Link to pathway encoded in the SEED database
| Legend: | A yellow background indicates genes that are enigmatic in some way in plants | A light pink background indicates genes that are unknown in plants | A dark pink background indicates genes that are unknown in all organisms | A pale blue background indicates evidence that genes are not present in plants | A dark gray background indicates probable pseudogenes |
| Abbrev | AT gene ID | AT gene name | Maize ortholog | Functional role | Curated localization | Localization data in AT | Localization data in Maize | Experimental data | Problems, open questions, predictions |
|---|---|---|---|---|---|---|---|---|---|
| Folate metabolism | |||||||||
| GCH1 | At3g07270 | GRMZM2G062420 | GTP cyclohydrolase I (EC 3.5.4.16) type 1 | # cytosolic (bioinformatic evidence in Arabidopsis) | Cytosol - P [PMID:12221287] | GTP cyclohydrolase activity shown by complementation of a yeast fol2 mutant with recombinant Arabidopsis At3g07270 or its tomato homolog, and by assaying GCH1 activity in extracts of complemented yeast cells [PMID:12221287]. | |||
| GCH1 | GRMZM2G106376 | ||||||||
| DPPse | At1g68760 | NUDT1, NUDX1 | No close homologs | Dihydroneopterin triphosphate diphosphatase (EC 3.6.1.n4) | # cytosolic (experimental evidence in Arabidopsis) | Cytosol- E [PMID:17804481] | At1g68760 is a non-specific Nudix hydrolase with higher activity towards nucleoside triphosphates than towards dihydroneopterin triphosphate [PMID:15611104]. At1g68760 is the only Arabidopsis Nudix enzyme shown to have 8-oxo-dGTP pyrophosphohydrolase (MutT) activity [PMID:17804481]. | The homolog from Lactococcus lactis, YlgG, shows higher dihydroneopterin triphosphate diphosphatase activity than At1g68760 [PMID:15611104]. Although At1g68760 hydrolyzes dihydroneopterin triphosphate, it prefers nucleoside triphosphates [PMID:15611104] [PMID:15878881]. Thus the true DPPse in Arabidopsis may remain to be found. | |
| Pase | Globally missing gene | Dihydroneopterin monophosphate phosphatase | # cytosolic (bioinformatic evidence in Arabidopsis) | Cytosol - P (preceding and succeeding steps are cytosolic) | Dihydroneopterin monophosphate is thought to be hydrolyzed by nonspecific phosphatase activity in E. coli [PMID:4362677]. The enzyme responsible in plants has not been identified. | ||||
| DHNA | At3g11750 | FOLB1 | GRMZM2G015588 | Dihydroneopterin aldolase (EC 4.1.2.25) | # cytosolic (bioinformatic evidence in Arabidopsis) | Cytosol - P [PMID:15107504] | Aldolase and epimerase activities with dihydroneopterin or dihydromonapterin shown by recombinant At3g11750, At5g62980, and a tomato homolog [PMID:15107504]. | ||
| DHNA | At5g62980 | FOLB2 | GRMZM2G095579 | Dihydroneopterin aldolase (EC 4.1.2.25) | # cytosolic (bioinformatic evidence in Arabidopsis) | Cytosol - P [PMID:15107504] | |||
| DHNA | At3g21730 | FOLB3 | Dihydroneopterin aldolase (EC 4.1.2.25) | # cytosolic (bioinformatic evidence in Arabidopsis) | Cytosol - P [PMID:15107504] | Not shown to be active. | |||
| ADCS | At2g28880 | ADCS, emb1997 | GRMZM2G416386 | Para-aminobenzoate synthase, amidotransferase component (EC 2.6.1.85) / Para-aminobenzoate synthase, aminase component (EC 2.6.1.85) | # plastidial (experimental evidence in Arabidopsis) | Plastid - E [PMID:14745019] | Aminodeoxychorismate synthase activity shown by transformation of an E. coli pabA pabB double mutant with recombinant proteins from Arabidopsis or tomato [PMID:14745019]. Both activities of the bifunctional enzyme, glutamine amidotransferase and aminodeoxychorismate synthase were shown by the Arabidopsis recombinant protein [PMID:20851095]. | ||
| ADCL | At5g57850 | GRMZM2G069596 | Aminodeoxychorismate lyase (EC 4.1.3.38) | # plastidial (experimental evidence in Arabidopsis) | Plastid - E [PMID:15500462] | Aminodeoxychorismate lyase activity shown by complementation of an E. coli pabC mutant, with either the Arabidopsis or the tomato recombinant proteins and also by ability of partially purified Arabidopsis and tomato recombinant proteins to convert 4-amino-4-deoxychorismate into p-aminobenzoate [PMID:15500462]. This protein has also amino acid aminotransferase activity [PMID:18318836]. | |||
| ADCL | GRMZM2G087103 | ||||||||
| HPPK-DHPS | At4g30000 | GRMZM2G095806 | 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase (EC 2.7.6.3) / Dihydropteroate synthase (EC 2.5.1.15) | # mitochondrial (bioinformatics evidence in Arabidopsis, experimental evidence in pea) [PMID:9118956] | Mitochondrion - P (predicted mitochondrial targeting sequence) | HPPK and DHPS activities shown by the enzyme purified from pea leaf mitochondria [PMID:9118956]. | |||
| HPPK-DHPS | At1g69190 | # cytosolic (experimental evidence in Arabidopsis) | Cytosol - E [PMID:17289662] | The At1g69190 protein is expressed only in seeds [PMID:17289662]. This protein has HPPK and DHPS activities in vitro [PMID:17289662] but appears to have no in vivo role in folate metabolism [PMID:21996493]. It may not occur in other plants. | |||||
| DHFS | At5g41480 | GLA1 | GRMZM2G304915 | Dihydrofolate synthase (EC 6.3.2.12) | # mitochondrial (experimental evidence in Arabidopsis) | Mitochondrion - E [PMID:11752472] | Dihydrofolate synthase activity shown by transformastion of fol3 yeast mutant with recombinant At5g41480 protein [PMID:11752472]. The At5g41480 knockout mutant is folate deficient and embryo lethal [PMID:12535338]. | ||
| DHFS | GRMZM2G169481 | ||||||||
| DHFR | At2g16370 | THY-1 | GRMZM2G139880 | Dihydrofolate reductase (EC 1.5.1.3) / Thymidylate synthase (EC 2.1.1.45) | # mitochondrial (experimental evidence in pea leaves and potato tuber) [PMID:8621617] | Dihydrofolate reductase and thymidylate synthase activities shown by purified pea enzyme [PMID:8621617]. Arabidopsis gene cloned and shown to have the domains for the two enzymatic activities [PMID:8374616]. Expression of the thymidylate synthase / dihydrofolate reductase shown in maize [PMID:10737138]. Daucus carota DHFR cloned and shown to have both domains [PMID:8329682]. | DHFR enzyme activity was shown to be solely mitochondrial in pea leaves and potato tubers [PMID:8621617]. A single experiment in PPDB detected one DHFR isoform in plastid membranes. | ||
| DHFR | At4g34570 | THY-2 | GRMZM2G005990 | Dihydrofolate reductase (EC 1.5.1.3) / Thymidylate synthase (EC 2.1.1.45) | # mitochondrial (experimental evidence in pea leaves and potato tuber) [PMID:8621617] | DHFR enzyme activity was shown to be solely mitochondrial in pea leaves and potato tubers [PMID:8621617]. A single experiment in PPDB detected one DHFR isoform in plastid membranes. | |||
| DHFR | GRMZM2G421493 | Dihydrofolate reductase (EC 1.5.1.3) / Thymidylate synthase (EC 2.1.1.45) | # mitochondrial (experimental evidence in pea leaves and potato tuber) [PMID:8621617] | Plastid membranes - E [PPDB in-house data] | DHFR enzyme activity was shown to be solely mitochondrial in pea leaves and potato tubers [PMID:8621617]. A single experiment in PPDB detected one DHFR isoform in plastid membranes. | ||||
| DHFR | GRMZM2G072608 | Dihydrofolate reductase (EC 1.5.1.3) / Thymidylate synthase (EC 2.1.1.45) | # mitochondrial (experimental evidence in pea leaves and potato tuber) [PMID:8621617] | DHFR enzyme activity was shown to be solely mitochondrial in pea leaves and potato tubers [PMID:8621617]. A single experiment in PPDB detected one DHFR isoform in plastid membranes. | |||||
| DHFR | At2g21550 | Absent | Dihydrofolate reductase (EC 1.5.1.3) / Thymidylate synthase (EC 2.1.1.45) | # mitochondrial (experimental evidence in pea leaves and potato tuber) [PMID:8621617] | |||||
| FPGS | At3g55630 | DFD | GRMZM2G393334 | Folylpolyglutamate synthase (EC 6.3.2.17) | # cytosolic (experimental evidence in Arabidopsis) | Cytosol - E [PMID:11752472] | Folylpolyglutamate synthase activity shown by complementation of the yeast met7 mutant with the three Arabidopsis FPGS proteins [PMID:11752472]. There is evidence for multiple targeting of the Arabidopsis FPGS proteins [PMID:21070407]. | ||
| FPGS | At3g10160 | DFC | GRMZM5G869779 | Folylpolyglutamate synthase (EC 6.3.2.17) | # mitochondrial (experimental evidence in Arabidopsis) | Mitochondrion - E [PMID:11752472] | |||
| FPGS | At5g05980 | DFB | Folylpolyglutamate synthase (EC 6.3.2.17) | # plastidial (experimental evidence in Arabidopsis) | Plastid - E [PMID:11752472] | ||||
| GGH | At1g78660 | GGH1 | GRMZM2G095955 | Gamma-glutamyl hydrolase (EC 3.4.19.9) | # vacuolar (bioinformatic evidence in Arabidopsis [PMID:15961386] and experimental evidence in pea leaves and red beet roots) | Vacuole - P [PMID:15961386] | Gamma-glutamyl hydrolase activity demonstrated for purified recombinant GGH1 and GGH2 [PMID:15961386] and for two recombinant GGH isoforms from tomato, which were found to form homo- or heterodimers [PMID:18757550]. | ||
| GGH | At1g78680 | GGH2 | Gamma-glutamyl hydrolase (EC 3.4.19.9) | # vacuolar (bioinformatic evidence in Arabidopsis [PMID:15961386] and experimental evidence in pea leaves and red beet roots) | Vacuole - P [PMID:15961386] | Gamma-glutamyl hydrolase activity demonstrated for purified recombinant GGH1 and GGH2 [PMID:15961386] and for two recombinant GGH isoforms from tomato, which were found to form homo- or heterodimers [PMID:18757550]. | |||
| GGH | At1g78670 | GGH3 | n/a | n/a | n/a | GGH3 lacks detectable enzyme activity [PMID:15961386]. | |||
| PAGT | At1g05560 | UGT1, UGT75B1 | GRMZM2G344993 | UDP-glucose:p-aminobenzoate glucosyltransferase | # cytosolic (experimental evidence in pea leaves [PMID:12668665]) | p-Aminobenzoate glucosyltransferase activity shown by recombinant At1g05560. At1g05560 knockout plants have a 95% reduction in p-aminobenzoate glucosyltransferase ativity [PMID:18385129]. | |||
| PAGT | GRMZM2G363554 | ||||||||
| PAGT | At2g43840 | UGT74F1 | Moderate p-aminobenzoate glucosyltransferase activity shown by recombinant At2g43840 and At2g43820 [PMID:18385129]. | ||||||
| PAGT | At2g43820 | UGT74F2 | Moderate p-aminobenzoate glucosyltransferase activity shown by recombinant At2g43840 and At2g43820 [PMID:18385129]. | ||||||
| GT | Missing gene | UDP-glucose:pterin glycosyltransferase | n/a | Neopterin and monapterin glycosides accumulate in tomato fruit overexpressing GCH1 [PMID:15365185]. | |||||
| Folate, pterin, and pABA-glucose transport | |||||||||
| Pterin transp | Missing gene | Plasma membrane pterin transporter | # plasma membrane | Arabidopsis leaf tissues take up and metabolize supplied dihydropterin-6-aldehyde and pterin-6-aldehyde [PMID:17550420]] [PMID:16623903], implying the presence of pterin carriers in the plasma membrane. | No pterin transporter has been found in plants. In Arabidopsis, nine proteins belong to the folate/biopterin transporter family. Five have been tested for transport in Leishmania BT1 pterin transport mutants, with negative results [PMID:19923217]. | ||||
| Pterin transp | Missing gene | Mitochondrial hydroxymethyldihydropterin transporter | # mitochondrial membrane | HPPK-DHPS is mitochondrial [PMID:9118956], implying the need for HMDHP import. | No pterin transporter has been found in plants. In Arabidopsis, nine proteins belong to the folate/biopterin transporter family. Five have been tested for transport in Leishmania BT1 pterin transport mutants, with negative results [PMID:19923217]. | ||||
| Folate transp | At5g66380 | FOLT1 | GRMZM5G840435 | Plastid folate carrier | # plastidial (experimental evidence in Arabidopsis) | Plastid - E [PMID:16055441] | Folate transport shown by complementation of the glyB line of Chinese hampster ovary (CHO) cells, which is deficient in folate transport, with At5g66380 [PMID:16055441]. | ||
| Folate transp | At2g32040 | GRMZM2G027603 | Folate carrier, cyanobacterial type | # plastidial (experimental evidence in Arabidopsis) | Plastid - E [PMID:16162503] | Folate transport shown by complementation of the E. coli double mutant pabA pabB and the folB mutant with modified recombinant At2g32040 [PMID:16162503]. | |||
| Folate transp | GRMZM2G469469 | ||||||||
| Folate transp | GRMZM2G073429 | ||||||||
| Folate transp | At1g30400 | MRP1 | GRMZM2G084181 | Vacuolar folate monoglutamate carrier | # vacuolar (experimental evidence in Arabidopsis) | Vacuole - E [PMID:14760709] | Folate transport shown by increased sensitivity of At1g30400 knockout mutants to the antifolate methotrexate, accompanied by impaired vacuolar antifolate sequestration [PMID:19136566]. | ||
| Folate transp | Missing gene | Plasma membrane folate carrier | # plasma membrane | Folates are metabolized when added to plant cell cultures and added folates can reverse the effects of folate synthesis inhibitors [PMID:21275646], implying the existence of a plasma membrane folate transporter. | No candidate genes suggested. | ||||
| Folate transp | Missing gene | Mitochondrial folate carrier | # mitochondrial membrane | Tetrahydrofolate is synthesized in the mitochondria [PMID:8621617] but is found in extramitochondrial compartments [PMID:21275646], implying the existence of a mitochondrial folate transporter. Also, when folate synthesis is blocked, Arabidopsis plantlets can survive if supplied with 5-formyltetrahydrofolate [PMID:9449840], which requires the transport of 5-formyltetrahydrofolate across the plasma membrane and the mitochondrial membrane to reach 5-formyltetrahydrofolate cycloligase, which is located in mitochondria [PMID:12207015]. | No candidate genes suggested. | ||||
| Folate transp | Missing gene | Vacuolar folate polyglutamates carrier | # vacuolar membrane | Folate polglutamates (FPG) are present in vacuoles [PMID:21070406] [PMID:15961386], but FPGS and the ATP needed for FPG synthesis are not [PMID:11752472] [PMID:11598242], implying the existence of a FPG transporter in the vacuolar membrane. | No candidate genes suggested. | ||||
| pABA glucose ester transp | Missing gene | Vacuolar p-aminobezoate glucose ester carrier | # vacuolar membrane | p-Aminobenzoate glucose ester is made in the cytosol but is located mainly in vacuoles [PMID:18385129], implying the need for a transporter in the vacuolar membrane to transport this ester, since it is an hydrophilic compound. | No candidate genes suggested. | ||||
| Table Notes | |||||||||
| Enzyme abbreviations (column "Abbrev") correspond to those in the folate pathway diagram (Fig. 5) and are defined in column "Functional role" ("Functional role"). Enzyme and transporter colour-coding is coordinated between the table and the pathway diagram and is explained at the top of the table (Legend). | |||||||||
| Arabidopsis gene IDs (column "AT gene ID") correspond to genome version AtGDB171/TAIR9 (www.plantgdb.org) (genome 3702 in the SEED database). Maize gene IDs (column "Maize ortholog") correspond to the Filtered Gene Set of the B73 cultivar genome sequence version AGPv2 (www.maizesequence.org) (genome 381124 in the SEED database). An attempt was made to establish orthology between Arabidopsis and maize genes, and the orthologous gene pairs are shown in the same rows. When one-on-one orthology could not be established, homologs appear in separate rows and are marked with an asterisk. | |||||||||
| Column "Curated localization" gives curated localizations (preceded by the # symbol) based on experimental and/or bioinformatics data for Arabidopsis, maize, or other plants; data are given specifically for Arabidopsis and maize in their respective columns. Abbreviations are: E - experimental evidence; P - predicted bioinformatically; PPDB - The Plant Proteome Database (ppdb.tc.cornell.edu). The column "Experimental data" briefly reviews experimental findings (other than enzyme localization) available for Arabidopsis, maize, or other plants. Publications are referenced by PubMed IDs (when available), which are linked to the PubMed database. The column "Problems, open questions, predictions" concerns gaps and inconsistencies in current knowledge. | |||||||||