Alternative titles; symbols
HGNC Approved Gene Symbol: GRK3
Cytogenetic location: 22q12.1 Genomic coordinates (GRCh38): 22:25,564,675-25,729,294 (from NCBI)
In the rat and the mouse, Benovic et al. (1991) identified a second beta-adrenergic receptor kinase (see ADRBK1, or BARK1; 109635). They isolated the receptor by screening a bovine brain cDNA library with a catalytic domain fragment of the beta-adrenergic receptor kinase. The enzyme, which they termed Bark2, showed overall amino acid identity of 85% with Bark1, with the protein kinase catalytic domain having 95% identity. In the rat, Bark2 mRNA was localized predominantly in neuronal tissues, although low levels were also observed in various tissues.
By PCR using primers designed from the catalytic domain of bovine Bark1, followed by cDNA library screening, Parruti et al. (1993) cloned BARK2 from a pituitary cDNA library. The deduced 688-amino acid protein shares 84% amino acid identity with BARK1 and 95% identity with bovine Bark2. The highest conservation is within the first 47 amino acids and in the catalytic domain, while the most variability is in the C-terminal G protein beta/gamma subunit-binding domain. Northern blot analysis detected a major doublet of about 8 and 7 kb in monocytes, granulocytes, and a neuroblastoma cell line, but not in several other cell lines examined. The 8-kb transcript was dominant in the neuroblastoma cell line. Minor transcripts of about 3.5 and 2 kb were also detected in cells expressing the longer variants. Parruti et al. (1993) found moderate expression of BARK2 in lung, heart, and adipose tissue.
Parruti et al. (1993) expressed BARK2 and BARK1 in COS-7 cells and assayed the in vitro phosphorylation of bovine rod outer segments (ROS). BARK2 was about 40% as efficient as BARK1 in this assay, in agreement with results obtained in a comparison of bovine Bark1 and Bark2.
The gene encoding Bark2 mapped to mouse chromosome 5, whereas that encoding Bark1 was localized to mouse chromosome 19 (Benovic et al., 1991). Calabrese et al. (1994) demonstrated by fluorescence in situ hybridization that the human ADRBK2 gene is located on 22q11.
Saccone et al. (2007) conducted a genomewide linkage screen of a simple heavy smoking quantitative trait, the maximum number of cigarettes smoked in a 24-hour period, using 2 independent samples: 289 Australians and 155 Finnish nuclear multiplex families, all of which were of European ancestry and were targeted for DNA analysis through probands with a heavy smoking phenotype. Genetic linkage was detected on chromosome 22q12 (SQTL2; 611004), and Saccone et al. (2007) found that the linkage signal was driven mainly by the microsatellite marker D22S315 that had a single-point lod score of 5.41 in the combined sample. This marker is located within an intron of the ADRBK2 gene.
Benovic, J. L., Onorato, J. J., Arriza, J. L., Stone, W. C., Lohse, M., Jenkins, N. A., Gilbert, D. J., Copeland, N. G., Caron, M. G., Lefkowitz, R. J. Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2: a new member of the receptor kinase family. J. Biol. Chem. 266: 14939-14946, 1991. [PubMed: 1869533]
Calabrese, G., Sallese, M., Stornaiuolo, A., Stuppia, L., Palka, G., De Blasi, A. Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2) genes. Genomics 23: 286-288, 1994. [PubMed: 7695743] [Full Text: https://doi.org/10.1006/geno.1994.1497]
Parruti, G., Ambrosini, G., Sallese, M., De Blasi, A. Molecular cloning, functional expression and mRNA analysis of human beta-adrenergic receptor kinase 2. Biochem. Biophys. Res. Commun. 190: 475-481, 1993. [PubMed: 8427589] [Full Text: https://doi.org/10.1006/bbrc.1993.1072]
Saccone, S. F., Pergadia, M. L., Loukola, A., Broms, U., Montgomery, G. W., Wang, J. C., Agrawal, A., Dick, D. M., Heath, A. C., Todorov, A. A., Maunu, H., Heikkila, K., Morley, K. I., Rice, J. P., Todd, R. D., Kaprio, J., Peltonen, L., Martin, N. G., Goate, A. M., Madden, P. A. F. Genetic linkage to chromosome 22q12 for a heavy-smoking quantitative trait in two independent samples. Am. J. Hum. Genet. 80: 856-866, 2007. [PubMed: 17436240] [Full Text: https://doi.org/10.1086/513703]