Biology:C6orf163

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Short description: Human gene


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


C6orf163 is a human protein encoded by the C6orf163 gene.

Gene

C6orf163 and nearby genes on chromosome 6.

C6orf163 is a 20.6 kb gene encoded on the plus strand of chromosome 6 (6q15). C6orf163 is predicted to be part of a readthrough locus with its neighboring genes on the plus strand, SMIM8 (small integral membrane protein 8, also known as C6orf162), LINC01590 (long intergenic non-coding RNA 1590), and CFAP206 (cilia and flagella associated protein 206).[1]

Transcript

C6orf163 has been observed to be near-ubiquitously expressed at low levels in RNA-seq datasets. It is expressed most highly in the testes.[1] There are 4 isoforms of C6orf163, the most common of which has 5 exons. The splice variants differ by truncation on the 5' end.[2] An additional unspliced mRNA variant has been identified, but it does not appear to code for a protein.[2]

Throughout early development, C6orf163 is expressed at moderate levels in many tissues. Its expression is highest at 10 weeks gestational time and decreases as development progresses.[3]

Protein

Predicted structure of human c6orf163 from Alphafold

The human C6orf163 protein is 329 amino acids long and has a molecular weight of 38 kDa.[4] Its predicted isoelectric point is 6.49.[5] According to the structural prediction from Alphafold,[6] it mainly consists of a long alpha helical region, which is a relatively rare structure in human proteins.[7] The long alpha helical structure is well conserved among orthologs.

C6orf163 contains a predicted leucine zipper motif from amino acids 247 to 269. This motif is typically involved in DNA binding, and is commonly found in transcription factors and other regulatory proteins. Leucine zippers form dimers to bind DNA, so the presence of this motif suggests that C6orf163 may exist as a dimer.

Alphafold structure predictions for selected orthologs show structural conservation. From left to right: Pseudonaja textilis (Eastern brown snake), Zalophus californianus (California sealion), and Egretta garzetta (Little egret).

C6orf163 has been experimentally found to undergo phosphorylation at 7 different residues and ubiquitination at 1 residue.[8][9] Additionally, it has been computationally predicted to undergo sumoylation,[10] lycine acetylation,[11] and mucin-type O-GlcNac glycosylation.[12]

C6orf163 has been found to interact with the protein DRC6[13] (Dynein regulatory complex subunit 6, also known as F-box and leucine rich repeat protein 13), which is a ubiquitin ligase that forms part of the SCF-type E3 ubiquitin ligase complex. DRC6 has been found to be involved in regulation of ciliary and flagellar motility.[14]

C6orf163 has a nuclear localization signal from amino acids 310 to 316. Antibody staining has shown C6orf163 to be localized to the nucleus and cytoplasm.[15][16]

Evolution

Conceptual translation of C6orf163 showing locations of notable motifs and conserved residues.

The C6orf163 protein is highly conserved among animals. Orthologs of C6orf163 have been identified in mammals, birds, reptiles, amphibians, fish, and some invertebrates including mollusks, echinoderms, and lancelets. The most distant c6orf163 ortholog identified is in the Japanese mud snail, Batillaria attramentaria. This ortholog has 23% sequence identity with the human protein.[17]

Homo sapiens C6orf163 has no known paralogs in humans.

Selected C6orf163 orthologs
Genus and species Common name Accession number Length (aa) Sequence identity (%) Date of divergence (MYA)
Homo sapiens human NP_001010868.2 328 100 0
Mus musculus mouse NP_001028427.1 328 74 87
Egretta garzetta little egret XP_009647262.2 330 47 319
Crocodylus porosus saltwater crocodile XP_019393256.1 350 43 319
Geotrypetes seraphini gaboon caecilian XP_033792248.1 313 33 353
Scyliorhinus canicula small-spotted catshark XP_038654713.1 330 27 464
Branchiostoma floridae Florida lancelet XP_035665671.1 297 29 556
Batillaria attramentaria Japanese mud snail KAG5690851.1 278 23 680

Clinical significance

A genome-wide association study analyzing genetic predictors of long-term treatment outcome for bipolar disorder showed that SNPs near C6orf163 were associated with the total number of manic and depressive episodes during follow up treatment and the number of depressive episodes during follow up, suggesting that C6orf163 may be involved in susceptibility to bipolar disorder.[18]

References

  1. ↑ 1.0 1.1 "C6orf163 chromosome 6 open reading frame 163 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/206412. 
  2. ↑ 2.0 2.1 "AceView: Gene:C6orf163, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView.". https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=C6orf163&submit=Go. 
  3. ↑ "Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development". Genome Biology 16 (1): 126. June 2015. doi:10.1186/s13059-015-0690-5. PMID 26076956. 
  4. ↑ "UniProt - Uncharacterized protein C6orf163". https://www.uniprot.org/uniprotkb/Q5TEZ5/entry. 
  5. ↑ "Expasy - Compute pI/Mw tool". https://web.expasy.org/compute_pi/. 
  6. ↑ "Highly accurate protein structure prediction with AlphaFold". Nature 596 (7873): 583–589. August 2021. doi:10.1038/s41586-021-03819-2. PMID 34265844. Bibcode: 2021Natur.596..583J. 
  7. ↑ "When a predicted coiled coil is really a single α-helix, in myosins and other proteins" (in en). Soft Matter 5 (13): 2493–2503. 2009-06-23. doi:10.1039/B822339D. ISSN 1744-6848. https://pubs.rsc.org/en/content/articlelanding/2009/sm/b822339d. 
  8. ↑ "C6orf163 (human)". https://www.phosphosite.org/proteinAction.action?id=1287831&showAllSites=true. 
  9. ↑ "Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels". Molecular & Cellular Proteomics 13 (7): 1690–1704. July 2014. doi:10.1074/mcp.M113.036392. PMID 24719451. 
  10. ↑ "GPS-SUMO: a tool for the prediction of sumoylation sites and SUMO-interaction motifs". Nucleic Acids Research 42 (Web Server issue): W325–W330. July 2014. doi:10.1093/nar/gku383. PMID 24880689. 
  11. ↑ "GPS-PAIL: prediction of lysine acetyltransferase-specific modification sites from protein sequences". Scientific Reports 6 (1): 39787. December 2016. doi:10.1038/srep39787. PMID 28004786. Bibcode: 2016NatSR...639787D. 
  12. ↑ "Precision mapping of the human O-GalNAc glycoproteome through SimpleCell technology". The EMBO Journal 32 (10): 1478–1488. May 2013. doi:10.1038/emboj.2013.79. PMID 23584533. 
  13. ↑ "FBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and cell migration". EMBO Reports 19 (3). March 2018. doi:10.15252/embr.201744799. PMID 29348145. 
  14. ↑ "UniProt - Q8NEE6 · DRC6_HUMAN". https://www.uniprot.org/uniprotkb/Q8NEE6/entry#function. 
  15. ↑ "C6orf163 Polyclonal Antibody (PA5-62706)". https://www.thermofisher.com/antibody/product/C6orf163-Antibody-Polyclonal/PA5-62706. 
  16. ↑ "Subcellular - C6orf163 - The Human Protein Atlas". https://www.proteinatlas.org/ENSG00000203872-C6orf163/subcellular. 
  17. ↑ "BLAST: Basic Local Alignment Search Tool". https://blast.ncbi.nlm.nih.gov/Blast.cgi. 
  18. ↑ "Genetics of long-term treatment outcome in bipolar disorder". Progress in Neuro-Psychopharmacology & Biological Psychiatry 65: 17–24. February 2016. doi:10.1016/j.pnpbp.2015.08.008. PMID 26297903. 



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