FNTA

Farnesyltransferase, CAAX box, alpha

PDB rendering based on 1d8d.

Available structures
PDB	1JCQ, 1LD7, 1LD8, 1MZC, 1S63, 1SA4, 1TN6, 2F0Y, 2H6F, 2H6G, 2H6H, 2H6I, 2IEJ, 3E37

Identifiers

Symbols

FNTA; FPTA; MGC99680; PGGT1A; PTAR2

External IDs

OMIM: 134635 MGI: 104683 HomoloGene: 1534 GeneCards: FNTA Gene

Gene Ontology
Molecular function	• protein farnesyltransferase activity • protein geranylgeranyltransferase activity • CAAX-protein geranylgeranyltransferase activity • protein binding • microtubule binding • transferase activity • alpha-tubulin binding
Cellular component	• cytoplasm • cytosol • microtubule associated complex
Biological process	• apoptosis • cellular component disassembly involved in apoptosis • transforming growth factor beta receptor signaling pathway • protein farnesylation • protein geranylgeranylation • positive regulation of tubulin deacetylation • positive regulation of deacetylase activity
Sources: Amigo / QuickGO

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 8:
42.89 – 42.94 Mb

Chr 8:
27.11 – 27.13 Mb

PubMed search

[1]

[2]

Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha is an enzyme that in humans is encoded by the FNTA gene.^[1]^[2]

Prenyltransferases attach either a farnesyl group or a geranylgeranyl group in thioether linkage to the cysteine residue of protein's with a C-terminal CAAX box. CAAX geranylgeranyltransferase and CAAX farnesyltransferase are heterodimers that share the same alpha subunit but have different beta subunits. This gene encodes the alpha subunit of these transferases. Alternative splicing results in multiple transcript variants encoding different isoforms.^[2]

Interactions

FNTA has been shown to interact with TGF beta receptor 1.^[3]

References

^ Andres DA, Milatovich A, Ozcelik T, Wenzlau JM, Brown MS, Goldstein JL, Francke U (Feb 1994). "cDNA cloning of the two subunits of human CAAX farnesyltransferase and chromosomal mapping of FNTA and FNTB loci and related sequences". Genomics 18 (1): 105–12. doi:10.1006/geno.1993.1432. PMID 8276393.
^ ^a ^b "Entrez Gene: FNTA farnesyltransferase, CAAX box, alpha". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2339.
^ Kawabata, M; Imamura T, Miyazono K, Engel M E, Moses H L (Dec. 1995). "Interaction of the transforming growth factor-beta type I receptor with farnesyl-protein transferase-alpha". J. Biol. Chem. (UNITED STATES) 270 (50): 29628–31. doi:10.1074/jbc.270.50.29628. ISSN 0021-9258. PMID 8530343.

Adamson P, Marshall CJ, Hall A, Tilbrook PA (1992). "Post-translational modifications of p21rho proteins.". J. Biol. Chem. 267 (28): 20033–8. PMID 1400319.
Manne V, Roberts D, Tobin A, et al. (1990). "Identification and preliminary characterization of protein-cysteine farnesyltransferase.". Proc. Natl. Acad. Sci. U.S.A. 87 (19): 7541–5. doi:10.1073/pnas.87.19.7541. PMC 54783. PMID 2217184. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=54783.
Armstrong SA, Hannah VC, Goldstein JL, Brown MS (1995). "CAAX geranylgeranyl transferase transfers farnesyl as efficiently as geranylgeranyl to RhoB.". J. Biol. Chem. 270 (14): 7864–8. doi:10.1074/jbc.270.14.7864. PMID 7713879.
Zhang FL, Diehl RE, Kohl NE, et al. (1994). "cDNA cloning and expression of rat and human protein geranylgeranyltransferase type-I.". J. Biol. Chem. 269 (5): 3175–80. PMID 8106351.
Sinensky M, Fantle K, Trujillo M, et al. (1994). "The processing pathway of prelamin A.". J. Cell. Sci.. 107 ( Pt 1): 61–7. PMID 8175923.
Andres DA, Goldstein JL, Ho YK, Brown MS (1993). "Mutational analysis of alpha-subunit of protein farnesyltransferase. Evidence for a catalytic role.". J. Biol. Chem. 268 (2): 1383–90. PMID 8419339.
Omer CA, Kral AM, Diehl RE, et al. (1993). "Characterization of recombinant human farnesyl-protein transferase: cloning, expression, farnesyl diphosphate binding, and functional homology with yeast prenyl-protein transferases.". Biochemistry 32 (19): 5167–76. doi:10.1021/bi00070a028. PMID 8494894.
Kawabata M, Imamura T, Miyazono K, et al. (1996). "Interaction of the transforming growth factor-beta type I receptor with farnesyl-protein transferase-alpha.". J. Biol. Chem. 270 (50): 29628–31. doi:10.1074/jbc.270.50.29628. PMID 8530343.
Wang T, Danielson PD, Li BY, et al. (1996). "The p21(RAS) farnesyltransferase alpha subunit in TGF-beta and activin signaling.". Science 271 (5252): 1120–2. doi:10.1126/science.271.5252.1120. PMID 8599089.
Nantais DE, Schwemmle M, Stickney JT, et al. (1996). "Prenylation of an interferon-gamma-induced GTP-binding protein: the human guanylate binding protein, huGBP1.". J. Leukoc. Biol. 60 (3): 423–31. PMID 8830800.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Goalstone ML, Draznin B (1996). "Effect of insulin on farnesyltransferase activity in 3T3-L1 adipocytes.". J. Biol. Chem. 271 (44): 27585–9. doi:10.1074/jbc.271.44.27585. PMID 8910345.
Prakash B, Praefcke GJ, Renault L, et al. (2000). "Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins.". Nature 403 (6769): 567–71. doi:10.1038/35000617. PMID 10676968.
Zeng Q, Si X, Horstmann H, et al. (2000). "Prenylation-dependent association of protein-tyrosine phosphatases PRL-1, -2, and -3 with the plasma membrane and the early endosome.". J. Biol. Chem. 275 (28): 21444–52. doi:10.1074/jbc.M000453200. PMID 10747914.
Ashar HR, James L, Gray K, et al. (2000). "Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules.". J. Biol. Chem. 275 (39): 30451–7. doi:10.1074/jbc.M003469200. PMID 10852915.
Guenzi E, Töpolt K, Cornali E, et al. (2001). "The helical domain of GBP-1 mediates the inhibition of endothelial cell proliferation by inflammatory cytokines.". EMBO J. 20 (20): 5568–77. doi:10.1093/emboj/20.20.5568. PMC 125279. PMID 11598000. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=125279.
Long SB, Hancock PJ, Kral AM, et al. (2001). "The crystal structure of human protein farnesyltransferase reveals the basis for inhibition by CaaX tetrapeptides and their mimetics.". Proc. Natl. Acad. Sci. U.S.A. 98 (23): 12948–53. doi:10.1073/pnas.241407898. PMC 60805. PMID 11687658. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=60805.
Bell IM, Gallicchio SN, Abrams M, et al. (2002). "3-Aminopyrrolidinone farnesyltransferase inhibitors: design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency.". J. Med. Chem. 45 (12): 2388–409. doi:10.1021/jm010531d. PMID 12036349.
Long SB, Casey PJ, Beese LS (2002). "Reaction path of protein farnesyltransferase at atomic resolution.". Nature 419 (6907): 645–50. doi:10.1038/nature00986. PMID 12374986.

PDB gallery

1d8d: CO-CRYSTAL STRUCTURE OF RAT PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH A K-RAS4B PEPTIDE SUBSTRATE AND FPP ANALOG AT 2.0A RESOLUTION

1d8e: Zinc-depleted FTase complexed with K-RAS4B peptide substrate and FPP analog.

1fpp: PROTEIN FARNESYLTRANSFERASE COMPLEX WITH FARNESYL DIPHOSPHATE

1ft1: CRYSTAL STRUCTURE OF PROTEIN FARNESYLTRANSFERASE AT 2.25 ANGSTROMS RESOLUTION

1ft2: CO-CRYSTAL STRUCTURE OF PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH A FARNESYL DIPHOSPHATE SUBSTRATE

1jcq: CRYSTAL STRUCTURE OF HUMAN PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH FARNESYL DIPHOSPHATE AND THE PEPTIDOMIMETIC INHIBITOR L-739,750

1jcr: CRYSTAL STRUCTURE OF RAT PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH THE NON-SUBSTRATE TETRAPEPTIDE INHIBITOR CVFM AND FARNESYL DIPHOSPHATE SUBSTRATE

1jcs: CRYSTAL STRUCTURE OF RAT PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH THE PEPTIDE SUBSTRATE TKCVFM AND AN ANALOG OF FARNESYL DIPHOSPHATE

1kzo: PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH FARNESYLATED K-RAS4B PEPTIDE PRODUCT AND FARNESYL DIPHOSPHATE SUBSTRATE BOUND SIMULTANEOUSLY

1kzp: PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH A FARNESYLATED K-RAS4B PEPTIDE PRODUCT

1ld7: Co-crystal structure of Human Farnesyltransferase with farnesyldiphosphate and inhibitor compound 66

1ld8: Co-crystal structure of Human Farnesyltransferase with farnesyldiphosphate and inhibitor compound 49

1mzc: Co-Crystal Structure Of Human Farnesyltransferase With Farnesyldiphosphate and Inhibitor Compound 33a

1n4p: Protein Geranylgeranyltransferase type-I Complexed with Geranylgeranyl Diphosphate

1n4q: Protein Geranylgeranyltransferase type-I Complexed with a GGPP Analog and a KKKSKTKCVIL Peptide

1n4r: Protein Geranylgeranyltransferase type-I Complexed with a Geranylgeranylated KKKSKTKCVIL Peptide Product

1n4s: Protein Geranylgeranyltransferase type-I Complexed with GGPP and a Geranylgeranylated KKKSKTKCVIL Peptide Product

1n94: Aryl Tetrahydropyridine Inhbitors of Farnesyltransferase: Glycine, Phenylalanine and Histidine Derivates

1n95: Aryl Tetrahydrophyridine Inhbitors of Farnesyltranferase: Glycine, Phenylalanine and Histidine Derivatives

1n9a: Farnesyltransferase complex with tetrahydropyridine inhibitors

1ni1: Imidazole and cyanophenyl farnesyl transferase inhibitors

1nl4: Crystal Structure of Rat Farnesyl Transferase in Complex With A Potent Biphenyl Inhibitor

1o1r: Structure of FPT bound to GGPP

1o1s: Structure of FPT bound to isoprenoid analog 3b

1o1t: Structure of FPT bound to the CVIM-FPP product

1o5m: Structure of FPT bound to the inhibitor SCH66336

1qbq: STRUCTURE OF RAT FARNESYL PROTEIN TRANSFERASE COMPLEXED WITH A CVIM PEPTIDE AND ALPHA-HYDROXYFARNESYLPHOSPHONIC ACID.

1s63: Human protein farnesyltransferase complexed with L-778,123 and FPP

1s64: Rat protein geranylgeranyltransferase type-I complexed with L-778,123 and a sulfate anion

1sa4: human protein farnesyltransferase complexed with FPP and R115777

1sa5: Rat protein farnesyltransferase complexed with FPP and BMS-214662

1tn6: Protein Farnesyltransferase Complexed with a Rap2a Peptide Substrate and a FPP Analog at 1.8A Resolution

1tn7: Protein Farnesyltransferase Complexed with a TC21 Peptide Substrate and a FPP Analog at 2.3A Resolution

1tn8: Protein Farnesyltransferase Complexed with a H-Ras Peptide Substrate and a FPP Analog at 2.25A Resolution

1tnb: Rat Protein Geranylgeranyltransferase Type-I Complexed with a GGPP analog and a substrate KKSKTKCVIF Peptide Derived from TC21

1tno: Rat Protein Geranylgeranyltransferase Type-I Complexed with a GGPP analog and a KKKSKTKCVIM Peptide Derived from K-Ras4B

1tnu: Rat Protein Geranylgeranyltransferase Type-I Complexed with a GGPP analog and a GCINCCKVL Peptide Derived from RhoB

1tny: Rat Protein Geranylgeranyltransferase Type-I Complexed with a GGPP analog and a FREKKFFCAIL Peptide Derived from the Heterotrimeric G Protein Gamma-2 Subunit

1tnz: Rat Protein Geranylgeranyltransferase Type-I Complexed with a GGPP analog and a RRCVLL Peptide Derived from Cdc42 splice isoform-2

1x81: Farnesyl transferase structure of Jansen compound

2bed: Structure of FPT bound to inhibitor SCH207736

2f0y: Crystal Structure Of Human Protein Farnesyltransferase Complexed With Farnesyl Diphosphate and hydantoin derivative

2h6f: Protein Farnesyltransferase Complexed with a Farnesylated DDPTASACVLS Peptide Product at 1.5A Resolution

2h6g: W102T Protein Farnesyltransferase Mutant Complexed with a Geranylgeranylated DDPTASACVLS Peptide Product at 1.85A Resolution

2h6h: Y365F Protein Farnesyltransferase Mutant Complexed with a Farnesylated DDPTASACVLS Peptide Product at 1.8A

2h6i: W102T/Y365F Protein Farnesyltransferase Double Mutant Complexed with a Geranylgeranylated DDPTASACVLS Peptide Product at 3.0A

2iej: Human Protein Farnesyltransferase Complexed with Inhibitor Compound STN-48 And FPP Analog at 1.8A Resolution

FNTA

Interactions

References

Further reading