CFAP298

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.[3][4][5] Male Alzheimer's patients have shown a decrease in expression of CFAP298 in their blood cells.[6][7] The CFAP298 gene lies within the critical region of Down Syndrome.[8] 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.
CFAP298
Identifiers
AliasesCFAP298, C21orf48, CILD26, FBB18, Kur, chromosome 21 open reading frame 59, C21orf59
External IDsOMIM: 615494 MGI: 1915251 HomoloGene: 10941 GeneCards: CFAP298
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

56683

68001

Ensembl

ENSG00000159079

n/a

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/an/a
PubMed search[1][2]
Wikidata
View/Edit HumanView/Edit Mouse

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.[9] 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.[10] 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.[11]

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.[12] Several post-translational modifications have been found by mass spectroscopy: five phosphorylation sites, one methylation site, one ubiquitination site, and one acetylation site.[12] 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,[13] 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.[14]

Localization

CFAP298 has been shown to localize to the cytosol and the nucleus,[15] but has been predicted, albeit with less strength, to localize to the cytoskeleton, peroxisome, and the mitochondria.[16]

Interactions

Through mass spectrometry, interactions with SUMO2,[17] a post-translational modification protein resembling ubiquitin, and Ubiquitin C[18] have been identified. Through two-hybrid experiments, an interaction with MAPK6, a protein kinase, has been found.[19]

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.[20] Zebrafish mutant in CFAP298 homologue have defects in ciliary motility.[20] 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.[21]

References
  1. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  2. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. Bullinger L, Döhner K, Bair E, Fröhling S, Schlenk RF, Tibshirani R, Döhner H, Pollack JR (April 2004). "Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia". N. Engl. J. Med. 350 (16): 1605–16. doi:10.1056/NEJMoa031046. PMID 15084693. S2CID 13205096.
  4. Greiner J, Schmitt M, Li L, Giannopoulos K, Bosch K, Schmitt A, Dohner K, Schlenk RF, Pollack JR, Dohner H, Bullinger L (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.
  5. 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.
  6. Maes OC, Xu S, Yu B, Chertkow HM, Wang E, Schipper HM (December 2007). "Transcriptional profiling of Alzheimer blood mononuclear cells by microarray". Neurobiol. Aging. 28 (12): 1795–809. doi:10.1016/j.neurobiolaging.2006.08.004. PMID 16979800. S2CID 8185187.
  7. Maes OC, Schipper HM, Chertkow HM, Wang E (June 2009). "Methodology for discovery of Alzheimer's disease blood-based biomarkers". J. Gerontol. A Biol. Sci. Med. Sci. 64 (6): 636–45. doi:10.1093/gerona/glp045. PMID 19366883.
  8. 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 (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.
  9. Ensembl http://ensembl.org
  10. C21orf59 GDS596 GEOprofile
  11. Genomatix http://www.genomatix.de
  12. Phosphosite
  13. Conserved Domains
  14. SDSC PELE
  15. Hu YH, Warnatz HJ, Vanhecke D, Wagner F, Fiebitz A, Thamm S, Kahlem P, Lehrach H, Yaspo ML, Janitz M (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.
  16. PsortII http://www.psort.org/
  17. Golebiowski, F.; Matic, I.; Tatham, M. H.; Cole, C.; Yin, Y.; Nakamura, A.; Cox, J.; Barton, G. J.; Mann, M.; Hay, R. T. (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.
  18. Kim, W.; Bennett, E. J.; Huttlin, E. L.; Guo, A.; Li, J.; Possemato, A.; Sowa, M. E.; Rad, R.; Rush, J.; Comb, M. J.; Harper, J. W.; Gygi, S. P. (2011). "Systematic and Quantitative Assessment of the Ubiquitin-Modified Proteome". Molecular Cell. 44 (2): 325–340. doi:10.1016/j.molcel.2011.08.025. PMC 3200427. PMID 21906983.
  19. Vinayagam, A.; Stelzl, U.; Foulle, R.; Plassmann, S.; Zenkner, M.; Timm, J.; Assmus, H. E.; Andrade-Navarro, M. A.; Wanker, E. E. (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.
  20. Schottenfeld, J. 2008. The role of PKD2 and C21ORF59 in patterning the left-right axis of the zebrafish embryo. (Doctoral dissertation). Retrieved from ProQuest Dissertations and Theses. (Accession Order No. AAT 3308052.)
  21. http://www.cell.com/cell-reports/pdf/S2211-1247(16)30062-6.pdf

Further reading
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