FOLM_ARATH
ID FOLM_ARATH Reviewed; 554 AA.
AC Q9SZV3; F4JPH1;
DT 29-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Folate synthesis bifunctional protein, mitochondrial {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:0000250|UniProtKB:O04862};
DE AltName: Full=2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase;
DE AltName: Full=7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase;
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:0000250|UniProtKB:O04862};
DE Flags: Precursor;
GN Name=MitHPPK/DHPS {ECO:0000303|PubMed:17289662};
GN OrderedLocusNames=At4g30000 {ECO:0000312|Araport:AT4G30000};
GN ORFNames=F6G3.30 {ECO:0000312|EMBL:CAB43835.1};
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|Proteomes:UP000006548};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=10617198; DOI=10.1038/47134;
RA Mayer K.F.X., Schueller C., Wambutt R., Murphy G., Volckaert G., Pohl T.,
RA Duesterhoeft A., Stiekema W., Entian K.-D., Terryn N., Harris B.,
RA Ansorge W., Brandt P., Grivell L.A., Rieger M., Weichselgartner M.,
RA de Simone V., Obermaier B., Mache R., Mueller M., Kreis M., Delseny M.,
RA Puigdomenech P., Watson M., Schmidtheini T., Reichert B., Portetelle D.,
RA Perez-Alonso M., Boutry M., Bancroft I., Vos P., Hoheisel J.,
RA Zimmermann W., Wedler H., Ridley P., Langham S.-A., McCullagh B.,
RA Bilham L., Robben J., van der Schueren J., Grymonprez B., Chuang Y.-J.,
RA Vandenbussche F., Braeken M., Weltjens I., Voet M., Bastiaens I., Aert R.,
RA Defoor E., Weitzenegger T., Bothe G., Ramsperger U., Hilbert H., Braun M.,
RA Holzer E., Brandt A., Peters S., van Staveren M., Dirkse W., Mooijman P.,
RA Klein Lankhorst R., Rose M., Hauf J., Koetter P., Berneiser S., Hempel S.,
RA Feldpausch M., Lamberth S., Van den Daele H., De Keyser A., Buysshaert C.,
RA Gielen J., Villarroel R., De Clercq R., van Montagu M., Rogers J.,
RA Cronin A., Quail M.A., Bray-Allen S., Clark L., Doggett J., Hall S.,
RA Kay M., Lennard N., McLay K., Mayes R., Pettett A., Rajandream M.A.,
RA Lyne M., Benes V., Rechmann S., Borkova D., Bloecker H., Scharfe M.,
RA Grimm M., Loehnert T.-H., Dose S., de Haan M., Maarse A.C., Schaefer M.,
RA Mueller-Auer S., Gabel C., Fuchs M., Fartmann B., Granderath K., Dauner D.,
RA Herzl A., Neumann S., Argiriou A., Vitale D., Liguori R., Piravandi E.,
RA Massenet O., Quigley F., Clabauld G., Muendlein A., Felber R., Schnabl S.,
RA Hiller R., Schmidt W., Lecharny A., Aubourg S., Chefdor F., Cooke R.,
RA Berger C., Monfort A., Casacuberta E., Gibbons T., Weber N., Vandenbol M.,
RA Bargues M., Terol J., Torres A., Perez-Perez A., Purnelle B., Bent E.,
RA Johnson S., Tacon D., Jesse T., Heijnen L., Schwarz S., Scholler P.,
RA Heber S., Francs P., Bielke C., Frishman D., Haase D., Lemcke K.,
RA Mewes H.-W., Stocker S., Zaccaria P., Bevan M., Wilson R.K.,
RA de la Bastide M., Habermann K., Parnell L., Dedhia N., Gnoj L., Schutz K.,
RA Huang E., Spiegel L., Sekhon M., Murray J., Sheet P., Cordes M.,
RA Abu-Threideh J., Stoneking T., Kalicki J., Graves T., Harmon G.,
RA Edwards J., Latreille P., Courtney L., Cloud J., Abbott A., Scott K.,
RA Johnson D., Minx P., Bentley D., Fulton B., Miller N., Greco T., Kemp K.,
RA Kramer J., Fulton L., Mardis E., Dante M., Pepin K., Hillier L.W.,
RA Nelson J., Spieth J., Ryan E., Andrews S., Geisel C., Layman D., Du H.,
RA Ali J., Berghoff A., Jones K., Drone K., Cotton M., Joshu C., Antonoiu B.,
RA Zidanic M., Strong C., Sun H., Lamar B., Yordan C., Ma P., Zhong J.,
RA Preston R., Vil D., Shekher M., Matero A., Shah R., Swaby I.K.,
RA O'Shaughnessy A., Rodriguez M., Hoffman J., Till S., Granat S., Shohdy N.,
RA Hasegawa A., Hameed A., Lodhi M., Johnson A., Chen E., Marra M.A.,
RA Martienssen R., McCombie W.R.;
RT "Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana.";
RL Nature 402:769-777(1999).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=cv. Columbia;
RA de los Reyes C., Quan R., Chen H., Bautista V., Kim C.J., Ecker J.R.;
RT "Arabidopsis ORF clones.";
RL Submitted (JUN-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION, TISSUE SPECIFICITY, AND INDUCTION BY SALT STRESS.
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).
CC -!- FUNCTION: Catalyzes the first two consecutive steps of tetrahydrofolate
CC biosynthesis. {ECO:0000250|UniProtKB:O04862}.
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:0000250|UniProtKB:O04862};
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:0000250|UniProtKB:O04862};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P0AC13};
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: Mitochondrion {ECO:0000250|UniProtKB:O04862}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9SZV3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9SZV3-2; Sequence=VSP_057628;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:17289662}.
CC -!- INDUCTION: Not induced by salt stress. {ECO:0000269|PubMed:17289662}.
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}.
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DR EMBL; AL078464; CAB43835.1; -; Genomic_DNA.
DR EMBL; AL161576; CAB80993.1; -; Genomic_DNA.
DR EMBL; CP002687; AEE85706.1; -; Genomic_DNA.
DR EMBL; CP002687; AEE85707.1; -; Genomic_DNA.
DR EMBL; BT033093; ACF06123.1; -; mRNA.
DR PIR; T08976; T08976.
DR RefSeq; NP_001190868.1; NM_001203939.1. [Q9SZV3-2]
DR RefSeq; NP_194729.1; NM_119146.3. [Q9SZV3-1]
DR AlphaFoldDB; Q9SZV3; -.
DR SMR; Q9SZV3; -.
DR STRING; 3702.AT4G30000.2; -.
DR PaxDb; Q9SZV3; -.
DR PRIDE; Q9SZV3; -.
DR ProteomicsDB; 230608; -. [Q9SZV3-1]
DR EnsemblPlants; AT4G30000.1; AT4G30000.1; AT4G30000. [Q9SZV3-1]
DR EnsemblPlants; AT4G30000.2; AT4G30000.2; AT4G30000. [Q9SZV3-2]
DR GeneID; 829123; -.
DR Gramene; AT4G30000.1; AT4G30000.1; AT4G30000. [Q9SZV3-1]
DR Gramene; AT4G30000.2; AT4G30000.2; AT4G30000. [Q9SZV3-2]
DR KEGG; ath:AT4G30000; -.
DR Araport; AT4G30000; -.
DR TAIR; locus:2126465; AT4G30000.
DR eggNOG; KOG2544; Eukaryota.
DR HOGENOM; CLU_008023_2_1_1; -.
DR OMA; HIMAILN; -.
DR OrthoDB; 1209962at2759; -.
DR PhylomeDB; Q9SZV3; -.
DR BioCyc; ARA:AT4G30000-MON; -.
DR UniPathway; UPA00077; UER00155.
DR UniPathway; UPA00077; UER00156.
DR PRO; PR:Q9SZV3; -.
DR Proteomes; UP000006548; Chromosome 4.
DR ExpressionAtlas; Q9SZV3; baseline and differential.
DR Genevisible; Q9SZV3; AT.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; HDA:TAIR.
DR GO; GO:0003848; F:2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004156; F:dihydropteroate synthase activity; IBA:GO_Central.
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:0046654; P:tetrahydrofolate biosynthetic process; IBA:GO_Central.
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 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Folate biosynthesis; Kinase; Magnesium;
KW Metal-binding; Mitochondrion; Multifunctional enzyme; Nucleotide-binding;
KW Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..42
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 43..554
FT /note="Folate synthesis bifunctional protein,
FT mitochondrial"
FT /id="PRO_0000432868"
FT DOMAIN 273..541
FT /note="Pterin-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00334"
FT REGION 90..215
FT /note="HPPK"
FT /evidence="ECO:0000305"
FT REGION 275..554
FT /note="DHPS"
FT BINDING 280
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P9WND1"
FT BINDING 320
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 357
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 376
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 449
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 494
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT BINDING 529..531
FT /ligand="(7,8-dihydropterin-6-yl)methyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:72950"
FT /evidence="ECO:0000250|UniProtKB:P0AC13"
FT VAR_SEQ 542..554
FT /note="VCDAMLRRRRSKG -> IDTAVSLCKNNMPREATFLL (in isoform
FT 2)"
FT /id="VSP_057628"
SQ SEQUENCE 554 AA; 60738 MW; 97732C1F17761157 CRC64;
MAPLLSQTLI HTGRFLLRRF LEPPPAVISA VAASRVCFHR YYSSKSLSLV SPLGLHCSSL
FSPPALCNSA FSSSATSTTI EVQSTEHEVV IALGSNIGNR MNNFREALRL MKRGGICVTR
HSCLYETAPV HVTDQPRFLN AAVRGVTKLG PHELLSVLKT IERDMGRKDG IRYGPRPLDL
DILFYGKMRI SSDKLIIPHE RLWERSFVLA PLVDLLGSAV DNDTVAHWHS LAIHPGGIFQ
AWERLGGESL IGQDGIQRVL PIGDKLWDFS NKTHVMGILN LTPDSFSDGG KFQSIDSAVS
RVRSMISEGA DIIDIGAQST RPMASRISSQ EELDRLLPVL EAVRGMPEME EKLISVDTFN
SEVASEAISN GADILNDVSA GTLDPNMHKV VAESGVPYMA MHMRGDPCTM QNKENLQYDD
VCKDVASELY LRVRDAELSG IPAWRVMIDP GIGFSKSVDH NLDIIMDLPK IREEMAKRSI
AVSHAPILVG PSRKRFLGDI CGRPEATDRD AATVASVTAG ILGGANIIRV HNVRHNADAA
KVCDAMLRRR RSKG
