ID   A4FUD0_BOVIN            Unreviewed;       935 AA.
AC   A4FUD0;
DT   17-APR-2007, integrated into UniProtKB/TrEMBL.
DT   17-APR-2007, sequence version 1.
DT   28-JUN-2023, entry version 132.
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 {ECO:0000313|EMBL:AAI14712.1,
GN   ECO:0000313|Ensembl:ENSBTAP00000012704.4,
GN   ECO:0000313|VGNC:VGNC:31730};
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913 {ECO:0000313|EMBL:AAI14712.1};
RN   [1] {ECO:0000313|EMBL:AAI14712.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=L1 Hereford {ECO:0000313|EMBL:AAI14712.1};
RC   TISSUE=Uterus {ECO:0000313|EMBL:AAI14712.1};
RA   Moore S., Alexander L., Brownstein M., Guan L., Lobo S., Meng Y.,
RA   Tanaguchi M., Wang Z., Yu J., Prange C., Schreiber K., Shenmen C.,
RA   Wagner L., Bala M., Barbazuk S., Barber S., Babakaiff R., Beland J.,
RA   Chun E., Del Rio L., Gibson S., Hanson R., Kirkpatrick R., Liu J.,
RA   Matsuo C., Mayo M., Santos R.R., Stott J., Tsai M., Wong D., Siddiqui A.,
RA   Holt R., Jones S.J., Marra M.A.;
RL   Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN   [2] {ECO:0000313|Ensembl:ENSBTAP00000012704.4, ECO:0000313|Proteomes:UP000009136}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Hereford {ECO:0000313|Ensembl:ENSBTAP00000012704.4,
RC   ECO:0000313|Proteomes:UP000009136};
RA   Rosen B.D., Bickhart D.M., Koren S., Schnabel R.D., Hall R., Zimin A.,
RA   Dreischer C., Schultheiss S., Schroeder S.G., Elsik C.G., Couldrey C.,
RA   Liu G.E., Van Tassell C.P., Phillippy A.M., Smith T.P.L., Medrano J.F.;
RT   "ARS-UCD1.2.";
RL   Submitted (MAR-2018) to the EMBL/GenBank/DDBJ databases.
RN   [3] {ECO:0000313|Ensembl:ENSBTAP00000012704.4}
RP   IDENTIFICATION.
RC   STRAIN=Hereford {ECO:0000313|Ensembl:ENSBTAP00000012704.4};
RG   Ensembl;
RL   Submitted (MAR-2023) to UniProtKB.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6S)-5,6,7,8-tetrahydrofolate + ATP + formate = (6S)-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:57454, ChEBI:CHEBI:456216; EC=6.3.4.3;
CC         Evidence={ECO:0000256|ARBA:ARBA00000508};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5,10-methenyltetrahydrofolate + H2O = (6S)-10-
CC         formyltetrahydrofolate + H(+); Xref=Rhea:RHEA:23700,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57454,
CC         ChEBI:CHEBI:57455; EC=3.5.4.9;
CC         Evidence={ECO:0000256|ARBA:ARBA00001660};
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; BC114711; AAI14712.1; -; mRNA.
DR   RefSeq; NP_001076946.1; NM_001083477.1.
DR   STRING; 9913.ENSBTAP00000012704; -.
DR   Ensembl; ENSBTAT00000012704.5; ENSBTAP00000012704.4; ENSBTAG00000009641.5.
DR   GeneID; 534382; -.
DR   KEGG; bta:534382; -.
DR   CTD; 4522; -.
DR   VEuPathDB; HostDB:ENSBTAG00000009641; -.
DR   VGNC; VGNC:31730; MTHFD1.
DR   eggNOG; KOG4230; Eukaryota.
DR   GeneTree; ENSGT00940000154746; -.
DR   HOGENOM; CLU_003601_2_0_1; -.
DR   OMA; QPIMFRR; -.
DR   OrthoDB; 651667at2759; -.
DR   TreeFam; TF300623; -.
DR   Reactome; R-BTA-196757; Metabolism of folate and pterines.
DR   UniPathway; UPA00193; -.
DR   Proteomes; UP000009136; Chromosome 10.
DR   Bgee; ENSBTAG00000009641; Expressed in liver and 108 other tissues.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004329; F:formate-tetrahydrofolate ligase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; IBA:GO_Central.
DR   GO; GO:0004487; F:methylenetetrahydrofolate dehydrogenase (NAD+) activity; IEA:Ensembl.
DR   GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IBA:GO_Central.
DR   GO; GO:0009257; P:10-formyltetrahydrofolate biosynthetic process; IEA:Ensembl.
DR   GO; GO:0007507; P:heart development; IEA:Ensembl.
DR   GO; GO:0009086; P:methionine biosynthetic process; IEA:Ensembl.
DR   GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR   GO; GO:0001780; P:neutrophil homeostasis; IEA:Ensembl.
DR   GO; GO:0009152; P:purine ribonucleotide biosynthetic process; IEA:Ensembl.
DR   GO; GO:0009070; P:serine family amino acid biosynthetic process; IEA:Ensembl.
DR   GO; GO:0061053; P:somite development; IEA:Ensembl.
DR   GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central.
DR   GO; GO:0019346; P:transsulfuration; IEA:Ensembl.
DR   CDD; cd00477; FTHFS; 1.
DR   CDD; cd01080; NAD_bind_m-THF_DH_Cyclohyd; 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   1: Evidence at protein level;
KW   Hydrolase {ECO:0000256|ARBA:ARBA00022801};
KW   One-carbon metabolism {ECO:0000256|ARBA:ARBA00022563};
KW   Oxidoreductase {ECO:0000256|ARBA:ARBA00023002};
KW   Proteomics identification {ECO:0007829|PeptideAtlas:A4FUD0};
KW   Reference proteome {ECO:0000313|Proteomes:UP000009136}.
FT   DOMAIN          7..125
FT                   /note="Tetrahydrofolate dehydrogenase/cyclohydrolase
FT                   catalytic"
FT                   /evidence="ECO:0000259|Pfam:PF00763"
FT   DOMAIN          129..293
FT                   /note="Tetrahydrofolate dehydrogenase/cyclohydrolase
FT                   NAD(P)-binding"
FT                   /evidence="ECO:0000259|Pfam:PF02882"
SQ   SEQUENCE   935 AA;  101177 MW;  BF41B702ED19850A CRC64;
     MAPAEILNGK VVSAQIKERL KNQVIQMKEE VPGFIPGLAI LQVGNRDDSN LYINMKLKAA
     EEIGIKATHI KLPRTATESE VLKCITSLNE DLTVHGFIVQ LPLDSENPIN TETLVNAIAP
     EKDVDGLNSI SAGKLARGDL SNCFIPCTPK GCLELIKETG VQIAGRHAVV VGRSKIVGAP
     MHDLLLWNHA TVTTCHSKTA NLKEEISKGD ILVVAAGQPE MVKGEWIKPG AIVIDCGINY
     VTDDTKPNGK KIVGDVAYTE AKERASFITP VPGGVGPMTV AMLMQSTVES AKRFLENFKP
     GKWIIQYNKL NLKTPVPSDI DISRSYKPKP IGNLAREVGL RTEEVELYGE TKAKVLLSAL
     ERLKHQPDGK YVVVTGITPT PLGEGKSTTT IGLVQALGTH LHQNVFACVR QPSQGPTFGI
     KGGAAGGGYS QVIPMEEFNL HLTGDIHAIT AANNLVAAAI DARMFHEETQ TDKALFNRLV
     PSVNGVRKFS DIQIRRLRRL GIEKTDPATL TDEEINRFAR LDIDPETITW QRVLDTNDRF
     LRKITIGQAP TEKGHSRTAQ FDISVASEIM AVLALTSSLE DMRERLGKMV VASSKKGEPI
     STEDLGVSGA LTVLMKDAIK PNLMQTLEGT PVFVHAGPFA NIAHGNSSII ADRIALKLVG
     PEGFVVTEAG FGADIGMEKF FNIKCRYSGL RPHVVVLVAT VRALKMHGGG PTVTAGLPLP
     KAYIEEDLEL VGKGFSNLKK QIENARMFGV PVVVAVNAFK TDTEAELDLV SRLAKEHGAF
     DAVKCTHWAE GGKGALALAE AVQRAAAAPS SFQLLYDLKL PVEDKIRIIA QKIYGADNIE
     LLPEAQHKAE VYTKQGFGNL PICMAKTHLS LSHNPELKGV PTGFVLPIRD IRASVGAGFL
     YPLVGTMSTM PGLPTRPCFY DIDLDPETEQ VNGLF
//