Molecular cloning of a member of a new class of low-molecular-weight GTP-binding proteins.

Abstract

We report the cloning of a low-molecular-weight GTP-binding protein that appears to be the first member of a new class of G proteins. This G protein was cloned from the HT4 neural cell line and has the closest homology to the tab, sec4, and yptl members of the low-molecular-weight (LMW) G-protein family. The amino acid sequence identity is only 30% with these other LMW G proteins, but in the four conserved GTP-binding domains, amino acid identity increases to 50-100%. A unique feature that distinguishes this G protein from other LMW G proteins is its carboxy-terminal amino acid sequence -Cys-Cys-Pro. In keeping with the current nomenclature for other members of the ras supedamily, we will designate this new class as rah (ras-related homolog). On the basis of sequence homology, rah may function in vesicular trafficking and possibly in neurotransmitter secretion.

Small GTPase Rah/Rab34 Is Associated with Membrane Ruffles and Macropinosomes and Promotes Macropinosome Formation

“…Because there was an in-frame termination codon (T416AA) upstream of A503TG in this clone, this ATG is most likely to serve the initiation codon. The coding region of the former truncated clone contains 208 amino acids (31), whereas that of this clone consisted of 259 amino acids and its calculated molecular weight was 29,128. Because Rah was most similar to Rab family proteins among small GTPase families and its amino acid sequence was identical to that of mouse Rab34 (accession number BC038638, the data of which were submitted while we were submitting this report), we compared its amino acid sequence with those of several other Rab family proteins (Fig.…”

“…Rah is a small GTPase postulated to be a member of Rab family due to the similarity of its effector domain and C-terminal sequences to those of several Rab proteins (31). Because only a truncated cDNA lacking the sequence encoding N-terminal portion was available (31), we have cloned in the present study the cDNA containing the entire coding region of mouse Rah.…”

Protein Prenylation: Genes, Enzymes, Targets, and Functions

“…Thus, a reasonable hypothesis compatible with these data is that the carboxyl-terminal cysteine is palmitoylated, and that the adjacent cysteine is geranylgeranylated. A novel carboxyl-terminal sequence, C-C-P, is found in Rah, a mammalian small GTP-binding protein related to Rho proteins (99). It is tempting to speculate that this may represent a new prenylation motif.…”

Control of RAS mRNA level by the mevalonate pathway.

“…Many additional proteins are modified with one or two 20-carbon geranylgeranyl groups (Rilling et al, 1990); these proteins include many guanine nucleotide-binding proteins involved in cell signalling (Mumby et al, 1990;Kinsella and Maltese, 1991;Khosravi-Far et al, 1991). In addition, an unidentified mammalian protein appears to be covalently modified with an isopentenyladenosine moiety (Faust and Dice, 1991), and genetic evidence suggests that other isoprenoid modifications may also exist (Morimoto et al, 1991). Prenylation is essential for the subsequent processing, intracellular localization, and biological activity of Ras and other prenylated proteins (Hancock et al, 1989;Schafer et al, 1989), suggesting that the prenyl group is required to direct the protein to the cellular locale where it can perform its biological function.…”