ID B7ZM99_HUMAN Unreviewed; 979 AA. AC B7ZM99; DT 03-MAR-2009, integrated into UniProtKB/TrEMBL. DT 03-MAR-2009, sequence version 1. DT 12-AUG-2020, entry version 102. DE RecName: Full=Formyltetrahydrofolate synthetase {ECO:0000256|ARBA:ARBA00015037}; DE EC=6.3.4.3 {ECO:0000256|ARBA:ARBA00012295}; GN Name=MTHFD1L {ECO:0000313|EMBL:AAI44369.1, GN ECO:0000313|Ensembl:ENSP00000478253}; 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, 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:0000213|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:0000213|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:0000213|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:0000313|Ensembl:ENSP00000478253} RP IDENTIFICATION. RG Ensembl; RL Submitted (SEP-2014) to UniProtKB. RN [7] {ECO:0000213|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). 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:0000256|ARBA:ARBA00000508}; 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 SMR; B7ZM99; -. DR IntAct; B7ZM99; 1. DR Antibodypedia; 33330; 151 antibodies. DR Ensembl; ENST00000611279; ENSP00000478253; ENSG00000120254. DR GeneID; 25902; -. DR UCSC; uc021zgs.2; human. DR CTD; 25902; -. DR EuPathDB; HostDB:ENSG00000120254.15; -. DR HGNC; HGNC:21055; MTHFD1L. DR OpenTargets; ENSG00000120254; -. DR GeneTree; ENSGT00940000157477; -. DR OMA; CGEIMTM; -. DR OrthoDB; 690393at2759; -. DR UniPathway; UPA00193; -. DR BioGRID-ORCS; 25902; 11 hits in 870 CRISPR screens. DR ChiTaRS; MTHFD1L; human. DR GenomeRNAi; 25902; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; ENSG00000120254; Expressed in left coronary artery and 197 other tissues. DR ExpressionAtlas; B7ZM99; baseline and differential. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0004329; F:formate-tetrahydrofolate ligase activity; IEA:InterPro. DR GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IEA:InterPro. DR GO; GO:0048702; P:embryonic neurocranium morphogenesis; IEA:Ensembl. DR GO; GO:0048703; P:embryonic viscerocranium morphogenesis; IEA:Ensembl. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. DR HAMAP; MF_01543; FTHFS; 1. 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 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:0000213|EPD:B7ZM99, KW ECO:0000213|MaxQB:B7ZM99, ECO:0000213|PeptideAtlas:B7ZM99, KW ECO:0000213|ProteomicsDB:B7ZM99}; KW Reference proteome {ECO:0000313|Proteomes:UP000005640}. FT DOMAIN 74..180 FT /note="THF_DHG_CYH" FT /evidence="ECO:0000259|Pfam:PF00763" FT DOMAIN 184..302 FT /note="THF_DHG_CYH_C" 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 //