Alternative titles; symbols
HGNC Approved Gene Symbol: SHROOM2
Cytogenetic location: Xp22.2 Genomic coordinates (GRCh38): X:9,786,429-9,949,443 (from NCBI)
SHROOM2 is involved in regulating the cytoskeletal organization and architecture of endothelial cells (Dietz et al., 2006).
APXL (SHROOM2) is a human homolog of the Xenopus laevis APX gene which is implicated in amiloride-sensitive sodium channel activity (Schiaffino et al., 1995). The full-length mRNA is approximately 7.5 kb, and Schiaffino et al. (1995) isolated several clones from a retinal cDNA library that corresponded to this mRNA. The authors found that, along with retina, the gene is expressed in melanoma cells, brain, placenta, lung, kidney, and pancreas. The deduced protein is 1,616 amino acids long. APXL was deleted in 2 patients with contiguous gene syndromes including ocular albinism type I (OA1; 300500) and in 1 patient with isolated OA1.
Dietz et al. (2006) cloned mouse Apxl (Shroom2) from a brain cDNA library and found that it encodes a deduced 1,480-amino acid protein containing a PDZ domain in the N terminus, an Apx/Shrm domain-1 (ASD1) motif in the center, and an ASD2 motif in the C terminus. Immunolocalization experiments on E10.5 mouse embryos showed predominant expression of Shroom2 in cells that exhibit polarized growth, including vascular endothelial cells and epithelial cells.
Dietz et al. (2006) showed by cosedimentation experiments that whereas both Shroom3 (604570) and Shroom2 bind F-actin through the ASD1 motif, Shroom2 binds cortical actin and Shroom3 binds stress fibers. In polarized MDCK cells, optimal localization of Shroom3 to the tight junction required both the PDZ domain and the ASD1 motif. Dietz et al. (2006) found that wildtype Shroom2 and Shroom4 (300579) are unable to induce apical constriction, but have the innate capacity to do so, as targeting their ASD2 motifs to the apical junctional complex resulted in constriction. Shroom2 colocalizes with nonmuscle myosin II (see 160775). The myosin II inhibitor blebbistatin reversed apical constriction induced by Shroom family members, suggesting that these proteins work through myosin II to regulate cell morphology.
Schiaffino et al. (1995) determined that the human APXL gene contains 10 exons and spans approximately 160 kb of Xp22.3 in the ocular albinism type 1 critical region.
Comparative mapping of the X chromosome in eutherian mammals has revealed distinct regions of conservation as well as evolutionary rearrangements between human and mouse. Dinulos et al. (1996) mapped the murine homologs of OA1 and APXL. They found that the 2 genes map to bands F2-F3 in both M. spretus and the laboratory strains C57BL/6J, defining a new rearrangement between human and mouse X chromosomes.
Dietz, M. L., Bernaciak, T. M., Vendetti, F., Kielec, J. M., Hildebrand, J. D. Differential actin-dependent localization modulates the evolutionarily conserved activity of Shroom family proteins. J. Biol. Chem. 281: 20542-20554, 2006. [PubMed: 16684770] [Full Text: https://doi.org/10.1074/jbc.M512463200]
Dinulos, M. B., Bassi, M. T., Rugarli, E. I., Chapman, V., Ballabio, A., Disteche, C. M. A new region of conservation is defined between human and mouse X chromosomes. Genomics 35: 244-247, 1996. [PubMed: 8661129] [Full Text: https://doi.org/10.1006/geno.1996.0347]
Schiaffino, M. V., Bassi, M. T., Rugarli, E. I., Renieri, A., Galli, L., Ballabio, A. Cloning of a human homologue of the Xenopus laevis APX gene from the ocular albinism type 1 critical region. Hum. Molec. Genet. 4: 373-382, 1995. [PubMed: 7795590] [Full Text: https://doi.org/10.1093/hmg/4.3.373]