Target type: biologicalprocess
The covalent attachment of a geranylgeranyl group to a protein. [GOC:jl]
Protein geranylgeranylation is a post-translational modification that involves the attachment of two geranylgeranyl groups, 20-carbon isoprenoids, to a cysteine residue near the C-terminus of specific proteins. This process is crucial for the proper functioning of a wide range of proteins, particularly those involved in cellular signaling, membrane trafficking, and cytoskeletal organization.
The geranylgeranylation process is carried out by a family of enzymes known as geranylgeranyl transferases (GGTases). These enzymes are highly specific for their target proteins, recognizing a conserved motif known as a "Ca-aX-X-L" sequence near the C-terminus.
The process begins with the binding of the target protein to the GGTase. This interaction is mediated by the recognition of the Ca-aX-X-L motif by the GGTase. Once bound, the GGTase catalyzes the transfer of two geranylgeranyl groups from a donor molecule, geranylgeranyl pyrophosphate (GGPP), to the cysteine residue in the target protein.
The geranylgeranyl groups are hydrophobic and therefore anchor the modified protein to the membrane. This anchoring is essential for the proper localization and function of many geranylgeranylated proteins.
Geranylgeranylation is a highly regulated process, with several factors influencing its activity, including the availability of GGPP, the expression levels of GGTases, and the presence of specific protein chaperones.
Several diseases are linked to defects in geranylgeranylation, including cancer, neurodegenerative disorders, and cardiovascular diseases. These defects can disrupt the function of essential proteins involved in cell signaling, membrane trafficking, and cytoskeletal organization.
In summary, protein geranylgeranylation is a vital post-translational modification that plays a crucial role in various cellular processes. This process involves the attachment of two geranylgeranyl groups to specific proteins, leading to their membrane association and functional regulation. Dysregulation of geranylgeranylation can have significant consequences for human health, highlighting its importance in maintaining normal cellular function.'
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| 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) |
| Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha | A protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha that is encoded in the genome of cow. [OMA:P29702, PRO:DNx] | Bos taurus (cattle) |
| Geranylgeranyl transferase type-2 subunit alpha | A geranylgeranyl transferase type-2 subunit alpha that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q92696] | 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) |
| 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) |
| 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 | |
| ne 10790 | |||
| 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 |