Target type: cellularcomponent
A protein complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. The complex binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs and suppresses their translation by blocking the recruitment of the 43S ribosomal complex to m7G cap-bound eIF4G. In humans it includes RPL13A, EPRS, SYNCRIP and GAPDH; mouse complexes lack SYNCRIP. [GOC:br, PMID:15479637, PMID:23071094]
The GAIT complex is a cytosolic multi-protein complex involved in the post-transcriptional regulation of gene expression by repressing translation of specific mRNAs. The cellular component of the GAIT complex consists of a core protein complex that includes the following:
* **GTPase-activating protein (GAP) domain containing, translation initiation factor 3 (eIF3) subunit 3 (eIF3G):** This protein serves as the scaffolding protein for the GAIT complex and binds to the 5' untranslated region (UTR) of target mRNAs. It plays a crucial role in bringing the complex to the mRNA and initiating the translational repression.
* **Nuclear receptor coactivator 1 (NCOA1):** This protein is a transcriptional coactivator that also functions as a component of the GAIT complex. It binds to the mRNA and assists in the recruitment of other GAIT complex proteins, particularly eIF3G.
* **Ribosomal protein S3 (RPS3):** This protein is a component of the 40S ribosomal subunit and serves as a linker between the GAIT complex and the ribosome. It contributes to the translational repression by preventing ribosome assembly on the target mRNA.
* **Protein kinase C-related kinase (PKC-related kinase):** This protein is a kinase that phosphorylates eIF3G, potentially enhancing the repression activity of the GAIT complex.
* **Other associated proteins:** In addition to the core proteins, other proteins have been associated with the GAIT complex, such as the ribosomal protein S29 (RPS29) and the protein arginine methyltransferase 5 (PRMT5). These proteins may play regulatory roles in the complex and contribute to the fine-tuning of its activity.
The GAIT complex is known to repress the translation of mRNAs involved in various cellular processes, including inflammation, angiogenesis, and erythropoiesis. Its activity is regulated by various factors, including hypoxia, iron deficiency, and cytokine signaling. The understanding of the GAIT complex composition and function is crucial for comprehending the intricate mechanisms of gene expression regulation and its implication in human diseases.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| 60S ribosomal protein L13a | A eukaryotic-type large ribosomal subunit protein uL13 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P40429] | Homo sapiens (human) |
| Bifunctional glutamate/proline--tRNA ligase | A bifunctional glutamate/proline--tRNA ligase that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
| Glyceraldehyde-3-phosphate dehydrogenase | A glyceraldehyde-3-phosphate dehydrogenase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P04406] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| coumarin | 2H-chromen-2-one: coumarin derivative | coumarins | fluorescent dye; human metabolite; plant metabolite |
| oxidopamine | oxidopamine : A benzenetriol that is phenethylamine in which the hydrogens at positions 2, 4, and 5 on the phenyl ring are replaced by hydroxy groups. It occurs naturally in human urine, but is also produced as a metabolite of the drug DOPA (used for the treatment of Parkinson's disease). Oxidopamine: A neurotransmitter analogue that depletes noradrenergic stores in nerve endings and induces a reduction of dopamine levels in the brain. Its mechanism of action is related to the production of cytolytic free-radicals. | benzenetriol; catecholamine; primary amino compound | drug metabolite; human metabolite; neurotoxin |
| pentamidine | pentamidine : A diether consisting of pentane-1,5-diol in which both hydroxyl hydrogens have been replaced by 4-amidinophenyl groups. A trypanocidal drug that is used for treatment of cutaneous leishmaniasis and Chagas disease. Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of PNEUMOCYSTIS pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects. | aromatic ether; carboxamidine; diether | anti-inflammatory agent; antifungal agent; calmodulin antagonist; chemokine receptor 5 antagonist; EC 2.3.1.48 (histone acetyltransferase) inhibitor; NMDA receptor antagonist; S100 calcium-binding protein B inhibitor; trypanocidal drug; xenobiotic |
| cinchophen | cinchophen: was heading 1963-94; ACIPHENOCHINOLIUM was see CHINOPHEN 1978-94; use QUINOLINES to search CINCHOPHEN 1966-94 | quinolines | |
| osthol | osthol: from Cnidium monnieri and Angelica pubescens (both Apiaceae); structure given in first source | botanical anti-fungal agent; coumarins | metabolite |
| nicotinamide mononucleotide | Nicotinamide Mononucleotide: 3-Carbamoyl-1-beta-D-ribofuranosyl pyridinium hydroxide-5'phosphate, inner salt. A nucleotide in which the nitrogenous base, nicotinamide, is in beta-N-glycosidic linkage with the C-1 position of D-ribose. Synonyms: Nicotinamide Ribonucleotide; NMN. | nicotinamide mononucleotide | Escherichia coli metabolite; mouse metabolite |
| 2-methyladenine | methyladenine : Any member of the class of 6-aminopurines that is adenine bearing a single methyl substituent. | ||
| isopentenyladenosine | Isopentenyladenosine: N(6)-[delta(3)-isopentenyl]adenosine. Isopentenyl derivative of adenosine which is a member of the cytokinin family of plant growth regulators. N(6)-(Delta(2)-isopentenyl)adenosine : A nucleoside analogue in which adenosine has been modified by substitution at the 6-amino nitrogen by a Delta(2)-isopentenyl group. | N-ribosyl-N(6)-isopentenyladenine; nucleoside analogue | antineoplastic agent; plant growth regulator; plant metabolite |
| benzonidazole | benznidazole : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of (2-nitroimidazol-1-yl)acetic acid with the aromatic amino group of benzylamine. Used for treatment of Chagas disease. benzonidazole: used in treatment of Chagas' disease | C-nitro compound; imidazoles; monocarboxylic acid amide | antiprotozoal drug |
| adenosine | quinquefolan B: isolated from roots of Panax quinquefolium L.; RN not in Chemline 10/87; RN from Toxlit | adenosines; purines D-ribonucleoside | analgesic; anti-arrhythmia drug; fundamental metabolite; human metabolite; vasodilator agent |
| xanthyletine | xanthyletine: structure | coumarins | |
| metrifudil | |||
| seselin | seselin: structure in first source | coumarins | metabolite |
| n(6)-benzyladenosine | N(6)-benzyladenosine: RN given refers to parent cpd | ||
| 2-methyladenosine | 2-methyladenosine : A methyladenosine in which the methyl group is located at position 2 on the adenine ring. | methyladenosine | |
| n(6)-cyclopentyladenosine | |||
| l 783281 | L 783281: structure in first source | ||
| scopoletin | hydroxycoumarin | plant growth regulator; plant metabolite | |
| 7-hydroxycoumarin | 7-oxycoumarin: derivatives have anti-oxidant properties umbelliferone : A hydroxycoumarin that is coumarin substituted by a hydroxy group ay position 7. | hydroxycoumarin | fluorescent probe; food component; plant metabolite |
| gentamicin sulfate | |||
| PF-06446846 | PF-06446846 : A triazolopyridine that is 3H-[1,2,3]triazolo[4,5-b]pyridine substituted by a 4-{(3-chloropyridin-2-yl)[(3R)-piperidin-3-yl]carbamoyl}phenyl group at position 3. It is a potent inhibitor of PCSK9. PF-06446846: inhibits translation of PCSK9 ;structure in first source | benzamides; monochloropyridine; piperidines; tertiary carboxamide; triazolopyridine | antilipemic drug; EC 3.4.21.61 (kexin) inhibitor |