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Literature summary for 2.5.1.59 extracted from

  • Gao, S.; Yu, R.; Zhou, X.
    The role of geranylgeranyltransferase I-mediated protein prenylation in the brain (2015), Mol. Neurobiol., 53, 6925-6937.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of GST-tagged GGTIbeta subunit Rattus norvegicus

Inhibitors

Inhibitors Comment Organism Structure
GGTi-2147 specific GGTIbeta enzyme inhibitor; specific GGTIbeta enzyme inhibitor Homo sapiens
GGTi-2147 specific GGTIbeta enzyme inhibitor; specific GGTIbeta enzyme inhibitor Mus musculus
GGTi-2147 specific GGTIbeta enzyme inhibitor; specific GGTIbeta enzyme inhibitor Rattus norvegicus
GGTI-2418 a GGTI inhibitor, in clinical trials as potential anti-tumor agent in breast cancer; a GGTI inhibitor, in clinical trials as potential anti-tumor agent in breast cancer Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
neuromuscular junction GGTI is localized at the neuromuscular junction and regulates agrin-induced clustering of acetylcholine receptors by interacting with muscle-specific receptor tyrosine kinase Rattus norvegicus 31594
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
geranylgeranyl diphosphate + Cdc42-cysteine Rattus norvegicus
-
S-geranylgeranyl-Cdc42 + diphosphate
-
?
geranylgeranyl diphosphate + protein-cysteine Rattus norvegicus
-
S-geranylgeranyl-protein + diphosphate
-
?
geranylgeranyl diphosphate + protein-cysteine Homo sapiens
-
S-geranylgeranyl-protein + diphosphate
-
?
geranylgeranyl diphosphate + protein-cysteine Mus musculus
-
S-geranylgeranyl-protein + diphosphate
-
?
geranylgeranyl diphosphate + Rac GTPase-cysteine Rattus norvegicus
-
S-geranylgeranyl-Rac GTPase + diphosphate
-
?
geranylgeranyl diphosphate + RhoA GTPase-cysteine Rattus norvegicus
-
S-geranylgeranyl-RhoA GTPase + diphosphate
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P49354 subunit alpha
-
Homo sapiens P53609 subunit beta
-
Mus musculus Q61239 subunit alpha
-
Mus musculus Q8BUY9 subunit beta
-
Rattus norvegicus P53610 subunit beta
-
Rattus norvegicus Q04631 subunit alpha
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Source Tissue

Source Tissue Comment Organism Textmining
brain high enzyme activity. GGTI expression and activity are particularly enriched in the adult brain and developmentally regulated after birth in various mammalian tissues Rattus norvegicus
-
brain high enzyme activity. GGTI expression and activity are particularly enriched in the adult brain and developmentally regulated after birth in various mammalian tissues Homo sapiens
-
brain high enzyme activity. GGTI expression and activity are particularly enriched in the adult brain and developmentally regulated after birth in various mammalian tissues Mus musculus
-
cell culture the expression of GGTIalpha in cultured hippocampal neurons gradually increases and peaks at approximately 8 days in vitro Rattus norvegicus
-
cell culture the expression of GGTIbeta in cultured hippocampal neurons gradually increases and peaks at approximately 8 days in vitro Rattus norvegicus
-
cerebellum
-
Rattus norvegicus
-
cerebellum GGTIbeta protein level and/or GGTI activity increase gradually from P0 to adult in rat cerebellum Rattus norvegicus
-
hippocampus hippocampal neurons and abundantly located in synaptosome and postsynaptic density fractions from P14 rat hippocampus, GGTIbeta protein level and/or GGTI activity increase gradually from P0 to adult in rat hippocampus. The expression of GGTIbeta in cultured hippocampal neurons gradually increases and peaks at approximately 8 days in vitro Rattus norvegicus
-
hippocampus hippocampal neurons and abundantly located in synaptosome and postsynaptic density fractions from P14 rat hippocampus. The expression of GGTIalpha in cultured hippocampal neurons gradually increases and peaks at approximately 8 days in vitro Rattus norvegicus
-
kidney
-
Rattus norvegicus
-
kidney
-
Homo sapiens
-
kidney
-
Mus musculus
-
liver low enzyme activity Rattus norvegicus
-
liver low enzyme activity Homo sapiens
-
liver low enzyme activity Mus musculus
-
lung
-
Rattus norvegicus
-
lung
-
Homo sapiens
-
lung
-
Mus musculus
-
nervous system
-
Rattus norvegicus
-
nervous system
-
Homo sapiens
-
nervous system
-
Mus musculus
-
neuron
-
Rattus norvegicus
-
neuron
-
Homo sapiens
-
neuron
-
Mus musculus
-
Purkinje cell
-
Rattus norvegicus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
geranylgeranyl diphosphate + Cdc42-cysteine
-
Rattus norvegicus S-geranylgeranyl-Cdc42 + diphosphate
-
?
geranylgeranyl diphosphate + protein-cysteine
-
Rattus norvegicus S-geranylgeranyl-protein + diphosphate
-
?
geranylgeranyl diphosphate + protein-cysteine
-
Homo sapiens S-geranylgeranyl-protein + diphosphate
-
?
geranylgeranyl diphosphate + protein-cysteine
-
Mus musculus S-geranylgeranyl-protein + diphosphate
-
?
geranylgeranyl diphosphate + Rac GTPase-cysteine
-
Rattus norvegicus S-geranylgeranyl-Rac GTPase + diphosphate
-
?
geranylgeranyl diphosphate + RhoA GTPase-cysteine
-
Rattus norvegicus S-geranylgeranyl-RhoA GTPase + diphosphate
-
?

Subunits

Subunits Comment Organism
More both alpha and beta subunits are composed primarily of alpha helices. The beta subunits of GGTI consist of 13 alpha helices, and 12 of them are folded into an alpha-alpha barrel. The helices of the alpha subunit are arranged in a crescent-shaped superhelix that wraps around the alpha-alpha barrel of beta subunit. This arrangement creates a deep, funnel-shaped cavity in the center of the barrel, and the active sites of GGTI are located within this cavity Rattus norvegicus
More both alpha and beta subunits are composed primarily of alpha helices. The beta subunits of GGTI consist of 13 alpha helices, and 12 of them are folded into an alpha-alpha barrel. The helices of the alpha subunit are arranged in a crescent-shaped superhelix that wraps around the alpha-alpha barrel of beta subunit. This arrangement creates a deep, funnel-shaped cavity in the center of the barrel, and the active sites of GGTI are located within this cavity Homo sapiens
More both alpha and beta subunits are composed primarily of alpha helices. The beta subunits of GGTI consist of 13 alpha helices, and 12 of them are folded into an alpha-alpha barrel. The helices of the alpha subunit are arranged in a crescent-shaped superhelix that wraps around the alpha-alpha barrel of beta subunit. This arrangement creates a deep, funnel-shaped cavity in the center of the barrel, and the active sites of GGTI are located within this cavity Mus musculus

Synonyms

Synonyms Comment Organism
geranylgeranyltransferase I
-
Rattus norvegicus
geranylgeranyltransferase I
-
Homo sapiens
geranylgeranyltransferase I
-
Mus musculus
GGTI
-
Rattus norvegicus
GGTI
-
Homo sapiens
GGTI
-
Mus musculus

General Information

General Information Comment Organism
malfunction high K+ or bicuculline-induced increases in dendritic spine density are significantly abolished by enzyme inhibition. GGTI not only regulates the basal neuronal dendritic growth but also mediates neuronal activity and BDNF-induced dendritogenesis. Dendrite development of Purkinje cells is dramatically impeded by downregulation of GGTIbeta expression or inhibiting GGTI activity in cultured cerebellar slices Rattus norvegicus
malfunction mice with lateral ventricular injection of GGTi-2147, a specific GGTI inhibitor, have significant reduction in the membrane association of Rac1 and in the dendritic spine densities in the hippocampus, the cerebellum, and the frontal cortex Mus musculus
physiological function role of geranylgeranyltransferase I-mediated protein prenylation in the brain. GGTI and geranylgeranylation are involved in neurodegenerative diseases, e.g., aging, Alzheimer's disease, multiple sclerosis, and Niemann-Pick disease type C, mechanism of GGTI-mediated isoprenylation in the pathogenesis of neurodegenerative and neurodevelopmental disorders, overview. GGTI is localized at the neuromuscular junction and regulates agrin-induced clustering of acetylcholine receptors by interacting with muscle-specific receptor tyrosine kinase. Importance of prenylation in synaptic function. GGTI promotes neuronal dendritogenesis via increasing the membrane association of Rac1 in CNS neurons Rattus norvegicus
physiological function role of geranylgeranyltransferase I-mediated protein prenylation in the brain. GGTI and geranylgeranylation are involved in neurodegenerative diseases, e.g., aging, Alzheimer's disease, multiple sclerosis, and Niemann-Pick disease type C, mechanism of GGTI-mediated isoprenylation in the pathogenesis of neurodegenerative and neurodevelopmental disorders, overview. Importance of prenylation in synaptic function. GGTI not only regulates the basal neuronal dendritic growth but also mediates neuronal activity and BDNF-induced dendritogenesis. GGTI promotes neuronal dendritogenesis via increasing the membrane association of Rac1 in CNS neurons Mus musculus
physiological function role of geranylgeranyltransferase I-mediated protein prenylation in the brain. GGTI and geranylgeranylation are involved in neurodegenerative diseases, e.g., aging, Alzheimer's disease, multiple sclerosis, and Niemann-Pick disease type C, mechanism of GGTI-mediated isoprenylation in the pathogenesis of neurodegenerative and neurodevelopmental disorders, overview. Importance of prenylation in synaptic function. GGTI not only regulates the basal neuronal dendritic growth but also mediates neuronal activity and BDNF-induced dendritogenesis. GGTI promotes neuronal dendritogenesis via increasing the membrane association of Rac1 in CNS neurons. Roles of the enzyme in aging, overview Homo sapiens
physiological function role of geranylgeranyltransferase I-mediated protein prenylation in the brain. GGTI and geranylgeranylation are involved in neurodegenerative diseases, e.g., aging, Alzheimer's disease, multiple sclerosis, and Niemann-Pick disease type C, mechanism of GGTI-mediated isoprenylation in the pathogenesis of neurodegenerative and neurodevelopmental disorders, overview. neuromuscular junction. GGTI is localized at the neuromuscular junction and regulates agrin-induced clustering of acetylcholine receptors by interacting with muscle-specific receptor tyrosine kinase. Importance of prenylation in synaptic function. GGTI promotes neuronal dendritogenesis via increasing the membrane association of Rac1 in CNS neurons Rattus norvegicus