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Information on EC 5.4.4.2 - isochorismate synthase and Organism(s) Arabidopsis thaliana and UniProt Accession Q9S7H8
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5.4.4.2 isochorismate synthaseIUBMB Comments
Requires Mg2+. The reaction is reversible.
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Word Map
- 5.4.4.2
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corticosteroid
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inhaled
- asthma
- children
- pulmonary
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long-acting
- airway
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labas
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asthmatic
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bronchodilator
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placebo
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fluticasone
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expiratory
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prescript
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short-acting
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double-blind
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physician
- bronchial
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beta2-agonists
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budesonide
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spirometry
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add-on
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wheezing
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randomised
- ketanserin
- 5-hydroxytryptamine
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leukotriene
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once-daily
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muscarinic
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monotherapy
- salmeterol
- sputum
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5-ht-induced
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urodynamic
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parallel-group
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8-oh-dpat
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datalink
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airflow
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run-in
The taxonomic range for the selected organisms is: Arabidopsis thaliana
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
ics, isochorismate synthase, amonabactin, salicylate synthase, isochorismate synthase 1, eds16, atics1, isochorismate hydroxymutase, menaquinone-specific isochorismate synthase, atics2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Amonabactin
-
-
-
-
Eds16
-
-
-
-
ICS1
ICS2
IcsI
-
-
-
-
isochorismate mutase
-
-
-
-
Isochorismic synthase
-
-
-
-
Sid2
-
-
-
-
Synthase, isochorismate
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
isomerization
-
-
-
-
PATHWAY SOURCE
PATHWAYS
KEGG
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
isochorismate hydroxymutase
Requires Mg2+. The reaction is reversible.
CAS REGISTRY NUMBER
COMMENTARY
37318-53-9
-
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
Chorismate
Isochorismate
-
reaction operates near equilibrium, equilibrium constant is 0.89. Enzyme does not convert chorismate directly to salicylic acid
-
r
Chorismate
Isochorismate
alternative pathway to produce salicyl acid in response to pathogens
-
-
?
Chorismate
Isochorismate
-
involved in biosynthesis of salicylic acid
-
-
?
additional information
?
-
isozyme ICS1 does not act as isochorismate pyruvate lyase (IPL, EC 4.2.99.21) and bifunctional salicylate synthase, it does not convert chorismate into salicylate
-
-
?
additional information
?
-
isozyme ICS1 does not act as isochorismate pyruvate lyase (IPL, EC 4.2.99.21) and bifunctional salicylate synthase, it does not convert chorismate into salicylate
-
-
?
additional information
?
-
-
isozyme ICS1 does not act as isochorismate pyruvate lyase (IPL, EC 4.2.99.21) and bifunctional salicylate synthase, it does not convert chorismate into salicylate
-
-
?
additional information
?
-
ICS2 participates in the synthesis of SA, but in limited amounts that become clearly detectable only when ICS1 is lacking
-
-
?
additional information
?
-
isozyme ICS2 does not act as isochorismate pyruvate lyase (IPL, EC 4.2.99.21) and bifunctional salicylate synthase, it does not convert chorismate into salicylate
-
-
?
additional information
?
-
isozyme ICS2 does not act as isochorismate pyruvate lyase (IPL, EC 4.2.99.21) and bifunctional salicylate synthase, it does not convert chorismate into salicylate
-
-
?
additional information
?
-
-
isozyme ICS2 does not act as isochorismate pyruvate lyase (IPL, EC 4.2.99.21) and bifunctional salicylate synthase, it does not convert chorismate into salicylate
-
-
?
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
Chorismate
Isochorismate
alternative pathway to produce salicyl acid in response to pathogens
-
-
?
Chorismate
Isochorismate
-
involved in biosynthesis of salicylic acid
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
salicylic acid
-
treatment of plants suppresses the enhancement of enzyme expression by O3
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
O3
-
exposure to O3 enhances the accumulation of salicylic acid and increases enzyme activity, but does not affect phenylalanine ammonia lyase activity. Treatment of plants suppresses the enhancement of enzyme expression by O3
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
-
Michaelis-Menten kinetics
-
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
-
Michaelis-Menten kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
isozymes ICS1 and ICS2 activities display a response to temperature that is more typical of most enzymes, with an approximate doubling in reaction rate per 10°C between 10 and about 33°C, while at temperatures higher than this, reaction rates decline
additional information
isozymes ICS1 and ICS2 activities display a response to temperature that is more typical of most enzymes, with an approximate doubling in reaction rate per 10°C between 10 and about 33°C, while at temperatures higher than this, reaction rates decline
additional information
-
isozymes ICS1 and ICS2 activities display a response to temperature that is more typical of most enzymes, with an approximate doubling in reaction rate per 10°C between 10 and about 33°C, while at temperatures higher than this, reaction rates decline
additional information
isozymes ICS1 and ICS2 activities display a response to temperature that is more typical of most enzymes, with an approximate doubling in reaction rate per 10°C between 10 and about 33°C, while at temperatures higher than this, reaction rates decline
additional information
isozymes ICS1 and ICS2 activities display a response to temperature that is more typical of most enzymes, with an approximate doubling in reaction rate per 10°C between 10 and about 33°C, while at temperatures higher than this, reaction rates decline
additional information
-
isozymes ICS1 and ICS2 activities display a response to temperature that is more typical of most enzymes, with an approximate doubling in reaction rate per 10°C between 10 and about 33°C, while at temperatures higher than this, reaction rates decline
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
activity is not regulated by light-dependent changes in stromal pH value, Mg2+ or redox potential
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
isozyme AtICS2 appears to be expressed constitutively, predominantly in the plant vasculature. AtICS2 expression in leaf tissue appears to be localized most strongly in the vasculature and hydathodes
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
genes ATICS1 and AtICS2 are both located on chromosome 1 on different sides of the centromere, and they are likely a result of a duplication event, since they are bordered by similar genes. At the DNA sequence level, the protein-coding regions of the two genes share a high degree of similarity, but this does not extend into the untranslated regions
malfunction
metabolism
physiological function
evolution
genes ATICS1 and AtICS2 are both located on chromosome 1 on different sides of the centromere, and they are likely a result of a duplication event, since they are bordered by similar genes. At the DNA sequence level, the protein-coding regions of the two genes share a high degree of similarity, but this does not extend into the untranslated regions
metabolism
enzyme ICS does not act as isochorismate pyruvate lyase (IPL, EC 4.2.99.21) and bifunctional salicylate synthase, it does not convert chorismate into salicylate. In Arabidopsis thaliana, salicylate is synthesized from chorismic acid, derived from the shikimic acid pathway, occuring in the plastid
physiological function
additional information
malfunction
the redox status of the plastoquinone pool in knockout mutant ics1 shows significant variation depending on the leaf age. Mutant plants treated with a phylloquinone precursor display symptoms of phenotypic reversion towards the wild type. The ics1 mutant also shows altered thylakoid structure with an increased number of stacked thylakoids per granum
malfunction
mutation sed111 in the gene salicylic acid induction-deficient 2 (SID2), which encodes isochorismate synthase 1. Mutation sed111 belongs to a series of mutants called suppressor of esd4 (sed), which delay flowering, enhance growth and reduce hyperaccumulation of SUMO conjugates. Mutations in the SUMO protease early in short days 4 (ESD4) cause hyperaccumulation of conjugates formed between SUMO and its substrates, and phenotypically are associated with extreme early flowering and impaired growth. Elevated salicylic acid levels conferred by increased expression of isochorismate synthase 1 contribute to hyperaccumulation of SUMO1 conjugates in the Arabidopsis thaliana mutant early in short days 4. Compared to wild-type plants, esd4 contains higher levels of SID2 mRNA and about threefold more salicylate, whereas sed111 contains lower salicylate levels
malfunction
significant reduction in the expression of ICS1 during immune responses is observed in the tcp8/tcp9 double mutant
metabolism
enzyme ICS does not act as isochorismate pyruvate lyase (IPL, EC 4.2.99.21) and bifunctional salicylate synthase, it does not convert chorismate into salicylate. In Arabidopsis thaliana, salicylate is synthesized from chorismic acid, derived from the shikimic acid pathway, occuring in the plastid
metabolism
isochorismate synthase 1 is a key enzyme in salicylate biosynthesis in Arabidopsis thaliana. The TCP family transcription factor AtTCP8 is a regulator of isozyme ICS1, it binds to a typical TCP binding site in the ICS1 promoter. Expression patterns of TCP8 and its corresponding gene TCP9 largely overlap with ICS1 under pathogen attack. Strong interactions between TCP8 and SAR deficient 1 (SARD1), WRKY family transcription factor 28 (WRKY28), NAC (NAM/ATAF1, ATAF2/CUC2) family transcription factor 019 (NAC019), as well as among TCP8, TCP9 and TCP20, implying a complex coordinated regulatory mechanism underlying ICS1 expression. There is a strong negative regulatory region between -128 and -316 bp, and the binding of repressor(s) to this region may be necessary for suppression of ICS1 expression during plant growth and development, TCP8 can bind at this region, while TCP5, TCP11 and TCP19 appear not to bind to the promoter region. TCP8 specifically binds to the TCP binding site in the ICS1 promoter in vitro and in vivo. Trans-activation capability of TCP8. TCP8/TCP9 positively regulate ICS1 expression with redundancy upon pathogen infection, and TCPs are involved in maintaining ICS1 expression, yeast one-hybrid (Y1H) screening and transactivation activity assay, detailed overview
physiological function
the enzyme is required for the appropriate hypersensitive disease defence response. It also takes part in the synthesis of phylloquinone, which is incorporated into photosystem I and is an important component of photosynthetic electron transport in plants role of ICS1 in regulation of state transition. Role of ICS1 in integration of the chloroplast ultrastructure, the redox status of the plastoquinone pool, and organization of the photosystems, which all are important for optimal immune defence and light acclimatory responses
physiological function
isochorismate synthase 1 is required for salicylate biosynthesis. SUMO homeostasis influences salicylate biosynthesis in wild-type plants, and also demonstrate that elevated levels of salicylate strongly increase the abundance of SUMO conjugates
physiological function
isozyme AtICS1 is required for increased salicylate biosynthesis in response to pathogens, and its expression can be stimulated throughout the leaf by virus infection and exogenous salicylate. Isozymes AtICS1 and AtICS2 can be successful in competing for chorismate in vivo
physiological function
-
Arabidopsis ICS1 represents a divergent isoform for inducible salicylic acid synthesis during defense
physiological function
isozymes AtICS1 and AtICS2 can be successful in competing for chorismate in vivo
additional information
homology modeling of isozymes ICS1 and ICS2 using Serratia marcescens anthranilate synthase (TrpE, PDB ID 1I7Q) as reference structure
additional information
homology modeling of isozymes ICS1 and ICS2 using Serratia marcescens anthranilate synthase (TrpE, PDB ID 1I7Q) as reference structure
additional information
-
homology modeling of isozymes ICS1 and ICS2 using Serratia marcescens anthranilate synthase (TrpE, PDB ID 1I7Q) as reference structure
additional information
homology modeling of isozymes ICS1 and ICS2 using Serratia marcescens anthranilate synthase (TrpE, PDB ID 1I7Q) as reference structure
additional information
homology modeling of isozymes ICS1 and ICS2 using Serratia marcescens anthranilate synthase (TrpE, PDB ID 1I7Q) as reference structure
additional information
-
homology modeling of isozymes ICS1 and ICS2 using Serratia marcescens anthranilate synthase (TrpE, PDB ID 1I7Q) as reference structure
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). ICS1_ARATH
569
0
62575
Swiss-Prot
Chloroplast (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
x * 60000, about, recombinant His6-tagged isozyme ICS1, SDS-PAGE
?
x * 60000, about, recombinant His6-tagged isozyme ICS2, SDS-PAGE
additional information
additional information
isozyme ICS1 structure comparisons with isozyme ICS2 and other enzymes, overview
additional information
isozyme ICS1 structure comparisons with isozyme ICS2 and other enzymes, overview
additional information
-
isozyme ICS1 structure comparisons with isozyme ICS2 and other enzymes, overview
additional information
isozyme ICS2 structure comparisons with isozyme ICS1 and other enzymes, overview
additional information
isozyme ICS2 structure comparisons with isozyme ICS1 and other enzymes, overview
additional information
-
isozyme ICS2 structure comparisons with isozyme ICS1 and other enzymes, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
precursor protein of 62000 Da is cleaved to 58000 Da upon import into plastid
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
genetic mapping and genome sequencing indicate that mutation sed111 is in the gene salicylic acid induction-deficient 2 (SID2), which encodes isochorismate synthase 1, ICS1. Mutation sed111 belongs to a series of mutants called suppressor of esd4 (sed), which delay flowering, enhance growth and reduce hyperaccumulation of SUMO conjugates. Mutations in the SUMO protease early in short days 4 (ESD4) cause hyperaccumulation of conjugates formed between SUMO and its substrates, and phenotypically are associated with extreme early flowering and impaired growth. Compared to wild-type plants, esd4 contains higher levels of SID2 mRNA and about threefold more salicylate, whereas sed111 contains lower salicylate levels. Other sed mutations also reduce the high SID2 mRNA abundance and free salicylate levels found in esd4-1. Sed, esd, and sid mutation analysis in Arabidopsis thaliana, detailed overview
additional information
-
plants defective in enzyme activity due to mutation sid2, level of salicylic acid and the activity of enzyme do not increase in response to O3 exposure
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His6-tagged isozyme ICS1 from Escherichia coli strain Rosetta DE3 pLysS by nickel affinity chromatography and gel filtration
recombinant His6-tagged isozyme ICS2 from Escherichia coli strain Rosetta DE3 pLysS by nickel affinity chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene ICS1, located on chromosome 1, cloning from seedling cDNA library, recombinant expression of His6-tagged isozyme ICS1 in Escherichia coli strain Rosetta DE3 pLysS
gene ICS1, yeast one-hybrid (Y1H) screening and transactivation activity assay in Saccharomyces cerevisiae strain YM4271
gene ICS2, located on chromosome 1, cloning from pFL61 library, functional recombinant expression of His6-tagged isozyme ICS2 in Escherichia coli strain Rosetta DE3 pLysS
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
a significant reduction in the expression of ICS1 during immune responses is observed in the tcp8 tcp9 double mutant. There is a strong negative regulatory region between -128 and -316 bp, and the binding of repressor(s) to this region may be necessary for suppression of ICS1 expression during plant growth and development, TCP8 can bind at this region, while TCP5, TCP11 and TCP19 appear not to bind to the promoter region. TCP8 specifically binds to the TCP binding site in the ICS1 promoter in vitro and in vivo
elevated salicylic acid levels confer increased expression of isochorismate synthase 1, ICS1
isozyme ICS1 expression is induced throughout the leaf by exogenous salicylate and virus infection. i.e. cucumber mosaic virus but not with tobacco mosaic virus
isozyme ICS1 expression is positively regulated by TCP family transcription factor AtTCP8, e.g. under pathogen attack of Pseudomonas syringae pv. maculicola ES4326. TCP8/TCP9 positively regulate ICS1 expression with redundancy upon pathogen infection, and TCPs are involved in maintaining ICS1 expression
isozyme ICS2 expression is not induced by salicylate, the AtICS2 promoter activity is not stimulated by virus infection
prevention of NPR1 nuclear localization causes over-accumulation of ICS1 transcripts in response to pathogen infection
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wildermuth, M.C.; Dewdney, J.; Wu, G.; Ausubel, F.M.
Isochorismate synthase is required to synthesize salicylic acid for plant defence
Nature
414
562-565
2001
Arabidopsis thaliana (Q9S7H8), Cyanidium caldarium, Glycine max
Ogawa, D.; Nakajima, N.; Sano, T.; Tamaoki, M.; Aono, M.; Kubo, A.; Kanna, M.; Ioki, M.; Kamada, H.; Saji, H.
Salicylic acid accumulation under O3 exposure is regulated by ethylene in tobacco plants
Plant Cell Physiol.
46
1062-1072
2005
Arabidopsis thaliana
Strawn, M.A.; Marr, S.K.; Inoue, K.; Inada, N.; Zubieta, C.; Wildermuth, M.C.
Arabidopsis isochorismate synthase functional in pathogen-induced salicylate biosynthesis exhibits properties consistent with a role in diverse stress responses
J. Biol. Chem.
282
5919-5933
2007
Arabidopsis thaliana (Q9S7H8), Arabidopsis thaliana
Ogawa, D.; Nakajima, N.; Tamaoki, M.; Aono, M.; Kubo, A.; Kamada, H.; Saji, H.
The isochorismate pathway is negatively regulated by salicylic acid signaling in O3-exposed Arabidopsis
Planta
226
1277-1285
2007
Arabidopsis thaliana
Garcion, C.; Lohmann, A.; Lamodiere, E.; Catinot, J.; Buchala, A.; Doermann, P.; Metraux, J.P.
Characterization and biological function of the ISOCHORISMATE SYNTHASE2 gene of Arabidopsis
Plant Physiol.
147
1279-1287
2008
Arabidopsis thaliana (Q9M9V6)
Zhang, X.; Chen, S.; Mou, Z.
Nuclear localization of NPR1 is required for regulation of salicylate tolerance, isochorismate synthase 1 expression and salicylate accumulation in Arabidopsis
J. Plant Physiol.
167
144-148
2010
Arabidopsis thaliana
Yuan, Y.; Chung, J.D.; Fu, X.; Johnson, V.E.; Ranjan, P.; Booth, S.L.; Harding, S.A.; Tsai, C.J.
Alternative splicing and gene duplication differentially shaped the regulation of isochorismate synthase in Populus and Arabidopsis
Proc. Natl. Acad. Sci. USA
106
22020-22025
2009
Arabidopsis thaliana, Populus tremuloides, Populus fremontii x Populus angustifolia
Gawronski, P.; Gorecka, M.; Bederska, M.; Rusaczonek, A.; Slesak, I.; Kruk, J.; Karpinski, S.
Isochorismate synthase 1 is required for thylakoid organization, optimal plastoquinone redox status, and state transitions in Arabidopsis thaliana
J. Exp. Bot.
64
3669-3679
2013
Arabidopsis thaliana (Q9S7H8), Arabidopsis thaliana, Arabidopsis thaliana Col-0 (Q9S7H8)
Macaulay, K.M.; Heath, G.A.; Ciulli, A.; Murphy, A.M.; Abell, C.; Carr, J.P.; Smith, A.G.
The biochemical properties of the two Arabidopsis thaliana isochorismate synthases
Biochem. J.
474
1579-1590
2017
Arabidopsis thaliana (Q9M9V6), Arabidopsis thaliana (Q9S7H8), Arabidopsis thaliana
Villajuana-Bonequi, M.; Elrouby, N.; Nordstroem, K.; Griebel, T.; Bachmair, A.; Coupland, G.
Elevated salicylic acid levels conferred by increased expression of isochorismate synthase 1 contribute to hyperaccumulation of SUMO1 conjugates in the Arabidopsis mutant early in short days 4
Plant J.
79
206-219
2014
Arabidopsis thaliana (Q9S7H8)
Wang, X.; Gao, J.; Zhu, Z.; Dong, X.; Wang, X.; Ren, G.; Zhou, X.; Kuai, B.
TCP transcription factors are critical for the coordinated regulation of isochorismate synthase 1 expression in Arabidopsis thaliana
Plant J.
82
151-162
2015
Arabidopsis thaliana (Q9S7H8), Arabidopsis thaliana, Arabidopsis thaliana Col-0 (Q9S7H8)
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