ID A0A3Q2HT03_HORSE Unreviewed; 906 AA.
AC A0A3Q2HT03;
DT 10-APR-2019, integrated into UniProtKB/TrEMBL.
DT 13-SEP-2023, sequence version 2.
DT 27-MAR-2024, entry version 25.
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|Ensembl:ENSECAP00000036406.2,
GN ECO:0000313|VGNC:VGNC:20414};
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796 {ECO:0000313|Ensembl:ENSECAP00000036406.2, ECO:0000313|Proteomes:UP000002281};
RN [1] {ECO:0000313|Ensembl:ENSECAP00000036406.2, ECO:0000313|Proteomes:UP000002281}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000036406.2,
RC ECO:0000313|Proteomes:UP000002281};
RX PubMed=19892987; DOI=10.1126/science.1178158;
RG Broad Institute Genome Sequencing Platform;
RG Broad Institute Whole Genome Assembly Team;
RA Wade C.M., Giulotto E., Sigurdsson S., Zoli M., Gnerre S., Imsland F.,
RA Lear T.L., Adelson D.L., Bailey E., Bellone R.R., Bloecker H., Distl O.,
RA Edgar R.C., Garber M., Leeb T., Mauceli E., MacLeod J.N., Penedo M.C.T.,
RA Raison J.M., Sharpe T., Vogel J., Andersson L., Antczak D.F., Biagi T.,
RA Binns M.M., Chowdhary B.P., Coleman S.J., Della Valle G., Fryc S.,
RA Guerin G., Hasegawa T., Hill E.W., Jurka J., Kiialainen A., Lindgren G.,
RA Liu J., Magnani E., Mickelson J.R., Murray J., Nergadze S.G., Onofrio R.,
RA Pedroni S., Piras M.F., Raudsepp T., Rocchi M., Roeed K.H., Ryder O.A.,
RA Searle S., Skow L., Swinburne J.E., Syvaenen A.C., Tozaki T., Valberg S.J.,
RA Vaudin M., White J.R., Zody M.C., Lander E.S., Lindblad-Toh K.;
RT "Genome sequence, comparative analysis, and population genetics of the
RT domestic horse.";
RL Science 326:865-867(2009).
RN [2] {ECO:0000313|Ensembl:ENSECAP00000036406.2}
RP IDENTIFICATION.
RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000036406.2};
RG Ensembl;
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 AlphaFoldDB; A0A3Q2HT03; -.
DR STRING; 9796.ENSECAP00000036406; -.
DR PaxDb; 9796-ENSECAP00000036406; -.
DR Ensembl; ENSECAT00000059229.2; ENSECAP00000036406.2; ENSECAG00000015580.3.
DR VGNC; VGNC:20414; MTHFD1.
DR GeneTree; ENSGT00940000154746; -.
DR InParanoid; A0A3Q2HT03; -.
DR OMA; QPIMFRR; -.
DR UniPathway; UPA00193; -.
DR Proteomes; UP000002281; Chromosome 24.
DR Bgee; ENSECAG00000015580; Expressed in liver and 23 other cell types or tissues.
DR ExpressionAtlas; A0A3Q2HT03; baseline.
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:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IBA:GO_Central.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central.
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; 3.
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; 2.
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; PS00766; THF_DHG_CYH_1; 1.
DR PROSITE; PS00767; THF_DHG_CYH_2; 1.
PE 1: Evidence at protein level;
KW One-carbon metabolism {ECO:0000256|ARBA:ARBA00022563};
KW Proteomics identification {ECO:0007829|PeptideAtlas:A0A3Q2HT03};
KW Reference proteome {ECO:0000313|Proteomes:UP000002281}.
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 906 AA; 98205 MW; F8DEDC0AC5F67432 CRC64;
MAPAEILNGK VVSAQIKQRL KNQVTQMKEQ VPGFTPCLAI LQVGNRDDSN LYINVKLKAA
EEIGIKATHI KLPRTATESE VLKYVTSLNE DSTVHGFIVQ LPLDSENPIN TEAVVNAIAP
EKDVDGLTSI NAGKLARGDL NDCFIPCTPK GCLELIKETG VQIAGRHAVV VGRSKIVGAP
MHDLLLWNHA TVTTCHSKTA KLDEEVNKGD ILVVAAGQPE MVKGEWIKPG AVVIDCGINY
IPDDTKPNGR KVVGDVAYSE AKERAGFITP VPGGVGPMTV AMLMQSTVES AKRFLEKFKP
GKWMIAYNNL DLKTPVPSDI QVSRSCKPKP IGNLAREIGL LSEEVELYGE TKAKILLSTL
ERLKHQPDGK YVVVTGITPT PLGEGKSTTT IGLVQALGAH LHQNVFACVR QPSQGPTFGI
KGGAAGGGYS QVIPMEEFNL HLTGDIHAIT AANNLVAAAI DARMFHELTQ TDKALFNRLV
PSVNGVKKFS DIQIRRLQKL GIEKTDPTTL TDEEINRFAR LDIDPETITW QRVLDTNDRF
LRKITIGQAS TEKGHTRTAQ FDISVASEIM AVLALTSSLE DMRDRLSKMV VASSKKGEPI
TTEDLGVSGA LTVLMKDAIK PNLMQTLEGT PVFVHAGPFA NIAHGNSSII ADRIALKLVG
PEGFVVTEAG FGADIGMEKF FNIKCRYSGL RPHVVVLNLE LVEKGFSNLR KQIENARMFG
VPVVVAVNAF RTDTEAELDL ISHLAKAHGA FDAVKCTHWA EGGRGALALA QAVQRAAEAP
SSFQLLYDLK LPVEDKIRII AQKIYGADDI ELLPEAQHKA EVYTKQGFGD LPICMAKTHL
SLSHNPEQKG VPTGFVLPIR DIRASVGAGF LYPLVGTMST MPGLPTRPCF YDIDLDPETE
QVNGLF
//
