C4orf17 has a total of three known splice variants.[8][2] There are 9 exons found within C4orf17's mRNA sequence. The two additional isoforms have 10 and 7 exons, respectively.
The C4orf17 gene encodes the Q53FE4 protein, otherwise knowns as the C4orf17 protein.[10]
Expression
In Ciona intestinalis, Ci-Spatial/C4orf17 is an essential part of beta-catenin signaling pathways in early embryonic development. Researchers isolated various cDNA clones and injected them with specific morpholinos. As a result, this study suggests that it is possible that Ci-Spatial/C4orf17 is involved in nuclear translocation of Ci-beta-catenin or enhancement of transcriptional activation.
Figure 1:C4orf17 expression in various tissues across 15 primates.
In humans, there is notable expression of C4orf17 in the testes and early spermatids.[9]
Figure 2: Immunofluorescent staining of human cell line. Sperm shows localization to mid piece
Localization
In humans, C4orf17 is specific to the testes.[10] During human fetal development, however, C4orf17 expression appeared in adrenal, intestinal, and renal tissues[11] at 20 weeks after conception.
Interactions
The C4orf17 protein interacts with numerous other proteins, such as ATRX, CHD3, KAT2B, KDM1A, PRMT1, and SUV39H1. These specific interactions suggest that C4orf17’s function is associated with chromatin modifications through histone methylation.[12]
A 2022 study,[14] nevertheless, further investigated the ADH gene cluster. According to the researchers, “Nucleotide variation in ADH genes can affect the catalytic properties of these enzymes and is associated with a variety of traits, including alcoholism and cancer,” (McQuillan et al., 2022). C4orf17 is one of the many genetic mutations listed as having a strong effect on ADH traits.
Evolutionary aspects
Orthologs
C4orf17 has a total of 86 orthologs recorded in the Ensembl database as well as 331 listed in NCBI. There were no orthologs found among invertebrates, protists, fungi, plants, or bacteria and archaea.[15] The C4orf17 gene likely arose approximately 463 million years ago[15]
Table 2: Percent identity accounts for exact matches, such as a DNA base or amino acids. Percent similarity accounts for identical and biochemically similar substitutions, such as substituted amino acids.
Paralogs
The C4orf17 protein is a SPATIAL (stromal protein associated with thymic and lymph node) domain-containing protein,[16] specifically at the interval 27-223 aa.[17] This suggests that it may be involved in spermatiddifferentiation. This family may also be referred to as “TBATA” or “TBATA-like.”
Protein Analysis Through Evolutionary Relationships (PANTHER) Classification System categorizes C4orf17 into the PTHR33772:SF2 protein family.[18]
Figure 3: Date of Divergence (MYA): C4orf17 (yellow), cytochrome c (orange), fibrinogen alpha chain (blue)Error creating thumbnail: Figure 4: The following figures exhibit conserved regions of C4orf17 among the orthologs listed in Table #. The size of the letters at the top of each figure represents the degree of conservation. Larger letters indicate more conservation compared to smaller letters.Conserved regions of the C4orf17 proteinError creating thumbnail: Conserved regions of the C4orf17 protein
Protein Divergence
The figure to the right named "Date of Divergence..." exhibits the evolution of human C4orf17, cytochrome c, and fibrinogen alpha chain. Cytochrome C has a weaker slope indicating fewer mutations over time, while the fibrinogen alpha chain has a taller slope, meaning it has evolved quicker than both human C4orf17 and cytochrome c. [10]
Figure 5 exhibits a conceptual translation of C4orf17 in humans. It is annotated to highlight exons, start and stop codons, and disordered regions among other genetic features.
SNPs
C4orf17 has a total of 14,681 SNPs recorded in the NCBI Variant Viewer, though only two are clinically significant.[19] Variants rs1397320372 and rs1417597081 are both single nucleotide, missense variants.
↑"Abetalipoproteinemia in Israel: evidence for a founder mutation in the Ashkenazi Jewish population and a contiguous gene deletion in an Arab patient". Molecular Genetics and Metabolism90 (4): 453–457. April 2007. doi:10.1016/j.ymgme.2006.12.010. PMID17275380.
.png)
.png){kind=link}