Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex. Contributes to the transfer of a farnesyl or geranylgeranyl moiety from farnesyl or geranylgeranyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. May positively regulate neuromuscular junction development downstream of MUSK via its function in RAC1 prenylation and activation. (updated: April 1, 2015)
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
No sequence conservation computed yet.
This protein is annotated as membranous in Gene Ontology.
Total structural coverage: 100%
No model available.
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The reference OMIM entry for this protein is 134635
Farnesyltransferase, caax box, alpha; fnta
Protein geranylgeranyltransferase type i, alpha subunit; pggt1a
DESCRIPTION
The FNTA gene encodes the alpha subunit for the heterodimeric enzymes CAAX farnesyltransferase and CAAX geranylgeranyltransferase (Zhang et al., 1994). The beta subunits are encoded by the FNTB (
134636) and PGGT1B (
602031) genes, respectively.
GENE FAMILY
Eukaryotic cells contain 3 distinct prenyltransferases that attach either a farnesyl group (15 carbons) or a geranylgeranyl group (20 carbons) in thioether linkage to C-terminal cysteine residues in a variety of cellular proteins (Schafer and Rine, 1992). These posttranslational modifications provide a mechanism for membrane localization of proteins that lack a transmembrane domain. Prenylation is a frequent covalent modification of proteins; Epstein et al. (1991) estimated that approximately 0.5% of all proteins in mammalian tissues are prenylated. The best characterized of the prenyltransferases, CAAX farnesyltransferase (FTase), attaches a farnesyl group from farnesyl pyrophosphate to cysteine residues at the fourth position from the C terminus of proteins that end in the so-called CAAX box, where C is cysteine, A is usually but not always an aliphatic amino acid, and X is typically methionine or serine. This enzyme has the remarkable property of farnesylating peptides as short as 4 residues in length that conform to the CAAX consensus sequence (summary by Andres et al., 1993).
CLONING
Epstein et al. (1991) noted that full-length cDNAs for the alpha and beta subunits of the rat farnesyltransferase were cloned, and both were shown to be essential for catalytic activity. Andres et al. (1993) used the rat cDNAs to clone cDNAs for the human alpha and beta (
134636) subunits. The human and rat amino acid sequences show 93% identity for the alpha subunit and 96% identity for the beta subunit.
GENE FUNCTION
CAAX farnesyltransferase is an alpha-beta heterodimeric enzyme with a molecular mass of approximately 100 kD. Geranylgeranyltransferase type I (GGTase-I) is also a heterodimeric enzyme. Zhang et al. (1994) analyzed tryptic digests of the bovine GGTase-I alpha subunit and showed that it is identical to that of bovine FTase; GGTase-I uses a different beta chain (PGGT1B;
602031). Coexpression of human PGGT1B and FNTA cDNAs in E. coli produced recombinant GGTase-I with electrophoretic and enzymatic properties indistinguishable from those of native GGTase-I. The beta chains of both FTase (FNTB;
134636) and GGTase are catalytic for specific substrates (e.g., p21ras; see
190020). A role for the alpha subunit had been uncertain until Wang et al. (1996) showed, using the 2-hybrid yeast assay, that FNTA is a specific cytoplasmic interactor of the transforming growth factor-beta (
190180) and activin type I (
102576) receptors. Wang et al. (1996) stated that because of these interactions FNTA is likely to be a key component of the signaling pathway which involves p21ras, an important substrate for farnesyltransferase. Membrane localization and activity of RAS is dependent on farnesylation; Wang et al. (1996) proposed that the actions of TGF-beta and activin on cell growth may be mediated through their ability to affect ras farnesylation via FNTA.
BIOCHEMICAL FEATURES
Long et al. (2002) presented a complete series of structures representing the major steps along the reaction coordinate of the enzyme protein farnesyltransferase. From these observations, Long et al. (2002) deduced the determinants of substrate specificity and an unusual ...
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Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 134635 was added.