CAPZA2

CAPZA2
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
Gene location (Human) Chr. Chromosome 7 (human) Band 7q31.2 Start 116,811,070 bp End 116,922,049 bp
Gene location (Mouse) Chr. Chromosome 6 (mouse) Band 6 A2|6 7.96 cM Start 17,636,233 bp End 17,666,971 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa monocyte Skeletal muscle tissue of rectus abdominis biceps brachii right ventricle Achilles tendon Skeletal muscle tissue of biceps brachii myocardium tail of epididymis mucosa of sigmoid colon Top expressed in triceps brachii muscle vastus lateralis muscle temporal muscle sternocleidomastoid muscle muscle of thigh stroma of bone marrow knee joint Region I of hippocampus proper ankle digastric muscle More reference expression data BioGPS n/a
Gene ontology Molecular function actin binding actin filament binding protein binding Cellular component F-actin capping protein complex extracellular region cytosol cortical cytoskeleton extracellular exosome membrane brush border actin cytoskeleton actin cortical patch Biological process barbed-end actin filament capping innate immune response blood coagulation actin filament capping endoplasmic reticulum to Golgi vesicle-mediated transport antigen processing and presentation of exogenous peptide antigen via MHC class II actin cytoskeleton organization protein-containing complex assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 830 12343 Ensembl ENSG00000198898 ENSMUSG00000015733 UniProt P47755 P47754 RefSeq (mRNA) NM_006136 NM_007604 RefSeq (protein) NP_006127 NP_031630 Location (UCSC) Chr 7: 116.81 – 116.92 Mb Chr 6: 17.64 – 17.67 Mb PubMed search
Wikidata
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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.

Structure

CapZ-alpha2 is a 33.0 kDa protein composed of 286 amino acids. CAPZA2 is located on human chromosome 7, position q31.2-q31.3. 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. 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. 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.

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. 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. 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.

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.

Interactions

CapZ-alpha2 has been shown to interact with:

• ACTA1
• ACTC1
• S100A1

External links

• Human CAPZA2 genome location and CAPZA2 gene details page in the UCSC Genome Browser.

Further reading

• 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.
• 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.