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The Calponin Family

Page updated 4/2/03

A family of actin binding proteins typified by smooth muscle specific protein which binds G and F-actin.  Calponins are abundant proteins in smooth muscle and are the products of three distinct genes.  The most abundant form is a-calponin (h1 or basic) is 292 amino acids (34kDa), b-calponin is 252 amino-acids in length have a deletion of amino-acids 217-256 of the same gene as a-calponin.  Two other genes encode neutral calponin (h2 calponin) and acidic calponin are expressed at lower levels in smooth and non-muscle cells. Other more widely expressed calponin members include SM22, and transgelin.  Calponin ironically has given its name to the CH or Calponin Homology domain present in many ABPs, despite the fact that calponin does not seem to bind actin through this region! (Gimona & Mital, 1998), but instead binds lipids (Bogatcheva  & Busev, 1995; Fujii et al, 1995).  The principle actin binding site is believed to exist (Mezgueldi et al, 1992; ) at a distinct region between the CH domain and the calponin repeats.  Calponin is an abundant heat stable, basic protein in smooth muscle where it is present as a 34kDa species.  In other tissues a more acidic isoform (acidic CaP) is present  it is calcium independent but binds calmodulin in a sensitive manner.  Binding of Ca2+/calmodulin inhibits actin binding.  Phosphorylation also inhibits actin binding. Calponin binds tropomyosin another actin binding protein.  Calponin binds many other proteins, many of which are also actin binding proteins (table 1) in addition to phospholipids (Bogatcheva & Busev, 1995).

Calponin Structure

Figure 1. The domain structure of calponin

The most celebrated feature of calponin is the so called Calponin Homology (CH) domain as mentioned previously.  Calponins have just one single CH domain.  Each CH domain is about 100 amino-acids in length and in the many  actin binding proteins that are known to bind actin through CH domains, these are present as two dissimilar domains.  When present singly as in calponin itself, it seems that the CH domain is insufficient to bind actin (like trying to pick up a pint with one hand while wearing boxing gloves!?) (Gimona & Mital, 1998). The fact that calponin does not bind actin through the CH domain is consistent with the observation that calponin competes neither with filamin (Panesenko & Gusev, 2001) or a-actinin for actin binding (Leinweber et al, 1999; Panesenko & Gusev, 2001), both of which bind through twin CH domains. The single CH domain in calponin is known to bind Ca2+/calmodulin, ERK, tropomyosin (Winder & Walsh, 1993). The structure of the single CH domain in calponin itself has overall similarity with the CH domains of those naturally arranged in tandem, such as in utrophin (Keep et al, 1999) or fimbrin (Goldsmith et al, 1997). The single calponin CH domain however has differs significantly possibly explaining why the single CH domain cannot bind actin (Bramham et al, 2002).

The regulatory domain (RD) contains the actin binding domain which has reported homology to troponin I (Takahashi et al, 1991).  There are also sites for phosphorylation by PKC (Ser 175) and by CaM/kinase II. 


The calponin repeat domain at the C terminus is proposed to form WD40 like structures through which many interactions with other proteins is made.  Secondary actin binding site may exist in the calponin repeats (Bonet-Kerrache & Mornet,1995), very possibly right next to the main site, at the start of repeat 1.  Kolakowski et al, 1995; Tang et al, 1997). An actin binding site is reported to exist within the repeats. Recently, (Kranewitter et al, 2001) it has been shown that Unc-87 is an actin filament bundling protein composed of seven calponin repeats, these authors have dubbed the calponin repeat CLICK-23 (from the fact that the repeat is 23amino-acids in length and is Calponin Like).

Protein Function Binding site on Calponin References
a-actinin Strengthens the a-actinin-actin complex Leinweber et al, 1999a
Actin Modulates actin: myosin II ATPase activity. Regulatory domain and  Mezgueldi,et al, 1992; 1995
Caldesmon Myosin II binding/regulation
Caltropin Myosin II binding/regulating Regulatory domain Wills et al, 1994
Calmodulin Inhibits actin binding to regulatory domain in Ca2+. Two sites, one in the CH (1-52)  domain, the other in the RD (145-163) Winder et al, 1993; 
ERK Extra-cellular  regulatory kinase CH domain Leinweber et al, 1999b
Hsp70 Heat shock protein 7-144 Bogatcheva et al, 1999; Ma et al, 2000
Myosin II Stimulated myosin II ATPase activity 146-176  Szymanski et al,1997; Lin et al,1993
Protein kinase C Activates kinase activity Calponin repeats (WD40) Leinweber et al, 2000
Tropomyosin Actin stability and myosin II regulation . Two sites, one in the CH (1-52)  domain, the other in the RD (145-163) Takahashi et al, 1988; Vancompernolle et al, 1990;Childs et al, 1992; Mezgueldi,et al, 1995.
Tubulin Microtubule binding and bundling?  May also connect other cytoskeletal elements e.g. actin to microtubules. Two sites, one in the actin and Calmodulin binding region 145-182, the other in the C terminal repeat region 183-292 Fuji et al, 1997; Fattoum et al, 2003
Table 1 Calponin-Binding proteins

Calponin Function
The function of the calponins has long been assumed to be to regulate the interact between actin filaments and myosin II in smooth muscle contraction and analogous interactions in non-muscle cells (
Takahashi et al, 1986; Winder & Walsh 1993; El-Mezgueldi 1996; Gusev 2001). The consensus has been that h1 calponin inhibits the actin-activated ATPase of myosin II thereby regulating  the interaction. However, the h1 gene has been knocked out in a mouse model (Yoshikawa et al, 1998) and the resulting phenotype has been a surprise.  The h1 calponin was found not to be compensated by up-regulation of other calponins and the most obvious effect was on the bone (as is the knock out of another ABP  ()).  h1 calponin is highly expressed in osteoblasts and may act as a negative regulator of the bone making process.  Analysis of the knock out mouse (Matthew et al, 2000), revealed that compared with wild type mouse there was no difference in Ca2+ sensitisation pathways but there was a clear increase in unloaded shortening velocity in K.O. mice muscle and that this could be overcome by adding back h1 calponin to the tissue.  These findings are consistent with a role for calponin in the regulation of actin:myosin interaction but the study also showed a drastic reduction in the expression of actin (about 50%). 


Applegate, D., Feng, W., Grren, R. S. & Taubman, M. B. (1994) Cloning and expression of a novel acidic calponin isoform from rat vacular smooth muscle., J.Biol.Chem. 269, 10683-10690.

Bańuelos, S., Saraste, M. & DJinovi´c Carugo, K. (1998) Structural comparisons of calponin homology domains: implications for actin binding. Curr. Biol. 6, 1419-1431.

Bárány, K., Polyák, E. & Bárány, M. (1992) Involvement of calponin and caldesmon in sustained contraction of arterial smooth muscle. BBRC. 187, 847-852.

Bartegi, A., Roustan, C., Kassab, R. & Fattoum, A. (1999) Fluorescence studies of the carboxyl-terminal domain of smooth muscle calponin. Eur.J.Biochem. 262, 335-341.

Bramham, J., Hodgkinson, J. L., Smith, B. O., Uhrin, D., Barlow, P. N. & Winder, S. J. (2002) Solution structure of the calponin CH domain and fitting to the 3D-helical reconstruction of F-actin:calponin. Structure. 10, 249-258.

Bogatcheva, N. V., Ma, Y. S., Urosev, D. & Gusev, N. B. (1999) Localization of calponin binding sites in the structure of 90 kDa heat shock protein (Hsp90)., FEBS letters. TBA, TBA.

Bogatcheva, N. V. & Busev, N. B. (1995) Interaction of smooth muscle calponin with phospholipids. FEBS letters. 371, 123-126.

Bonet-Kerrache, A. & Mornet, D. (1995) Importance of the C-terminal part of actin in interactions with calponin. BBRC. 206, 127-132.

Childs, T. J., Watson, M. H., Novy, R. E., Lin, J. J.-C. & Mak, A. S. (1992) Calponin and tropomyosin interactions. BBA. 1121, 41-46.

Danninger, C. & Gimona, M. (2000). "Live dynamics of GFP-calponin: isoform-specific modulation of the actin cytoskeleton and autoregulation by C-terminal sequences. J.Cell Sci. 113, 3725-3736.

Djinovic Carugo, K., Bańuelos, S. & Saraste, M. (1997) Crystal structure of a calponin homology domain. Nature Struct. Biol. 4, 175-179

EL-Mezgueldi, M. (1996) Calponin.  Int. J. Biochem.Cell Biol. 28, 1185-1189.

EL-Mezgueldi, M. & Marston, S. B. (1996) The effects of smooth muscle calponin on the strong and weak myosin binding sites of F-actin.  J.Biol.Chem. 271, 28161-28167.

Fattoum, A., Roustan, C., Smycznski, C., Der Terrossian, E. & Kassab, R. (2003) Mapping the microtubule binding regions of calponin. Biochemistry. 42, 1274-1282.

Fu, Y., Liu, H. W., Forsythe, S. M., Kogut, P., McConville, J. F., Halayko, A. J., Camoretti-Mercado, B. & Solway, J. (2000) Mutagenesis analysis of human SM22: characterization of actin binding. J. Appl. Physiol. 89, 1985-1990.

Fuji, T., Hiromori, T., Hamamoto, M. & Suzuki, T. (1997) Interaction of chicken gizzard smooth muscle calponin with brain microtubules. J.Biochem. 122, 344-351.

Fujii, T., Yamana, K., Ogoma, Y. & Kondo, Y. (1995) Interaction of calponin with phospholipids. J.Biochem. 117, 999-1003.

Fujii, T., Oomatsuzawa, A., Kuzumaki, N. & Kondo, Y. (1994) Calcium-dependent regulation of smooth muscle calponin by S100. J.Biochem. 116, 121-127.

Gimona, M. & Mital, R. (1998). The single CH domain of calponin is neither  sufficient nor necessary for F-actin binding. J.Cell Sci. 111, 1813-1821.

Goldsmith, S. C., Pokala, N., Shen, W., Federov, A. A., Matsudaira, P. & Almo, S. A. (1997) The structure of an actin-cross-linking domain from human fimbrin. Nature Struct. Biol. 4, 708-712.

Gong, B.-J., Mabuchi, K., Takahashi, K., Nadal-Ginard, B. & Tao, T. (1993) Characterization of wild type and mutant chicken gizzard a calponin expressed in E.coli., J.Biochem. 114, 453-456.

Gusev, N. B. (2001) Some properties of caldesmon and calponin and the participation of these proteins in regulation of smooth muscle contraction and cytoskeleton formation., Biochemistry (Moscow). 66, 1112-1121.

Haeberle, J. R. (1994) Calponin decreases the rate of cross-bridge cycling and increases maximum force production by smooth muscle myosin in an in vitro motility assay., J.Biol.Chem. 269, 12424-12431.

Ichikawa, K., Ito, M., Okubo, S., Konishi, T., Nakano, T., Mino, T., Nakamura, F., Naka, M. & Tanaka, T. (1993) Calponin phosphatase from smooth muscle: a possible role of type 1 protein phosphatase in smooth muscle relaxation., BBRC. 193, 827-833.

Kolakowski, J., Makuch, R., Stepowski, D. & Dabrowska, R. (1995) Interaction of calponin with actin and its functional implications., Biochem.J. 306, 199-204.

Kranewitter, W. J., Ylanne, J. & Gimona, M. (2001) UNC-87 is an actin-bundling protein., J.Biol.Chem. 276, 6306-6312.

Keep, N. H., Norwood, F. L. M., Moores, C. A., Winder, S. J. & Kendrick-Jones, J. (1999) The 2.0Ĺ structure of the second calponin homology domain from the actin-binding region of the dystrophin homologue utrophin, J.Mol.Biol. 285, 1257-1264.

Leinweber, B., Tang, Z. X., Stafford, W. F. & Chalovich, J. M. (1999a) Calponin interaction with a-actinin-actin: evidence for a structural role for calponin., Biophys. J. 77, 3208-3217.

Leinweber, B., Parissenti, A. M., Gallant, C., Gangopadhyay, S. S., Kirwan-Rhude, A., Leavis, P. C. & Morgan, K. G. (2000) Regulation of protein kinase C by the cytoskeletal protein calponin., J.Biol.Chem. 275, 40329-40336.

Leinweber, B. D., Leavis, P. C., Grabarek, Z., Wang, C.-L. A. & Morgan, K. G. (1999b) Extracellular regulated kinase (ERK) interaction with actin and the calponin homology (CH) domain of actin-binding proteins., Biochem.J. 344, 117-123.

Leinweber, B., Parissenti, A. M., Gallant, C., Gangopadhyay, S. S., Kirwan-Rhude, A., Leavis, P. C. & Morgan, K. G. (2000) Regulation of protein kinase C by the cytoskeletal protein calponin., J.Biol.Chem. 275, 40329-40336.

Lin, Y., Ye, L.-H., Ishikawa, R., Fujita, K. & Kohama, K. (1993) Stimulatory effect of calponin on myosin ATPase activity., J.Biochem. 113, 643-645.

Lehman, W. (1991) Calponin and the composition of smooth muscle thin filaments., J.Muscle Res.Cell Mot. 12, 221-224.

Matthew, J. D., Khromov, A. S., McDuffie, M. J., Somlyo, A. V., Somlyo, A. P., Taniguchi, S. & Takahashi, K. (2000) Contractile properties and proteins of smooth muscles of a calponin knockout mouse., J.Physiol. 529.3, 811-824.

Mezgueldi, M., Fattoum, A., Derancourt, J. & Kassab, R. (1992) Mapping of the functional domains in the amino-terminal region of calponin., J.Biol.Chem. 267, 15943-15951.

Mezgueldi, M., Mendre, C., Calas, B., Kassab, R. & Fattoum, A. (1995) Characterization of the regulatory domain of gizzard calponin, J. Biol. Chem. 270, 8867-8876.

Ma, Y.-S., Bogatcheva, N. V. & Gusev, N. B. (2000) Heat shock protein (hsp90) interacts with smooth muscle calponin and affects calponin-binding to actin., BBA. 1476, 300-310.

Miki, M., Walsh, M. P. & Hartshorne, D. J. (1992) The mechanism of inhibition of the actin-activated myosin MgATPase by calponin., BBRC. 187, 867-871.

Nakamura, F., Mino, T., Yamamoto, J., Naka, M. & Tanaka, T. (1993) Identification of the regulatory site in smooth muscle calponin that is phosphorylated by protein kinase C., J.Biol.Chem. 268, 6194-6201.

Nishida, W., Kitami, Y. & Hiwada, K. (1993) cDNA cloning and mRNA expression of calponin and SM22 in rat aorta smooth muscle cells., Gene. 130, 297-302.

North, A. J., Gimona, M., Cross, R. A. & Small, J. V. (1994) Calponin is localised in both the contractile apparatus and the cytoskeleton of smooth muscle cells., J.Cell Sci. 107, 437-444.

Noda, S., Ito, M., Watanabe, S., Takahashi, K. & Maruyama, K. (1992) Conformational changes of actin induced by calponin., BBRC. 185, 481-487.

Panasenko, O. O. & Gusev, N. B. (2001) Mutual effects of a-actinin, calponin and filamin on actin binding, Biochim.Biophys.Acta. 1544, 393-405.

Stradal, T., Kranewitter, W., Winder, S.J. & Gimona, M. (1998) CH domains revisited. FEBS letters 431, 134-137.

Stafford III, W. F., Mabuchi, K., Takahashi, K. & Tao, T. (1995) Physical characterization of calponin., J.Biol.Chem. 270, 10576-10579.

Shirinsky, V. P., Biryukov, K. G., Mettasch, J. H. & Sellers, J. R. (1992) Inhibition of the relative movement of actin and myosin by caldesmon and calponin., J.Biol.Chem. 267, 15886-15892.

Strasser, P., Gimona, M., Moessler, H., Herzog, M. & Small, J. V. (1993) Mammalian calponin. Identification and expression of genetic variants., FEBS letters. 330, 13-18.

Szymanski, P. T., Grabarek, Z. & Tao, T. (1997) Correlation between calponin and myosin subfragment 1 binding to F-actin and ATPase inhibition., Biochem. J. 321, 519-523.

Szymanski, P. T. & Tao, T. (1993) Interaction between calponin and smooth muscle myosin., FEBS letters. 331, 256-259.

Takahashi, K., Abe, M., Hiwada, K. & Kokubu, T. (1988) A novel troponinT-like protein (calponin) in vascular smooth muscle: interaction with tropomyosin paracrystals., J.Hypertension. 6, S40-S43.

Takahashi, K. & Nadal-Ginard, B. (1991) J.Biol.Chem. 266, 13284-13288.

Tang, J. X., Szymanski, P. T., Janmey, P. A. & Tao, T. (1997) Electrostatic effects of smooth muscle calponin on actin assembly, Eur.J. Biochem. 247, 432-440.

Trabelsi-Terzidis, H., Fattoum, A., Represa, A., Dessi, F., Ben-ari, Y. & Der Terrossian, E. (1995) Expression of an acidic isoform of calponin in rat brain: Western blots on one- or two-dimensional gels and immunolocalization in cultured cells., Biochem. J. 306, 211-215.

Walsh, M. P. (2000) Calponin - knocked out but not down! J. Physiol. 529.3, 517.

Wills, F. L., McCubbin, W. D. & Kay, C. M. (1993) Characterization of the smooth muscle calponin and calmodulin complex., Biochemistry. 32, 2321-2328.

Wills, F. L., McCubbin, W. D. & Kay, C. M. (1994) Smooth muscle calponin-caltropin interaction: Effect on biological activity and stability of calponin., Biochemistry. 33, 5562-5569.

Winder, S. J., Allen, B. G., Fraser, E. D., Kang, H.-M., Kargacin, G. J. & Walsh, M. P. (1993) Calponin phosphorylation in vitro and in intact muscle., Biochem.J. 296, 827-836.

Winder, S. J., Sutherland, C. & Walsh, M. P. (1992) A comparison of the effects of calponin on smooth and skeletal muscle actomysoin systems in the presence and absence of caldesmon., Biochem.J. 288, 733-739.

Winder, S. J. & Walsh, M. P. (1993) Calponin: Thin filament-linked regulation of smooth muscle contraction., Cellular Signalling. 5, 677-686.

Winder, S. J., Walsh, M. P., Vasulka, C. & Johnson, J. D. (1993) Calponin-calmodulin interaction: Properties and effects on smooth and skeletal muscle actin binding and actomyosin ATPases., Biochemistry. 32, 13327-13333.

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