ID   A4FUD0_BOVIN            Unreviewed;       935 AA.
AC   A4FUD0;
DT   17-APR-2007, integrated into UniProtKB/TrEMBL.
DT   17-APR-2007, sequence version 1.
DT   07-APR-2021, entry version 122.
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};
DE   AltName: Full=Formyltetrahydrofolate synthetase {ECO:0000256|ARBA:ARBA00015037};
DE   AltName: Full=Methenyltetrahydrofolate cyclohydrolase {ECO:0000256|ARBA:ARBA00013842};
DE   AltName: Full=Methylenetetrahydrofolate dehydrogenase {ECO:0000256|ARBA:ARBA00017700};
GN   Name=MTHFD1 {ECO:0000313|EMBL:AAI14712.1,
GN   ECO:0000313|Ensembl:ENSBTAP00000012704, 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}
RP   IDENTIFICATION.
RC   STRAIN=Hereford {ECO:0000313|Ensembl:ENSBTAP00000012704};
RG   Ensembl;
RL   Submitted (MAR-2016) to UniProtKB.
RN   [3] {ECO:0000313|Ensembl:ENSBTAP00000012704, ECO:0000313|Proteomes:UP000009136}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Hereford {ECO:0000313|Ensembl:ENSBTAP00000012704,
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.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADP(+) = 5,10-
CC         methenyltetrahydrofolate + NADPH; Xref=Rhea:RHEA:22812,
CC         ChEBI:CHEBI:15636, ChEBI:CHEBI:57455, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349; EC=1.5.1.5;
CC         Evidence={ECO:0000256|ARBA:ARBA00000568};
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   SMR; A4FUD0; -.
DR   STRING; 9913.ENSBTAP00000012704; -.
DR   PRIDE; A4FUD0; -.
DR   Ensembl; ENSBTAT00000012704; ENSBTAP00000012704; ENSBTAG00000009641.
DR   GeneID; 534382; -.
DR   KEGG; bta:534382; -.
DR   CTD; 4522; -.
DR   VGNC; VGNC:31730; MTHFD1.
DR   eggNOG; KOG4230; Eukaryota.
DR   GeneTree; ENSGT00940000154746; -.
DR   HOGENOM; CLU_003601_2_0_1; -.
DR   OMA; KVDTYTK; -.
DR   OrthoDB; 690393at2759; -.
DR   TreeFam; TF300623; -.
DR   UniPathway; UPA00193; -.
DR   Proteomes; UP000009136; Chromosome 10.
DR   Bgee; ENSBTAG00000009641; Expressed in liver and 19 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:0006555; P:methionine metabolic 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:0006164; P:purine nucleotide 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; cd01080; NAD_bind_m-THF_DH_Cyclohyd; 1.
DR   HAMAP; MF_01543; FTHFS; 1.
DR   HAMAP; MF_01576; THF_DHG_CYH; 1.
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   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; SSF51735; SSF51735; 1.
DR   SUPFAM; SSF52540; SSF52540; 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   Proteomics identification {ECO:0007829|PeptideAtlas:A4FUD0};
KW   Reference proteome {ECO:0000313|Proteomes:UP000009136}.
FT   DOMAIN          6..125
FT                   /note="THF_DHG_CYH"
FT                   /evidence="ECO:0000259|Pfam:PF00763"
FT   DOMAIN          129..293
FT                   /note="THF_DHG_CYH_C"
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
//