ID   Q7ZXF4_XENLA            Unreviewed;       934 AA.
AC   Q7ZXF4;
DT   01-JUN-2003, integrated into UniProtKB/TrEMBL.
DT   01-JUN-2003, sequence version 1.
DT   27-MAR-2024, entry version 113.
DE   RecName: Full=C-1-tetrahydrofolate synthase, cytoplasmic {ECO:0000256|ARBA:ARBA00017592};
DE            EC=1.5.1.5 {ECO:0000256|ARBA:ARBA00012859};
DE            EC=3.5.4.9 {ECO:0000256|ARBA:ARBA00012776};
DE            EC=6.3.4.3 {ECO:0000256|ARBA:ARBA00012295};
GN   Name=mthfd1.L {ECO:0000313|RefSeq:NP_001080574.1,
GN   ECO:0000313|Xenbase:XB-GENE-992138};
GN   Synonyms=mthfd1 {ECO:0000313|RefSeq:NP_001080574.1,
GN   ECO:0000313|Xenbase:XB-GENE-992138};
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355 {ECO:0000313|EMBL:AAH45019.1};
RN   [1] {ECO:0000313|RefSeq:NP_001080574.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=12454917; DOI=10.1002/dvdy.10174;
RA   Klein S.L., Strausberg R.L., Wagner L., Pontius J., Clifton S.W.,
RA   Richardson P.;
RT   "Genetic and genomic tools for Xenopus research: The NIH Xenopus
RT   initiative.";
RL   Dev. Dyn. 225:384-391(2002).
RN   [2] {ECO:0000313|EMBL:AAH45019.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo {ECO:0000313|EMBL:AAH45019.1};
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3] {ECO:0000313|RefSeq:NP_001080574.1}
RP   IDENTIFICATION.
RG   RefSeq;
RL   Submitted (NOV-2023) to UniProtKB.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6R)-5,10-methenyltetrahydrofolate + H2O = (6R)-10-
CC         formyltetrahydrofolate + H(+); Xref=Rhea:RHEA:23700,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57455,
CC         ChEBI:CHEBI:195366; EC=3.5.4.9;
CC         Evidence={ECO:0000256|ARBA:ARBA00036357};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6S)-5,6,7,8-tetrahydrofolate + ATP + formate = (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; Evidence={ECO:0000256|ARBA:ARBA00036012};
CC   -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC       {ECO:0000256|ARBA:ARBA00004777}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000256|ARBA:ARBA00011738}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the
CC       formate--tetrahydrofolate ligase family.
CC       {ECO:0000256|ARBA:ARBA00006985}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the tetrahydrofolate
CC       dehydrogenase/cyclohydrolase family. {ECO:0000256|ARBA:ARBA00005559}.
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DR   EMBL; BC045019; AAH45019.1; -; mRNA.
DR   RefSeq; NP_001080574.1; NM_001087105.1.
DR   IntAct; Q7ZXF4; 1.
DR   STRING; 8355.Q7ZXF4; -.
DR   PaxDb; 8355-Q7ZXF4; -.
DR   DNASU; 380266; -.
DR   GeneID; 380266; -.
DR   KEGG; xla:380266; -.
DR   AGR; Xenbase:XB-GENE-992138; -.
DR   CTD; 380266; -.
DR   Xenbase; XB-GENE-992138; mthfd1.L.
DR   OMA; QPIMFRR; -.
DR   OrthoDB; 651667at2759; -.
DR   UniPathway; UPA00193; -.
DR   Proteomes; UP000186698; Chromosome 8L.
DR   Bgee; 380266; Expressed in kidney and 19 other cell types or tissues.
DR   GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR   GO; GO:0004329; F:formate-tetrahydrofolate ligase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IEA:UniProtKB-EC.
DR   GO; GO:0035999; P:tetrahydrofolate interconversion; IEA:UniProtKB-UniPathway.
DR   CDD; cd00477; FTHFS; 1.
DR   CDD; cd01080; NAD_bind_m-THF_DH_Cyclohyd; 1.
DR   Gene3D; 1.10.8.770; -; 1.
DR   Gene3D; 3.10.410.10; Formyltetrahydrofolate synthetase, domain 3; 1.
DR   Gene3D; 3.40.50.10860; Leucine Dehydrogenase, chain A, domain 1; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2.
DR   HAMAP; MF_01543; FTHFS; 1.
DR   HAMAP; MF_01576; THF_DHG_CYH; 1.
DR   InterPro; IPR046346; Aminoacid_DH-like_N_sf.
DR   InterPro; IPR000559; Formate_THF_ligase.
DR   InterPro; IPR020628; Formate_THF_ligase_CS.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR000672; THF_DH/CycHdrlase.
DR   InterPro; IPR020630; THF_DH/CycHdrlase_cat_dom.
DR   InterPro; IPR020867; THF_DH/CycHdrlase_CS.
DR   InterPro; IPR020631; THF_DH/CycHdrlase_NAD-bd_dom.
DR   PANTHER; PTHR48099:SF1; C-1-TETRAHYDROFOLATE SYNTHASE, CYTOPLASMIC; 1.
DR   PANTHER; PTHR48099; C-1-TETRAHYDROFOLATE SYNTHASE, CYTOPLASMIC-RELATED; 1.
DR   Pfam; PF01268; FTHFS; 1.
DR   Pfam; PF00763; THF_DHG_CYH; 1.
DR   Pfam; PF02882; THF_DHG_CYH_C; 1.
DR   PRINTS; PR00085; THFDHDRGNASE.
DR   SUPFAM; SSF53223; Aminoacid dehydrogenase-like, N-terminal domain; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   PROSITE; PS00721; FTHFS_1; 1.
DR   PROSITE; PS00722; FTHFS_2; 1.
DR   PROSITE; PS00766; THF_DHG_CYH_1; 1.
DR   PROSITE; PS00767; THF_DHG_CYH_2; 1.
PE   2: Evidence at transcript level;
KW   One-carbon metabolism {ECO:0000256|ARBA:ARBA00022563};
KW   Reference proteome {ECO:0000313|Proteomes:UP000186698}.
FT   DOMAIN          6..124
FT                   /note="Tetrahydrofolate dehydrogenase/cyclohydrolase
FT                   catalytic"
FT                   /evidence="ECO:0000259|Pfam:PF00763"
FT   DOMAIN          128..292
FT                   /note="Tetrahydrofolate dehydrogenase/cyclohydrolase
FT                   NAD(P)-binding"
FT                   /evidence="ECO:0000259|Pfam:PF02882"
SQ   SEQUENCE   934 AA;  100549 MW;  B0DCDA5CA5E4824C CRC64;
     MPAEILSGKV VSGLVRERLK TEVAAMKEKV PGFSPGLAIV QVGDRDDSNL YISMKLKAAA
     EIGISASHVK LPKTATEAEV LSKIMSINED PAYHGMIVQL PLDSDHPINT EKVTNAVSPA
     KDVDGLTSIN AGKLARGDLG DCFIPCTPKG CMDLIKQTGV QIPGKRAVVI GRSKIVGAPM
     HDLLLWNHAT VTTCHSKTAS LNEEVSRADI LVVGAGKPEM VKGDWIKPGA IVIDCGINYV
     PDPNKPSGKR VVGDVAYVEA KEKASYITPV PGGVGPMTVA MLMENTVESA KRYLVQFQPH
     KWNIEYNKLH LKVPVPSDIE ISRSCIPKPI AKISEEIGLL SQEVELYGQT KAKVLLSTLK
     RLQNREDGKY VVVTGITPTP LGEGKSTTTI GLVQALGAHL NLNVFACVRQ PSQGPTFGIK
     GGAAGGGYSQ VIPMEEFNLH LTGDIHAITA ANNLVAAAID ARIFHELTQS DKALYSRLVP
     SNNGVRKFSD IQIRRLRRLG IEKTDPAALT EEEINKFVRL DIDPDTITWQ RVLDTNDRFL
     RKITIGQAPT EKGFTRTAQF DISVASEIMA VLALTDGLDN MRERLGKMVV ASSKKGEPVS
     TEDLGVSGAL TVLMKDAVKP NLMQTMEGNP VFVHAGPFAN IAHGNSSILA DKIALKLVGP
     EGFVVTEAGF GADIGMEKFF NIKCRYSGLR PHVVVLVSTV RALKMHGGGP TVTAGVPLPK
     EYTEENLDLI EKGCSNLRKQ IENATIFGVP VVVAVNAFKT DTEAELDIVC DLAKKAGAFD
     AIRCTHWADG GKGAVALAQA VQRASQAPSN FKFLYDVQLP IADKIRIIAQ KIYGADDIEL
     LPEAQKKADL YTKQGFGNLP VCMAKTHLSL SHNPELKGVP TGFVLPIRDI RASVGAGFLY
     PLVGTMSTMP GLPTRPCFYD IDLDPVSEQV NGLF
//