Protein Variants | Comment | Organism |
---|---|---|
additional information | a missense mutation in cct5 causes muscle impairment within cct5tf212b, mapping of tf212b links the phenotype-causing mutation to the gene encoding the TRiC subunit Cct5 on chromosome 24, severe reduction in the amount of myofibrils. Knockdown of cct5 by two independent morpholinos, both validated for their functionality, results in a reduction of birefringence comparable with cct5tf212b homozygotes. A second mutant allele of cct5, cct5hi2972Tg, carries a single retroviral insertion in cct5 and fails to complement the bire-fringence reduction of cct5tf212b. In addition, both cct5 mutants are significantly ameliorated by injection of full-length cct5 mRNA, confirming that the phenotype-causing mutation of cct5tf212b resides within cct5. In addition to the trunk muscle, the head musculature of cct5tf212b mutants is also affected. Mutations in other TRiC subunits, e.g. CCT3 or CCT4, also cause impaired myofibril assembly. Mutants cct3sa1761 and cct4x0114 null develop into relatively normal larvae that exhibit skeletal muscle defects grossly similar to the other cct mutants | Danio rerio |
Localization | Comment | Organism | GeneOntology No. | Textmining |
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myofibril | - |
Danio rerio | 30016 | - |
sarcomere | - |
Danio rerio | 30017 | - |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Danio rerio | Q9PW76 AND Q6PBW6 AND Q7T2P2 AND Q6P123 AND Q6NVI6 AND E9QGU4 AND B3DKJ0 AND A0A0R4IJT8 | genes CCT1-5, 6a, 7, and 8 encoding subunits CCT-alpha (TCP-1 protein), CCT-beta, CCT-gamma, CCT-delta, CCT-epsilon, CCT-zeta, CCT-eta, and CCT-theta | - |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
skeletal muscle | - |
Danio rerio | - |
Synonyms | Comment | Organism |
---|---|---|
CCT | - |
Danio rerio |
TriC | - |
Danio rerio |
General Information | Comment | Organism |
---|---|---|
malfunction | in zebrafish, TRiC loss causes specific defects in sarcomere and neurite formation. A missense mutation in the CCT5 subunit of TRiC leads to skeletal muscle defects, mutant cct5tf212b. Loss of individual subunits abolishes Z-disk localization. Expression of GFP-tagged subunit CCT3 in the musculature significantly ameliorates the muscle integrity deficits of transgenic cct3sa1761 homozygotes, as evaluated by birefringence analysis, indicating that the fusion protein is functional and integrated normally into TRiC. All cct mutants show retina degeneration, except for cct5tf212b, phenotypes, overview | Danio rerio |
physiological function | the TCP-1 ring complex (TRiC) is a multi-subunit group II chaperonin that assists nascent or misfolded proteins to attain their native conformation in an ATP-dependent manner. Zebrafish chaperonin TRiC has a specific role in the biogenesis of skeletal muscle alpha-actin during sarcomere assembly in myofibers. TRiC only enhances the folding of skeletal alpha-actin at the sarcomeric Z-disk. ATP binding by subunit CCT5 is required for folding of alpha-actin, but probably not tubulin. TRiC function is required for myopathic actin to form rods in nemaline myopathy. TRiC causes aggregation of myopathic alpha-actin mutant variants in nemaline myopathy. ATP Binding by CCT5 is specific for skeletal muscle alpha-actin but not tubulin processing. TRiC function is required for nemaline rod formation resulting from the expression of disease-causing skeletal muscle alpha-actin variants | Danio rerio |