Wikipedia

Calponin 1

(Redirected from CNN1)

Calponin 1 is a basic smooth muscle protein that in humans is encoded by the CNN1 gene.[5]

CNN1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCNN1, HEL-S-14, SMCC, Sm-Calp, calponin 1
External IDsOMIM: 600806; MGI: 104979; HomoloGene: 995; GeneCards: CNN1; OMA:CNN1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

1264

12797

Ensembl

ENSG00000130176

ENSMUSG00000001349

UniProt

P51911

Q08091

RefSeq (mRNA)

NM_001299
NM_001308341
NM_001308342

NM_009922

RefSeq (protein)

NP_001290
NP_001295270
NP_001295271

NP_034052

Location (UCSC)Chr 19: 11.54 – 11.55 MbChr 9: 22.01 – 22.02 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The CNN1 gene is located at 19p13.2-p13.1 in the human chromosomal genome and contains 7 exons, encoding the protein calponin 1, an actin filament-associated regulatory protein.[6] Human calponin 1 is a 33.2-KDa protein consists of 297 amino acids with an isoelectric point of 9.1,[7] thus calponin 1 is also known as basic calponin.

Evolution

edit
 
Figure 1: Evolutionary lineage of vertebrate CNN1.

Three homologous genes, Cnn1, Cnn2 and Cnn3, have evolved in vertebrates, encoding three isoforms of calponin: calponin 1,[7][8] calponin 2,[9] calponin 3,[10] respectively. Protein sequence alignment shows that calponin 1 is highly conserved in mammals but more diverged among lower vertebrates.

Smooth muscle-specific expression

edit

The expression of CNN1 is specific to differentiated mature smooth muscle cells, suggesting a role in contractile functions. Calponin 1 is up-regulated in smooth muscle tissues during postnatal development[11] with a higher content in phasic smooth muscle of the digestive tract.[12]

Structure-function relationship

edit
 
Figure 2. Structural and functional domains of calponin. The linear structural map summarized primarily from studies of chicken calponin 1 illustrates the structural and functional domains of calponin. The CH domain, two actin-binding sites, three repeating sequence motifs, and the C-terminal variable region are outlined. The CH domain overlaps with the ERK signaling binding region. Amino acid sequences of the two actin-binding sites in the three isoforms and the three repeating motifs of calponin 1 are shown in the insets. The regulatory phosphorylation sites Ser175 and Thr184 are located in the second actin-binding site that overlaps with the first repeating motif. Potentially phosphorylatable serine residues corresponding to Ser175 are conserved in repeats 2 and 3, while a Thr184 equivalent is conserved in repeat 2. Different from calponin 1 and calponin 3, calponin 2 has a potentially phosphorylatable additional serine at position 177.

The majority of structure-function relationship studies of calponin were with experiments using chicken calponin 1. Primary structure of calponin consists of a conserved N-terminal calponin homology (CH) domain, a conserved middle region containing two actin-binding sites, and a C-terminal variable region that contributes to the differences among there isoforms.

The CH domain

edit

The CH domain was found in a number of actin-binding proteins (such as α-actinin, spectrin, and filamin) to form the actin-binding region or serve as a regulatory structure.[13] However, the CH domain in calponin is not the binding site for actin nor does it regulate the modes of calponin-F-actin binding.[14] Nonetheless, CH domain in calponin was found to bind to extra-cellular regulated kinase (ERK) for calponin to play a possible role as an adaptor protein in the ERK signaling cascades.[15]

Actin-binding sites

edit

Calponin binds actin to promote and sustain polymerization. The binding of calponin to F-actin inhibits the MgATPase activity of smooth muscle myosin.[16][17][18] Calponin binds F-actin through two sites at residues 144-162 and 171–188 in chicken calponin 1. The two actin-binding sites are conserved in the three calponin isoforms.

There are three repeating sequence motifs in calponin next to the C-terminal region. This repeating structure is conserved in all three isoforms and across species. Outlined in Fig. 2, the first repeating motif overlaps with the second actin-binding site and contains protein kinase C (PKC) phosphorylation sites Ser175 and Thr184 that are not present in the first actin-binding site. This feature is consistent with the hypothesis that the second actin-binding site plays a regulatory role in the binding of calponin to the actin filament. Similar sequences as well as potential phosphorylation sites are present in repeats 2 and 3 whereas their function is unknown.

C-terminal variable region

edit

The C-terminal segment of calponin has diverged significantly among the three isoforms. The variable lengths and amino acid sequences of the C-terminal segment produce the size and charge differences among the calponin isoforms. The corresponding charge features rendered calponin 1, 2 and 3 the names of basic, neutral and acidic calponins.[19][20][21]

The C-terminal segment of calponin has an effect on weakening the binding of calponin to F-actin. Deletion of the C-terminal tail strongly enhanced the actin-binding and bundling activities of all three isoforms of calponin.[22][23] The C-terminal tail regulates the interaction with F-actin by altering the function of the second actin-bing site of calponin.[24]

Regulation of smooth muscle contractility

edit

Numerous in vitro experimental data indicate that calponin 1 functions as an inhibitory regulator of smooth muscle contractility through inhibiting actomyosin interactions.[6][25][26] In this regulation, binding of Ca2+-calmodulin and PKC phosphorylation dissociate calponin 1 from the actin filament and facilitate smooth muscle contraction.[27]

In vivo data also support the role of calponin 1 as regulator of smooth muscle contractility. While aortic smooth muscle of adult Wistar Kyoto rats, which naturally lacks calponin 1, is fully contractile, it has a decreased sensitivity to norepinephrine activation.[28][29] Matrix metalloproteinase-2 proteolysis of calponin 1 resulted in vascular hypocontractility to phenylephrine.[30] Vas deferens smooth muscle from calponin 1 knockout mice showed faster maximum shortening velocity.[31] Calponin 1 knockout mice exhibited blunted MAP response to phenylephrine administration.[32]

Phosphorylation regulation

edit

There is a large collection of in vitro evidences demonstrating the phosphorylation regulation of calponin. The primary phosphorylation sites are Ser175 and Thr184 in the second actin-binding site (Fig. 2). Experimental data showed that Ser175 and Thr184 in calponin 1 are phosphorylated by PKC in vitro.[27] Direct association was found between calponin 1 and PKCα[33] and PKCε.[15] Calmodulin-dependent kinase II and Rho-kinase are also found to phosphorylate calponin at Ser175 and Thr184 in vitro.[34][35] Of these two residues, the main site of regulatory phosphorylation by calmodulin-dependent kinase II and Rho-kinase is Ser175. Dephosphorylation of calponin is catalyzed by type 2B protein phosphatase[36][37]

Unphosphorylated calponin binds to actin and inhibits actomyosin MgATPase. Ser175 phosphorylation alters the molecular conformation of calponin and dissociates calponin from F-actin.[38] The consequence is to release the inhibition of actomyosin MgATPase and increase the production of force.[18][39][40]

Despite the overwhelming evidence for the phosphorylation regulation of calponin obtained from in vitro studies, phosphorylated calponin is not readily detectable in vivo or in living cells under physiological conditions.[41][42] Based on the observation that PKC phosphorylation of calponin 1 weakens the binding affinity for the actin filaments,[38] the phosphorylated calponin may not be stable in the actin cytoskeleton thus be degraded in the cell.

Notes

edit

References

edit
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000130176 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000001349 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: calponin 1, basic, smooth muscle".
  6. ^ a b Takahashi K, Abe M, Hiwada K, Kokubu T (December 1988). "A novel troponin T-like protein (calponin) in vascular smooth muscle: interaction with tropomyosin paracrystals". Journal of Hypertension Supplement. 6 (4): S40–3. doi:10.1097/00004872-198812040-00008. PMID 3241227. S2CID 38679688.
  7. ^ a b Gao J, Hwang JM, Jin JP (January 1996). "Complete nucleotide sequence, structural organization, and an alternatively spliced exon of mouse h1-calponin gene". Biochemical and Biophysical Research Communications. 218 (1): 292–7. doi:10.1006/bbrc.1996.0051. PMID 8573148.
  8. ^ Strasser P, Gimona M, Moessler H, Herzog M, Small JV (September 1993). "Mammalian calponin. Identification and expression of genetic variants". FEBS Letters. 330 (1): 13–8. doi:10.1016/0014-5793(93)80909-e. PMID 8370452. S2CID 41687174.
  9. ^ Masuda H, Tanaka K, Takagi M, Ohgami K, Sakamaki T, Shibata N, Takahashi K (August 1996). "Molecular cloning and characterization of human non-smooth muscle calponin". Journal of Biochemistry. 120 (2): 415–24. doi:10.1093/oxfordjournals.jbchem.a021428. PMID 8889829.
  10. ^ Applegate D, Feng W, Green RS, Taubman MB (April 1994). "Cloning and expression of a novel acidic calponin isoform from rat aortic vascular smooth muscle". The Journal of Biological Chemistry. 269 (14): 10683–90. doi:10.1016/S0021-9258(17)34113-3. PMID 8144658.
  11. ^ Hossain MM, Hwang DY, Huang QQ, Sasaki Y, Jin JP (January 2003). "Developmentally regulated expression of calponin isoforms and the effect of h2-calponin on cell proliferation". American Journal of Physiology. Cell Physiology. 284 (1): C156–67. doi:10.1152/ajpcell.00233.2002. PMID 12388067. S2CID 2107783.
  12. ^ Jin JP, Walsh MP, Resek ME, McMartin GA (1996). "Expression and epitopic conservation of calponin in different smooth muscles and during development". Biochemistry and Cell Biology. 74 (2): 187–96. doi:10.1139/o96-019. PMID 9213427.
  13. ^ Gimona M, Djinovic-Carugo K, Kranewitter WJ, Winder SJ (February 2002). "Functional plasticity of CH domains". FEBS Letters. 513 (1): 98–106. doi:10.1016/s0014-5793(01)03240-9. PMID 11911887. S2CID 2288740.
  14. ^ Galkin VE, Orlova A, Fattoum A, Walsh MP, Egelman EH (June 2006). "The CH-domain of calponin does not determine the modes of calponin binding to F-actin". Journal of Molecular Biology. 359 (2): 478–85. doi:10.1016/j.jmb.2006.03.044. PMID 16626733.
  15. ^ a b Leinweber BD, Leavis PC, Grabarek Z, Wang CL, Morgan KG (November 1999). "Extracellular regulated kinase (ERK) interaction with actin and the calponin homology (CH) domain of actin-binding proteins". The Biochemical Journal. 344 (1): 117–23. doi:10.1042/0264-6021:3440117. PMC 1220621. PMID 10548541.
  16. ^ Abe M, Takahashi K, Hiwada K (November 1990). "Effect of calponin on actin-activated myosin ATPase activity". Journal of Biochemistry. 108 (5): 835–8. doi:10.1093/oxfordjournals.jbchem.a123289. PMID 2150518.
  17. ^ Mezgueldi M, Fattoum A, Derancourt J, Kassab R (August 1992). "Mapping of the functional domains in the amino-terminal region of calponin". The Journal of Biological Chemistry. 267 (22): 15943–51. doi:10.1016/S0021-9258(19)49625-7. PMID 1639822.
  18. ^ a b Winder SJ, Walsh MP (November 1993). "Calponin: thin filament-linked regulation of smooth muscle contraction". Cellular Signalling. 5 (6): 677–86. doi:10.1016/0898-6568(93)90029-l. PMID 8130072.
  19. ^ Jin JP, Zhang Z, Bautista JA (2008). "Isoform diversity, regulation, and functional adaptation of troponin and calponin". Critical Reviews in Eukaryotic Gene Expression. 18 (2): 93–124. doi:10.1615/critreveukargeneexpr.v18.i2.10. PMID 18304026.
  20. ^ Wu KC, Jin JP (2008). "Calponin in non-muscle cells". Cell Biochemistry and Biophysics. 52 (3): 139–48. doi:10.1007/s12013-008-9031-6. PMID 18946636. S2CID 6365920.
  21. ^ Liu R, Jin JP (2015). "Calponin: A mechanical tension-modulated regulator of cytoskeleton and cell motility". Current Topics in Biochemical Research. 16: 1–15.
  22. ^ Bartegi A, Roustan C, Kassab R, Fattoum A (June 1999). "Fluorescence studies of the carboxyl-terminal domain of smooth muscle calponin effects of F-actin and salts". European Journal of Biochemistry. 262 (2): 335–41. doi:10.1046/j.1432-1327.1999.00390.x. PMID 10336616.
  23. ^ Danninger C, Gimona M (November 2000). "Live dynamics of GFP-calponin: isoform-specific modulation of the actin cytoskeleton and autoregulation by C-terminal sequences". Journal of Cell Science. 113 (21): 3725–36. doi:10.1242/jcs.113.21.3725. PMID 11034901.
  24. ^ Burgstaller G, Kranewitter WJ, Gimona M (May 2002). "The molecular basis for the autoregulation of calponin by isoform-specific C-terminal tail sequences". Journal of Cell Science. 115 (Pt 10): 2021–9. doi:10.1242/jcs.115.10.2021. PMID 11973344.
  25. ^ Takahashi K, Hiwada K, Kokubu T (November 1986). "Isolation and characterization of a 34,000-dalton calmodulin- and F-actin-binding protein from chicken gizzard smooth muscle". Biochemical and Biophysical Research Communications. 141 (1): 20–6. doi:10.1016/s0006-291x(86)80328-x. PMID 3606745.
  26. ^ Allen BG, Walsh MP (September 1994). "The biochemical basis of the regulation of smooth-muscle contraction". Trends in Biochemical Sciences. 19 (9): 362–8. doi:10.1016/0968-0004(94)90112-0. PMID 7985229.
  27. ^ a b Naka M, Kureishi Y, Muroga Y, Takahashi K, Ito M, Tanaka T (September 1990). "Modulation of smooth muscle calponin by protein kinase C and calmodulin". Biochemical and Biophysical Research Communications. 171 (3): 933–7. doi:10.1016/0006-291x(90)90773-g. PMID 2222454.
  28. ^ Nigam R, Triggle CR, Jin JP (August 1998). "h1- and h2-calponins are not essential for norepinephrine- or sodium fluoride-induced contraction of rat aortic smooth muscle". Journal of Muscle Research and Cell Motility. 19 (6): 695–703. doi:10.1023/a:1005389300151. PMID 9742453. S2CID 29905113.
  29. ^ Facemire C, Brozovich FV, Jin JP (May 2000). "The maximal velocity of vascular smooth muscle shortening is independent of the expression of calponin". Journal of Muscle Research and Cell Motility. 21 (4): 367–73. doi:10.1023/a:1005680614296. PMID 11032347. S2CID 30450046.
  30. ^ Castro MM, Cena J, Cho WJ, Walsh MP, Schulz R (March 2012). "Matrix metalloproteinase-2 proteolysis of calponin-1 contributes to vascular hypocontractility in endotoxemic rats". Arteriosclerosis, Thrombosis, and Vascular Biology. 32 (3): 662–8. doi:10.1161/ATVBAHA.111.242685. PMID 22199370.
  31. ^ Takahashi K, Yoshimoto R, Fuchibe K, Fujishige A, Mitsui-Saito M, Hori M, Ozaki H, Yamamura H, Awata N, Taniguchi S, Katsuki M, Tsuchiya T, Karaki H (December 2000). "Regulation of shortening velocity by calponin in intact contracting smooth muscles". Biochemical and Biophysical Research Communications. 279 (1): 150–7. doi:10.1006/bbrc.2000.3909. PMID 11112431.
  32. ^ Masuki S, Takeoka M, Taniguchi S, Nose H (March 2003). "Enhanced baroreflex sensitivity in free-moving calponin knockout mice". American Journal of Physiology. Heart and Circulatory Physiology. 284 (3): H939–46. doi:10.1152/ajpheart.00610.2002. PMID 12433658.
  33. ^ Somara S, Bitar KN (December 2008). "Direct association of calponin with specific domains of PKC-alpha". American Journal of Physiology. Gastrointestinal and Liver Physiology. 295 (6): G1246–54. doi:10.1152/ajpgi.90461.2008. PMC 2604804. PMID 18948438.
  34. ^ Walsh MP (December 1991). "The Ayerst Award Lecture 1990. Calcium-dependent mechanisms of regulation of smooth muscle contraction". Biochemistry and Cell Biology. 69 (12): 771–800. doi:10.1139/o91-119. PMID 1818584.
  35. ^ Kaneko T, Amano M, Maeda A, Goto H, Takahashi K, Ito M, Kaibuchi K (June 2000). "Identification of calponin as a novel substrate of Rho-kinase". Biochemical and Biophysical Research Communications. 273 (1): 110–6. doi:10.1006/bbrc.2000.2901. PMID 10873572.
  36. ^ Fraser ED, Walsh MP (July 1995). "Dephosphorylation of calponin by type 2B protein phosphatase". Biochemistry. 34 (28): 9151–8. doi:10.1021/bi00028a026. PMID 7619814.
  37. ^ Ichikawa K, Ito M, Okubo S, Konishi T, Nakano T, Mino T, Nakamura F, Naka M, Tanaka T (June 1993). "Calponin phosphatase from smooth muscle: a possible role of type 1 protein phosphatase in smooth muscle relaxation". Biochemical and Biophysical Research Communications. 193 (3): 827–33. doi:10.1006/bbrc.1993.1700. PMID 8391807.
  38. ^ a b Jin JP, Walsh MP, Sutherland C, Chen W (September 2000). "A role for serine-175 in modulating the molecular conformation of calponin". The Biochemical Journal. 350 (2): 579–88. doi:10.1042/0264-6021:3500579. PMC 1221287. PMID 10947974.
  39. ^ Tang DC, Kang HM, Jin JP, Fraser ED, Walsh MP (April 1996). "Structure-function relations of smooth muscle calponin. The critical role of serine 175". The Journal of Biological Chemistry. 271 (15): 8605–11. doi:10.1074/jbc.271.15.8605. PMID 8621490.
  40. ^ Gerthoffer WT, Pohl J (November 1994). "Caldesmon and calponin phosphorylation in regulation of smooth muscle contraction". Canadian Journal of Physiology and Pharmacology. 72 (11): 1410–4. doi:10.1139/y94-203. PMID 7767886.
  41. ^ Bárány M, Bárány K (November 1993). "Calponin phosphorylation does not accompany contraction of various smooth muscles". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1179 (2): 229–33. doi:10.1016/0167-4889(93)90146-g. PMID 8218366.
  42. ^ Gimona M, Sparrow MP, Strasser P, Herzog M, Small JV (May 1992). "Calponin and SM 22 isoforms in avian and mammalian smooth muscle. Absence of phosphorylation in vivo". European Journal of Biochemistry. 205 (3): 1067–75. doi:10.1111/j.1432-1033.1992.tb16875.x. PMID 1576991.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Calponin_1&oldid=1237493867"