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 27-MAR-2024, entry version 176. 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 = (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: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 CC formate--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}; 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; 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; 165. DR IntAct; Q6UB35; 44. DR MINT; Q6UB35; -. DR STRING; 9606.ENSP00000478253; -. DR ChEMBL; CHEMBL4295869; -. DR GlyGen; Q6UB35; 2 sites, 1 O-linked glycan (2 sites). 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; 9606-ENSP00000478253; -. DR PeptideAtlas; Q6UB35; -. DR ProteomicsDB; 67402; -. [Q6UB35-1] DR ProteomicsDB; 67403; -. [Q6UB35-2] DR Pumba; Q6UB35; -. DR Antibodypedia; 33330; 179 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 AGR; HGNC:21055; -. 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; KFWNLKC; -. DR OrthoDB; 651667at2759; -. 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; 21 hits in 1156 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 168 other cell types or tissues. DR ExpressionAtlas; Q6UB35; baseline and differential. 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 CDD; cd05212; NAD_bind_m-THF_DH_Cyclohyd_like; 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; IPR020631; THF_DH/CycHdrlase_NAD-bd_dom. DR PANTHER; PTHR48099; C-1-TETRAHYDROFOLATE SYNTHASE, CYTOPLASMIC-RELATED; 1. DR PANTHER; PTHR48099:SF12; MONOFUNCTIONAL C1-TETRAHYDROFOLATE SYNTHASE, MITOCHONDRIAL; 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 Genevisible; Q6UB35; HS. 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 //