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| | A: Except for testes, most cells express four major isoforms of AKAP12 protein. The 305 kDa isoforms is the myristylated AKAP12alpha whereas the 287 kDa isoforms is AKAP12beta. The 250 kDa and 43 kDa isoforms are proteolytic cleavage products common to the AKAP12alpha and beta isoforms.
B: Human AKAP12alpha encodes a 1,780 amino acids full-length protein. The first about 1,000 amino acids of human and rodent AKAP12 share 83% identity followed by about 600 amino acids with less than 20% identity. The N-terminal homology domain (green) shows about 40% identity to the Xgl (Xenopus gravin-like) gene in Xenopus. Both human and rodent AKAP12 share a shorter C-terminal domain containing the PKA-RII binding (AKAP) domain (green box in human AKAP12). |
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| Expression | AKAP12 isoforms are expressed in most tissue and organ types, with high expression levels in the testes, ovary, brain, lung and heart. Most mesenchyme, smooth muscle and some epithelial cells (breast, prostate, lung, ovary) express significant AKAP12 levels. Lower levels of AKAP12 are found in endothelial cells, although express in these cells is usually associated with wounding and/or inflammation. |
| Localisation | Most cell types display a cortical cytoskeletal staining pattern for AKAP12, with enrichment at the plasma membrane (presumably, the myristylated isoforms) and in the perinucleus. However, some staining has been observed in cell nuclei, probably directed by 4 SV40 Tag-like nuclear localization signals (NLS) found in the N-terminal third of the protein. |
| Function | 1) Facilitates the sensitization/resensitization reaction of beta-adrenergic receptors.
2) Scaffolds protein kinase (PK) A and PKC.
3) Autoantigen in some cases of myasthenia gravis.
4) Anti-angiogenic factor. The rodent orthologue has been shown to inhibit brain angiogenesis and induce the blood-brain barrier, and to inhibit VEGF-mediated metastasis. 5) Potential tumor suppressor. The rodent orthologue has been shown to suppress Src- and Ras-induced oncogenic proliferation in vitro and metastatic potential in vivo. |
| Homology | Southern blotting analysis as well as analysis of sequenced genomes indicates that vertebrates encode single AKAP12 orthologues, with no gene family members. Thus, the protein diversity of this gene stems from promoter choice, alternative splicing, proteolytic maturation and post-translational modification. AKAP12 has limited sequence homology based on short domains. For example, the C-terminal AKAP domain is homologous to the analogous domain in AKP79. Also, AKAP12 shares some so-called MARCKS protein-like effector domains- positively charged stretches of amino acids involved in plasma membrane targeting. |
| Molecular cloning and preliminary characterization of a novel cytoplasmic antigen recognized by myasthenia gravis sera. |
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