ID   FTHS_ARATH              Reviewed;         634 AA.
AC   Q9SPK5;
DT   21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   02-SEP-2026, entry version 147.
DE   RecName: Full=Formate--tetrahydrofolate ligase;
DE            EC=6.3.4.3;
DE   AltName: Full=10-formyletrahydrofolate synthetase;
DE            Short=FHS;
DE            Short=FTHFS;
DE   AltName: Full=Formyltetrahydrofolate synthetase;
GN   Name=THFS; OrderedLocusNames=At1g50480; ORFNames=F11F12.17, F17J6.2;
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;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=cv. Columbia; TISSUE=Hypocotyl;
RA   Skavdahl M., Olson B.J.S.C., Markwell J., Osterman J.C.;
RT   "Nucleotide sequence of a cDNA encoding 10-formyletrahydrofolate synthetase
RT   from Arabidopsis thaliana.";
RL   (er) Plant Gene Register PGR99-133(1999).
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   GENOME REANNOTATION.
RC   STRAIN=cv. Columbia;
RG   The Arabidopsis Information Resource (TAIR);
RT   "Community-consensus reference genome of Arabidopsis thaliana Col-0.";
RL   Submitted (FEB-2026) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6S)-5,6,7,8-tetrahydrofolate + formate + ATP = (6R)-10-
CC         formyltetrahydrofolate + ADP + phosphate; Xref=Rhea:RHEA:20221,
CC         ChEBI:CHEBI:15740, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:57453, ChEBI:CHEBI:195366, ChEBI:CHEBI:456216;
CC         EC=6.3.4.3;
CC   -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the formate--tetrahydrofolate ligase family.
CC       {ECO:0000305}.
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DR   EMBL; AF162279; AAD56290.1; -; mRNA.
DR   EMBL; AC012561; AAF87882.1; -; Genomic_DNA.
DR   EMBL; AC079279; AAG51185.1; -; Genomic_DNA.
DR   EMBL; CP002684; AEE32555.1; -; Genomic_DNA.
DR   EMBL; OZ408683; CAO7030462.1; -; Genomic_DNA.
DR   EMBL; AY054637; AAK96828.1; -; mRNA.
DR   EMBL; AY081549; AAM10111.1; -; mRNA.
DR   PIR; C96541; C96541.
DR   RefSeq; NP_564571.1; NM_103931.4.
DR   AlphaFoldDB; Q9SPK5; -.
DR   SMR; Q9SPK5; -.
DR   BioGRID; 26695; 7.
DR   FunCoup; Q9SPK5; 3946.
DR   IntAct; Q9SPK5; 1.
DR   STRING; 3702.Q9SPK5; -.
DR   GlyGen; Q9SPK5; 1 site.
DR   iPTMnet; Q9SPK5; -.
DR   MetOSite; Q9SPK5; -.
DR   PaxDb; 3702-Q9SPK5; -.
DR   ProteomicsDB; 248554; -.
DR   GeneID; 841470; -.
DR   KEGG; ath:AT1G50480; -.
DR   Araport; AT1G50480; -.
DR   TAIR; AT1G50480; THFS.
DR   eggNOG; ENOG502QSVW; Eukaryota.
DR   HOGENOM; CLU_003601_3_3_1; -.
DR   InParanoid; Q9SPK5; -.
DR   OMA; KFWNLKC; -.
DR   PhylomeDB; Q9SPK5; -.
DR   BioCyc; ARA:AT1G50480-MONOMER; -.
DR   BRENDA; 6.3.4.3; 399.
DR   UniPathway; UPA00193; -.
DR   CD-CODE; 4299E36E; Nucleolus.
DR   PRO; PR:Q9SPK5; -.
DR   Proteomes; UP000006548; Chromosome 1.
DR   GO; GO:0048046; C:apoplast; HDA:TAIR.
DR   GO; GO:0009507; C:chloroplast; HDA:TAIR.
DR   GO; GO:0005737; C:cytoplasm; ISM:TAIR.
DR   GO; GO:0005829; C:cytosol; HDA:TAIR.
DR   GO; GO:0005634; C:nucleus; HDA:TAIR.
DR   GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR   GO; GO:0005507; F:copper ion binding; HDA:TAIR.
DR   GO; GO:0004329; F:formate-tetrahydrofolate ligase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; IEA:UniProtKB-ARBA.
DR   GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IEA:UniProtKB-ARBA.
DR   GO; GO:0009257; P:10-formyltetrahydrofolate biosynthetic process; IEA:UniProtKB-ARBA.
DR   GO; GO:0046655; P:folic acid metabolic process; IEA:UniProtKB-ARBA.
DR   GO; GO:0006555; P:L-methionine metabolic process; IEA:UniProtKB-ARBA.
DR   GO; GO:0006164; P:purine nucleotide biosynthetic process; IEA:UniProtKB-ARBA.
DR   GO; GO:0035999; P:tetrahydrofolate interconversion; IEA:UniProtKB-UniPathway.
DR   CDD; cd00477; FTHFS; 1.
DR   FunFam; 3.40.50.300:FF:000245; C-1-tetrahydrofolate synthase, cytoplasmic; 1.
DR   FunFam; 3.40.50.300:FF:001123; C-1-tetrahydrofolate synthase, cytoplasmic isoform X2; 1.
DR   FunFam; 3.30.1510.10:FF:000003; Formate--tetrahydrofolate ligase; 1.
DR   FunFam; 1.10.8.770:FF:000001; Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like; 1.
DR   FunFam; 3.10.410.10:FF:000001; Putative formate--tetrahydrofolate ligase; 1.
DR   Gene3D; 3.30.1510.10; Domain 2, N(10)-formyltetrahydrofolate synthetase; 1.
DR   Gene3D; 3.10.410.10; Formyltetrahydrofolate synthetase, domain 3; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2.
DR   HAMAP; MF_01543; FTHFS; 1.
DR   InterPro; IPR000559; Formate_THF_ligase.
DR   InterPro; IPR020628; Formate_THF_ligase_CS.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   Pfam; PF01268; FTHFS; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   PROSITE; PS00721; FTHFS_1; 1.
DR   PROSITE; PS00722; FTHFS_2; 1.
PE   2: Evidence at transcript level;
KW   ATP-binding; Ligase; Nucleotide-binding; One-carbon metabolism;
KW   Reference proteome.
FT   CHAIN           1..634
FT                   /note="Formate--tetrahydrofolate ligase"
FT                   /id="PRO_0000199417"
FT   BINDING         78..85
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   634 AA;  67802 MW;  5BD9D10603D2FF9A CRC64;
     MSSSTRKLEV VSPVPADIDI ANSVEPLHIS EIAKDLNINP LHYDLYGKYK AKVLLSAFDE
     LQGQEDGYYV VVGGITPTPL GEGKSTTTVG LCQALGAYLD KKVVTCLRQP SQGPTFGIKG
     GAAGGGYSQV IPMDEFNLHL TGDIHAITAS NNLLAAAIDT RIFHETSQSD KALFNRLCPP
     NKEGKRSFSD IMFRRLTKLG ISKTSPEELT PEEIKKFARL DIDPASITWR RVMDVNDRFL
     RKITIGQGPE EKGMTRETGF DISVASEIMA VLALTTSLGD MRERLGKMVI GNSKAGDPIT
     ADDLGVGGAL TVLMKDAINP TLMQTLEGTP VLVHAGPFAN IAHGNSSIVA DKIALKLVGP
     GGFVVTEAGF GSDIGTEKFM NIKCRYSGLT PQCAIVVATV RALKMHGGGP DVVAGRPLDR
     AYVSENVSLV EAGCVNLAKH ISNTKAYGVN VIVAVNMFAT DTEAELNAVR KFSMDAGAFD
     AVVCSHHAHS GKGAVDLGIA VEKACQNITQ PLRFLYPLDI GIKDKIEAIA KSYGASGVEY
     SDQAEKQIEM YTQQGFSNLP ICMSKTQYSF SHDASKKGAP SGFVLPIRDV RGSIGAGFIY
     PLVGTMSTMP GLPTRPCFYE IDIDTETGKV RGLS
//