DHFS_ARATH
ID DHFS_ARATH Reviewed; 530 AA.
AC F4JYE9; Q7Y203; Q8W041; Q9FN53;
DT 14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Dihydrofolate synthetase {ECO:0000303|PubMed:11752472};
DE Short=AtDFA {ECO:0000303|PubMed:11752472};
DE EC=6.3.2.12 {ECO:0000269|PubMed:11752472};
DE AltName: Full=Protein GLOBULAR ARREST 1 {ECO:0000303|PubMed:12535338};
DE Flags: Precursor;
GN Name=DHFS {ECO:0000303|PubMed:11752472};
GN Synonyms=DFA {ECO:0000303|PubMed:11752472},
GN GLA1 {ECO:0000303|PubMed:12535338};
GN OrderedLocusNames=At5g41480 {ECO:0000312|EMBL:AED94683.1};
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 [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=cv. Columbia, and cv. Wassilewskija;
RX PubMed=11752472; DOI=10.1073/pnas.261585098;
RA Ravanel S., Cherest H., Jabrin S., Grunwald D., Surdin-Kerjan Y., Douce R.,
RA Rebeille F.;
RT "Tetrahydrofolate biosynthesis in plants: molecular and functional
RT characterization of dihydrofolate synthetase and three isoforms of
RT folylpolyglutamate synthetase in Arabidopsis thaliana.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:15360-15365(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=9405937; DOI=10.1093/dnares/4.4.291;
RA Kotani H., Nakamura Y., Sato S., Kaneko T., Asamizu E., Miyajima N.,
RA Tabata S.;
RT "Structural analysis of Arabidopsis thaliana chromosome 5. II. Sequence
RT features of the regions of 1,044,062 bp covered by thirteen physically
RT assigned P1 clones.";
RL DNA Res. 4:291-300(1997).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 213-530.
RC STRAIN=cv. Columbia;
RX PubMed=14593172; DOI=10.1126/science.1088305;
RA Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M.,
RA Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G.,
RA Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L.,
RA Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C.,
RA Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J.,
RA Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A.,
RA Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C.,
RA Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X.,
RA Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M.,
RA Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K.,
RA Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A.,
RA Ecker J.R.;
RT "Empirical analysis of transcriptional activity in the Arabidopsis
RT genome.";
RL Science 302:842-846(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 213-530.
RC STRAIN=cv. Columbia;
RA Totoki Y., Seki M., Ishida J., Nakajima M., Enju A., Kamiya A.,
RA Narusaka M., Shin-i T., Nakagawa M., Sakamoto N., Oishi K., Kohara Y.,
RA Kobayashi M., Toyoda A., Sakaki Y., Sakurai T., Iida K., Akiyama K.,
RA Satou M., Toyoda T., Konagaya A., Carninci P., Kawai J., Hayashizaki Y.,
RA Shinozaki K.;
RT "Large-scale analysis of RIKEN Arabidopsis full-length (RAFL) cDNAs.";
RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=12535338; DOI=10.1046/j.1365-313x.2003.01621.x;
RA Ishikawa T., Machida C., Yoshioka Y., Kitano H., Machida Y.;
RT "The GLOBULAR ARREST1 gene, which is involved in the biosynthesis of
RT folates, is essential for embryogenesis in Arabidopsis thaliana.";
RL Plant J. 33:235-244(2003).
CC -!- FUNCTION: Conversion of folates to polyglutamate derivatives, including
CC tetrahydrofolate (PubMed:11752472, PubMed:12535338). Required during
CC embryogenesis; from maternal tissues until the globular stage, and from
CC the embryo after the globular stage (PubMed:12535338).
CC {ECO:0000269|PubMed:11752472, ECO:0000269|PubMed:12535338}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7,8-dihydropteroate + ATP + L-glutamate = 7,8-dihydrofolate +
CC ADP + H(+) + phosphate; Xref=Rhea:RHEA:23584, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17839, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57451, ChEBI:CHEBI:456216;
CC EC=6.3.2.12; Evidence={ECO:0000269|PubMed:11752472};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 7,8-
CC dihydrofolate from folate: step 1/1. {ECO:0000269|PubMed:11752472,
CC ECO:0000269|PubMed:12535338}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:11752472}.
CC -!- TISSUE SPECIFICITY: Expressed in seedlings, leaves, inflorescence
CC stems, flower buds and roots. {ECO:0000269|PubMed:12535338}.
CC -!- DEVELOPMENTAL STAGE: Observed, in embryos from the early stage to the
CC mature stage, with higher levels in embryo proper, and weaker signals
CC in suspensor cells and other tissues surrounding the embryo.
CC {ECO:0000269|PubMed:12535338}.
CC -!- DISRUPTION PHENOTYPE: Defective embryos with development arrested after
CC the globular stage, at the transition to the heart stage.
CC {ECO:0000269|PubMed:12535338}.
CC -!- SIMILARITY: Belongs to the folylpolyglutamate synthase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB08519.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AJ250872; CAC80838.1; -; mRNA.
DR EMBL; AB006707; BAB08519.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CP002688; AED94683.1; -; Genomic_DNA.
DR EMBL; BT008673; AAP40483.1; -; mRNA.
DR EMBL; AK229500; BAF01357.1; -; mRNA.
DR RefSeq; NP_198963.2; NM_123512.3.
DR AlphaFoldDB; F4JYE9; -.
DR SMR; F4JYE9; -.
DR STRING; 3702.AT5G41480.1; -.
DR PaxDb; F4JYE9; -.
DR PRIDE; F4JYE9; -.
DR ProteomicsDB; 224160; -.
DR EnsemblPlants; AT5G41480.1; AT5G41480.1; AT5G41480.
DR GeneID; 834149; -.
DR Gramene; AT5G41480.1; AT5G41480.1; AT5G41480.
DR KEGG; ath:AT5G41480; -.
DR Araport; AT5G41480; -.
DR TAIR; locus:2177916; AT5G41480.
DR eggNOG; KOG2525; Eukaryota.
DR HOGENOM; CLU_015869_4_1_1; -.
DR InParanoid; F4JYE9; -.
DR OMA; NLGWRIS; -.
DR OrthoDB; 840266at2759; -.
DR BioCyc; MetaCyc:AT5G41480-MON; -.
DR BRENDA; 6.3.2.12; 399.
DR UniPathway; UPA00077; UER00818.
DR PRO; PR:F4JYE9; -.
DR Proteomes; UP000006548; Chromosome 5.
DR ExpressionAtlas; F4JYE9; baseline and differential.
DR Genevisible; F4JYE9; AT.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008841; F:dihydrofolate synthase activity; IGI:TAIR.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004326; F:tetrahydrofolylpolyglutamate synthase activity; IEA:InterPro.
DR GO; GO:0009793; P:embryo development ending in seed dormancy; IMP:TAIR.
DR GO; GO:0009396; P:folic acid-containing compound biosynthetic process; IBA:GO_Central.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.1190.10; -; 1.
DR Gene3D; 3.90.190.20; -; 1.
DR InterPro; IPR001645; Folylpolyglutamate_synth.
DR InterPro; IPR018109; Folylpolyglutamate_synth_CS.
DR InterPro; IPR036565; Mur-like_cat_sf.
DR InterPro; IPR036615; Mur_ligase_C_dom_sf.
DR InterPro; IPR013221; Mur_ligase_cen.
DR PANTHER; PTHR11136; PTHR11136; 1.
DR Pfam; PF08245; Mur_ligase_M; 1.
DR SUPFAM; SSF53244; SSF53244; 1.
DR SUPFAM; SSF53623; SSF53623; 1.
DR TIGRFAMs; TIGR01499; folC; 1.
DR PROSITE; PS01011; FOLYLPOLYGLU_SYNT_1; 1.
DR PROSITE; PS01012; FOLYLPOLYGLU_SYNT_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Ligase; Magnesium; Metal-binding; Mitochondrion;
KW Nucleotide-binding; One-carbon metabolism; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..33
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 34..530
FT /note="Dihydrofolate synthetase"
FT /evidence="ECO:0000255"
FT /id="PRO_0000434439"
FT BINDING 104..107
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 128
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 197
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 227
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 371
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 393
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT CONFLICT 11
FT /note="I -> N (in Ref. 1; CAC80838)"
FT /evidence="ECO:0000305"
FT CONFLICT 263
FT /note="E -> K (in Ref. 4; AAP40483 and 5; BAF01357)"
FT /evidence="ECO:0000305"
FT CONFLICT 379
FT /note="E -> K (in Ref. 1; CAC80838)"
FT /evidence="ECO:0000305"
FT CONFLICT 464
FT /note="V -> A (in Ref. 1; CAC80838)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 530 AA; 56904 MW; 62F2FE8F8AF5A3CB CRC64;
MRTLWNHFST ISYIKISPRM RRISAANLIS NRNLSTISST EDPELRDFVG FLESLKNYEK
SGVPKGAGTD SDDGFDLGRM KRLMLRLRNP HYKYKVVHVA GTKGKGSTSA FLSNILRAGG
YSVGCYSSPH ILSIKERISC NGEPVSASTL NDLFYSVKPI LEQSIQEENG SLSHFEILTG
IAFSLFEKEN VDIAVIEAGL GGARDATNVI ESSNLAASVI TTIGEEHMAA LGGSLESIAE
AKSGIIKHGR PVVLGGPFLP HIEGILRSKA ASVSSSVILA SNIGSSSSIK GIINKNGIGL
CQSCDIVIQN EKDDQPIVEL SDVNLRMLGH HQLQNAVTAT CVSLCLRDQG CGRVTDEAIR
IGLENTRLLG RSQFLTPKEA ETLLLPGATV LLDGAHTKES ARALKEMIKK DFPEKRLVFV
VAMASDKDHV SFAKELLSGL KPEAVILTEA DIGGGKIRST ESSVLKESWI KAADELGSRS
MEASENKTVL GSLKLAYKIL SDDTTSSDSG MVIVTGSLHI VSSVLASLQH
