Alternative titles; symbols
HGNC Approved Gene Symbol: ARHGDIB
Cytogenetic location: 12p12.3 Genomic coordinates (GRCh38): 12:14,942,015-14,961,601 (from NCBI)
Members of the Rho (or ARH) protein family (see 165390) and other Ras-related small GTP-binding proteins (see 179520) are involved in diverse cellular events, including cell signaling, proliferation, cytoskeletal organization, and secretion. The GTP-binding proteins are active only in the GTP-bound state. At least 3 classes of proteins tightly regulate cycling between the GTP-bound and GDP-bound states: GTPase-activating proteins (GAPs), guanine nucleotide-releasing factors (GRFs), and GDP-dissociation inhibitors (GDIs). The GDIs, including ARHGDIB, decrease the rate of GDP dissociation from Ras-like GTPases (summary by Scherle et al., 1993).
By using a subtractive hybridization approach, Scherle et al. (1993) identified a B-cell cDNA encoding ARHGDIB, which shares homology to RhoGDI (ARHGDIA; 601925). They designated the gene LyGDI for 'lymphoid-specific GDI.' Northern blot analysis revealed that LyGDI is expressed as a 1.4-kb transcript only in hematopoietic tissues. Antibodies against LyGDI recognized a 27-kD protein on Western blots of B- and T-cell line lysates. Scherle et al. (1993) found that LyGDI bound RhoA and, in vitro, inhibited GDP dissociation from RhoA. Stimulation of T lymphocytes with phorbol ester led to phosphorylation of LyGDI.
Independently, Lelias et al. (1993) cloned the LyGDI gene from human and from mouse, and designated it GDP-dissociation inhibitor D4. The sequence of the predicted 201-amino acid human protein was 67% identical to that of bovine RhoGDI. Mouse and human D4 shared 89% amino acid sequence identity.
Leffers et al. (1993) identified 3 human proteins related to bovine RhoGDI and found that they corresponded to 3 proteins in the keratinocyte 2-dimensional-gel protein database, called IEF (for 'isoelectric focusing') 8120, IEF8118, and IEF1120. By screening an embryonic lung fibroblast library with an oligonucleotide based on the protein sequence of IEF8120, Leffers et al. (1993) isolated cDNAs encoding ARHGDIB. They reported that ARHGDIB had a pI of 4.79. Northern blot analysis revealed that ARHGDIB was expressed abundantly in lung, and at lower levels in several other tissues. Overexpression of ARHGDIB in mammalian cells caused them to 'round up' and disrupted the actin cytoskeleton, mimicking the phenotypic changes associated with inactivation of Rho proteins.
By fluorescence in situ hybridization, Adra et al. (1994) mapped the ARHGDIB gene to chromosome 12p12.3.
Adra, C. N., Kobayashi, H., Rowley, J. D., Lim, B. Assignment of the human GDID4 gene, a GDP/GTP-exchange regulator, to chromosome 12p12.3. Genomics 24: 188-190, 1994. [PubMed: 7896279] [Full Text: https://doi.org/10.1006/geno.1994.1601]
Leffers, H., Nielsen, M. S., Andersen, A. H., Honore, B., Madsen, P., Vandekerckhove, J., Celis, J. E. Identification of two human Rho GDP dissociation inhibitor proteins whose overexpression leads to disruption of the actin cytoskeleton. Exp. Cell Res. 209: 165-174, 1993. [PubMed: 8262133] [Full Text: https://doi.org/10.1006/excr.1993.1298]
Lelias, J.-M., Adra, C. N., Wulf, G. M., Guillemot, J.-C., Khagad, M., Caput, D., Lim, B. cDNA cloning of a human mRNA preferentially expressed in hematopoietic cells and with homology to a GDP-dissociation inhibitor for the rho GTP-binding proteins. Proc. Nat. Acad. Sci. 90: 1479-1483, 1993. [PubMed: 8434008] [Full Text: https://doi.org/10.1073/pnas.90.4.1479]
Scherle, P., Behrens, T., Staudt, L. M. Ly-GDI, a GDP-dissociation inhibitor of the RhoA GTP-binding protein, is expressed preferentially in lymphocytes. Proc. Nat. Acad. Sci. 90: 7568-7572, 1993. [PubMed: 8356058] [Full Text: https://doi.org/10.1073/pnas.90.16.7568]