodulin-like protein is a specific light chain of human unconventional myosin X. Rogers, M.S., Strehler, E.E. J. Biol. Chem. (2001) [Pubmed]
  17. Localization of the intronless gene coding for calmodulin-like protein CLP to human chromosome 10p13-ter. Berchtold, M.W., Koller, M., Egli, R., Rhyner, J.A., Hameister, H., Strehler, E.E. Hum. Genet. (1993) [Pubmed]
  18. Human calmodulin-like protein is an epithelial-specific protein regulated during keratinocyte differentiation. Rogers, M.S., Kobayashi, T., Pittelkow, M.R., Strehler, E.E. Exp. Cell Res. (2001) [Pubmed]
  19. Cation binding and conformation of human calmodulin-like protein. Durussel, I., Rhyner, J.A., Strehler, E.E., Cox, J.A. Biochemistry (1993) [Pubmed]
  20. Characterization of the human calmodulin-like protein expressed in Escherichia coli. Rhyner, J.A., Koller, M., Durussel-Gerber, I., Cox, J.A., Strehler, E.E. Biochemistry (1992) [Pubmed]
  21. Effects of renal dysfunction on the pharmacokinetics of loracarbef. Therasse, D.G., Farlow, D.S., Davidson, R.L., Quadracci, L.J., Hatcher, B.L., Cerimele, B.J., DeSante, K.A. Clin. Pharmacol. Ther. (1993) [Pubmed]
  22. Isepamicin disposition in subjects with various degrees of renal function. Halstenson, C.E., Kelloway, J.S., Affrime, M.B., Lin, C.C., Teal, M.A., Shapiro, B.E., Awni, W.M. Antimicrob. Agents Chemother. (1991) [Pubmed]
  23. Disposition of cefmetazole in healthy volunteers and patients with impaired renal function. Halstenson, C.E., Guay, D.R., Opsahl, J.A., Hirata, C.A., Olanoff, L.S., Novak, E., Ko, H., Cathcart, K.S., Matzke, G.R. Antimicrob. Agents Chemother. (1990) [Pubmed]
  24. Disposition of cefpodoxime proxetil in healthy volunteers and patients with impaired renal function. St Peter, J.V., Borin, M.T., Hughes, G.S., Kelloway, J.S., Shapiro, B.E., Halstenson, C.E. Antimicrob. Agents Chemother. (1992) [Pubmed]
  25. Effect of concomitant administration of piperacillin on the dispositions of netilmicin and tobramycin in patients with end-stage renal disease. Halstenson, C.E., Hirata, C.A., Heim-Duthoy, K.L., Abraham, P.A., Matzke, G.R. Antimicrob. Agents Chemother. (1990) [Pubmed]
  26. The HMG box of SRY is a calmodulin binding domain. Harley, V.R., Lovell-Badge, R., Goodfellow, P.N., Hextall, P.J. FEBS Lett. (1996) [Pubmed]
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