Alternative titles; symbols
HGNC Approved Gene Symbol: ARF4
Cytogenetic location: 3p14.3 Genomic coordinates (GRCh38): 3:57,571,363-57,597,344 (from NCBI)
ARF4 is a small GTPase predicted to regulate endomembrane trafficking (Pearring et al., 2017).
Monaco et al. (1990) used degenerate PCR with genomic DNA to identify a member of the human ADP-ribosylation factor (ARF) gene family. The gene, designated ARF4, encodes a predicted 180-amino acid protein that is approximately 80% identical to the other human ARFs (see, for example, 103180) and 73% identical to yeast ARF. By DNA sequence analysis, the authors stated that ARF4 is the most divergent member of the human ARFs. A processed pseudogene that is 94% identical at the nucleotide level was also identified. Northern blot analysis detected a 1.8-kb mRNA in IMR-32 neuroblastoma cells.
Using immunofluorescence analysis, Pearring et al. (2017) detected Arf4 expression in all mouse retinal layers. Arf4 localized to the cis-medial Golgi in mouse embryonic fibroblasts (MEFs). Western blot analysis of MEFs detected Arf4 at an apparent molecular mass of 17 kD.
By fluorescence in situ hybridization, Vorobieva et al. (1995) mapped the ARF4 gene, which they called ARF2, to chromosome 3p21.2-p21.1.
Kim (1998) mapped the ARF4 gene to chromosome 3p14.1 by PCR analysis of somatic cell hybrid DNA and radiation hybrid analysis.
Pearring et al. (2017) reported that global knockout of Arf4 in mice was embryonic lethal, with mutant animals showing severe defects in ciliary assembly. However, Arf4 -/- embryonic node had normal-functioning cilia, and Arf4 -/- embryos exhibited normal left-right asymmetry and formed a D-looped heart. Visceral endoderm cells of Arf4 -/- embryos showed disrupted microvilli and lysosomes. The authors found that knockout of Arf4 at postnatal day-2 (P2) resulted in elevated mortality by P10. Survivors at P10 were smaller than littermates, and necropsy revealed reduced size of pancreas, yellowish feces in lower intestine, and abnormal microvilli in visceral endoderm. Fur on Arf4-knockout mice changed from black to gray at 6 to 7 weeks. Eye and kidney appeared normal in Arf4-knockout mice and in animals with specific eye- or kidney-targeted Arf4 deletion. In Arf4-knockout pancreas, alpha and beta cells looked normal, but acinar cells of the exocrine pancreas were variably affected, with loss of exocrine pancreas markers and degeneration, and accumulation of surrounding adipocytes with large intracellular lipid droplets.
Kim, H.-S. Human ADP-ribosylation factor 4 (ARF4) gene map position 3p14.1. Chromosome Res. 6: 663 only, 1998. [PubMed: 10099884] [Full Text: https://doi.org/10.1023/a:1009230216005]
Monaco, L., Murtagh, J. J., Newman, K. B., Tsai, S.-C., Moss, J., Vaughan, M. Selective amplification of an mRNA and related pseudogene for a human ADP-ribosylation factor, a guanine nucleotide-dependent protein activator of cholera toxin. Proc. Nat. Acad. Sci. 87: 2206-2210, 1990. [PubMed: 2107548] [Full Text: https://doi.org/10.1073/pnas.87.6.2206]
Pearring, J. N., San Agustin, J. T., Lobanova, E. S., Gabriel, C. J., Lieu, E. C., Monis, W. J., Stuck, M. W., Strittmatter, L., Jaber, S. M., Arshavsky, V. Y., Pazour, G. J. Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic kidney disease or retinal degeneration. PLoS Genet. 13: e1006740, 2017. Note: Electronic Article. [PubMed: 28410364] [Full Text: https://doi.org/10.1371/journal.pgen.1006740]
Vorobieva, N., Protopopov, A., Protopopova, M., Kashuba, V., Allikmets, R. L., Modi, W., Zabarovsky, E. R., Klein, G., Kisselev, L., Graphodatsky, A. Localization of human ARF2 and NCK genes and 13 other NotI-linking clones to chromosome 3 by fluorescence in situ hybridization. Cytogenet. Cell Genet. 68: 91-94, 1995. [PubMed: 7956370] [Full Text: https://doi.org/10.1159/000133898]