ID V9GZ78_HUMAN Unreviewed; 854 AA.
AC V9GZ78; V9GY75;
DT 19-FEB-2014, integrated into UniProtKB/TrEMBL.
DT 05-JUN-2019, sequence version 2.
DT 27-MAR-2024, entry version 65.
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:ENSP00000477501.2};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000313|Ensembl:ENSP00000477501.2, ECO:0000313|Proteomes:UP000005640};
RN [1] {ECO:0000313|Ensembl:ENSP00000477501.2, ECO:0000313|Proteomes:UP000005640}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [2] {ECO:0007829|PubMed:24275569}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [3] {ECO:0007829|PubMed:25944712}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [4] {ECO:0000313|Ensembl:ENSP00000477501.2}
RP IDENTIFICATION.
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 EMBL; AL122035; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR Antibodypedia; 52; 190 antibodies from 30 providers.
DR Ensembl; ENST00000554768.6; ENSP00000477501.2; ENSG00000100714.18.
DR Ensembl; ENST00000557539.2; ENSP00000476468.2; ENSG00000100714.18.
DR Ensembl; ENST00000652179.1; ENSP00000498649.1; ENSG00000100714.18.
DR Ensembl; ENST00000697173.1; ENSP00000513159.1; ENSG00000100714.18.
DR UCSC; uc059cjf.1; human.
DR UCSC; uc059cjh.1; human.
DR HGNC; HGNC:7432; MTHFD1.
DR VEuPathDB; HostDB:ENSG00000100714; -.
DR GeneTree; ENSGT00940000154746; -.
DR HOGENOM; CLU_2800585_0_0_1; -.
DR HOGENOM; CLU_3424336_0_0_1; -.
DR OMA; QPIMFRR; -.
DR UniPathway; UPA00193; -.
DR ChiTaRS; MTHFD1; human.
DR Proteomes; UP000005640; Chromosome 14.
DR Bgee; ENSG00000100714; Expressed in right lobe of liver and 202 other cell types or tissues.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
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 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; 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|EPD:V9GZ78,
KW ECO:0007829|MaxQB:V9GZ78};
KW Reference proteome {ECO:0000313|Proteomes:UP000005640}.
FT DOMAIN 2..44
FT /note="Tetrahydrofolate dehydrogenase/cyclohydrolase
FT catalytic"
FT /evidence="ECO:0000259|Pfam:PF00763"
FT DOMAIN 48..212
FT /note="Tetrahydrofolate dehydrogenase/cyclohydrolase
FT NAD(P)-binding"
FT /evidence="ECO:0000259|Pfam:PF02882"
SQ SEQUENCE 854 AA; 92570 MW; 520330E633569ACE CRC64;
MKYITSLNED STVHGFLVQL PLDSENSINT EEVINAIAPE KDVDGLTSIN AGKLARGDLN
DCFIPCTPKG CLELIKETGV PIAGRHAVVV GRSKIVGAPM HDLLLWNNAT VTTCHSKTAH
LDEEVNKGDI LVVATGQPEM VKGEWIKPGA IVIDCGINYV PDDKKPNGRK VVGDVAYDEA
KERASFITPV PGGVGPMTVA MLMQSTVESA KRFLEKFKPG KWMIQYNNLN LKTPVPSDID
ISRSCKPKPI GKLAREIGLL SEEVELYGET KAKVLLSALE RLKHRPDGKY VVVTGITPTP
LGEGKSTTTI GLVQALGAHL YQNVFACVRQ PSQGPTFGIK GGAAGGGYSQ VIPMEEFNLH
LTGDIHAITA ANNLVAAAID ARIFHELTQT DKALFNRLVP SVNGVRRFSD IQIRRLKRLG
IEKTDPTTLT DEEINRFARL DIDPETITWQ RVLDTNDRFL RKITIGQAPT EKGHTRTAQF
DISVASEIMA VLALTTSLED MRERLGKMVV ASSKKGEPVS AEDLGVSGAL TVLMKDAIKP
NLMQTLEGTP VFVHAGPFAN IAHGNSSIIA DRIALKLVGP EGFVVTEAGF GADIGMEKFF
NIKCRYSGLC PHVVVLVATV RALKMHGGGP TVTAGLPLPK AYIQENLELV EKGFSNLKKQ
IENARMFGIP VVVAVNAFKT DTESELDLIS RLSREHGAFD AVKCTHWAEG GKGALALAQA
VQRAAQAPSS FQLLYDLKLP VEDKIRIIAQ KIYGADDIEL LPEAQHKAEV YTKQGFGNLP
ICMAKTHLSL SHNPEQKGVP TGFILPIRDI RASVGAGFLY PLVGTMSTMP GLPTRPCFYD
IDLDPETEQV NGLF
//
