FOLC_ARATH
ID FOLC_ARATH Reviewed; 484 AA.
AC Q1ENB6; Q9LE77;
DT 29-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2006, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Folate synthesis bifunctional protein {ECO:0000303|PubMed:17289662};
DE Includes:
DE RecName: Full=6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase {ECO:0000303|PubMed:17289662};
DE Short=HPPK {ECO:0000303|PubMed:17289662};
DE EC=2.7.6.3 {ECO:0000269|PubMed:17289662};
DE AltName: Full=2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase;
DE AltName: Full=7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase;
DE Short=PPPK;
DE Includes:
DE RecName: Full=Dihydropteroate synthase {ECO:0000303|PubMed:17289662};
DE Short=DHPS {ECO:0000303|PubMed:17289662};
DE EC=2.5.1.15 {ECO:0000269|PubMed:17289662};
GN Name=CytHPPK/DHPS {ECO:0000303|PubMed:17289662};
GN OrderedLocusNames=At1g69190 {ECO:0000312|Araport:AT1G69190};
GN ORFNames=F23O10.22 {ECO:0000312|EMBL:AAG52504.1},
GN F4N2.15 {ECO:0000312|EMBL:AAF27067.1};
OS Arabidopsis thaliana (Mouse-ear cress).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX NCBI_TaxID=3702 {ECO:0000312|EMBL:CAI29255.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION BY SALT STRESS, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=cv. Columbia;
RX PubMed=17289662; DOI=10.1074/jbc.m701158200;
RA Storozhenko S., Navarrete O., Ravanel S., De Brouwer V., Chaerle P.,
RA Zhang G.F., Bastien O., Lambert W., Rebeille F., Van Der Straeten D.;
RT "Cytosolic hydroxymethyldihydropterin pyrophosphokinase/dihydropteroate
RT synthase from Arabidopsis thaliana: a specific role in early development
RT and stress response.";
RL J. Biol. Chem. 282:10749-10761(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=11130712; DOI=10.1038/35048500;
RA Theologis A., Ecker J.R., Palm C.J., Federspiel N.A., Kaul S., White O.,
RA Alonso J., Altafi H., Araujo R., Bowman C.L., Brooks S.Y., Buehler E.,
RA Chan A., Chao Q., Chen H., Cheuk R.F., Chin C.W., Chung M.K., Conn L.,
RA Conway A.B., Conway A.R., Creasy T.H., Dewar K., Dunn P., Etgu P.,
RA Feldblyum T.V., Feng J.-D., Fong B., Fujii C.Y., Gill J.E., Goldsmith A.D.,
RA Haas B., Hansen N.F., Hughes B., Huizar L., Hunter J.L., Jenkins J.,
RA Johnson-Hopson C., Khan S., Khaykin E., Kim C.J., Koo H.L.,
RA Kremenetskaia I., Kurtz D.B., Kwan A., Lam B., Langin-Hooper S., Lee A.,
RA Lee J.M., Lenz C.A., Li J.H., Li Y.-P., Lin X., Liu S.X., Liu Z.A.,
RA Luros J.S., Maiti R., Marziali A., Militscher J., Miranda M., Nguyen M.,
RA Nierman W.C., Osborne B.I., Pai G., Peterson J., Pham P.K., Rizzo M.,
RA Rooney T., Rowley D., Sakano H., Salzberg S.L., Schwartz J.R., Shinn P.,
RA Southwick A.M., Sun H., Tallon L.J., Tambunga G., Toriumi M.J., Town C.D.,
RA Utterback T., Van Aken S., Vaysberg M., Vysotskaia V.S., Walker M., Wu D.,
RA Yu G., Fraser C.M., Venter J.C., Davis R.W.;
RT "Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana.";
RL Nature 408:816-820(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=cv. Columbia;
RX PubMed=27862469; DOI=10.1111/tpj.13415;
RA Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA Town C.D.;
RT "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT genome.";
RL Plant J. 89:789-804(2017).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION BY OXIDATIVE STRESS.
RX PubMed=21996493; DOI=10.1016/j.phytochem.2011.09.008;
RA Navarrete O., Van Daele J., Stove C., Lambert W., Van Der Straeten D.,
RA Storozhenko S.;
RT "A folate independent role for cytosolic HPPK/DHPS upon stress in
RT Arabidopsis thaliana.";
RL Phytochemistry 73:23-33(2012).
CC -!- FUNCTION: Catalyzes the first two consecutive steps of tetrahydrofolate
CC biosynthesis (PubMed:17289662). Plays a role in seed stress response
CC and survival (PubMed:17289662, PubMed:21996493).
CC {ECO:0000269|PubMed:17289662, ECO:0000269|PubMed:21996493}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6-hydroxymethyl-7,8-dihydropterin + ATP = (7,8-dihydropterin-
CC 6-yl)methyl diphosphate + AMP + H(+); Xref=Rhea:RHEA:11412,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:44841,
CC ChEBI:CHEBI:72950, ChEBI:CHEBI:456215; EC=2.7.6.3;
CC Evidence={ECO:0000269|PubMed:17289662};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate =
CC 7,8-dihydropteroate + diphosphate; Xref=Rhea:RHEA:19949,
CC ChEBI:CHEBI:17836, ChEBI:CHEBI:17839, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:72950; EC=2.5.1.15;
CC Evidence={ECO:0000269|PubMed:17289662};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P0AC13};
CC -!- ACTIVITY REGULATION: Inhibited by sulfanilamide.
CC {ECO:0000269|PubMed:17289662}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=30 uM for ATP {ECO:0000269|PubMed:17289662};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 2-amino-
CC 4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate from 7,8-
CC dihydroneopterin triphosphate: step 4/4. {ECO:0000305}.
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 7,8-
CC dihydrofolate from 2-amino-4-hydroxy-6-hydroxymethyl-7,8-
CC dihydropteridine diphosphate and 4-aminobenzoate: step 1/2.
CC {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:17289662}.
CC -!- TISSUE SPECIFICITY: Expressed exclusively in reproductive tissues.
CC {ECO:0000269|PubMed:17289662}.
CC -!- DEVELOPMENTAL STAGE: Expressed in early stages of seed development,
CC until the late globular stage of embryo. Not detected at the heart
CC stage of embryo development. {ECO:0000269|PubMed:17289662}.
CC -!- INDUCTION: Up-regulated by slat stress (PubMed:17289662). Up-regulated
CC by oxidative stress (PubMed:21996493). {ECO:0000269|PubMed:17289662,
CC ECO:0000269|PubMed:21996493}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype (PubMed:17289662). Increased
CC sensitivity to oxidative stress (PubMed:21996493).
CC {ECO:0000269|PubMed:17289662, ECO:0000269|PubMed:21996493}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the HPPK family.
CC {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the DHPS family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF27067.1; Type=Erroneous gene model prediction; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC Sequence=AAG52504.1; Type=Erroneous gene model prediction; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
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DR EMBL; AJ866732; CAI29255.1; -; mRNA.
DR EMBL; AC008262; AAF27067.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC018364; AAG52504.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CP002684; AEE34892.1; -; Genomic_DNA.
DR PIR; H96715; H96715.
DR RefSeq; NP_001319354.1; NM_001334402.1.
DR PDB; 7MPY; X-ray; 2.30 A; A/B=2-484.
DR PDBsum; 7MPY; -.
DR AlphaFoldDB; Q1ENB6; -.
DR SMR; Q1ENB6; -.
DR STRING; 3702.AT1G69190.1; -.
DR iPTMnet; Q1ENB6; -.
DR PaxDb; Q1ENB6; -.
DR PRIDE; Q1ENB6; -.
DR ProteomicsDB; 228972; -.
DR EnsemblPlants; AT1G69190.1; AT1G69190.1; AT1G69190.
DR GeneID; 843250; -.
DR Gramene; AT1G69190.1; AT1G69190.1; AT1G69190.
DR KEGG; ath:AT1G69190; -.
DR Araport; AT1G69190; -.
DR TAIR; locus:2026471; AT1G69190.
DR eggNOG; KOG2544; Eukaryota.
DR HOGENOM; CLU_008023_2_1_1; -.
DR InParanoid; Q1ENB6; -.
DR OMA; FMYETEP; -.
DR OrthoDB; 1209962at2759; -.
DR PhylomeDB; Q1ENB6; -.
DR BioCyc; ARA:AT1G69190-MON; -.
DR BRENDA; 2.5.1.15; 399.
DR BRENDA; 2.7.6.3; 399.
DR SABIO-RK; Q1ENB6; -.
DR UniPathway; UPA00077; UER00155.
DR UniPathway; UPA00077; UER00156.
DR PRO; PR:Q1ENB6; -.
DR Proteomes; UP000006548; Chromosome 1.
DR ExpressionAtlas; Q1ENB6; baseline and differential.
DR Genevisible; Q1ENB6; AT.
DR GO; GO:0005829; C:cytosol; IDA:TAIR.
DR GO; GO:0003848; F:2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase activity; IDA:TAIR.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004156; F:dihydropteroate synthase activity; IDA:TAIR.
DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046656; P:folic acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0006979; P:response to oxidative stress; IMP:TAIR.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IDA:TAIR.
DR CDD; cd00739; DHPS; 1.
DR CDD; cd00483; HPPK; 1.
DR Gene3D; 3.20.20.20; -; 1.
DR Gene3D; 3.30.70.560; -; 1.
DR InterPro; IPR045031; DHP_synth.
DR InterPro; IPR006390; DHP_synth_dom.
DR InterPro; IPR011005; Dihydropteroate_synth-like.
DR InterPro; IPR000550; Hppk.
DR InterPro; IPR035907; Hppk_sf.
DR InterPro; IPR000489; Pterin-binding_dom.
DR PANTHER; PTHR20941; PTHR20941; 1.
DR Pfam; PF01288; HPPK; 1.
DR Pfam; PF00809; Pterin_bind; 1.
DR SUPFAM; SSF51717; SSF51717; 1.
DR SUPFAM; SSF55083; SSF55083; 1.
DR TIGRFAMs; TIGR01496; DHPS; 1.
DR TIGRFAMs; TIGR01498; folK; 1.
DR PROSITE; PS00792; DHPS_1; 1.
DR PROSITE; PS00793; DHPS_2; 1.
DR PROSITE; PS00794; HPPK; 1.
DR PROSITE; PS50972; PTERIN_BINDING; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cytoplasm; Folate biosynthesis; Kinase;
KW Magnesium; Metal-binding; Multifunctional enzyme; Nucleotide-binding;
KW Reference proteome; Transferase.
FT CHAIN 1..484
FT /note="Folate synthesis bifunctional protein"
FT /id="PRO_0000432867"
FT DOMAIN 202..470
FT /note="Pterin-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT REGION 15..141
FT /note="HPPK"
FT /evidence="ECO:0000305"
FT REGION 204..484
FT /note="DHPS"
FT BINDING 209
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P9WND1"
FT BINDING 249
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 286
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 305
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 378
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 423
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 458..460
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT STRAND 12..20
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 25..38
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 41..46
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 63..74
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 76..90
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 104..114
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 126..130
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 132..139
FT /evidence="ECO:0007829|PDB:7MPY"
FT TURN 147..149
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 153..158
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 165..173
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 175..178
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 184..191
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 203..210
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 224..236
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 258..274
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 276..278
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 282..286
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 290..298
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 302..306
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 315..322
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 327..330
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 350..367
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 372..374
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 375..378
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 384..386
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 387..395
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 397..407
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 409..412
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 416..418
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 424..430
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 435..437
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 439..451
FT /evidence="ECO:0007829|PDB:7MPY"
FT STRAND 455..461
FT /evidence="ECO:0007829|PDB:7MPY"
FT HELIX 462..475
FT /evidence="ECO:0007829|PDB:7MPY"
SQ SEQUENCE 484 AA; 54110 MW; 3F9985DBA8655369 CRC64;
MDFTSLETTT FEEVVIALGS NVGNRMNNFK EALRLMKDYG ISVTRHSCLY ETEPVHVTDQ
PRFLNAAIRG VTKLKPHELL NVLKKIEKEM GREENGLRYG PRPLDLDILF YGKHKIISDK
LIIPHERIWE RPFVLAPLVD LLGTEDIDND KIVAYWHSLS MHSGGIFQAW ERLGGESLLG
KDGIIQRVIP IGDHLWDFSK KTYVMGILNL TPDSFSDGGK FQSVDTAVSR VRSMISEGVD
IIDIGAQSTR PMASRISSQE EIDRLIPVLK VVRGMAEMKG KLISVDTFNS EVALEAIRNG
ADILNDVSGG SLDENMHKVV ADSDVPYMIM HMRGDPCTMQ NKENLEYNEI CKDVATELYE
RVREAELSGI PAWRIMIDPG IGFSKGIDHN LDIVMELPKI REEMAKKSIG LSHAPILIGP
SRKRFLGDIC GRPEASERDA ATVACVTAGI LKGANIIRVH NVRDNVDAAR LCDAMMTKRF
KNVD
