CFAP298 explained

Cilia- and flagella-associated protein 298 is a protein encoded by CFAP298 gene. It is of interest in part for its association with various diseases. It has been found in high levels in the bone marrow of patients with a negative prognosis of acute myeloid leukemia and an abnormal karyotype.^{[1] [2] [3]} Male Alzheimer's patients have shown a decrease in expression of CFAP298 in their blood cells.^{[4] [5]} The CFAP298 gene lies within the critical region of Down Syndrome.^[6] There are no clear paralogs in humans, but the gene has homologues widely conserved among animals, fungi, and algae.

Gene

CFAP298 is a gene found on the 21st chromosome at 21q22.1. A total of thirteen splice variants have been found, but only eleven protein coding ones.^[7] The most common form of CFAP298 mRNA has 1427 base pairs broken into seven exons. Its closest neighbors on the chromosome are TCP10L, EVA1C, LOC100506185, OR7E23P, and SYNJ1.

Gene Expression

The CFAP298 primary sequence is found in high quantity in most tissues. Some tissues with notable less expression are the ganglions, the heart, and the liver.^[8] It is suspected CFAP298 is found in the brain early in development due to the two achaete-scute complex homologue transcription factor binding sites found in the promoter.^[9]

Protein

The CFAP298 primary sequence consists of 290 amino acids with mass 33.093 kDa. The isoelectric point is 7.283, but is reduced to 5.86 if fully phosphorylated.^[10] Several post-translational modifications have been found by mass spectroscopy: five phosphorylation sites, one methylation site, one ubiquitination site, and one acetylation site. Most of these modifications happen in the latter half of the protein.

Structure

The majority of the protein consists of the domain DUF2870. This domain is primarily found in homologues of CFAP298, but also in other uncharacterized proteins,^[11] and it contains the majority of the sites that are modified after translation. The protein is predicted to consist mostly of alpha helices and lack beta strands.^[12]

Localization

CFAP298 has been shown to localize to the cytosol and the nucleus,^[13] but has been predicted, albeit with less strength, to localize to the cytoskeleton, peroxisome, and the mitochondria.^[14]

Interactions

Through mass spectrometry, interactions with SUMO2,^[15] a post-translational modification protein resembling ubiquitin, and Ubiquitin C^[16] have been identified. Through two-hybrid experiments, an interaction with MAPK6, a protein kinase, has been found.^[17]

Recent Studies

A study in zebrafish has shown CFAP298 is found in high concentrations in the Kupffer vesicles, and is intracellularly localized to the basal body of the cilia.^[18] Zebrafish mutant in CFAP298 homologue have defects in ciliary motility.^[18] Additionally, motile cilia in zebrafish and xenopus CFAP298 mutants are immotile and mispolarized, suggesting CFAP298 plays roles in planar cell polarity as well as ciliary motility.^[19]

Further reading

• Denoeud F, Kapranov P, Ucla C, Frankish A, Castelo R, Drenkow J, Lagarde J, Alioto T, Manzano C, Chrast J, Dike S, Wyss C, Henrichsen CN, Holroyd N, Dickson MC, Taylor R, Hance Z, Foissac S, Myers RM, Rogers J, Hubbard T, Harrow J, Guigó R, Gingeras TR, Antonarakis SE, Reymond A . 6 . Prominent use of distal 5' transcription start sites and discovery of a large number of additional exons in ENCODE regions . Genome Research . 17 . 6 . 746–59 . June 2007 . 17567994 . 1891335 . 10.1101/gr.5660607 .
• Hu YH, Warnatz HJ, Vanhecke D, Wagner F, Fiebitz A, Thamm S, Kahlem P, Lehrach H, Yaspo ML, Janitz M . 6 . Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins . BMC Genomics . 7 . 155 . June 2006 . 16780588 . 1526728 . 10.1186/1471-2164-7-155 . free .
• Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ . 6 . Immunoaffinity profiling of tyrosine phosphorylation in cancer cells . Nature Biotechnology . 23 . 1 . 94–101 . January 2005 . 15592455 . 10.1038/nbt1046 . 7200157 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .

Notes and References

1. Bullinger L, Döhner K, Bair E, Fröhling S, Schlenk RF, Tibshirani R, Döhner H, Pollack JR . 6 . Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia . The New England Journal of Medicine . 350 . 16 . 1605–16 . April 2004 . 15084693 . 10.1056/NEJMoa031046 . 13205096 . free .
2. Greiner J, Schmitt M, Li L, Giannopoulos K, Bosch K, Schmitt A, Dohner K, Schlenk RF, Pollack JR, Dohner H, Bullinger L . 6 . Expression of tumor-associated antigens in acute myeloid leukemia: Implications for specific immunotherapeutic approaches . Blood . 108 . 13 . 4109–17 . December 2006 . 16931630 . 10.1182/blood-2006-01-023127 . 15937337 . free .
3. Bullinger L, Ehrich M, Döhner K, Schlenk RF, Döhner H, Nelson MR, van den Boom D . Quantitative DNA methylation predicts survival in adult acute myeloid leukemia . Blood . 115 . 3 . 636–42 . January 2010 . 19903898 . 10.1182/blood-2009-03-211003 . 13349367 . free .
4. Maes OC, Xu S, Yu B, Chertkow HM, Wang E, Schipper HM . Transcriptional profiling of Alzheimer blood mononuclear cells by microarray . Neurobiology of Aging . 28 . 12 . 1795–809 . December 2007 . 16979800 . 10.1016/j.neurobiolaging.2006.08.004 . 8185187 .
5. Maes OC, Schipper HM, Chertkow HM, Wang E . Methodology for discovery of Alzheimer's disease blood-based biomarkers . The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences . 64 . 6 . 636–45 . June 2009 . 19366883 . 10.1093/gerona/glp045 .
6. Moncaster JA, Pineda R, Moir RD, Lu S, Burton MA, Ghosh JG, Ericsson M, Soscia SJ, Mocofanescu A, Folkerth RD, Robb RM, Kuszak JR, Clark JI, Tanzi RE, Hunter DG, Goldstein LE . 6 . Alzheimer's disease amyloid-beta links lens and brain pathology in Down syndrome . PLOS ONE . 5 . 5 . e10659 . May 2010 . 20502642 . 2873949 . 10.1371/journal.pone.0010659 . free . 2010PLoSO...510659M .
7. Ensembl http://ensembl.org
8. C21orf59 GDS596 GEOprofile
9. Web site: Genomatix . 2012-04-20 . 2021-12-02 . https://web.archive.org/web/20211202010908/https://www.genomatix.de/ . dead .
10. Web site: Cilia- and flagella-associated protein 298 . Phosphosite .
11. https://www.ncbi.nlm.nih.gov/cdd Conserved Domains
12. SDSC PELE
13. Hu YH, Warnatz HJ, Vanhecke D, Wagner F, Fiebitz A, Thamm S, Kahlem P, Lehrach H, Yaspo ML, Janitz M . 6 . Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins . BMC Genomics . 7 . 155 . June 2006 . 16780588 . 1526728 . 10.1186/1471-2164-7-155 . free .
14. Web site: PsortII .
15. Golebiowski F, Matic I, Tatham MH, Cole C, Yin Y, Nakamura A, Cox J, Barton GJ, Mann M, Hay RT . 6 . System-wide changes to SUMO modifications in response to heat shock . Science Signaling . 2 . 72 . ra24 . May 2009 . 19471022 . 10.1126/scisignal.2000282 . 33450256 .
16. Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP . 6 . Systematic and quantitative assessment of the ubiquitin-modified proteome . Molecular Cell . 44 . 2 . 325–40 . October 2011 . 21906983 . 3200427 . 10.1016/j.molcel.2011.08.025 .
17. Vinayagam A, Stelzl U, Foulle R, Plassmann S, Zenkner M, Timm J, Assmus HE, Andrade-Navarro MA, Wanker EE . 6 . A directed protein interaction network for investigating intracellular signal transduction . Science Signaling . 4 . 189 . rs8 . September 2011 . 21900206 . 10.1126/scisignal.2001699 . 7418133 .
18. Schottenfeld . Jodi . The role of PKD2 and C21ORF59 in patterning the left-right axis of the zebrafish embryo . 2008 . . 236339661 .
19. Jaffe KM, Grimes DT, Schottenfeld-Roames J, Werner ME, Ku TS, Kim SK, Pelliccia JL, Morante NF, Mitchell BJ, Burdine RD . 6 . c21orf59/kurly Controls Both Cilia Motility and Polarization . Cell Reports . 14 . 8 . 1841–9 . March 2016 . 26904945 . 4775428 . 10.1016/j.celrep.2016.01.069 .