Alternative titles; symbols
HGNC Approved Gene Symbol: AK4
Cytogenetic location: 1p31.3 Genomic coordinates (GRCh38): 1:65,147,552-65,232,145 (from NCBI)
Adenylate kinases (AKs), such as AK3L1, are a family of structurally and functionally related enzymes that catalyze a similar reaction, MgNTP + AMP = MgNDP + ADP (N = A or G). AKs are important for maintenance of homeostasis of the adenine and guanine nucleotide pools (Xu et al., 1992).
Xu et al. (1992) cloned AK3L1, which they called AK3, from a human frontal cortex cDNA library. The deduced 223-amino acid protein shares 58% amino acid identity with bovine Ak3 (609290). Both proteins have an N terminus capable of forming an amphipathic alpha helix necessary for translocation into mitochondria.
Yoneda et al. (1998) cloned mouse and rat Ak4 cDNAs. They determined that human AK3L1 shares higher amino acid identity with mouse and rat Ak4 (90.1% and 89.2%, respectively) than it does with the rodent Ak3 proteins. Therefore, they suggested that the human gene be referred to as AK4. By in situ hybridization, Yoneda et al. (1998) examined expression of rat Ak4 during embryonic development and in adult animals. No expression was detected in day-9 embryos, but by day 11, Ak4 was detected in liver, brain, and nasal epithelium. Expression was maintained in liver through to adulthood, but brain Ak4 expression was dynamic, with expression gradually confined to the CA3 subfield of the hippocampus later in development. In adult rats, Ak4 expression predominated in hippocampus, cerebellum, and liver.
Noma et al. (2001) cloned cDNAs for the human adenylate kinases AK3 (609290) and AK4. Northern blot analysis detected several AK4 transcripts, the longest of which was 8.0 kb. Expression was highest in kidney and heart, moderate in liver, weak in brain, and barely detectable in placenta and lung. Western blot analysis of human and mouse tissues showed a similar expression pattern; the apparent molecular mass was 29 kD. Subcellular fractionation of mouse liver and kidney detected Ak4 in the mitochondrial fraction.
Noma et al. (1999) determined that the 5-prime flanking region of the AK3L1 gene contains a TATA-less promoter and a high GC content. It also contains binding sites for AP2 (see 107580), Sp1 (189906), and GCF (189901).
Hartz (2005) mapped the AK3L1 gene to chromosome 1p31.3 based on an alignment of the AK3L1 sequence (GenBank X60673) with the genomic sequence.
AK3L1 Pseudogene
In the course of their efforts to identify the gene causing neurofibromatosis (NF1; 162200), Viskochil et al. (1990) found a gene first designated HB15, which Xu et al. (1992) subsequently concluded is probably a processed pseudogene of AK3L1. It is intronless and contains a polyadenylate tract, but retains coding potential because the open reading frame was not impaired by any observed base substitutions. This presumed processed pseudogene of AK3L1 is located within an intron of the NF1 gene (613113) on chromosome 17.
Hartz, P. A. Personal Communication. Baltimore, Md. 3/28/2005.
Noma, T., Adachi, N., Nakazawa, A. Cloning and functional characterization of the promoter region of the gene encoding human adenylate kinase isozyme 3. Biochem. Biophys. Res. Commun. 264: 990-997, 1999. [PubMed: 10544043] [Full Text: https://doi.org/10.1006/bbrc.1999.1616]
Noma, T., Fujisawa, K., Yamashiro, Y., Shinohara, M., Nakazawa, A., Gondo, T., Ishihara, T., Yoshinobu, K. Structure and expression of human mitochondrial adenylate kinase targeted to the mitochondrial matrix. Biochem. J. 358: 225-232, 2001. [PubMed: 11485571] [Full Text: https://doi.org/10.1042/0264-6021:3580225]
Viskochil, D., Buchberg, A. M., Xu, G., Cawthon, R. M., Stevens, J., Wolff, R. K., Culver, M., Carey, J. C., Copeland, N. G., Jenkins, N. A., White, R., O'Connell, P. Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell 62: 187-192, 1990. [PubMed: 1694727] [Full Text: https://doi.org/10.1016/0092-8674(90)90252-a]
Xu, G., O'Connell, P., Stevens, J., White, R. Characterization of human adenylate kinase 3 (AK3) cDNA and mapping of the AK3 pseudogene to an intron of the NF1 gene. Genomics 13: 537-542, 1992. [PubMed: 1639383] [Full Text: https://doi.org/10.1016/0888-7543(92)90122-9]
Yoneda, T., Sato, M., Maeda, M., Takagi, H. Identification of a novel adenylate kinase system in the brain: cloning of the fourth adenylate kinase. Molec. Brain Res. 62: 187-195, 1998. [PubMed: 9813319] [Full Text: https://doi.org/10.1016/s0169-328x(98)00249-6]