C10orf53 Explained

C10orf53 is a protein that in humans is encoded by the C10orf53 gene.[1] The gene is located on the positive strand of the DNA and is 30,611 nucleotides in length.[2] The protein is 157 amino acids and the gene has 3 exons. C10orf53 orthologs are found in mammals, birds, reptiles, amphibians, fish, and invertebrates.[3] It is primarily expressed in the testes and at very low levels in the cerebellum, liver, placenta, and trachea.

Gene

Chromosome 10 open reading frame 53 (10orf53), also known as uncharacterized protein family 0728 (UPF0728), in humans, is encoded by Chromosome 10 (10q11.23), spanning 30,611 nucleotides. The gene is located on the positive strand with 3 identified exons.

Transcript

IsoformAccession #Length

(amino acids)

Length (nucleotides)Exons translatedAdditional comments
aNM_182554.4

NP_872360.2

15730,6113Less common isoform
bNM_001042427.3

NP_001035892.1

9317,8823More common isoform – alternative 3’ exon and distinct C-terminus
The table outlines the two identified isoforms of C10orf53. The most common isoform has 93 amino acids which is a shorter amino acid sequence due to an alternative 3’ terminal exon and distinct C-terminus. Isoform A has a higher frequency of analysis due to it being the longer isoform. The analysis in this article is focused on isoform A.

Structure

The molecular weight predicted was 17.6 kDa.[4] The isoelectric point for C10orf53 is estimated to be 6.36 pl

Secondary

MPKNAVVILRYGPYSAAGLPVEHHTFRLQGLQAVLAIDGHEVILEKIEDWNVVELMVNEEVIFHCNI 67

CCCCCSSSSSSCCCHHCCSSSSSCHHHHHHHHHHHHHCCCSSSSSSSCCCCSSSSSSCCCSSSSSCC 67

KDLEFGKLTPSSDKRTTSSSRLTFHQLSSPCRMKVSPLQQFPQKTQDLTCTVLAQIGSCIHFQTNLC 134

CCCCCCCCCHHHHHHHHHHHHHHHHCCCCHHHHCCCHHHHCCCCCCCSSSSSHHHHCCSSSSSCCCC 134

DLGWPGLDHMLISGLEKRGTQPY 157

CCCCCCCHHHHHHHHHHCCCCCC 157The secondary structure above illustrates the estimated secondary structure for Isoform A of C10orf53. The C that are italicized indicate that the amino acid is located within a coil, the bolded S is referring to the amino acid being in a strand, and the underlined H shows the amino acid is in a helix. The strand and helix structures can then be translated into the predicted tertiary structure done through I-TASSER.

Tertiary

The predicted tertiary structure of C10orf53 is shown. The tertiary structure contains the seven helix and 8 strand structures predicted through I-TASSER.

Regulation

Gene

C10orf53 is primarily expressed in the testes, but also has very low levels of expression in the cerebellum, liver, placenta, and trachea. It is tissue-specific to the testes due to the low expression in other tissues compared to the testes. C10orf53 majorly is secreted in the cytoplasm of cells and has moderate levels in the nucleus and mitochondria.[5]

Protein

C10orf53 was found to have two phosphorylation sites, two SUMOylation sites, and one lysine acetylation site.[6] All of these regions are shown in the conceptual translation of C10orf53.

Evolution

C10orf53 is predicted to have a slower evolution compared to the gene, fibrinogen alpha, but it also has a quicker evolution compared to cytochrome c. Fibrinogen alpha is considered as a gene that had evolved rather quickly when examining the gene in different organisms. When two organisms diverged into different taxa, the gene went through alterations that made it significantly different from other organisms, causing it to have a quick rate of evolution. In contrast, Cytochrome C is relatively conserved throughout different organisms, which shows that it has a slow rate of evolution. C10orf53 has a rate of evolution that is smaller than fibrinogen alpha, but larger than cytochrome c.

Homology

A group of distantly and closely related orthologs were chosen and categorized by their date of divergence from humans. The percent similarity and percent identity in relation to humans showed the predicted conservation between C10orf53 in humans compared to their orthologs.

Interacting Proteins

Protein[7] Protein NameIdentificationFunction[8]
PIGRPolymeric Immunoglobulin ReceptorAffinity chromatographyAids in the movement of polymeric IgA and IgM across mucosal epithelial cells
DSCC1DNA Replication And Sister Chromatid Cohesion 1Affinity chromatographyLoads PCNA onto primed templates to manipulate replication forks
UXTUbiquitously Expressed Prefoldin Like ChaperoneAffinity chromatographyRegulates androgen receptor transcription
ZG16BZymogen Granule Protein 16BAffinity chromatographyLocated in the extracellular exosome and enables carbohydrate binding activity
SPECC1LSperm Antigen With Calponin Homology And Coiled-Coil Domains 1 LikeAffinity chromatographyHelps with spindle organization and cytokinesis
MNAT1CDK Activating KinaseAffinity chromatographyCreates the CDK-activating kinase enzyme complex
SPTBSpectrin Beta, ErythrocyticAffinity chromatographyComposes the cytoskeletal network in erythrocyte membranes
The table contains all predicted proteins that were found to interact with C10orf53. It includes the protein acronym and name, the means that identification occurred, and the function of each protein. Due to the related function of some of the proteins, this provides evidence that these interactions coincide with the predicted location.

Clinical Significance

A study was conducted that compared the relative spermatogenesis in humans to the relative expression of RNAs correlated to teratozoospermia. In non-afflicted humans, there is a relatively high expression of C10orf53 across the RNAs tested. However, when a human had teratozoospermia, those levels dropped to almost zero.[9] Another study examined the expression of C10orf53 in spermatogenesis and testis development in mice during development. C10orf53 is only highly expressed from day 30-56 of mice development, with the expression decreasing slightly on each five-day period until 56 days were reached.[10] The final study looked at research done within the past five years has correlated African American prostate cancer patients with the presence of C10orf535. When examining the exosome found in Caucasian populations associated with prostate cancer (PCC) against the African American exosome (PAA), C10orf53 was unique only to PAA.[11]

Notes and References

  1. Web site: C10orf53 chromosome 10 open reading frame 53 [Homo sapiens (human)] - Gene ]. National Center for Biotechnology Information (NCBI) . U.S. National Library of Medicine . 2022-12-16 .
  2. Web site: C10orf53 Gene . GeneCards . 2022-12-16 .
  3. Web site: BLAST: Basic Local Alignment Search Tool . 2022-12-16 . National Center for Biotechnology Information (NCBI) . U.S. Library of Medicine .
  4. Web site: Statistical Analysis of Protein Sequences (SAPS) . European Bioinformatics Institute (EMBL-EBI) . European Molecular Biology Laboratory (EMBL) . 2022-12-16 .
  5. Web site: PSORT II Prediction . 2022-12-16 . psort.hgc.jp . Program to predict the subcellular localization sites of proteins from their amino acid sequences. .
  6. Web site: Group-based Prediction System (GPS) 5.0 . Kinase-specific Phosphorylation Site Prediction . 2022-12-16 . Huazhong University of Science and Technology . Wuhan, Hubei, China .
  7. Web site: PSICQUIC View . 2022-12-16 . www.ebi.ac.uk.
  8. Web site: GeneCards - Human Genes Gene Database Gene Search . 2022-12-16 . www.genecards.org.
  9. Platts AE, Dix DJ, Chemes HE, Thompson KE, Goodrich R, Rockett JC, Rawe VY, Quintana S, Diamond MP, Strader LF, Krawetz SA . 6 . Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs . Human Molecular Genetics . 16 . 7 . 763–773 . April 2007 . 17327269 . 10.1093/hmg/ddm012 . free .
  10. Shima JE, McLean DJ, McCarrey JR, Griswold MD . The murine testicular transcriptome: characterizing gene expression in the testis during the progression of spermatogenesis . Biology of Reproduction . 71 . 1 . 319–330 . July 2004 . 15028632 . 10.1095/biolreprod.103.026880 . 16839090 . free .
  11. Panigrahi GK, Praharaj PP, Kittaka H, Mridha AR, Black OM, Singh R, Mercer R, van Bokhoven A, Torkko KC, Agarwal C, Agarwal R, Abd Elmageed ZY, Yadav H, Mishra SK, Deep G . 6 . Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients . Cancer Medicine . 8 . 3 . 1110–1123 . March 2019 . 30623593 . 6434210 . 10.1002/cam4.1885 .