CFAP298

CFAP298
Identifiers
Aliases	CFAP298 , C21orf48, CILD26, FBB18, Kur, chromosome 21 open reading frame 59, C21orf59
External IDs	OMIM: 615494 MGI: 1915251 HomoloGene: 10941 GeneCards: CFAP298
Gene location (Mouse) Chr. Chromosome 16 (mouse) [1] Band 16|16 C3.3 Start 90,722,697 bp [1] End 90,732,002 bp [1]
RNA expression pattern Bgee Human Mouse (ortholog) n/a Top expressed in secondary oocyte seminiferous tubule spermatid spermatocyte olfactory epithelium yolk sac utricle superior frontal gyrus supraoptic nucleus stria vascularis BioGPS More reference expression data
Gene ontology Molecular function protein binding Cellular component cytosol cytoplasm nucleus cytoskeleton cilium cell projection Biological process cell projection morphogenesis regulation of cilium movement cilium assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 56683 68001 Ensembl ENSG00000159079 ENSMUSG00000022972 UniProt P57076 Q8BL95 RefSeq (mRNA) NM_017835 NM_021254 NM_026502 RefSeq (protein) NP_067077 NP_001337263 NP_001337264 NP_001337265 NP_001337266 NP_080778 Location (UCSC) n/a Chr 16: 90.72 – 90.73 Mb PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

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. ^{[4] [5] [6]} Male Alzheimer's patients have shown a decrease in expression of CFAP298 in their blood cells. ^{[7] [8]} The CFAP298 gene lies within the critical region of Down Syndrome. ^[9] There are no clear paralogs in humans, but the gene has homologues widely conserved among animals, fungi, and algae.

A phylogenetic tree showing the wide conservation c21orf59.

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. ^[10] 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. ^[11] 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. ^[12]

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. ^[13] Several post-translational modifications have been found by mass spectroscopy: five phosphorylation sites, one methylation site, one ubiquitination site, and one acetylation site. ^[13] 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, ^[14] 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. ^[15]

Localization

CFAP298 has been shown to localize to the cytosol and the nucleus, ^[16] but has been predicted, albeit with less strength, to localize to the cytoskeleton, peroxisome, and the mitochondria. ^[17]

Interactions

Through mass spectrometry, interactions with SUMO2, ^[18] a post-translational modification protein resembling ubiquitin, and Ubiquitin C ^[19] have been identified. Through two-hybrid experiments, an interaction with MAPK6, a protein kinase, has been found. ^[20]

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. ^[21] Zebrafish mutant in CFAP298 homologue have defects in ciliary motility. ^[21] 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. ^[22]

References

1. GRCm38: Ensembl release 89: ENSMUSG00000022972 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Bullinger L, Döhner K, Bair E, Fröhling S, Schlenk RF, Tibshirani R, et al. (April 2004). "Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia". The New England Journal of Medicine. 350 (16): 1605–16. doi: 10.1056/NEJMoa031046 . PMID   15084693. S2CID   13205096.
5. Greiner J, Schmitt M, Li L, Giannopoulos K, Bosch K, Schmitt A, et al. (December 2006). "Expression of tumor-associated antigens in acute myeloid leukemia: Implications for specific immunotherapeutic approaches". Blood. 108 (13): 4109–17. doi: 10.1182/blood-2006-01-023127 . PMID   16931630. S2CID   15937337.
6. Bullinger L, Ehrich M, Döhner K, Schlenk RF, Döhner H, Nelson MR, van den Boom D (January 2010). "Quantitative DNA methylation predicts survival in adult acute myeloid leukemia". Blood. 115 (3): 636–42. doi: 10.1182/blood-2009-03-211003 . PMID   19903898. S2CID   13349367.
7. Maes OC, Xu S, Yu B, Chertkow HM, Wang E, Schipper HM (December 2007). "Transcriptional profiling of Alzheimer blood mononuclear cells by microarray". Neurobiology of Aging. 28 (12): 1795–809. doi:10.1016/j.neurobiolaging.2006.08.004. PMID   16979800. S2CID   8185187.
8. Maes OC, Schipper HM, Chertkow HM, Wang E (June 2009). "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. doi: 10.1093/gerona/glp045 . PMID   19366883.
9. Moncaster JA, Pineda R, Moir RD, Lu S, Burton MA, Ghosh JG, et al. (May 2010). "Alzheimer's disease amyloid-beta links lens and brain pathology in Down syndrome". PLOS ONE. 5 (5): e10659. Bibcode:2010PLoSO...510659M. doi: 10.1371/journal.pone.0010659 . PMC   2873949 . PMID   20502642.
10. Ensembl http://ensembl.org
11. C21orf59 GDS596 GEOprofile
12. "Genomatix". Archived from the original on 2021-12-02. Retrieved 2012-04-20.
13. "Cilia- and flagella-associated protein 298". Phosphosite.
14. Conserved Domains
15. SDSC PELE
16. Hu YH, Warnatz HJ, Vanhecke D, Wagner F, Fiebitz A, Thamm S, et al. (June 2006). "Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins". BMC Genomics. 7: 155. doi:10.1186/1471-2164-7-155. PMC   1526728 . PMID   16780588.
17. "PsortII".
18. Golebiowski F, Matic I, Tatham MH, Cole C, Yin Y, Nakamura A, et al. (May 2009). "System-wide changes to SUMO modifications in response to heat shock". Science Signaling. 2 (72): ra24. doi:10.1126/scisignal.2000282. PMID   19471022. S2CID   33450256.
19. Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, et al. (October 2011). "Systematic and quantitative assessment of the ubiquitin-modified proteome". Molecular Cell. 44 (2): 325–40. doi:10.1016/j.molcel.2011.08.025. PMC   3200427 . PMID   21906983.
20. Vinayagam A, Stelzl U, Foulle R, Plassmann S, Zenkner M, Timm J, et al. (September 2011). "A directed protein interaction network for investigating intracellular signal transduction". Science Signaling. 4 (189): rs8. doi:10.1126/scisignal.2001699. PMID   21900206. S2CID   7418133.
21. Schottenfeld, Jodi (2008). The role of PKD2 and C21ORF59 in patterning the left-right axis of the zebrafish embryo (Thesis). OCLC   236339661. Gale   A195982386.
22. Jaffe KM, Grimes DT, Schottenfeld-Roames J, Werner ME, Ku TS, Kim SK, et al. (March 2016). "c21orf59/kurly Controls Both Cilia Motility and Polarization". Cell Reports. 14 (8): 1841–9. doi:10.1016/j.celrep.2016.01.069. PMC   4775428 . PMID   26904945.

External links

• Human CFAP298 genome location and CFAP298 gene details page in the UCSC Genome Browser .

Further reading

• Denoeud F, Kapranov P, Ucla C, Frankish A, Castelo R, Drenkow J, et al. (June 2007). "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. doi:10.1101/gr.5660607. PMC   1891335 . PMID   17567994.
• Hu YH, Warnatz HJ, Vanhecke D, Wagner F, Fiebitz A, Thamm S, et al. (June 2006). "Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins". BMC Genomics. 7: 155. doi:10.1186/1471-2164-7-155. PMC   1526728 . PMID   16780588.
• Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, et al. (January 2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells". Nature Biotechnology. 23 (1): 94–101. doi:10.1038/nbt1046. PMID   15592455. S2CID   7200157.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID   9373149.
• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID   8125298.