Chromosome 13 Open Reading Frame 46 is a protein which in humans is encoded by the C13orf46 gene. In humans, C13orf46 is ubiquitously expressed at low levels in tissues, including the lungs, stomach, prostate, spleen, and thymus. This gene encodes eight alternatively spliced mRNA transcript, which produce five different protein isoforms.
Gene
An alternative name for C13orf46 is LOC100507747. C13orf46 spans 47,563 base pairs, contains 11 exons, and is on the minus strand of chromosome 13 at 13q34.
Gene neighbors
The neighboring genes around C13orf46 include LINC00454, LINC00452, SWINGN, RASA3, and LOC124903221.
LINC00454 and LINC00452 (Long Intergenic NonProtein Coding RNA 454 & 452) are both long non-coding RNAs (lncRNA) that regulate epigenetic gene expression, chromatin remodeling, and levels of gene transcription and translation. Both LINC00454 and LINC00452 expression are restricted to the testis. LINC00454 has been associated with Factor X Deficiency while LINC00452 has been found to promote ovarian carcinogenesis.
SWINGN (SWI/SNF Complex Interacting GAS6 Enhancer Non-Coding RNA) is also a lncRNA that neighbors C13orf46. SWINGN regulates the activation of the GAS6 (Growth Arrest Specific 6) oncogene, by interacting with matrix associated and actin dependent regulators of chromatin.
The RASA3 (RAS p21 Protein Activator 3) gene encodes the Ras GTPase activating protein. This protein binds inositol 1,3,4,5-tetrakisphosphate to stimulate the activity of Ras p21 and negatively regulates the Ras signaling pathway. RASA3 is most highly expressed in fat, lymph nodes, and the spleen. The encoded protein is localized to the cell membrane.
mRNA
Eight different transcript variants have been identified for C13orf46. These transcript variants are alternatively spliced to include variations of 11 different exons. Depending on the different transcript variant that is translated, 5 different possible protein isoforms are encoded by C13orf46. The most common protein product encoded by C13orf46 is isoform 1, which is 212 amino acids long.
Protein
The primary protein isoform of the C13orf46 gene consists of 212 amino acids. The longest encoded isoform, known as C13orf46 protein isoform X1, is 624 amino acids long. Other protein isoforms encoded by the C13orf46 gene are similar to either of these two versions of the C13orf46 protein. Varying forms of the primary 212 amino acid protein is encoded by transcript variants 1, X5, X6, and X7. Variations of the longest C13orf46 protein isoform are encoded by transcript variants X1, X2, X3, and X4.
Protein isoform 1
Properties and composition
C13orf46 Isoform 1 has a theoretical isoelectric point of 4.84 and a predicted molecular weight of 23.4 kDA. Higher relative amounts of glutamic acid (15.1%) and aspartic acid (7.5%) are found within this isoform, while the amino acids phenylalanine (0.9%) and threonine (0.5%) are found to be less abundant within the protein composition. C13orf46 Isoform 1 also has a glutamic acid rich region where multiple glutamic acid and lysine doublets are present, some of which occur side by side. A total of 14 multiplets are found within the protein overall, 12 of which are charged. C13orf46 Isoform 1 is not predicted to contain any charge clusters, hydrophobic segments, or transmembrane segments.
Structure
C13orf46 Protein Isoform 1 is predicted to consist of 7 alpha helices and 2 beta strands in addition to regions of random free coils.
Domains and motifs
C13orf46 Isoform 1 has two identified disordered regions spanning between amino acid residues 1 through 148 and 168 to 190. In addition, C13orf46 Isoform 1 has a glutamic acid rich region spanning along amino acid residues 109 to 191.
Regulation and post translational modifications
C13orf46 Isoform 1 is predicted to undergo several post-translational modifications such as phosphorylation, O-GlcNAcylation, mucin type GalNAc O-glycosylation, palmitoylation, and sumoylation. PKA, PKC, CKII, PKG, GSK3, cdc2, RSK, and ATM are kinases that are predicted to bind and phosphorylate the human C13orf46 Isoform 1. There is also one predicted phosphoprotein-binding phosphosite on the protein.