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GTP-binding protein Di-Ras3 (DIRAS3) also known as aplysia ras homology member I (ARHI) is a protein that in humans is encoded by the DIRAS3 gene. This gene is a member of the ras superfamily, and is expressed in normal ovarian and breast epithelial cells, but not in ovarian and breast cancers. It is an imprinted gene, with monoallelic expression of the paternal allele, which is associated with growth suppression. Thus, this gene appears to be a putative tumor suppressor gene whose function is abrogated in ovarian and breast cancers.〔 It is maternally imprinted, and is linked to breast cancer as well as ovarian cancer. The ''ARHI'' gene includes one promoter, two exons and one intron with a 687 bp protein-coding region that encodes a 26-kDa protein. The ARHI protein (italic for gene, nonitalic for protein) is a GTPase belonging to the Ras superfamily and shares 50-60% homology with Ras and Rap, two other small GTP binding proteins.〔 This gene is a maternally imprinted putative tumor suppressor, and reduced expression of ARHI has been reported in 70% of invasive breast cancers. == Structure and function == While ARHI is structurally similar to other GTPase proteins, its function is remarkably different from Ras. Ras is an oncogenic protein involved in cellular proliferation and signal transduction, and while the Ras superfamily is generally positive growth regulators, ''ARHI'' is a tumor-suppressor gene. In contrast to Ras, ARHI works as an inhibitor for cell growth, thus functioning as a negative growth regulator. ARHI has also been shown to have less GTPase activity than most Ras proteins even though the proteins share a very similar structure. The underlying cause for these dramatic differences in function is thought to be structural variations between ARHI and the Ras superfamily. The negative growth regulation exhibited by ARHI is most likely due to a unique 34-amino-acid N-terminus extension. This sequence is not generally found in the Ras superfamily, most of which show no inhibitory activity towards cell growth and even act as positive growth regulators. Deletion of this tail results in a significant drop in ARHI's ability to inhibit cell growth. This change in structure has no effect on protein expression levels or its GTP-binding ability, suggesting the extension’s primary function is giving rise to this protein’s negative growth regulation. The reduced GTPase activity observed in ARHI is thought to arise from critical differences in three specific amino acid residues in the effector domain. These residues are highly conserved in other Ras proteins, and are critical for the GTPase activity. In Ras, they are specifically G12, A59, and Q61. ARHI has three different amino acids in the effector domain: A46, K93, and G95. While ARHI still binds GTP with high affinity, its hydrolysis of GTP to GDP is relatively low because of these differences. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「DIRAS3 (gene)」の詳細全文を読む スポンサード リンク
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