C1TM_HUMAN
ID C1TM_HUMAN Reviewed; 978 AA.
AC Q6UB35; Q2TBF3; Q8WVW0; Q96HG8; Q9H789; Q9UFU8;
DT 01-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Monofunctional C1-tetrahydrofolate synthase, mitochondrial {ECO:0000305|PubMed:16171773};
DE EC=6.3.4.3 {ECO:0000269|PubMed:16171773};
DE AltName: Full=Formyltetrahydrofolate synthetase;
DE Flags: Precursor;
GN Name=MTHFD1L {ECO:0000312|HGNC:HGNC:21055}; Synonyms=FTHFSDC1;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=12937168; DOI=10.1074/jbc.m304319200;
RA Prasannan P., Pike S., Peng K., Shane B., Appling D.R.;
RT "Human mitochondrial C1-tetrahydrofolate synthase: gene structure, tissue
RT distribution of the mRNA, and immunolocalization in Chinese hamster ovary
RT calls.";
RL J. Biol. Chem. 278:43178-43187(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=15013446; DOI=10.1016/j.bbrc.2004.01.035;
RA Sugiura T., Nagano Y., Inoue T., Hirotani K.;
RT "A novel mitochondrial C1-tetrahydrofolate synthetase is upregulated in
RT human colon adenocarcinoma.";
RL Biochem. Biophys. Res. Commun. 315:204-211(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP PROTEIN SEQUENCE OF 32-66, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=16171773; DOI=10.1016/j.abb.2005.08.007;
RA Walkup A.S., Appling D.R.;
RT "Enzymatic characterization of human mitochondrial C1-tetrahydrofolate
RT synthase.";
RL Arch. Biochem. Biophys. 442:196-205(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 62-978 (ISOFORM 1).
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 79-978 (ISOFORM 1).
RC TISSUE=Cervix, Eye, and Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 522-530; 564-575 AND 926-935, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Mammary carcinoma;
RA Bienvenut W.V., Matallanas D., Cooper W.N., Kolch W.;
RL Submitted (JUL-2007) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 591-978 (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-189, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-357, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
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 [14]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-444.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: May provide the missing metabolic reaction required to link
CC the mitochondria and the cytoplasm in the mammalian model of one-carbon
CC folate metabolism complementing thus the enzymatic activities of
CC MTHFD2. {ECO:0000250, ECO:0000269|PubMed:16171773}.
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:0000269|PubMed:16171773};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20222;
CC Evidence={ECO:0000305|PubMed:16171773};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=500 uM for THF monoglutamate {ECO:0000269|PubMed:16171773};
CC KM=16 uM for THF triglutamate {ECO:0000269|PubMed:16171773};
CC KM=3.6 uM for THF pentaglutamate {ECO:0000269|PubMed:16171773};
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC {ECO:0000269|PubMed:16171773}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16171773}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:12937168}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6UB35-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6UB35-2; Sequence=VSP_034565, VSP_034566;
CC -!- TISSUE SPECIFICITY: Detected in most tissues, highest expression found
CC in placenta, thymus and brain. Low expression is found in liver and
CC skeletal muscle. Up-regulated in colon adenocarcinoma.
CC {ECO:0000269|PubMed:12937168, ECO:0000269|PubMed:15013446}.
CC -!- DOMAIN: This monofunctional enzyme consists of two major domains: an N-
CC terminal inactive methylene-THF dehydrogenase and cyclohydrolase domain
CC and an active larger formyl-THF synthetase C-terminal domain.
CC -!- MISCELLANEOUS: May participate in the progression of colorectal cancer
CC by conferring growth advantage. Could be a new molecular target for
CC cancer therapy.
CC -!- SIMILARITY: In the N-terminal section; belongs to the tetrahydrofolate
CC dehydrogenase/cyclohydrolase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the formate--
CC tetrahydrofolate ligase family. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be a trifunctional enzyme but only a
CC formyltetrahydrofolate synthetase activity was detected and not a
CC dehydrogenase/cyclohydrogenase activity. {ECO:0000305|PubMed:12937168}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH08629.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAB15009.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY374130; AAQ82696.1; -; mRNA.
DR EMBL; AY374131; AAQ82697.1; -; mRNA.
DR EMBL; AB127387; BAD93193.1; -; mRNA.
DR EMBL; CH471051; EAW47762.1; -; Genomic_DNA.
DR EMBL; AL035086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL133260; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL049694; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL117452; CAB55934.1; -; mRNA.
DR EMBL; BC008629; AAH08629.1; ALT_INIT; mRNA.
DR EMBL; BC017477; AAH17477.2; -; mRNA.
DR EMBL; BC110319; AAI10320.1; -; mRNA.
DR EMBL; AK024798; BAB15009.1; ALT_INIT; mRNA.
DR CCDS; CCDS5228.1; -. [Q6UB35-1]
DR CCDS; CCDS56457.1; -. [Q6UB35-2]
DR PIR; T17244; T17244.
DR RefSeq; NP_001229696.1; NM_001242767.1.
DR RefSeq; NP_001229697.1; NM_001242768.1.
DR RefSeq; NP_001229698.1; NM_001242769.1. [Q6UB35-2]
DR RefSeq; NP_056255.2; NM_015440.4. [Q6UB35-1]
DR AlphaFoldDB; Q6UB35; -.
DR SMR; Q6UB35; -.
DR BioGRID; 117409; 132.
DR IntAct; Q6UB35; 37.
DR MINT; Q6UB35; -.
DR STRING; 9606.ENSP00000478253; -.
DR ChEMBL; CHEMBL4295869; -.
DR GlyGen; Q6UB35; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q6UB35; -.
DR PhosphoSitePlus; Q6UB35; -.
DR SwissPalm; Q6UB35; -.
DR BioMuta; MTHFD1L; -.
DR DMDM; 74749360; -.
DR EPD; Q6UB35; -.
DR jPOST; Q6UB35; -.
DR MassIVE; Q6UB35; -.
DR MaxQB; Q6UB35; -.
DR PaxDb; Q6UB35; -.
DR PeptideAtlas; Q6UB35; -.
DR PRIDE; Q6UB35; -.
DR ProteomicsDB; 67402; -. [Q6UB35-1]
DR ProteomicsDB; 67403; -. [Q6UB35-2]
DR Antibodypedia; 33330; 161 antibodies from 29 providers.
DR DNASU; 25902; -.
DR Ensembl; ENST00000367307.8; ENSP00000356276.4; ENSG00000120254.16. [Q6UB35-2]
DR Ensembl; ENST00000367321.8; ENSP00000356290.3; ENSG00000120254.16. [Q6UB35-1]
DR GeneID; 25902; -.
DR KEGG; hsa:25902; -.
DR MANE-Select; ENST00000367321.8; ENSP00000356290.3; NM_015440.5; NP_056255.2.
DR UCSC; uc003qoa.4; human. [Q6UB35-1]
DR CTD; 25902; -.
DR DisGeNET; 25902; -.
DR GeneCards; MTHFD1L; -.
DR HGNC; HGNC:21055; MTHFD1L.
DR HPA; ENSG00000120254; Low tissue specificity.
DR MIM; 611427; gene.
DR neXtProt; NX_Q6UB35; -.
DR OpenTargets; ENSG00000120254; -.
DR PharmGKB; PA134927803; -.
DR VEuPathDB; HostDB:ENSG00000120254; -.
DR eggNOG; KOG4230; Eukaryota.
DR GeneTree; ENSGT00940000157477; -.
DR HOGENOM; CLU_1011786_0_0_1; -.
DR InParanoid; Q6UB35; -.
DR OMA; CGEIMTM; -.
DR OrthoDB; 690393at2759; -.
DR PhylomeDB; Q6UB35; -.
DR TreeFam; TF300623; -.
DR BRENDA; 6.3.4.3; 2681.
DR PathwayCommons; Q6UB35; -.
DR Reactome; R-HSA-196757; Metabolism of folate and pterines.
DR SignaLink; Q6UB35; -.
DR SIGNOR; Q6UB35; -.
DR UniPathway; UPA00193; -.
DR BioGRID-ORCS; 25902; 19 hits in 1075 CRISPR screens.
DR ChiTaRS; MTHFD1L; human.
DR GeneWiki; MTHFD1L; -.
DR GenomeRNAi; 25902; -.
DR Pharos; Q6UB35; Tbio.
DR PRO; PR:Q6UB35; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q6UB35; protein.
DR Bgee; ENSG00000120254; Expressed in right coronary artery and 167 other tissues.
DR ExpressionAtlas; Q6UB35; baseline and differential.
DR Genevisible; Q6UB35; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IDA:BHF-UCL.
DR GO; GO:0004329; F:formate-tetrahydrofolate ligase activity; IDA:BHF-UCL.
DR GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IEA:InterPro.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0009257; P:10-formyltetrahydrofolate biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0048702; P:embryonic neurocranium morphogenesis; ISS:BHF-UCL.
DR GO; GO:0048703; P:embryonic viscerocranium morphogenesis; ISS:BHF-UCL.
DR GO; GO:0006760; P:folic acid-containing compound metabolic process; IDA:BHF-UCL.
DR GO; GO:0015942; P:formate metabolic process; IDA:BHF-UCL.
DR GO; GO:0001843; P:neural tube closure; ISS:BHF-UCL.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central.
DR CDD; cd00477; FTHFS; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR HAMAP; MF_01543; FTHFS; 1.
DR InterPro; IPR046346; Aminiacid_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; 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 SUPFAM; SSF53223; SSF53223; 1.
DR PROSITE; PS00721; FTHFS_1; 1.
DR PROSITE; PS00722; FTHFS_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Direct protein sequencing;
KW Ligase; Mitochondrion; Nucleotide-binding; One-carbon metabolism;
KW Phosphoprotein; Reference proteome; Transit peptide.
FT TRANSIT 1..31
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:16171773"
FT CHAIN 32..978
FT /note="Monofunctional C1-tetrahydrofolate synthase,
FT mitochondrial"
FT /id="PRO_0000343177"
FT REGION 1..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 31..348
FT /note="Methylenetetrahydrofolate dehydrogenase and
FT cyclohydrolase"
FT REGION 349..978
FT /note="Formyltetrahydrofolate synthetase"
FT BINDING 423..430
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 189
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 189
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q3V3R1"
FT MOD_RES 357
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 596
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3V3R1"
FT VAR_SEQ 261..275
FT /note="LHEADIVVLGSPKPE -> TESRSVTRLECRRVI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12937168"
FT /id="VSP_034565"
FT VAR_SEQ 276..978
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12937168"
FT /id="VSP_034566"
FT VARIANT 444
FT /note="L -> R (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_044346"
FT CONFLICT 79
FT /note="I -> V (in Ref. 7; AAI10320)"
FT /evidence="ECO:0000305"
FT CONFLICT 870
FT /note="R -> M (in Ref. 9; BAB15009)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 978 AA; 105790 MW; 7D655CD8D2503378 CRC64;
MGTRLPLVLR QLRRPPQPPG PPRRLRVPCR ASSGGGGGGG GGREGLLGQR RPQDGQARSS
CSPGGRTPAA RDSIVREVIQ NSKEVLSLLQ EKNPAFKPVL AIIQAGDDNL MQEINQNLAE
EAGLNITHIC LPPDSSEAEI IDEILKINED TRVHGLALQI SENLFSNKVL NALKPEKDVD
GVTDINLGKL VRGDAHECFV SPVAKAVIEL LEKSGVNLDG KKILVVGAHG SLEAALQCLF
QRKGSMTMSI QWKTRQLQSK LHEADIVVLG SPKPEEIPLT WIQPGTTVLN CSHDFLSGKV
GCGSPRIHFG GLIEEDDVIL LAAALRIQNM VSSGRRWLRE QQHRRWRLHC LKLQPLSPVP
SDIEISRGQT PKAVDVLAKE IGLLADEIEI YGKSKAKVRL SVLERLKDQA DGKYVLVAGI
TPTPLGEGKS TVTIGLVQAL TAHLNVNSFA CLRQPSQGPT FGVKGGAAGG GYAQVIPMEE
FNLHLTGDIH AITAANNLLA AAIDTRILHE NTQTDKALYN RLVPLVNGVR EFSEIQLARL
KKLGINKTDP STLTEEEVSK FARLDIDPST ITWQRVLDTN DRFLRKITIG QGNTEKGHYR
QAQFDIAVAS EIMAVLALTD SLADMKARLG RMVVASDKSG QPVTADDLGV TGALTVLMKD
AIKPNLMQTL EGTPVFVHAG PFANIAHGNS SVLADKIALK LVGEEGFVVT EAGFGADIGM
EKFFNIKCRA SGLVPNVVVL VATVRALKMH GGGPSVTAGV PLKKEYTEEN IQLVADGCCN
LQKQIQITQL FGVPVVVALN VFKTDTRAEI DLVCELAKRA GAFDAVPCYH WSVGGKGSVD
LARAVREAAS KRSRFQFLYD VQVPIVDKIR TIAQAVYGAK DIELSPEAQA KIDRYTQQGF
GNLPICMAKT HLSLSHQPDK KGVPRDFILP ISDVRASIGA GFIYPLVGTM STMPGLPTRP
CFYDIDLDTE TEQVKGLF
