Alternative titles; symbols
HGNC Approved Gene Symbol: OLA1
Cytogenetic location: 2q31.1 Genomic coordinates (GRCh38): 2:174,072,447-174,248,532 (from NCBI)
OLA1 belongs to the Obg family of GTPases. It is a translational regulator of p21 (CDKN1A; 116899) that plays a critical role in cell proliferation (Ding et al., 2016).
Koller-Eichhorn et al. (2007) identified human GTPBP9, which they called OLA1, as the homolog of the E. coli P-loop NTPase YchF, a member of the Obg-related family of GTPases belonging to the TRAFAC (translation factors) class. The deduced 396-amino acid protein consists of an N-terminal G domain, flanked on either side by an inserted coiled-coil, and a C-terminal TGS domain.
Scott (2007) mapped the GTPBP9 gene to chromosome 2q31.1 based on an alignment of the GTPBP9 sequence (GenBank AC013467) with the genomic sequence (build 36.2).
Koller-Eichhorn et al. (2007) demonstrated that OLA1 binds and hydrolyzes ATP more efficiently than GTP and thus is a member of a new subclass of NTPases in the Obg family of GTPases. They showed that members of this protein family from different species also have ATPase activity and are not exclusively GTPases. By performing x-ray crystallography with AMPPCP, a nonhydrolyzable analog of ATP, Koller-Eichhorn et al. (2007) found that one cause of the altered nucleotide specificity of this subclass of NTPases is a substitution of a hydrophobic amino acid for a glutamine in all members of the Obg family. They noted that the same substitution inactivates Ras-like GTPases.
Ding et al. (2016) found that Ola1 +/- mice were viable, fertile, and indistinguishable from wildtype mice. In contrast, 80 to 90% of Ola1 -/- mice died within 24 hours of birth. Dead Ola1 -/- mice were cyanotic and smaller than wildtype. Ola1 -/- embryos showed delayed progression from day 8.5 and relative lung immaturity. Surviving Ola1 -/- mice were half as big as wildtype mice in adulthood. Ola1 -/- embryonic fibroblasts showed reduced proliferation in vitro, which was associated with altered expression of cell cycle regulators, including accumulation of p53 (TP53; 191170) and/or p21. Accumulation of p21 could be prevented by reconstitution of Ola1 or treatment with an Eif2-alpha (EIF2A; 609234) dephosphorylation inhibitor. Immunohistochemistry demonstrated p21 overexpression in Ola1 -/- embryos. Deletion of p21 partially rescued growth retardation in Ola1 -/- mice, but double knockout had no effect on developmental delay or lethality. Ding et al. (2016) concluded that OLA1 is required for normal developmental progression and plays an important role in promoting cell proliferation, at least partly through suppression of p21.
Ding, Z., Liu, Y., Rubio, V., He, J., Minze, L. J., Shi, Z.-Z. OLA1, a translational regulator of p21, maintains optimal cell proliferation necessary for developmental progression. Molec. Cell. Biol. 36: 2568-2582, 2016. [PubMed: 27481995] [Full Text: https://doi.org/10.1128/MCB.00137-16]
Koller-Eichhorn, R., Marquardt, T., Gail, R., Wittinghofer, A., Kostrewa, D., Kutay, U., Kambach, C. Human OLA1 defines an ATPase subfamily in the OBG family of GTP-binding proteins. J. Biol. Chem. 282: 19928-19937, 2007. [PubMed: 17430889] [Full Text: https://doi.org/10.1074/jbc.M700541200]
Scott, A. F. Personal Communication. Baltimore, Md. 6/29/2007.