Alternative titles; symbols
HGNC Approved Gene Symbol: REM1
Cytogenetic location: 20q11.21 Genomic coordinates (GRCh38) : 20:31,475,288-31,484,895 (from NCBI)
The RGK family of RAS-like GTP-binding proteins, including REM1, RAD (179503), and GEM (600164), share unique structural and biochemical properties (Pan et al., 2000).
Using database analysis with the conserved C-terminal RGK family motif, followed by screening a human lymph node phage library, Pan et al. (2000) cloned REM1, which they called GES. The deduced 298-amino acid protein has a predicted molecular mass of 32.9 kD. REM1 contains 4 GTP-binding domains unique to its family, extended N- and C-terminal domains beyond the RAS-related domain, a putative calmodulin-binding domain, and a conserved C-terminal motif. REM1 shares 43.8%, 44.1%, and 87.9% similarity to RAD, GEM and murine Rem1, respectively. Northern blot analysis detected highest expression in uterus and heart, with lower expression in skeletal muscle, pancreas, spleen, thymus, prostate, testis, small intestine, colon and lymph node. In situ hybridization analysis revealed high expression in endothelial linings of heart and uterus, and in secretory tissues including islets of Langerhans, breast lobule/duct epithelium, uterine endometrial gland epithelium, colon mucosa, and acinar cells of pancreas and prostate.
Using in vitro assays, Pan et al. (2000) reported that recombinant REM1 bound GTP and GDP, exhibited low intrinsic GTPase activity, and interacted with calmodulin in a Ca(2+)-dependent manner. By immunofluorescence microscopy, they showed that overexpression of REM1 in several primary human endothelial cell lines resulted in development of cytoplasmic processes and an elongated or dendritic-like morphology. Transfection of murine Rem1 into human endothelial cells promoted similar morphologic changes. REM1-transfected endothelial cells also showed reorganization of the actin cytoskeleton and reduction in focal adhesion size. Conversely, transfection of a dominant-negative REM1 mutant into endothelial cells completely blocked matrigel-induced endothelial cell sprouting.
Liu et al. (2020) identified the mechanism by which beta-adrenergic agonists stimulate voltage-gated calcium channels. Liu et al. (2020) expressed alpha-1C or beta-2B subunits conjugated to ascorbate peroxidase in mouse hearts, and used multiplexed quantitative proteomics to track hundreds of proteins in the proximity of CaV1.2 (CACNA1C; 114205). They observed that the calcium-channel inhibitor Rad (179503) is enriched in the CaV1.2 microenvironment but is depleted during beta-adrenergic stimulation. Phosphorylation by protein kinase A (see 176911) of specific serine residues on Rad decreases its affinity for beta subunits and relieves constitutive inhibition of CaV1.2, observed as an increase in channel open probability. Expression of Rad or its homolog Rem in HEK293T cells also imparted stimulation of CaV1.3 (CACNA1D; 114206) and CaV2.2 (CACNA1B; 601012) by protein kinase A, revealing an evolutionarily conserved mechanism that confers adrenergic modulation upon voltage-gated calcium channels.
Stumpf (2020) mapped the REM1 gene to chromosome 20q11.21 based on an alignment of the REM1 sequence (GenBank BC039813) with the genomic sequence (GRCh38).
Liu, G., Papa, A., Katchman, A. N., Zakharov, S. I., Roybal, D., Hennessey, J. A., Kushner, J., Yang, L., Chen, B.-X., Kushnir, A., Dangas, K., Gygi, S. P., Pitt, G. S., Colecraft, H. M., Ben-Johny, M., Kalocsay, M., Marx, S. O. Mechanism of adrenergic Ca(V)1.2 stimulation revealed by proximity proteomics. Nature 577: 695-700, 2020. [PubMed: 31969708] [Full Text: https://doi.org/10.1038/s41586-020-1947-z]
Pan, J. Y., Fieles, W. E., White, A. M., Egerton, M. M., Silberstein, D. S. Ges, a human GTPase of the Rad/Gem/Kir family, promotes endothelial cell sprouting and cytoskeleton reorganization. J. Cell Biol. 149: 1107-1115, 2000. Note: Erratum: J. Cell Biol. 150: following 401, 2000. [PubMed: 10831614] [Full Text: https://doi.org/10.1083/jcb.149.5.1107]
Stumpf, A. M. Personal Communication. Baltimore, Md. 06/22/2020.