DIRAS3 encompasses a 7.2-kb region and includes 2.0 kb of the 5- flanking region, two exons, an intron, and a 1.2-kb 3-flanking region. The first exon contains only the 5-noncoding region consisting of 81 nucleotides, whereas the second exon contains the entire protein-coding region. The two exons are separated by an intron of 3.2 kb. There are three CpG island regions. CPG island I (nucleotide (nt) -1232 to -914) is located about 1 kb upstream of the transcription initiation site; CpG island II (nt -206 to +79) is near the transcription initiation region and adjacent exon 1; CpG island III (nt +3343 to +3691) is located in the protein-encoding region of exon 2.

The entire protein-coding region is located within exon 2 and encodes a 229-residue small GTP-binding protein.

No known pseudogenes.

DIRAS3 encodes a 26-kDa GTPase. The DIRAS3 gene ORF contains three motifs typical of Ras/Rap family members: (1) a highly conserved GTP binding domain, (2) a putative effector domain YLPTIENTY, and (3) the membrane localizing CAAX motif at the COOH terminus. DIRAS3 contains a unique 34 amino-acid extension at the N-terminus and differs from other members of Ras-superfamily.

DIRAS3 is expressed in brain, heart, liver, lung, pancreas, breast and ovary.

DIRAS is associated at the cell membrane through its prenylation at the C-terminal cysteine residue. Mutation of the conserved CAAX box at the C-terminus led to a loss of its membrane association.

DIRAS3 is a maternally imprinted tumor suppressor gene that belongs to the Ras superfamily of small G proteins. DIRAS3 regulates cell cycle, motility, angiogenesis, autophagy and tumor dormancy. Introduction of this gene into cancer cells that lack DIRAS3 expression inhibits proliferation and motility of cancer cells. DIRAS3 truncates signaling through the Ras/MAP pathway, induces p21^WAF1/CIP1, down-regulates cyclin D1, and triggers apoptosis. DIRAS3 is required for autophagy and that re-expression of DIRAS3 protein in ovarian cancer cells will induce autophagic cell death in culture. In xenografts, re-expression of DIRAS3 also induces autophagy, but can also promote tumor dormancy in the presence of factors that promote survival in the cancer microenvironment.

DIRAS3 shares 56% amino acid homology with Rap1A, 56% with Rap1B, 58% with Rap 2A, 62% with Rap2B, 59% with K-Ras, and 54% with H-Ras. DIRAS3 shares about 40% homology with DIRAS1 and DIRAS2.

Mutations have not been detected.