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Information on EC 2.5.1.39 - 4-hydroxybenzoate polyprenyltransferase and Organism(s) Homo sapiens and UniProt Accession Q96H96
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2.5.1.39 4-hydroxybenzoate polyprenyltransferaseIUBMB Comments
This enzyme, involved in the biosynthesis of ubiquinone, attaches a polyprenyl side chain to a 4-hydroxybenzoate ring, producing the first ubiquinone intermediate that is membrane bound. The number of isoprenoid subunits in the side chain varies in different species. The enzyme does not have any specificity concerning the length of the polyprenyl tail, and accepts tails of various lengths with similar efficiency [2,4,5].
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
Synonyms
osppt1a, smppt, 4-hydroxybenzoate octaprenyltransferase, coq2p, 4-hydroxybenzoate polyprenyltransferase, nonaprenyl-4-hydroxybenzoate transferase, 4-hydroxybenzoate:polyprenyl transferase, para-hydroxybenzoate-polyprenyl transferase, 4-hydroxybenzoate polyprenyl diphosphate transferase, 4-hydroxybenzoate octaprenyl transferase, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
4-hydroxybenzoate transferase
-
-
-
-
dimethylallyltransferase, p-hydroxybenzoate poly-
-
-
-
-
nonaprenyl-4-hydroxybenzoate transferase
-
-
-
-
p-hydroxybenzoate dimethylallyltransferase
-
-
-
-
p-hydroxybenzoate polyprenyltransferase
-
-
-
-
p-hydroxybenzoic acid-polyprenyl transferase
-
-
-
-
p-hydroxybenzoic-polyprenyl transferase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
alkenyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
polyprenyl-diphosphate:4-hydroxybenzoate polyprenyltransferase
This enzyme, involved in the biosynthesis of ubiquinone, attaches a polyprenyl side chain to a 4-hydroxybenzoate ring, producing the first ubiquinone intermediate that is membrane bound. The number of isoprenoid subunits in the side chain varies in different species. The enzyme does not have any specificity concerning the length of the polyprenyl tail, and accepts tails of various lengths with similar efficiency [2,4,5].
CAS REGISTRY NUMBER
COMMENTARY
9030-77-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
solanesyl diphosphate + 4-hydroxybenzoate
diphosphate + nonaprenyl-4-hydroxybenzoate
-
-
-
?
decaprenyl diphosphate + 4-hydroxybenzoate
diphosphate + decaprenyl-4-hydroxybenzoate
-
-
-
?
decaprenyl diphosphate + 4-hydroxybenzoate
diphosphate + decaprenyl-4-hydroxybenzoate
preferred substrate
-
-
?
solanesyl diphosphate + 4-hydroxybenzoate
diphosphate + 3-solanesyl-4-hydroxybenzoate
-
-
-
-
?
solanesyl diphosphate + 4-hydroxybenzoate
diphosphate + 3-solanesyl-4-hydroxybenzoate
-
-
-
-
ir
additional information
?
-
the enzyme is required for biosynthesis of CoQ2, i.e. ubiquinone
-
-
?
additional information
?
-
the enzyme catalyzes the prenylation of 4-hydroxybenzoate with an all-trans polyprenyl group
-
-
?
additional information
?
-
-
decaprenyl diphosphate and 4-hydroxybenzoate are condensed in a reaction catalyzed by 4-hydroxybenzoate:polyprenyl transferase, i.e. COQ2
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
decaprenyl diphosphate + 4-hydroxybenzoate
diphosphate + decaprenyl-4-hydroxybenzoate
-
-
-
?
solanesyl diphosphate + 4-hydroxybenzoate
diphosphate + nonaprenyl-4-hydroxybenzoate
-
-
-
?
additional information
?
-
the enzyme is required for biosynthesis of CoQ2, i.e. ubiquinone
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-nitrobenzoate
-
inhibition of COQ2 by 4-nitrobenzoate, leading to 40-50% residual CoQ10, is associated with increased oxidative stress and reduced viability, together with moderately decreased ATP levels and ATP/ADP ratio
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3-[(cholamidopropyl)dimethylammonio]-1-propanesulfonate
-
0.05% final concentration, significant stimulation of activity
additional information
-
not stimulated by sodium deoxycholate, lysophosphatidyl choline, or octylglucoside
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
CoQ10 synthesis is significantly decreased in cultured skin fibroblasts of mutant S109N
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
malfunction
metabolism
-
the enzyme catalyzes one of the first steps in ubiquinone or coenzyme Q, CoQ, biosynthesis
malfunction
CoQ10 deficiency caused by mutation S109N in para-hydroxybenzoate-polyprenyl transferase, COQ2, leads to early myoclonic epilepsy, hypertrophic cardiomyopathy and subsequently a nephrotic syndrome, phenotype and clinical features, detailed overview
malfunction
enzyme mutations cause reduced CoQ10 levels, renal dysfunction associated with mitochondriopathies, and/or an epileptic phenotype, overview. The prevalence of renal symptoms in COQ2 defects may be related to differential expression of proteins involved in ubiquinone metabolism
malfunction
-
the consequence of severe CoQ10 deficiency on bioenergetics, oxidative stress, and antioxidant defenses in cultured skin fibroblasts harboring COQ2 mutations is examined. COQ2 mutant fibroblasts have 30% CoQ10 with partial defect in ATP synthesis, as well as significantly increased reactive oxygen species production and oxidation of lipids and proteins
malfunction
-
cell viability in skin fibroblasts with CoQ10 deficiency due to different molecular defects including mutations in COQ2. Treatment of multiple cell lines with increasing dosages of 4-nitrobenzoate, which inhibits 4-hydroxybenzoate:polyprenyltransferase, leads to dose-dependent decreases of CoQ in mammalian cells without directly inducing oxidative stress or mitochondrial respiration impairment. Fibroblasts from a patient with a homozygous COQ2 mutation require uridine to maintain cell growth and proposed that deficiency of CoQ10 impaired pyrimidine biosynthesis due to dependence of dihydro-orotate dehydrogenase on ubiquinol. Oxidative stress plays an important role in the demise of COQ2 mutant fibroblasts by activating cell-death related pathways, which are averted by antioxidant supplementation
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). COQ2_HUMAN
371
6
40489
Swiss-Prot
Mitochondrion (Reliability: 1)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
the enzyme contains 6 transmembrane sequences and an UbiA domain
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
R197H/N228S
naturally occurring lethal enzyme mutation, renal phenotype including collapsing glomerulonepritis and steroid-resistant nephrotic syndome
S109N
naturally occurring lethal mutation causing a severe phenotype, CoQ10 synthesis is significantly decreased in cultured skin fibroblasts, a kidney sample reveals focal segmental glomerulosclerosis lesions, The affected glomeruli demonstrate mesangial hypercellularity, segmental sclerosis of glomerular capillaries, enlarged podocytes with intracytoplasmic hyaline vacuoles and adhesions to the Bowman's capsule, podocytes are enlarged and show extensive foot process effacement, overview
S146N
naturally occurring lethal enzyme mutation, the mutation causes oliguria, oligohydramnios, hypertension, and seizures
Y297C
naturally occurring lethal enzyme mutation causing a severe phenotype, with end-stage renal failure, focal segmental glomeruloslerosis, steroid-resistant nephrotic syndome, developmental delay and developmental regression, optic atrophy, seizures, myoclonic seizures, refractory seizures, status epilepticus, and nystagmoid movements, overview
additional information
-
in patients with encephalomyopathy, nephropathy and severe CoQ10 deficiency, a homozygous mutation was identified in the CoQ10 biosynthesis gene COQ2. mRNA levels of this gene are significantly increased in patients fibroblast, and its activity is significantly lower in fibroblasts of patients with mutation c.890A.G relative to controls and CoQ10-deficient fibroblasts from ataxic patient. Wild-type enzyme is able to complement Coq2 defective Sacharomyces cerevisiae
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene COQ2, DNA and amino acid sequence determination and analysis, functional expression in and complementation of yeast Coq2 null mutant cells, CoQ biosynthesis rate is lower in the yeast cells when rescued with the human enzyme compared to cells rescued with the yeast enzyme
gene COQ2, DNA and amino acid sequence determination and analysis, genotyping
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
in patients with encephalomyopathy, nephropathy and severe CoQ10 deficiency, a homozygous mutation was identified in the CoQ10 biosynthesis gene COQ2. mRNA levels of this gene are significantly increased in patients fibroblast, and its activity is significantly lower in fibroblasts of patients with mutation c.890A.G relative to controls and CoQ10-deficient fibroblasts from ataxic patient
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Forsgren, M.; Attersand, A.; Lake, S.; Gruenler, J.; Swiezewska, E.; Dallner, G.; Climent, I.
Isolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of CoQ
Biochem. J.
382
519-526
2004
Saccharomyces cerevisiae, Homo sapiens (Q96H96)
Buron, M.I.; Herman, M.D.; Alcain, F.J.; Villalba, J.M.
Stimulation of polyprenyl 4-hydroxybenzoate transferase activity by sodium cholate and 3-[(cholamidopropyl)dimethylammonio]-1-propanesulfonate
Anal. Biochem.
353
15-21
2006
Homo sapiens
Mollet, J.; Giurgea, I.; Schlemmer, D.; Dallner, G.; Chretien, D.; Delahodde, A.; Bacq, D.; de Lonlay, P.; Munnich, A.; Roetig, A.
Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders
J. Clin. Invest.
117
765-772
2007
Homo sapiens
Lopez-Martin, J.M.; Salviati, L.; Trevisson, E.; Montini, G.; DiMauro, S.; Quinzii, C.; Hirano, M.; Rodriguez-Hernandez, A.; Cordero, M.D.; Sanchez-Alcazar, J.A.; Santos-Ocana, C.; Navas, P.
Missense mutation of the COQ2 gene causes defects of bioenergetics and de novo pyrimidine synthesis
Hum. Mol. Genet.
16
1091-1097
2007
Saccharomyces cerevisiae, Homo sapiens
Quinzii, C.M.; Lopez, L.C.; Von-Moltke, J.; Naini, A.; Krishna, S.; Schuelke, M.; Salviati, L.; Navas, P.; DiMauro, S.; Hirano, M.
Respiratory chain dysfunction and oxidative stress correlate with severity of primary CoQ10 deficiency
FASEB J.
22
1874-1885
2008
Homo sapiens
Quinzii, C.M.; Tadesse, S.; Naini, A.; Hirano, M.
Effects of inhibiting CoQ10 biosynthesis with 4-nitrobenzoate in human fibroblasts
PLoS ONE
7
e30606
2012
Homo sapiens
Scalais, E.; Chafai, R.; Van Coster, R.; Bindl, L.; Nuttin, C.; Panagiotaraki, C.; Seneca, S.; Lissens, W.; Ribes, A.; Geers, C.; Smet, J.; De Meirleir, L.
Early myoclonic epilepsy, hypertrophic cardiomyopathy and subsequently a nephrotic syndrome in a patient with CoQ10 deficiency caused by mutations in para-hydroxybenzoate-polyprenyl transferase (COQ2)
Eur. J. Paediatr. Neurol.
17
625-630
2013
Homo sapiens (Q96H96), Homo sapiens
Diomedi-Camassei,F.; Di Giandomenico, S.; Santorelli, F.M.; Caridi, G.; Piemonte, F.; Montini, G.; Ghiggeri, G.M.; Murer, L.; Barisoni, L.; Pastore, A.; Onetti Muda, A.; Valente, M.L.; Bertini, E.; Emma, F.
COQ2 nephropathy: a newly described inherited mitochondriopathy with primary renal involvement
J. Am. Soc. Nephrol.
18
2773-2780
2007
Homo sapiens (Q96H96)
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