C6orf163 Explained

C6orf163 is a human protein encoded by the C6orf163 gene.

Gene

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).

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.

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

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.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

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.

Genus and species
Common nameAccession numberLength (aa)Sequence identity (%)Date of divergence (MYA)
Homo sapienshumanNP_001010868.23281000
Mus musculusmouseNP_001028427.13287487
Egretta garzettalittle egretXP_009647262.233047319
Crocodylus porosussaltwater crocodileXP_019393256.135043319
Geotrypetes seraphinigaboon caecilianXP_033792248.131333353
Scyliorhinus caniculasmall-spotted catsharkXP_038654713.133027464
Branchiostoma floridaeFlorida lanceletXP_035665671.129729556
Batillaria attramentariaJapanese mud snailKAG5690851.127823680

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]

Notes and References

  1. Web site: C6orf163 chromosome 6 open reading frame 163 [Homo sapiens (human)] - Gene - NCBI ]. 2022-12-15 . www.ncbi.nlm.nih.gov.
  2. Web site: AceView: Gene:C6orf163, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView. . 2022-10-19 . www.ncbi.nlm.nih.gov.
  3. Szabo L, Morey R, Palpant NJ, Wang PL, Afari N, Jiang C, Parast MM, Murry CE, Laurent LC, Salzman J . 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 . 26076956 . 4506483 . 10.1186/s13059-015-0690-5 . free .
  4. Web site: UniProt - Uncharacterized protein C6orf163 . 2022-12-15 . www.uniprot.org.
  5. Web site: Expasy - Compute pI/Mw tool . 2022-12-15 . web.expasy.org.
  6. Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, Tunyasuvunakool K, Bates R, Žídek A, Potapenko A, Bridgland A, Meyer C, Kohl SA, Ballard AJ, Cowie A, Romera-Paredes B, Nikolov S, Jain R, Adler J, Back T, Petersen S, Reiman D, Clancy E, Zielinski M, Steinegger M, Pacholska M, Berghammer T, Bodenstein S, Silver D, Vinyals O, Senior AW, Kavukcuoglu K, Kohli P, Hassabis D . Highly accurate protein structure prediction with AlphaFold . Nature . 596 . 7873 . 583–589 . August 2021 . 34265844 . 8371605 . 10.1038/s41586-021-03819-2 . 235959867 . 2021Natur.596..583J .
  7. Peckham M, Knight PJ . 2009-06-23 . When a predicted coiled coil is really a single α-helix, in myosins and other proteins . Soft Matter . en . 5 . 13 . 2493–2503 . 10.1039/B822339D . 1744-6848. subscription .
  8. Web site: C6orf163 (human) . 2022-12-07 . www.phosphosite.org.
  9. Mertins P, Yang F, Liu T, Mani DR, Petyuk VA, Gillette MA, Clauser KR, Qiao JW, Gritsenko MA, Moore RJ, Levine DA, Townsend R, Erdmann-Gilmore P, Snider JE, Davies SR, Ruggles KV, Fenyo D, Kitchens RT, Li S, Olvera N, Dao F, Rodriguez H, Chan DW, Liebler D, White F, Rodland KD, Mills GB, Smith RD, Paulovich AG, Ellis M, Carr SA . 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 . 24719451 . 4083109 . 10.1074/mcp.M113.036392 . free .
  10. Zhao Q, Xie Y, Zheng Y, Jiang S, Liu W, Mu W, Liu Z, Zhao Y, Xue Y, Ren J . 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 . 24880689 . 4086084 . 10.1093/nar/gku383 .
  11. Deng W, Wang C, Zhang Y, Xu Y, Zhang S, Liu Z, Xue Y . GPS-PAIL: prediction of lysine acetyltransferase-specific modification sites from protein sequences . Scientific Reports . 6 . 1 . 39787 . December 2016 . 28004786 . 5177928 . 10.1038/srep39787 . 2016NatSR...639787D .
  12. Steentoft C, Vakhrushev SY, Joshi HJ, Kong Y, Vester-Christensen MB, Schjoldager KT, Lavrsen K, Dabelsteen S, Pedersen NB, Marcos-Silva L, Gupta R, Bennett EP, Mandel U, Brunak S, Wandall HH, Levery SB, Clausen H . Precision mapping of the human O-GalNAc glycoproteome through SimpleCell technology . The EMBO Journal . 32 . 10 . 1478–1488 . May 2013 . 23584533 . 3655468 . 10.1038/emboj.2013.79 .
  13. Fung E, Richter C, Yang HB, Schäffer I, Fischer R, Kessler BM, Bassermann F, D'Angiolella V . FBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and cell migration . EMBO Reports . 19 . 3 . March 2018 . 29348145 . 5836097 . 10.15252/embr.201744799 .
  14. Web site: UniProt - Q8NEE6 · DRC6_HUMAN . 2022-12-07 . www.uniprot.org.
  15. Web site: C6orf163 Polyclonal Antibody (PA5-62706) . 2022-12-07 . www.thermofisher.com.
  16. Web site: Subcellular - C6orf163 - The Human Protein Atlas . 2022-12-07 . www.proteinatlas.org.
  17. Web site: BLAST: Basic Local Alignment Search Tool . 2022-12-15 . blast.ncbi.nlm.nih.gov.
  18. Fabbri C, Serretti A . Genetics of long-term treatment outcome in bipolar disorder . Progress in Neuro-Psychopharmacology & Biological Psychiatry . 65 . 17–24 . February 2016 . 26297903 . 10.1016/j.pnpbp.2015.08.008 . 41881629 .

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