Target type: molecularfunction
Catalysis of the reaction: geranylgeranyl diphosphate + protein-cysteine = S-geranylgeranyl-protein + diphosphate. This reaction is the formation of a thioether linkage between the C-1 atom of the geranylgeranyl group and a cysteine residue fourth from the C-terminus of the protein. The protein substrates have the C-terminal sequence CA1A2X, where the terminal residue, X, is preferably leucine and A2 should not be aromatic. Known substrates include most g-subunits of heterotrimeric G proteins and Ras-related GTPases such as members of the Ras and Rac/Rho families. [EC:2.5.1.59, PMID:8621375]
CAAX-protein geranylgeranyltransferase activity is a critical enzymatic process that modifies proteins by attaching a geranylgeranyl lipid group to their C-terminus. This lipidation process, also known as prenylation, is essential for the proper localization, membrane association, and signaling of many proteins. The CAAX motif, found at the C-terminus of target proteins, serves as a recognition site for the enzyme. The enzyme, a heterodimer composed of α and β subunits, catalyzes the transfer of a geranylgeranyl group from a donor molecule, geranylgeranyl diphosphate, to the cysteine residue within the CAAX motif. The geranylgeranyl group is a 20-carbon isoprenoid lipid, which is hydrophobic and facilitates the association of the protein with cellular membranes. This prenylation event is essential for proper protein function. It can alter protein-protein interactions, membrane targeting, and the formation of signaling complexes. The modification is critical for diverse cellular processes, including cell growth, differentiation, and signal transduction. Proteins that undergo CAAX prenylation play vital roles in various cellular pathways, including Ras signaling, cytoskeletal dynamics, and protein trafficking. Defects in CAAX-protein geranylgeranyltransferase activity can lead to a variety of human diseases, including cancer, neurological disorders, and immune deficiencies. This enzyme is a target for drug development, as inhibitors of its activity have shown promise in treating certain cancers.'
"
| Protein | Definition | Taxonomy |
|---|---|---|
| Geranylgeranyl transferase type-1 subunit beta | A geranylgeranyl transferase type-1 subunit beta that is encoded in the genome of cow. [OMA:Q5EAD5, PRO:DNx] | Bos taurus (cattle) |
| Geranylgeranyl transferase type-1 subunit beta | A geranylgeranyl transferase type-1 subunit beta that is encoded in the genome of human. [PRO:DNx, UniProtKB:P53609] | Homo sapiens (human) |
| Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha | A protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha that is encoded in the genome of human. [PRO:DNx, UniProtKB:P49354] | Homo sapiens (human) |
| Geranylgeranyl transferase type-1 subunit beta | A geranylgeranyl transferase type-1 subunit beta that is encoded in the genome of human. [PRO:DNx, UniProtKB:P53609] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| 1,10-phenanthroline | 1,10-phenanthroline: RN given refers to parent cpd; inhibits Zn-dependent metalloproteinases | phenanthroline | EC 2.7.1.1 (hexokinase) inhibitor; EC 3.4.19.3 (pyroglutamyl-peptidase I) inhibitor |
| 2,2'-dipyridyl | 2,2'-bipyridine : A bipyridine in which the two pyridine moieties are linked by a bond between positions C-2 and C-2'. 2,2'-Dipyridyl: A reagent used for the determination of iron. | bipyridine | chelator; ferroptosis inhibitor |
| ethylenediamine | ethylenediamine : An alkane-alpha,omega-diamine in which the alkane is ethane. ethylenediamine: RN given refers to parent cpd; edamine is the recommended contraction for the ethylenediamine radical | alkane-alpha,omega-diamine | GABA agonist |
| cortisone acetate | Cortisone Acetate: The acetate ester of cortisone that is used mainly for replacement therapy in adrenocortical insufficiency and in the treatment of many allergic and inflammatory disorders. | corticosteroid hormone | |
| gliotoxin | gliotoxin : A pyrazinoindole with a disulfide bridge spanning a dioxo-substituted pyrazine ring; mycotoxin produced by several species of fungi. Gliotoxin: A fungal toxin produced by various species of Trichoderma, Gladiocladium fimbriatum, Aspergillus fumigatus, and Penicillium. It is used as an immunosuppressive agent. | dipeptide; organic disulfide; organic heterotetracyclic compound; pyrazinoindole | antifungal agent; EC 2.5.1.58 (protein farnesyltransferase) inhibitor; immunosuppressive agent; mycotoxin; proteasome inhibitor |
| sch 37370 | N-acetyldesloratadine: dual antagonist of platelet-activating factor and histamine | ||
| desloratadine | desloratadine : Loratadine in which the ethoxycarbonyl group attached to the piperidine ring is replaced by hydrogen. The major metabolite of loratidine, desloratadine is an antihistamine which is used for the symptomatic relief of allergic conditions including rhinitis and chronic urticaria. It does not readily enter the central nervous system, so does not cause drowsiness. desloratadine: major metabolite of loratadine | benzocycloheptapyridine | anti-allergic agent; cholinergic antagonist; drug metabolite; H1-receptor antagonist |
| b 581 | B 581 : A dipeptide obtained from the tetrapeptide Cys-Val-Phe-Met by reduction of the amide carbonyl groups of the Cys and Val residues. B 581: blocks farnesylated but not geranylgeranylated or myristylated, oncogenic Ras signaling & transformation | dipeptide | EC 2.5.1.58 (protein farnesyltransferase) inhibitor; peptidomimetic |
| r115777 | |||
| lonafarnib | lonafarnib : A 4-{2-[4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperidin-1-yl]-2-oxoethyl}piperidine-1-carboxamide that has R configuration. It is used as oral farnesyltransferase inhibitor. lonafarnib: inhibitor of farnesyl protein transferase | 4-{2-[4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperidin-1-yl]-2-oxoethyl}piperidine-1-carboxamide | antineoplastic agent; EC 2.5.1.58 (protein farnesyltransferase) inhibitor |
| tipifarnib | imidazoles; monochlorobenzenes; primary amino compound; quinolone | antineoplastic agent; apoptosis inducer; EC 2.5.1.58 (protein farnesyltransferase) inhibitor | |
| l 778,123 | L-778,123 (free base) : A member of the class of imidazoles that is 1H-imidazole substituted by (4-cyanophenyl)methyl and [4-(3-chlorophenyl)-3-oxopiperazin-1-yl]methyl groups at positions 1 and 5, respectively. It is a dual inhibitor of FPTase and GGPTase-I. | imidazoles; monochlorobenzenes; nitrile; piperazinone; tertiary amino compound | antineoplastic agent; EC 2.5.1.58 (protein farnesyltransferase) inhibitor; EC 2.5.1.59 (protein geranylgeranyltransferase type I) inhibitor |
| halenaquinone | halenaquinone: RN given refers to (S)-isomer; structure in first source | ||
| fti 276 | FTI 276: a ras CAAX (C - Cys; A - aliphatic amino acid; X - Ser or Met) peptidomimetic; inhibits farnesyltransferase; FTI-277 is the methyl ester derivative of FTI-276 | methionine derivative | |
| lb42908 | LB42908 : A member of the class of pyrrolecarboxamides that is 1H-pyrrole substituted by [1-(3a,7a-dihydro-1,3-benzodioxol-5-ylmethyl)-1H-imidazol-5-yl]methyl, (4-methylpiperazin-1-yl)carbonyl, and naphthalen-1-yl groups at positions 1, 3 and 4, respectively. It is a potent inhibitor of Ras farnesyltransferase (IC50= 0.9nM against H-Ras and 2.4nM against K-Ras) with potential anticancer activity. LB42908: structure in first source | ||
| farnesyl pyrophosphate | 2-trans,6-trans-farnesyl diphosphate : The trans,trans-stereoisomer of farnesyl diphosphate. farnesyl pyrophosphate: a sesquiterpene that dimerizes to SQUALENE; RN given refers to cpd without isomeric designation | farnesyl diphosphate | Escherichia coli metabolite; mouse metabolite |
| a 228839 | A 228839: an immunosuppressive agent; structure in first source | ||
| bms 214662 | 7-cyano-2,3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine: a farnesyltransferase inhibitor; structure in first source BMS-214662 : A member of the class of benzodiazepines that is 2,3,4,5-tetrahydro-1H-1,4-benzodiazepine substituted by (1H-imidazol-5-yl)methyl, benzyl, (thiophen-2-yl)sulfonyl, and cyano groups at positions 1, 3R, 4 and 7, respectively. It is a potent inhibitor of farnesyltransferase (IC50 = 1.35nM) which was under clinical development for the treatment of solid tumors. | benzenes; benzodiazepine; imidazoles; nitrile; sulfonamide; thiophenes | antineoplastic agent; apoptosis inducer; EC 2.5.1.58 (protein farnesyltransferase) inhibitor |
| fti 277 | |||
| ggti 286 | GGTI 286: the methyl ester of GGTI-287; inhibits geranylgeranyltransferase | ||
| chaetomellic acid a | chaetomellic acid A: structure given in first source; an inhibitor of farnesyl-protein transferase | ||
| kurasoin a | kurasoin A: protein farnesyltransferase inhibitor; isolated from Paecilomyces; structure in first source | ||
| kurasoin b | kurasoin B: protein farnesyltransferase inhibitor; isolated from Paecilomyces; structure in first source | ||
| manumycin | manumycin A : A polyketide with formula C31H38N2O7 initially isolated from Streptomyces parvulus as a result of a random screening program for farnesyl transferase (FTase) inhibitors. It is a natural product that exhibits anticancer and antibiotic properties. manumycin: an NSAID; RN given for (1S-(1alpha,3(2E,4E,6S*),5alpha,5(1E,3E,5E),6alpha))-isomer; a farnesyl protein transferase inhibitor; from Streptomyces parvulus; MF C31-H38-N2-O7; structure given in first source | enamide; epoxide; organic heterobicyclic compound; polyketide; secondary carboxamide; tertiary alcohol | antiatherosclerotic agent; antimicrobial agent; antineoplastic agent; apoptosis inducer; bacterial metabolite; EC 1.8.1.9 (thioredoxin reductase) inhibitor; EC 2.5.1.58 (protein farnesyltransferase) inhibitor; marine metabolite |
| clavaric acid | clavaric acid: inhibits farnesyl-protein transferase; isolated from Clavariadelphus truncatus; structure in first source | ||
| ggti 298 | GGTI 298: inhibits geranylgeranyltransferase-I; structure in first source | leucine derivative | |
| sch 44342 | SCH 44342: inhibits farnesyl protein transferase; structure in first source | ||
| lonafarnib | 4-{2-[4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperidin-1-yl]-2-oxoethyl}piperidine-1-carboxamide : A benzocycloheptapyridine that is benzo[5,6]cyclohepta[1,2-b]pyridine which is substituted at positions 3 and 10 by bromines, at position 8 by chlorine, and at position 11 by an N-acetylpiperidin-4-yl group in which one of the hydrogens of the acetyl moiety has been replaced by a 1-carbamoylpiperidin-4-yl group. | benzocycloheptapyridine; heteroarylpiperidine; N-acylpiperidine; organobromine compound; organochlorine compound; ureas | |
| lb42708 | LB42708: farnesyltransferase inhibitor; structure in first source | ||
| actinoplanic acid a | actinoplanic acid A: isolated from Actinoplanes; inhibits farnesyl-protein transferase; structure in first source | ||
| moverastin a | moverastin A: inhibits cancer cell migration; isolated from Aspergillus; structure in first source |