ID B7ZM99_HUMAN Unreviewed; 979 AA. AC B7ZM99; DT 03-MAR-2009, integrated into UniProtKB/TrEMBL. DT 03-MAR-2009, sequence version 1. DT 03-MAY-2023, entry version 115. DE RecName: Full=formate--tetrahydrofolate ligase {ECO:0000256|ARBA:ARBA00012295}; DE EC=6.3.4.3 {ECO:0000256|ARBA:ARBA00012295}; GN Name=MTHFD1L {ECO:0000313|EMBL:AAI44369.1, GN ECO:0000313|Ensembl:ENSP00000478253.1}; 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|EMBL:AAI44369.1}; RN [1] {ECO:0000313|Ensembl:ENSP00000478253.1, ECO:0000313|Proteomes:UP000005640} 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., 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 [2] {ECO:0000313|EMBL:AAI44369.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain {ECO:0000313|EMBL:AAI44369.1}, and Testicle RC {ECO:0000313|EMBL:AAI36686.1}; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RA Gerhard D.S., Wagner L., Feingold E.A., Shenmen C.M., Grouse L.H., RA Schuler G., Klein S.L., Old S., Rasooly R., Good P., Guyer M., Peck A.M., RA Derge J.G., Lipman D., Collins F.S., Jang W., Sherry S., Feolo M., RA Misquitta L., Lee E., Rotmistrovsky K., Greenhut S.F., Schaefer C.F., RA Buetow K., Bonner T.I., Haussler D., Kent J., Kiekhaus M., Furey T., RA Brent M., Prange C., Schreiber K., Shapiro N., Bhat N.K., Hopkins R.F., RA Hsie F., Driscoll T., Soares M.B., Casavant T.L., Scheetz T.E., RA Brown-stein M.J., Usdin T.B., Toshiyuki S., Carninci P., Piao Y., RA Dudekula D.B., Ko M.S., Kawakami K., Suzuki Y., Sugano S., Gruber C.E., RA Smith M.R., Simmons B., Moore T., Waterman R., Johnson S.L., Ruan Y., RA Wei C.L., Mathavan S., Gunaratne P.H., Wu J., Garcia A.M., Hulyk S.W., RA Fuh E., Yuan Y., Sneed A., Kowis C., Hodgson A., Muzny D.M., McPherson J., RA Gibbs R.A., Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., RA Sanchez A., Whiting M., Madari A., Young A.C., Wetherby K.D., Granite S.J., RA Kwong P.N., Brinkley C.P., Pearson R.L., Bouffard G.G., Blakesly R.W., RA Green E.D., Dickson M.C., Rodriguez A.C., Grimwood J., Schmutz J., RA Myers R.M., Butterfield Y.S., Griffith M., Griffith O.L., Krzywinski M.I., RA Liao N., Morin R., Morrin R., Palmquist D., Petrescu A.S., Skalska U., RA Smailus D.E., Stott J.M., Schnerch A., Schein J.E., Jones S.J., Holt R.A., RA Baross A., Marra M.A., Clifton S., Makowski K.A., Bosak S., Malek J.; 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 [3] {ECO:0007829|PubMed:19608861} RP IDENTIFICATION BY MASS 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 [4] {ECO:0007829|PubMed:21269460} 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., Burckstummer 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 [5] {ECO:0007829|PubMed:23186163} RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=23186163; 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 [6] {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 [7] {ECO:0000313|Ensembl:ENSP00000478253.1} RP IDENTIFICATION. RG Ensembl; RL Submitted (JAN-2023) to UniProtKB. 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; AL035086; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL049694; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL133260; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; KF458323; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC136685; AAI36686.1; -; mRNA. DR EMBL; BC144368; AAI44369.1; -; mRNA. DR RefSeq; NP_001229696.1; NM_001242767.1. DR RefSeq; XP_016866191.1; XM_017010702.1. DR RefSeq; XP_016866192.1; XM_017010703.1. DR Antibodypedia; 33330; 161 antibodies from 29 providers. DR DNASU; 25902; -. DR Ensembl; ENST00000611279.4; ENSP00000478253.1; ENSG00000120254.16. DR GeneID; 25902; -. DR UCSC; uc021zgs.2; human. DR CTD; 25902; -. DR HGNC; HGNC:21055; MTHFD1L. DR VEuPathDB; HostDB:ENSG00000120254; -. DR GeneTree; ENSGT00940000157477; -. DR OrthoDB; 651667at2759; -. DR UniPathway; UPA00193; -. DR BioGRID-ORCS; 25902; 21 hits in 1156 CRISPR screens. DR ChiTaRS; MTHFD1L; human. DR GenomeRNAi; 25902; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; ENSG00000120254; Expressed in right coronary artery and 167 other tissues. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. 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:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IEA:InterPro. DR GO; GO:0035999; P:tetrahydrofolate interconversion; IEA:UniProtKB-UniPathway. 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. PE 1: Evidence at protein level; KW ATP-binding {ECO:0000256|ARBA:ARBA00022840}; 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|EPD:B7ZM99, KW ECO:0007829|MaxQB:B7ZM99}; KW Reference proteome {ECO:0000313|Proteomes:UP000005640}. FT DOMAIN 84..180 FT /note="Tetrahydrofolate dehydrogenase/cyclohydrolase FT catalytic" FT /evidence="ECO:0000259|Pfam:PF00763" FT DOMAIN 184..298 FT /note="Tetrahydrofolate dehydrogenase/cyclohydrolase FT NAD(P)-binding" FT /evidence="ECO:0000259|Pfam:PF02882" FT REGION 1..71 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" SQ SEQUENCE 979 AA; 105889 MW; D5BB0E871BC20444 CRC64; MGTRLPLVLR QLRRPPQPPG PPRRLRVPCR ASSGGGGGGG GGREGLLGQR RPQDGQARSS CSPGGRTPAA RDSIVREVIQ NSKEVLSLLQ EKNPAFKPVL AIIQAGDDNL MQEINQNLAE EAGLNITHIC LPPDSSEAEI IDEILKINED TRVHGLALQI SENLFSNKVL NALKPEKDVD GVTDINLGKL VRGDAHECFV SPVAKAVIEL LEKSVGVNLD GKKILVVGAH GSLEAALQCL FQRKGSMTMS IQWKTRQLQS KLHEADIVVL GSPKPEEIPL TWIQPGTTVL NCSHDFLSGK VGCGSPRIHF GGLIEEDDVI LLAAALRIQN MVSSGRRWLR EQQHRRWRLH CLKLQPLSPV PSDIEISRGQ TPKAVDVLAK EIGLLADEIE IYGKSKAKVR LSVLERLKDQ ADGKYVLVAG ITPTPLGEGK STVTIGLVQA LTAHLNVNSF ACLRQPSQGP TFGVKGGAAG GGYAQVIPME EFNLHLTGDI HAITAANNLL AAAIDTRILH ENTQTDKALY NRLVPLVNGV REFSEIQLAR LKKLGINKTD PSTLTEEEVS KFARLDIDPS TITWQRVLDT NDRFLRKITI GQGNTEKGHY RQAQFDIAVA SEIMAVLALT DSLADMKARL GRMVVASDKS GQPVTADDLG VTGALTVLMK DAIKPNLMQT LEGTPVFVHA GPFANIAHGN SSVLADKIAL KLVGEEGFVV TEAGFGADIG MEKFFNIKCR ASGLVPNVVV LVATVRALKM HGGGPSVTAG VPLKKEYTEE NIQLVADGCC NLQKQIQITQ LFGVPVVVAL NVFKTDTRAE IDLVCELAKR AGAFDAVPCY HWSVGGKGSV DLARAVREAA SKRSRFQFLY DVQVPIVDKI RTIAQAVYGA KDIELSPEAQ AKIDRYTQQG FGNLPICMAK THLSLSHQPD KKGVPRDFIL PISDVRASIG AGFIYPLVGT MSTMPGLPTR PCFYDIDLDT ETEQVKGLF //