Disease relevance of CanA1

• Inhibition, mutation, or forced expression of calcineurin pathway genes result in defects or alterations in cardiomyocyte maturation, heart valve formation, vascular development, skeletal muscle differentiation and fiber-type switching, and cardiac and skeletal muscle hypertrophy [1].
• The interstitial deletion D14 affecting the importin-alpha 2 gene of Drosophila, or imp-alpha 2(D14), causes recessive female sterility characterized by a block of nurse cell-oocyte transport during oogenesis [2].

Psychiatry related information on CanA1

• Calcineurin in animal behavior [3].

High impact information on CanA1

• The Ca(2+)-dependent protein phosphatase, calcineurin, binds the cyclophilin-cyclosporin A and FKBP-FK506 complexes, indicating that calcineurin might mediate the actions of these drugs [4].
• Cryptococcus neoformans cbp1 mutant strains exhibit modest defects in growth under stress conditions and virulence, similar to but less severe than the phenotypes of calcineurin mutants [5].
• Calcineurin is the conserved target of the immunosuppressants cyclosporin A and FK506 [5].
• In vitro and in vivo, the CsA-resistant calcineurin mutants bind FKBP12-FK506 but have reduced affinity for cyclophilin A-CsA [6].
• Together, these findings demonstrate a vital role for the phosphatase in this specific facet of Drosophila myogenesis and show conserved fly and vertebrate calcineurin genes contribute prominently to fundamental processes of muscle formation and function [7].

Biological context of CanA1

• It has been suggested that the intracellular signal transduction of PBAN in B. mori involves Ca(2+), calmodulin, and calcineurin (also known as protein phosphatase 2B) [8].
• We have cloned two cDNAs encoding calcineurin heterosubunits from a pheromone gland cDNA library of B. mori [8].
• Twelve exons, spread over a total of 6.6 kilobases, were found to encode a 64.6-kDa protein 73% identical to either human calcineurin A alpha or beta [9].
• Genomic clones containing the full coding sequences of the two subunits of the Ca2+/calmodulin-stimulated protein phosphatase, calcineurin, were isolated from a Drosophila melanogaster genomic library using highly conserved human cDNA probes [9].
• Here, we demonstrate that a mutation in the canB2 gene, which encodes a regulatory subunit of Drosophila calcineurin, can suppress a pupal developmental arrest phenotype to adult viability [7].

Anatomical context of CanA1

• Calcineurin is a calcium-activated protein phosphatase involved in multiple aspects of cardiac and skeletal muscle development and disease [7].
• The ability to investigate calcineurin signaling pathways in vertebrates and model genetic organisms provides a great potential to more fully comprehend the functions of calcineurin and its interacting genes in heart, blood vessel, and muscle development [1].
• Inhibiting CnA with cyclosporin A (CsA) leads to nephron deficit in rat metanephric organ cultures and apoptosis in various renal cell lines [10].
• Calcineurin function is required for myofilament formation and troponin I isoform transition in Drosophila indirect flight muscle [11].
• It is believed that the cyclosporin/cyclophilin complex inhibits a Ca(2+)-activated protein phosphatase, calcineurin, involved in T-cell activation [12].

Associations of CanA1 with chemical compounds

• CnA is a serine/threonine phosphatase activated by intracellular calcium [10].

Other interactions of CanA1

• Three clones encoded a 19.3-kDa protein whose sequence is 88% identical to that of human calcineurin B, the Ca(2+)-binding regulatory subunit of calcineurin [9].
• Motifs characteristic of the putative catalytic centers of protein phosphatase-1 and -2A and calcineurin are almost perfectly conserved [9].

Analytical, diagnostic and therapeutic context of CanA1

• Molecular cloning and characterization of the genes encoding the two subunits of Drosophila melanogaster calcineurin [9].
• The PCR analyses also point to the presence in Drosophila and mammals of three or more different genes encoding PP2B, the enzyme recently identified as the target of certain immunosuppressant drugs [13].

References