Alternative titles; symbols
HGNC Approved Gene Symbol: GAS2L1
Cytogenetic location: 22q12.2 Genomic coordinates (GRCh38): 22:29,306,650-29,312,787 (from NCBI)
Zucman-Rossi et al. (1996) sequenced 40 kb of DNA on a chromosome 22 cosmid and identified 2 new genes, GAS2L1, which they called GAR22, and RRP22 (602220). Northern blot analysis revealed a 2.5-kb mRNA expressed at low levels in all tissues tested. The authors identified 2 alternatively spliced mRNA species from fetal brain. The deduced amino acid sequence of GAR22 is 41% identical to mouse Gas2 (602835), an actin-associated protein expressed at high levels in growth-arrested cells.
Goriounov et al. (2003) cloned alternatively spliced GAR22-alpha and -beta isoforms. The alpha isoform contains 337 amino acids and has a calculated molecular mass of 36.3 kD. The beta isoform contains 681 amino acids with a calculated molecular mass of 72.6 kD. The isoforms share the first 337 amino acids, which contain a calponin homology (CH) family actin-binding domain, followed by a GAS2-related (GAR) family microtubule-binding domain. GAR22-beta shares 56% amino acid similarity with GAR17-beta (GAS2L2; 611398) over the first 337 amino acids, with 62% identity over the CH domains and 75% identity over the GAR domains. The GAR22-alpha and beta isoforms share 89% and 87% identity to mouse Gar22-alpha and beta isoforms, respectively. Northern blot analysis of human tissues detected 2.6-kb GAR22-beta and 3.1-kb GAR22-alpha transcripts in all tissues tested with highest expression in brain, kidney, heart, and liver. Goriounov et al. (2003) stated that expression of the GAR22-beta transcript was much more abundant than that of GAR22-alpha. Western blot analysis detected mouse Gar22-beta protein in testis and brain, but mouse Gar22-alpha protein was not detected in mouse tissues. Immunostaining of mouse testicular tissues localized mouse Gar22-beta to the cytoplasm of germ cells and to the head of spermatozoa. Immunofluorescence studies of GAR22 isoforms and mutant constructs localized the alpha isoform to actin filaments in NIH3T3 cells. The GAR22 CH domain localized to actin filaments, and GAR domain colocalized with microtubules in COS-7 cells. The GAR22-beta C-terminal CT22 region also colocalized with microtubules.
Using in vitro binding assays, Goriounov et al. (2003) showed that the GAR22-alpha isoform bound preassembled microfilaments but did not bind microtubules, while the GAR22-beta isoform bound both microfilaments and microtubules, confirming that the GAR22 CH domain binds actin and that the GAR and CT22 domains bind microtubules. They showed that the CT22 domain protected microtubules from nocodazole-induced depolymerization. Using actively proliferating or arrested cell lines, they demonstrated that the GAR22-beta protein was induced by growth arrest and that it is likely to be phosphorylated. GAR22-alpha protein was not detected. Immunofluorescence and colocalization experiments in COS-7 cells, demonstrated that both GAR22-beta and GAR17-beta may crosslink microfilaments and microtubules.
Zucman-Rossi et al. (1996) determined that the GAS2L1 gene contains 5 exons. Goriounov et al. (2003) stated that the GAR22 gene undergoes alternative splicing of exon 5B.
Zucman-Rossi et al. (1996) mapped GAS2L1 and RRP22 (602220) between the EWS (133450) and BAM22 (600157) loci at chromosome 22q12.
Goriounov, D., Leung, C. L., Liem, R. K. H. Protein products of human Gas2-related genes on chromosomes 17 and 22 (hGAR17 and hGAR22) associate with both microfilaments and microtubules. J. Cell Sci. 116: 1045-1058, 2003. [PubMed: 12584248] [Full Text: https://doi.org/10.1242/jcs.00272]
Zucman-Rossi, J., Legoix, P., Thomas, G. Identification of new members of the Gas2 and Ras families in the 22q12 chromosome region. Genomics 38: 247-254, 1996. [PubMed: 8975699] [Full Text: https://doi.org/10.1006/geno.1996.0625]