ID A4FUD0_BOVIN Unreviewed; 935 AA. AC A4FUD0; DT 17-APR-2007, integrated into UniProtKB/TrEMBL. DT 17-APR-2007, sequence version 1. DT 13-SEP-2023, entry version 133. 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 (MAY-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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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:InterPro. 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 ATP-binding {ECO:0000256|ARBA:ARBA00022840}; KW Hydrolase {ECO:0000256|ARBA:ARBA00022801}; KW Ligase {ECO:0000256|ARBA:ARBA00022598}; KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741}; 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 //