capz actin capping protein


Summary: An actin capping protein that binds to the barbed-ends of ACTIN filaments. It is a heterodimer consisting of an alpha and a beta subunit. It regulates actin assembly by stabilizing actin oligomers for elongation. In SKELETAL MUSCLE, CapZ is localized to the Z-disk.

Top Publications

  1. Hug C, Miller T, Torres M, Casella J, Cooper J. Identification and characterization of an actin-binding site of CapZ. J Cell Biol. 1992;116:923-31 pubmed
    ..The primary structure of this region is not similar to that of potential actin-binding sites identified in other proteins. In addition, the primary structure of this region is not conserved across species. ..
  2. Tanaka H, Yoshimura Y, Nishina Y, Nozaki M, Nojima H, Nishimune Y. Isolation and characterization of cDNA clones specifically expressed in testicular germ cells. FEBS Lett. 1994;355:4-10 pubmed
    ..Detailed analyses of mRNA expression revealed that the genes corresponding to the cloned cDNAs were exclusively expressed in testes and were developmentally controlled. ..
  3. Hart M, Korshunova Y, Cooper J. Vertebrates have conserved capping protein alpha isoforms with specific expression patterns. Cell Motil Cytoskeleton. 1997;38:120-32 pubmed
    ..Most tissues have both alpha1 and alpha2 isoforms but the ratio of alpha1:alpha2 varies widely. Together, these findings support the hypothesis that the CP alpha isoforms have conserved, unique and essential roles in vertebrates. ..
  4. Charpentier T, Thompson L, Liriano M, Varney K, Wilder P, Pozharski E, et al. The effects of CapZ peptide (TRTK-12) binding to S100B-Ca2+ as examined by NMR and X-ray crystallography. J Mol Biol. 2010;396:1227-43 pubmed publisher
  5. Yamashita A, Maeda K, Maeda Y. Crystal structure of CapZ: structural basis for actin filament barbed end capping. EMBO J. 2003;22:1529-38 pubmed
    ..The mobile extensions probably form flexible links to the end of the actin filament with a pseudo 2(1) helical symmetry, enabling the docking of the two in a symmetry mismatch. ..
  6. Cooper J, Caldwell J, Gattermeir D, Torres M, Amatruda J, Casella J. Variant cDNAs encoding proteins similar to the alpha subunit of chicken CapZ. Cell Motil Cytoskeleton. 1991;18:204-14 pubmed
    ..alpha 2 has four poly(A)+RNA transcripts, one of which is rare in liver. alpha 1 has two transcripts. alpha 1 and alpha 2 are encoded by different single-copy genes by Southern analysis of chicken genomic DNA. ..
  7. Lee Y, Jeong S, Hong S, Cho B, Ha W, Park S, et al. Prognostic value of CAPZA1 overexpression in gastric cancer. Int J Oncol. 2013;42:1569-77 pubmed publisher
    ..The present study suggests that CAPZA1 could be a marker of good prognosis in gastric cancer and shows that CAPZA1 is associated with decreased cancer cell migration and invasion. ..
  8. van Duijn T, Anthony E, Hensbergen P, Deelder A, Hordijk P. Rac1 recruits the adapter protein CMS/CD2AP to cell-cell contacts. J Biol Chem. 2010;285:20137-46 pubmed publisher
    ..These data identify CD2AP as a novel Rac1-associated adapter protein that participates in the regulation of epithelial cell-cell contact. ..
  9. Ou K, Yu K, Kesuma D, Hooi M, Huang N, Chen W, et al. Novel breast cancer biomarkers identified by integrative proteomic and gene expression mapping. J Proteome Res. 2008;7:1518-28 pubmed publisher
    ..Our study thus illustrates how the systematic integration of proteomic and transcriptomic data from both cell line and primary tissue samples can prove advantageous for accelerating cancer biomarker discovery. ..

More Information


  1. Pappas C, Bhattacharya N, Cooper J, Gregorio C. Nebulin interacts with CapZ and regulates thin filament architecture within the Z-disc. Mol Biol Cell. 2008;19:1837-47 pubmed publisher
    ..We propose a novel molecular model of Z-disc architecture in which nebulin interacts with CapZ from a thin filament of an adjacent sarcomere, thus providing a structural link between sarcomeres. ..
  2. Narita A, Takeda S, Yamashita A, Maeda Y. Structural basis of actin filament capping at the barbed-end: a cryo-electron microscopy study. EMBO J. 2006;25:5626-33 pubmed
    ..This binding scheme accounted for the results of newly performed and previously published mutation experiments, and led us to propose a two-step binding model. This is the first determination of an actin filament end structure. ..
  3. Taoka M, Ichimura T, Wakamiya Tsuruta A, Kubota Y, Araki T, Obinata T, et al. V-1, a protein expressed transiently during murine cerebellar development, regulates actin polymerization via interaction with capping protein. J Biol Chem. 2003;278:5864-70 pubmed
  4. Inman K, Yang R, Rustandi R, Miller K, Baldisseri D, Weber D. Solution NMR structure of S100B bound to the high-affinity target peptide TRTK-12. J Mol Biol. 2002;324:1003-14 pubmed
  5. Barron Casella E, Torres M, Scherer S, Heng H, Tsui L, Casella J. Sequence analysis and chromosomal localization of human Cap Z. Conserved residues within the actin-binding domain may link Cap Z to gelsolin/severin and profilin protein families. J Biol Chem. 1995;270:21472-9 pubmed
    ..The human alpha 2 gene (CAPZA2) has been mapped to chromosome 7 position q31.2-q31.3 and the beta gene (CAPZB) to chromosome 1 region p36.1. ..
  6. Schafer D, Jennings P, Cooper J. Dynamics of capping protein and actin assembly in vitro: uncapping barbed ends by polyphosphoinositides. J Cell Biol. 1996;135:169-79 pubmed
    ..A major hypothesis for why capping protein beta-subunit isoforms exist is thereby excluded. Fourth, the proposed capping protein regulators, Hsc70 and S100, had no effect on capping protein binding to actin in vitro. ..
  7. Soeno Y, Abe H, Kimura S, Maruyama K, Obinata T. Generation of functional beta-actinin (CapZ) in an E. coli expression system. J Muscle Res Cell Motil. 1998;19:639-46 pubmed
  8. Liriano M, Varney K, Wright N, Hoffman C, Toth E, Ishima R, et al. Target binding to S100B reduces dynamic properties and increases Ca(2+)-binding affinity for wild type and EF-hand mutant proteins. J Mol Biol. 2012;423:365-85 pubmed publisher
    ..Therefore, a model for how S100B-TRTK-12 complex formation increases Ca(2+) binding is discussed, which considers changes in protein dynamics upon binding the target TRTK-12. ..
  9. Barkalow K, Falet H, Italiano J, van Vugt A, Carpenter C, Schreiber A, et al. Role for phosphoinositide 3-kinase in Fc gamma RIIA-induced platelet shape change. Am J Physiol Cell Physiol. 2003;285:C797-805 pubmed
  10. Lin Y, Li J, Swanson E, Russell B. CapZ and actin capping dynamics increase in myocytes after a bout of exercise and abates in hours after stimulation ends. J Appl Physiol (1985). 2013;114:1603-9 pubmed publisher
    ..This adaptive mechanism, which is probably regulating thin-filament addition, declines a few hours after the end of a bout of exercise. ..
  11. Kitanishi T, Sakai J, Kojima S, Saitoh Y, Inokuchi K, Fukaya M, et al. Activity-dependent localization in spines of the F-actin capping protein CapZ screened in a rat model of dementia. Genes Cells. 2010;15:737-47 pubmed publisher
    ..We conclude that activity-dependent, synapse-specific regulation of CapZ redistribution might be important in both maintenance and remodeling of synaptic connections in neurons receiving specific spatial and temporal patterns of inputs. ..
  12. Li H, Cook J, Terry M, Spitzer N, Ferrari M. Calcium transients regulate patterned actin assembly during myofibrillogenesis. Dev Dyn. 2004;229:231-42 pubmed
  13. Vig P, Hearst S, Shao Q, Lopez M, Murphy H, Safaya E. Glial S100B protein modulates mutant ataxin-1 aggregation and toxicity: TRTK12 peptide, a potential candidate for SCA1 therapy. Cerebellum. 2011;10:254-66 pubmed publisher
    ..Taken together, our results suggest that glial S100B may augment degenerative changes in SCA1 PCs by modulating mutant ataxin-1 toxicity/solubility through an unknown signaling pathway. ..
  14. Durham J, Herman I. Inhibition of angiogenesis in vitro: a central role for beta-actin dependent cytoskeletal remodeling. Microvasc Res. 2009;77:281-8 pubmed publisher
    ..Altogether, these findings suggest that endothelial-specific targeting and beta cap73 over-expression may represent an innovative therapeutic approach capable of abrogating pathologic angiogenesis. ..
  15. Goch G, Vdovenko S, Kozłowska H, Bierzynski A. Affinity of S100A1 protein for calcium increases dramatically upon glutathionylation. FEBS J. 2005;272:2557-65 pubmed
    ..The glutathionylated protein binds TRTK-12 peptide in a calcium-dependent manner. S100A1 protein can act, therefore, as a linker between the calcium and redox signalling pathways. ..
  16. Bior B, Ballif B. Dab1 stabilizes its interaction with Cin85 by suppressing Cin85 phosphorylation at serine 587. FEBS Lett. 2013;587:60-6 pubmed publisher
    ..These data provide an early glimpse into how Cin85 phosphorylation might alter the composition of its scaffolding partners to regulate its diverse roles including vesicular trafficking, receptor endocytosis and actin remodeling. ..
  17. Krause M, Dent E, Bear J, Loureiro J, Gertler F. Ena/VASP proteins: regulators of the actin cytoskeleton and cell migration. Annu Rev Cell Dev Biol. 2003;19:541-64 pubmed
    ..Phosphorylation by these kinases appears to modulate Ena/VASP function within cells, although the mechanism underlying this regulation remains to be determined. ..
  18. Kitazawa M, Yamakuni T, Song S, Kato C, Tsuchiya R, Ishida M, et al. Intracellular cAMP controls a physical association of V-1 with CapZ in cultured mammalian endocrine cells. Biochem Biophys Res Commun. 2005;331:181-6 pubmed
  19. Persson M, Gullberg M, Tolf C, Lindberg A, Mansson A, Kocer A. Transportation of nanoscale cargoes by myosin propelled actin filaments. PLoS ONE. 2013;8:e55931 pubmed publisher
    ..The attachment of quantum dots via CapZ, without appreciable modulation of actomyosin function, is useful in fundamental studies as exemplified here by tracking with nanometer accuracy. ..
  20. Morzel M, Chambon C, Lefevre F, Paboeuf G, Laville E. Modifications of trout (Oncorhynchus mykiss) muscle proteins by preslaughter activity. J Agric Food Chem. 2006;54:2997-3001 pubmed
    ..Persistent under-representation of desmin, a key cytoskeletal protein, in fish submitted to intense muscular activity suggests that such a preslaughter treatment can have an effect on post-mortem muscle integrity. ..
  21. Jaiswal R, Stepanik V, Rankova A, Molinar O, Goode B, McCartney B. Drosophila homologues of adenomatous polyposis coli (APC) and the formin diaphanous collaborate by a conserved mechanism to stimulate actin filament assembly. J Biol Chem. 2013;288:13897-905 pubmed publisher
    ..These results suggest that APC-Dia interactions in actin assembly are conserved and may underlie important in vivo functions in a broad range of animal phyla. ..
  22. Shumilina E, Negulyaev Y, Morachevskaya E, Hinssen H, Khaitlina S. Regulation of sodium channel activity by capping of actin filaments. Mol Biol Cell. 2003;14:1709-16 pubmed
    ..Our data show that actin-capping protein can participate in the cytoskeleton-associated regulation of sodium transport in nonexcitable cells. ..
  23. Kuhlman P, Fowler V. Purification and characterization of an alpha 1 beta 2 isoform of CapZ from human erythrocytes: cytosolic location and inability to bind to Mg2+ ghosts suggest that erythrocyte actin filaments are capped by adducin. Biochemistry. 1997;36:13461-72 pubmed
    ..The erythrocyte actin filaments may thus represent a specialized class of membrane-associated actin filaments that are capped by adducin instead of capZ. ..
  24. Gemoll T, Roblick U, Szymczak S, Braunschweig T, Becker S, Igl B, et al. HDAC2 and TXNL1 distinguish aneuploid from diploid colorectal cancers. Cell Mol Life Sci. 2011;68:3261-74 pubmed publisher
    ..The results suggest that distinct protein expression patterns, affecting TXNL1 and HDAC2, distinguish aneuploid with poor prognosis from diploid colorectal cancers. ..
  25. Hearst S, Walker L, Shao Q, Lopez M, Raucher D, Vig P. The design and delivery of a thermally responsive peptide to inhibit S100B-mediated neurodegeneration. Neuroscience. 2011;197:369-80 pubmed publisher
    ..Overall, our data suggest that thermal targeting of ELP-based therapeutic peptides to the cerebellum is a novel treatment strategy for cerebellar neurodegenerative disorders. ..
  26. Bao Y, Kake T, Hanashima A, Nomiya Y, Kubokawa K, Kimura S. Actin capping proteins, CapZ (?-actinin) and tropomodulin in amphioxus striated muscle. Gene. 2012;510:78-86 pubmed publisher
    ..These results suggest that unlike most of vertebrates, such as fish, amphibian, bird, and mammal, CapZ from amphioxus striated muscle is derived from two genes CAPZA and CAPZB, and Tmod is derived from one TMOD gene. ..
  27. Mahoney D, Safdar A, Parise G, Melov S, Fu M, MacNeil L, et al. Gene expression profiling in human skeletal muscle during recovery from eccentric exercise. Am J Physiol Regul Integr Comp Physiol. 2008;294:R1901-10 pubmed publisher
  28. Pyle W. Searching for the missing link: a role for the actin capping protein in heart failure. Can J Cardiol. 2004;20:1429-32 pubmed
    ..Future research is required to determine the mechanisms by which changes in CapZ impact myocardial function and intracellular signalling, and to develop feasible strategies that can manipulate CapZ in the intact heart. ..
  29. Eyers C, McNeill H, Knebel A, Morrice N, Arthur S, Cuenda A, et al. The phosphorylation of CapZ-interacting protein (CapZIP) by stress-activated protein kinases triggers its dissociation from CapZ. Biochem J. 2005;389:127-35 pubmed
    ..Osmotic shock or anisomycin triggered the dissociation of CapZIP from CapZ in Jurkat cells, suggesting that phosphorylation of CapZIP may regulate the ability of CapZ to remodel actin filament assembly in vivo. ..
  30. Sun D, Zhou M, Kowolik C, Trisal V, Huang Q, Kernstine K, et al. Differential expression patterns of capping protein, protein phosphatase 1, and casein kinase 1 may serve as diagnostic markers for malignant melanoma. Melanoma Res. 2011;21:335-43 pubmed publisher
    ..In addition, because capping protein Z-line ?1, PP1CB, and CSNK1A1 are involved in cell motility, which underlies invasion and metastasis of human cancer; they may be novel targets for antimetastatic therapies as well. ..
  31. DiNubile M. Erythrocyte membrane fractions contain free barbed filament ends despite sufficient concentrations of retained capper(s) to prevent barbed end growth. Cell Motil Cytoskeleton. 1999;43:10-22 pubmed
    ..Growth from such complexes in vivo could be limited by the availability of polymerization-competent G-actin. ..
  32. Pyle W, Hart M, Cooper J, Sumandea M, de Tombe P, Solaro R. Actin capping protein: an essential element in protein kinase signaling to the myofilaments. Circ Res. 2002;90:1299-306 pubmed
  33. Hartman T, Martin J, Solaro R, Samarel A, Russell B. CapZ dynamics are altered by endothelin-1 and phenylephrine via PIP2- and PKC-dependent mechanisms. Am J Physiol Cell Physiol. 2009;296:C1034-9 pubmed publisher
    ..This study demonstrates for the first time that endothelin and phenylephrine alter CapZ dynamics through PIP2- and PKC-dependent pathways, which might destabilize the existing framework and permit sarcomeric remodelling to proceed...
  34. Odagaki S, Kumanogoh H, Nakamura S, Maekawa S. Biochemical interaction of an actin-capping protein, CapZ, with NAP-22. J Neurosci Res. 2009;87:1980-5 pubmed publisher
    ..Hence, the CapZ-NAP-22 complex could work as the nucleation site of actin polymerization or as the actin filament-anchoring site on the membrane microdomain. ..
  35. Geyer C, Inselman A, Sunman J, Bornstein S, Handel M, Eddy E. A missense mutation in the Capza3 gene and disruption of F-actin organization in spermatids of repro32 infertile male mice. Dev Biol. 2009;330:142-52 pubmed publisher
  36. Dupont A, Chwastyniak M, Beseme O, Guihot A, Drobecq H, Amouyel P, et al. Application of saturation dye 2D-DIGE proteomics to characterize proteins modulated by oxidized low density lipoprotein treatment of human macrophages. J Proteome Res. 2008;7:3572-82 pubmed publisher
    ..In conclusion, we have demonstrated the effects of oxLDL in the modulation of several proteins in human macrophages and established a functional profile of the human macrophage during the atherosclerotic process. ..
  37. Lin Y, Swanson E, Li J, Mkrtschjan M, Russell B. Cyclic mechanical strain of myocytes modifies CapZβ1 post translationally via PKCε. J Muscle Res Cell Motil. 2015;36:329-37 pubmed publisher
    ..A hypothetical model is presented proposing that one destination of the mechanotransduction signaling pathways might be for PTMs of CapZ thereby regulating actin capping and filament assembly. ..
  38. Smith J, Diez G, Klemm A, Schewkunow V, Goldmann W. CapZ-lipid membrane interactions: a computer analysis. Theor Biol Med Model. 2006;3:30 pubmed
    ..CapZ may therefore play an essential role in providing a stable membrane anchor for actin filaments. ..
  39. Frizzo J, Tramontina F, Bortoli E, Gottfried C, Leal R, Lengyel I, et al. S100B-mediated inhibition of the phosphorylation of GFAP is prevented by TRTK-12. Neurochem Res. 2004;29:735-40 pubmed
    ..These data suggest a role for S100B in the assembly of intermediate filaments in astrocytes. ..
  40. Mukherjee K, Ishii K, Pillalamarri V, Kammin T, Atkin J, Hickey S, et al. Actin capping protein CAPZB regulates cell morphology, differentiation, and neural crest migration in craniofacial morphogenesis†. Hum Mol Genet. 2016;25:1255-70 pubmed publisher
    ..In addition, capzb over-expression results in embryonic lethality. Therefore, proper capzb dosage is important during embryogenesis, and regulates both cell behavior and tissue morphogenesis. ..
  41. Staneva I, Huang Y, Liu Z, Wallin S. Binding of two intrinsically disordered peptides to a multi-specific protein: a combined Monte Carlo and molecular dynamics study. PLoS Comput Biol. 2012;8:e1002682 pubmed publisher
    ..Our results highlight the importance of overall physical properties of IDP segments, such as net charge or presence of strongly hydrophobic amino acids, for molecular recognition via coupled folding-binding. ..
  42. Chugh P, Clark A, Smith M, Cassani D, Dierkes K, Ragab A, et al. Actin cortex architecture regulates cell surface tension. Nat Cell Biol. 2017;19:689-697 pubmed publisher
    ..Our results indicate that actin network architecture, alongside myosin activity, is key to cell surface tension regulation. ..
  43. Fowler V. The human erythrocyte plasma membrane: a Rosetta Stone for decoding membrane-cytoskeleton structure. Curr Top Membr. 2013;72:39-88 pubmed publisher
    ..Future studies will reveal the structure and dynamics of actin filament capping, mechanisms of precise length regulation, and spectrin-actin lattice symmetry. ..
  44. Eckert C, Goretzki A, Faberova M, Kollmar M. Conservation and divergence between cytoplasmic and muscle-specific actin capping proteins: insights from the crystal structure of cytoplasmic Cap32/34 from Dictyostelium discoideum. BMC Struct Biol. 2012;12:12 pubmed publisher
    ..Hence, the crystal structure of Cap32/34 raises the possibility of different binding behaviours of the CP variants toward the barbed end of actin filaments, a feature, which might have arisen from adaptation to different environments. ..
  45. Yang F, Pyle W. Reduced cardiac CapZ protein protects hearts against acute ischemia-reperfusion injury and enhances preconditioning. J Mol Cell Cardiol. 2012;52:761-72 pubmed publisher
    ..The cardioprotected phenotype of CapZ transgenic mice is associated with an altered translocation of PKC-isoforms to cardiac myofilaments. ..
  46. Takaichi R, Odagaki S, Kumanogoh H, Nakamura S, Morita M, Maekawa S. Inhibitory effect of NAP-22 on the phosphatase activity of synaptojanin-1. J Neurosci Res. 2012;90:21-7 pubmed publisher
  47. Sosnik J, Buffone M, Visconti P. Analysis of CAPZA3 localization reveals temporally discrete events during the acrosome reaction. J Cell Physiol. 2010;224:575-80 pubmed publisher
    ..In addition, the actin polymerization inhibitor latrunculin A was unable to alter CAPZA3 movement. ..
  48. Tokuhiro K, Miyagawa Y, Tanaka H. Characterizing mouse male germ cell-specific actin capping protein alpha3 (CPalpha3): dynamic patterns of expression in testicular and epididymal sperm. Asian J Androl. 2008;10:711-8 pubmed publisher
    ..After inducing the acrosomal reaction, the CPalpha3 and ACTB localization was virtually identical to the localization before the acrosomal reaction. CPalpha3 might play an important role in sperm morphogenesis and/or sperm function. ..
  49. Kilby P, Van Eldik L, Roberts G. Identification of the binding site on S100B protein for the actin capping protein CapZ. Protein Sci. 1997;6:2494-503 pubmed
    ..We believe we may have identified a binding site that could be common to many S100 protein-protein interactions. ..
  50. David V, Gouin E, Troys M, Grogan A, Segal A, Ampe C, et al. Identification of cofilin, coronin, Rac and capZ in actin tails using a Listeria affinity approach. J Cell Sci. 1998;111 ( Pt 19):2877-84 pubmed
    ..Our findings suggest that these latter proteins, which are known to play critical roles in cellular actin rearrangements, may also be involved in the dynamics of Listeria-induced actin assembly. ..
  51. Popp D, Yamamoto A, Iwasa M, Nitanai Y, Ma da Y. Single molecule polymerization, annealing and bundling dynamics of SipA induced actin filaments. Cell Motil Cytoskeleton. 2008;65:165-77 pubmed publisher
    ..Taken together these three effects, rapid SipA induced actin polymerization, filament annealing and bundle formation due to molecular crowding can explain how Salmonella invades cells at molecular level...
  52. McGregor E, Kempster L, Wait R, Gosling M, Dunn M, Powell J. F-actin capping (CapZ) and other contractile saphenous vein smooth muscle proteins are altered by hemodynamic stress: a proteonomic approach. Mol Cell Proteomics. 2004;3:115-24 pubmed
    ..The observed changes would favor the generation of contractile stress fibers. ..
  53. Miyagawa Y, Tanaka H, Iguchi N, Kitamura K, Nakamura Y, Takahashi T, et al. Molecular cloning and characterization of the human orthologue of male germ cell-specific actin capping protein alpha3 (cpalpha3). Mol Hum Reprod. 2002;8:531-9 pubmed
    ..CPalpha3 may play a physiologically important role in sperm architecture as well as in fertility of the human male. ..