Coiled-coil domain containing 130 is a protein that in humans is encoded by the CCDC130 gene. It is part of the U4/U5/U6 tri-snRNP in the U5 portion. This tri-snRNP comes together with other proteins to form complex B of the mature spliceosome. The mature protein is approximately 45 kilodaltons (kDa) and is extremely hydrophilic due to the abnormally high number of charged and polar amino acids. CCDC130 is a highly conserved protein, it has orthologous genes in some yeasts and plants that were found using nucleotide and protein versions of the basic local alignment search tool (BLAST) from the National Center for Biotechnology Information. GEO profiles for CCDC130 have shown that this protein is ubiquitously expressed, but the highest levels of expression are found in T-lymphocytes.
Function
While the specific function of CCDC130 is still unknown, there have been several studies and research papers identifying it as a component of the U5 portion of the U4/U5/U6 tri-snRNP that helps form Complex B of the human spliceosome after coming together with Complex A. Complex B then undergoes more modifications and conformational changes before becoming a mature spliceosome. In one study, the conservation of spliceosomal components is discussed by comparing the human spliceosome with that of yeast. In this study, CCDC130 is categorized as a known splicing factor and its homolog in yeast is Yju2. This yeast protein is a splicing factor that helps form the complete, active spliceosome and promotes the first step of splicing, which involves cleavage at the 5' splice site of the first exon. Based on this information, it is likely that CCDC130 plays a similar role in the human spliceosome, but due to the higher complexity of the human spliceosome, this protein may perform other functions or a completely different function. Due to its high number of phosphorylation sites, it is likely that this protein is activated and recruited to the spliceosomal complex through phosphorylation or dephosphorylation (see Post-translational modifications). Since this gene is ubiquitously expressed and expressed 2.9 times higher than the average gene, it is clear that this protein plays an integral part in the proper function of the spliceosome.
Gene
Aliases
Coiled-coil domain containing 130 has several aliases, including CCDC130, SB115, LOC81576, and MGC10471.
Locus
CCDC130 is located on the short arm of chromosome 19 in humans. The exact locus is 19p13.2. The entire gene spans from 13858753-13874106 on the + strand of chromosome 19. CCDC130 is bordered upstream by CACNA1A on the - strand, glatobu, smagly, and socho on the + strand, and downstream by MGC3207, C19orf53, ZSWIM4 on the + strand and joypaw, smeygly, floytobu, smawgly, and wycho on the - strand. Glatobu, smagly, socho, joypaw, smeygly, floytobu, smawgly, and wycho have only been verified by cDNA sequences in GenBank and have no information available about their function. There are also several small genes found within the CCDC130 sequence, with snugly, glytobu, stygly, and glartobu occurring on the + strand and chacho, zoycho, spogly, glotobu, glutobu, and sneygly occurring on the - strand. All of these small genes have extremely low levels of expression (under 3% of the expression of the average gene), with stygly having the highest expression at 2.8% of the average.
Promoter
There were several predicted promoters found for CCDC130 using ElDorado from Genomatix, but the promoter that corresponds the closest to the protein sequence is 760 bases and spans from 13858094-13858853 on chromosome 19.
Homology and evolution
Paralogs
There is only one paralog identified for CCDC130, which is CCDC94, the only other known human member in the CWC16 family of proteins. The two have about 27% identity, most of which is located in the COG5134 domain and at the C-terminus. CCDC94 has three predicted serine phosphorylation sites at positions 213, 220, and 306 that line up with serines in CCDC130 in the multiple sequence alignment and a threonine phosphorylation site that lines up with a phosphorylated serine in CCDC130.
Orthologs and homologs
CCDC130 is a highly conserved protein, with true orthologs present in primates, other mammals, amphibians, reptiles, fish, and even invertebrates, such as insects and marine invertebrates. Bird orthologs have not been found in nucleotide or protein BLASTs There have been homologous genes documented in yeasts and other fungi, as well as plants. It is unclear when the most distant homolog of CCDC130 arose, but it was well before the divergence of autotrophs and heterotrophs