CAPZA2
| CAPZA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | CAPZA2, CAPPA2, CAPZ, capping actin protein of muscle Z-line alpha subunit 2, capping actin protein of muscle Z-line subunit alpha 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 601571; MGI: 106222; HomoloGene: 55956; GeneCards: CAPZA2; OMA:CAPZA2 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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F-actin-capping protein subunit alpha-2 also known as CapZ-alpha2 is a protein that in humans is encoded by the CAPZA2 gene.[5]
Structure
[edit]CapZ-alpha2 is a 33.0 kDa protein composed of 286 amino acids.[6] CAPZA2 is located on human chromosome 7, position q31.2-q31.3.[7] 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.[7] 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.[8] 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.[8]
Function
[edit]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.[9][10] 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.[11] 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.[12]
Clinical Significance
[edit]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.[13]
Interactions
[edit]CapZ-alpha2 has been shown to interact with:
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000198898 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000015733 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: CAPZA2 capping protein (actin filament) muscle Z-line, alpha 2".
- ^ "Protein sequence of human CAPZA2 (Uniprot ID: P47755)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 5 October 2015. Retrieved 18 September 2015.
- ^ a b Barron-Casella EA, Torres MA, Scherer SW, Heng HH, Tsui LC, Casella JF (Sep 1995). "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. doi:10.1074/jbc.270.37.21472. PMID 7665558.
- ^ a b Hart MC, Korshunova YO, Cooper JA (1997). "Vertebrates have conserved capping protein alpha isoforms with specific expression patterns". Cell Motility and the Cytoskeleton. 38 (2): 120–32. doi:10.1002/(SICI)1097-0169(1997)38:2<120::AID-CM2>3.0.CO;2-B. PMID 9331217.
- ^ a b c Schafer DA, Waddle JA, Cooper JA (1993). "Localization of CapZ during myofibrillogenesis in cultured chicken muscle". Cell Motility and the Cytoskeleton. 25 (4): 317–35. doi:10.1002/cm.970250403. PMID 8402953.
- ^ Almenar-Queralt A, Gregorio CC, Fowler VM (Apr 1999). "Tropomodulin assembles early in myofibrillogenesis in chick skeletal muscle: evidence that thin filaments rearrange to form striated myofibrils". Journal of Cell Science. 112 (8): 1111–23. doi:10.1242/jcs.112.8.1111. PMID 10085247.
- ^ a b Ivanenkov VV, Dimlich RV, Jamieson GA (Apr 1996). "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. doi:10.1006/bbrc.1996.0542. PMID 8660341.
- ^ Yang F, Aiello DL, Pyle WG (Feb 2008). "Cardiac myofilament regulation by protein phosphatase type 1alpha and CapZ". Biochemistry and Cell Biology. 86 (1): 70–8. doi:10.1139/o07-150. PMID 18364747.
- ^ Mahoney DJ, Safdar A, Parise G, Melov S, Fu M, MacNeil L, Kaczor J, Payne ET, Tarnopolsky MA (Jun 2008). "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. doi:10.1152/ajpregu.00847.2007. PMC 2707850. PMID 18321953.
External links
[edit]- Human CAPZA2 genome location and CAPZA2 gene details page in the UCSC Genome Browser.
Further reading
[edit]- Dawson SJ, White LA (May 1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". The Journal of Infection. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151.
- Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Hart MC, Korshunova YO, Cooper JA (1997). "Vertebrates have conserved capping protein alpha isoforms with specific expression patterns". Cell Motility and the Cytoskeleton. 38 (2): 120–32. doi:10.1002/(SICI)1097-0169(1997)38:2<120::AID-CM2>3.0.CO;2-B. PMID 9331217.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Miyagawa Y, Tanaka H, Iguchi N, Kitamura K, Nakamura Y, Takahashi T, Matsumiya K, Okuyama A, Nishimune Y (Jun 2002). "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. doi:10.1093/molehr/8.6.531. PMID 12029070.
- Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (May 2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nature Biotechnology. 21 (5): 566–9. doi:10.1038/nbt810. PMID 12665801. S2CID 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 (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.