CAPZA2 explained

F-actin-capping protein subunit alpha-2 also known as CapZ-alpha2 is a protein that in humans is encoded by the CAPZA2 gene.^[1]

Structure

CapZ-alpha2 is a 33.0 kDa protein composed of 286 amino acids.^[2] CAPZA2 is located on human chromosome 7, position q31.2-q31.3.^[3] The primary sequence of CapZ-alpha2 contains three C-terminal, regularly spaced leucines at positions 258, 262 and 266 found in consensus sequence of KxxxLxxE/DLxxALxxK/R that are critical for actin binding; these residues are conserved within the CapZ-beta isoform.^[3] CapZ-alpha2 is 85% identical to CapZ-alpha1, and differ by a small number of key amino acids; 21 amino acid differences perpetrate isoform specificity.^[4] CapZ-alpha2 is expressed in a variety of tissues, including cardiac muscle and skeletal muscle, where it caps sarcomeric actin at Z-discs; the ratio of CapZ-alpha2 to CapZ-alpha1 varies significantly among different tissues.^[4]

Function

CapZ binds the barbed end of actin filaments and prevents addition or loss of actin monomers to filaments. It has also been observed that CapZ functions to organize myofilaments during myofibrillogenesis and is present at Z-discs in muscle prior to the striation of actin filaments, suggesting that CapZ may function to direct the polarity and organization of sarcomeric actin during I-band formation.^{[5] [6]} The function of CapZ-alpha2 may be modulated by the calcium-binding protein S100A in skeletal and cardiac muscle tissues, as crosslinking studies have shown S100A to directly interact with the C-terminal region of CapZ-alpha in the presence of calcium.^[7] CapZ appears to regulate intracellular signaling of contractile proteins in cardiac muscle. It has been demonstrated that the presence of CapZ at Z-discs modulates the ability of protein phosphatase 1 (PP1) to dephosphorylate cardiac myofilament proteins, including myosin binding protein C, troponin T and myosin regulatory light chain; likely because extraction of CapZ decreased the amount of myofilament-associated PP1.^[8]

Clinical Significance

In humans undergoing exercise-induced muscle damage via 300 maximal eccentric contractions, skeletal muscle biopsies subjected to DNA microarrays showed that CapZ-alpha expression was upregulated, suggesting that CapZ-alpha may be involved in skeletal muscle growth and remodeling, and/or stress management.^[9]

Interactions

CapZ-alpha2 has been shown to interact with:

• ACTA1^[5]
• ACTC1^[5]
• S100A1^[7]

Further reading

• Dawson SJ, White LA . Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin . The Journal of Infection . 24 . 3 . 317–20 . May 1992 . 1602151 . 10.1016/S0163-4453(05)80037-4 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Hart MC, Korshunova YO, Cooper JA . Vertebrates have conserved capping protein alpha isoforms with specific expression patterns . Cell Motility and the Cytoskeleton . 38 . 2 . 120–32 . 1997 . 9331217 . 10.1002/(SICI)1097-0169(1997)38:2<120::AID-CM2>3.0.CO;2-B .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Miyagawa Y, Tanaka H, Iguchi N, Kitamura K, Nakamura Y, Takahashi T, Matsumiya K, Okuyama A, Nishimune Y . Molecular cloning and characterization of the human orthologue of male germ cell-specific actin capping protein alpha3 (cpalpha3) . Molecular Human Reproduction . 8 . 6 . 531–9 . Jun 2002 . 12029070 . 10.1093/molehr/8.6.531 . free .
• Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J . Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides . Nature Biotechnology . 21 . 5 . 566–9 . May 2003 . 12665801 . 10.1038/nbt810 . 23783563 .
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .

Notes and References

1. Web site: Entrez Gene: CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2.
2. Web site: Protein sequence of human CAPZA2 (Uniprot ID: P47755). Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). 18 September 2015. https://web.archive.org/web/20151005192258/http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P47755. 5 October 2015. dead.
3. Barron-Casella EA, Torres MA, Scherer SW, Heng HH, Tsui LC, Casella JF . 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 . The Journal of Biological Chemistry . 270 . 37 . 21472–9 . Sep 1995 . 7665558 . 10.1074/jbc.270.37.21472. free.
4. Hart MC, Korshunova YO, Cooper JA . Vertebrates have conserved capping protein alpha isoforms with specific expression patterns . Cell Motility and the Cytoskeleton . 38 . 2 . 120–32 . 1997 . 9331217 . 10.1002/(SICI)1097-0169(1997)38:2<120::AID-CM2>3.0.CO;2-B .
5. Schafer DA, Waddle JA, Cooper JA . Localization of CapZ during myofibrillogenesis in cultured chicken muscle . Cell Motility and the Cytoskeleton . 25 . 4 . 317–35 . 1993 . 8402953 . 10.1002/cm.970250403 .
6. Almenar-Queralt A, Gregorio CC, Fowler VM . Tropomodulin assembles early in myofibrillogenesis in chick skeletal muscle: evidence that thin filaments rearrange to form striated myofibrils . Journal of Cell Science . 112 . 1111–23 . Apr 1999 . 10085247 . 8. 10.1242/jcs.112.8.1111 .
7. Ivanenkov VV, Dimlich RV, Jamieson GA . Interaction of S100a0 protein with the actin capping protein, CapZ: characterization of a putative S100a0 binding site in CapZ alpha-subunit . Biochemical and Biophysical Research Communications . 221 . 1 . 46–50 . Apr 1996 . 8660341 . 10.1006/bbrc.1996.0542.
8. Yang F, Aiello DL, Pyle WG . Cardiac myofilament regulation by protein phosphatase type 1alpha and CapZ . Biochemistry and Cell Biology . 86 . 1 . 70–8 . Feb 2008 . 18364747 . 10.1139/o07-150 .
9. Mahoney DJ, Safdar A, Parise G, Melov S, Fu M, MacNeil L, Kaczor J, Payne ET, Tarnopolsky MA . Gene expression profiling in human skeletal muscle during recovery from eccentric exercise . American Journal of Physiology. Regulatory, Integrative and Comparative Physiology . 294 . 6 . R1901-10 . Jun 2008 . 18321953 . 10.1152/ajpregu.00847.2007 . 2707850.