The function of this gene is currently unknown. There is evidence that CCDC78 plays a role in skeletal muscle contraction. This is supported by structural similarities to other muscle proteins and by localization assays. CCDC78's predicted structure was similar to that of tropomyosin (see below).[9] The gene product is found primarily in the perinuclear region, the sarcolemmal membrane, and in the reticular pattern of the sarcoplasm. However, localization assays predict it to also be found in the cytoplasm.[8]
Coiled-coil domain-containing 78 (CCDC78) is a protein in humans encoded by the CCDC78 gene. It has several aliases including C16orf25, FLJ34512, CNM4, and JFP10. It is located on the (-) strand on chromosome 16 (16p13.3). Its gene neighborhood includes NARFL (also on the minus strand), HAGHL, FAM173A, and METRN. The CCDC78 gene is 10,892 base pairs long, and the protein contains 438 amino acids. The protein weighs approximately 4.852 KDal. There are several isoforms, including one indicated with a unique congenital myopathy. Several expression profiles show it has ubiquitous expression at moderate levels. Although no paralogs exist several orthologs do.
Paralog: Noun. (plural paralogues) (genetics) either of a pair of genes that derives from the same ancestral gene. (genomics) a pair of genes that derives from the same ancestral gene and now reside at different locations within the same genome.
Orthologs are genes in different species that evolved from a common ancestral gene by speciation. Normally, orthologs retain the same function in the course of evolution. Identification of orthologs is critical for reliable prediction of gene function in newly sequenced genomes.
Cytosol is the part of the cytoplasm that is not held by any of the organelles in the cell. On the other hand, cytoplasm is the part of the cell which is contained within the entire cell membrane. It is the total content within the cell membrane other than the contents of the nucleus of the cell.
Organelles: any of a number of organized or specialized structures within a living cell.
Expression of CCDC78
When looking at EST profiles in humans, CCDC78 seems to show ubiquitous expression at moderate levels
(Omnipresence or ubiquity is the property of being present everywhere.)
Predicted post-translational modification: Phosphorylation of several serine residues has been predicted by using tools at ExPasy.
Predicted Secondary Structure
Secondary structure of CCDC78 was predicted using the protein secondary structure prediction tool PELE. As would be expected with a coiled-coil domain containing protein, there are several α-helices. The model was predicted to be 98% accurate to 65% of the protein. The predicted image can be seen below. This predicted model is closely related to tropomyosin - a contractile protein.
The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group donates a hydrogen bond to the backbone C=O group of the amino acid located three or four residues earlier along the protein sequence.
Protein-protein Interactions
*Only one protein has been found to interact with CCDC78. An analysis performed from IntAct showed an interaction between CCDC78 and dAK1_1 in Yersinia pestis.
What is EST database?
EST. The EST database is a collection of short single-read transcript sequences from GenBank. These sequences provide a resource to evaluate gene expression, find potential variation, and annotate genes.
The identification of a CCDC78 mutation in a family with congenital myopathy is an important step in terms of bridging the knowledge gap for these disorders, related to both diagnostic assessment and understanding of the disease pathogenesis. A substantial portion of congenital myopathies are genetically unresolved, and CCDC78 now represents an excellent new candidate gene for individuals without an identified gene mutation. In particular, CCDC78 may be considered in cases wherein muscle biopsy reveals frequent internal nuclei and/or core-like areas. Future studies are needed to address the possibility of a larger association between CCDC78 mutation and individuals who have congenital myopathies without a known genetic cause. Notably, however, our initial examination suggests that it is unlikely to be a frequent cause of classic CNM.
Another important aspect of this study is the identification of CCDC78, a previously uncharacterized protein, as a gene product of potential importance for the regulation of essential muscle function(s). Our initial analyses, encompassing immunofluorescence studies and morpholino-mediated splice-site alteration in the zebrafish, point to a potential function for CCDC78 in the regulation of the structure and function of the triad, the subcellular structure within the muscle containing RyR1 and disturbed in all previously characterized forms of CNM. Given that interplay between RyR1, the other known causes of CNM, and the regulation of excitation-contraction coupling is still uncertain, the uncovering of CCDC78 offers the potential for significant advancement in the understanding of this disease process. Future studies are needed for further delineation of these exciting potential function(s) of CCDC78 in the skeletal muscle and at the triad.
Comentários