ID AL1L1_HUMAN Reviewed; 902 AA. AC O75891; B4DG36; E9PBX3; Q68CS1; Q8TBP8; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 15-FEB-2005, sequence version 2. DT 24-JAN-2024, entry version 214. DE RecName: Full=Cytosolic 10-formyltetrahydrofolate dehydrogenase {ECO:0000305|PubMed:19933275}; DE Short=10-FTHFDH; DE Short=FDH {ECO:0000303|PubMed:19933275}; DE EC=1.5.1.6 {ECO:0000269|PubMed:19933275, ECO:0000269|PubMed:21238436}; DE AltName: Full=Aldehyde dehydrogenase family 1 member L1 {ECO:0000312|HGNC:HGNC:3978}; GN Name=ALDH1L1 {ECO:0000312|HGNC:HGNC:3978}; Synonyms=FTHFD; 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] (ISOFORM 1). RA Hong M.H., Lee Y., Kim J.W., Kang B.S., Choe I.S.; RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Amygdala; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Colon carcinoma; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Urinary bladder; 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 [7] RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHOPANTETHEINYLATION AT SER-354 BY RP AASDHPPT, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-354, AND DOMAIN. RX PubMed=19933275; DOI=10.1074/jbc.m109.080556; RA Strickland K.C., Hoeferlin L.A., Oleinik N.V., Krupenko N.I., RA Krupenko S.A.; RT "Acyl carrier protein-specific 4'-phosphopantetheinyl transferase activates RT 10-formyltetrahydrofolate dehydrogenase."; RL J. Biol. Chem. 285:1627-1633(2010). RN [8] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=21238436; DOI=10.1016/j.cbi.2011.01.008; RA Strickland K.C., Krupenko N.I., Dubard M.E., Hu C.J., Tsybovsky Y., RA Krupenko S.A.; RT "Enzymatic properties of ALDH1L2, a mitochondrial 10-formyltetrahydrofolate RT dehydrogenase."; RL Chem. Biol. Interact. 191:129-136(2011). RN [9] RP TISSUE SPECIFICITY. RX PubMed=20498374; DOI=10.1074/jbc.m110.128843; RA Krupenko N.I., Dubard M.E., Strickland K.C., Moxley K.M., Oleinik N.V., RA Krupenko S.A.; RT "ALDH1L2 is the mitochondrial homolog of 10-formyltetrahydrofolate RT dehydrogenase."; RL J. Biol. Chem. 285:23056-23063(2010). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9; SER-629; SER-631 AND RP SER-825, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; 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 [11] {ECO:0007744|PDB:2CQ8} RP STRUCTURE BY NMR OF 303-405. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of RSGI RUH-033, a PP-binding domain of 10-FTHFDH from RT human cDNA."; RL Submitted (NOV-2005) to the PDB data bank. RN [12] {ECO:0007744|PDB:2BW0, ECO:0007744|PDB:2CFI} RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-307 IN COMPLEX WITH SUBSTRATE RP ANALOG. RX PubMed=17057331; DOI=10.1107/s0907444906026849; RA Kursula P., Schuler H., Flodin S., Nilsson-Ehle P., Ogg D.J., Savitsky P., RA Nordlund P., Stenmark P.; RT "Structures of the hydrolase domain of human 10-formyltetrahydrofolate RT dehydrogenase and its complex with a substrate analogue."; RL Acta Crystallogr. D 62:1294-1299(2006). RN [13] RP VARIANT [LARGE SCALE ANALYSIS] VAL-511. 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: Cytosolic 10-formyltetrahydrofolate dehydrogenase that CC catalyzes the NADP(+)-dependent conversion of 10-formyltetrahydrofolate CC to tetrahydrofolate and carbon dioxide (PubMed:19933275, CC PubMed:21238436). May also have an NADP(+)-dependent aldehyde CC dehydrogenase activity towards formaldehyde, acetaldehyde, CC propionaldehyde, and benzaldehyde (By similarity). CC {ECO:0000250|UniProtKB:P28037, ECO:0000269|PubMed:19933275, CC ECO:0000269|PubMed:21238436}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(6R)-10-formyltetrahydrofolate + H2O + NADP(+) = (6S)-5,6,7,8- CC tetrahydrofolate + CO2 + H(+) + NADPH; Xref=Rhea:RHEA:10180, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:57453, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, CC ChEBI:CHEBI:195366; EC=1.5.1.6; CC Evidence={ECO:0000269|PubMed:19933275, ECO:0000269|PubMed:21238436}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10181; CC Evidence={ECO:0000305|PubMed:19933275}; CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P28037}. CC -!- INTERACTION: CC O75891-4; Q92624: APPBP2; NbExp=3; IntAct=EBI-12400198, EBI-743771; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305|PubMed:19933275}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=O75891-1; Sequence=Displayed; CC Name=2; CC IsoId=O75891-2; Sequence=VSP_045569; CC Name=3; CC IsoId=O75891-3; Sequence=VSP_047260; CC Name=4; CC IsoId=O75891-4; Sequence=VSP_057429, VSP_057430; CC -!- TISSUE SPECIFICITY: Highly expressed in liver, pancreas and kidney. CC {ECO:0000269|PubMed:20498374}. CC -!- DOMAIN: The N-terminal hydrolase domain has an NADP-independent CC formyltetrahydrofolate hydrolase activity, releasing formate and CC tetrahydrofolate. {ECO:0000250|UniProtKB:P28037}. CC -!- DOMAIN: The C-terminal aldehyde dehydrogenase domain has an NADP- CC dependent dehydrogenase activity. It catalyzes the oxidation of CC formate, released by the hydrolysis of formyltetrahydrofolate, into CC CO2. {ECO:0000250|UniProtKB:P28037}. CC -!- DOMAIN: The carrier domain is phosphopantetheinylated and uses the 4'- CC phosphopantetheine/4'-PP swinging arm to transfer the formyl group CC released by the N-terminal formyltetrahydrofolate hydrolase activity to CC the C-terminal aldehyde dehydrogenase domain that catalyzes its NADP- CC dependent oxidation into CO2. The overall NADP-dependent physiological CC reaction requires the 3 domains (N-terminal hydrolase, C-terminal CC aldehyde dehydrogenase and carrier domains) to convert CC formyltetrahydrofolate into tetrahydrofolate and CO2. CC {ECO:0000250|UniProtKB:P28037}. CC -!- PTM: Phosphopantetheinylation at Ser-354 by AASDHPPT is required for CC the formyltetrahydrofolate dehydrogenase activity. CC {ECO:0000269|PubMed:19933275}. CC -!- SIMILARITY: In the N-terminal section; belongs to the GART family. CC {ECO:0000305}. CC -!- SIMILARITY: In the C-terminal section; belongs to the aldehyde CC dehydrogenase family. ALDH1L subfamily. {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; AF052732; AAC35000.1; -; mRNA. DR EMBL; AK294392; BAG57647.1; -; mRNA. DR EMBL; CR749807; CAH18667.1; -; mRNA. DR EMBL; AC079848; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471052; EAW79370.1; -; Genomic_DNA. DR EMBL; BC027241; AAH27241.1; -; mRNA. DR CCDS; CCDS3034.1; -. [O75891-1] DR CCDS; CCDS58850.1; -. [O75891-2] DR CCDS; CCDS58851.1; -. [O75891-3] DR RefSeq; NP_001257293.1; NM_001270364.1. [O75891-3] DR RefSeq; NP_001257294.1; NM_001270365.1. [O75891-2] DR RefSeq; NP_036322.2; NM_012190.3. [O75891-1] DR RefSeq; XP_006713544.1; XM_006713481.2. [O75891-1] DR RefSeq; XP_011510657.1; XM_011512355.1. [O75891-1] DR PDB; 2BW0; X-ray; 1.70 A; A=1-307. DR PDB; 2CFI; X-ray; 1.85 A; A=1-307. DR PDB; 2CQ8; NMR; -; A=305-401. DR PDB; 7YJJ; EM; 6.31 A; B/C/D/E=405-902. DR PDBsum; 2BW0; -. DR PDBsum; 2CFI; -. DR PDBsum; 2CQ8; -. DR PDBsum; 7YJJ; -. DR AlphaFoldDB; O75891; -. DR EMDB; EMD-33872; -. DR SMR; O75891; -. DR BioGRID; 116052; 32. DR IntAct; O75891; 83. DR MINT; O75891; -. DR STRING; 9606.ENSP00000273450; -. DR DrugBank; DB00116; Tetrahydrofolic acid. DR iPTMnet; O75891; -. DR PhosphoSitePlus; O75891; -. DR BioMuta; ALDH1L1; -. DR EPD; O75891; -. DR jPOST; O75891; -. DR MassIVE; O75891; -. DR MaxQB; O75891; -. DR PaxDb; 9606-ENSP00000273450; -. DR PeptideAtlas; O75891; -. DR ProteomicsDB; 19312; -. DR ProteomicsDB; 50249; -. [O75891-1] DR ProteomicsDB; 74038; -. DR Pumba; O75891; -. DR ABCD; O75891; 1 sequenced antibody. DR Antibodypedia; 33051; 611 antibodies from 37 providers. DR DNASU; 10840; -. DR Ensembl; ENST00000273450.7; ENSP00000273450.3; ENSG00000144908.14. [O75891-3] DR Ensembl; ENST00000393431.6; ENSP00000377081.2; ENSG00000144908.14. [O75891-4] DR Ensembl; ENST00000393434.7; ENSP00000377083.3; ENSG00000144908.14. [O75891-1] DR Ensembl; ENST00000452905.6; ENSP00000395881.2; ENSG00000144908.14. [O75891-2] DR Ensembl; ENST00000455064.6; ENSP00000414126.3; ENSG00000144908.14. [O75891-4] DR Ensembl; ENST00000472186.5; ENSP00000420293.1; ENSG00000144908.14. [O75891-1] DR GeneID; 10840; -. DR KEGG; hsa:10840; -. DR MANE-Select; ENST00000393434.7; ENSP00000377083.3; NM_012190.4; NP_036322.2. DR UCSC; uc003eim.3; human. [O75891-1] DR UCSC; uc062njt.1; human. DR AGR; HGNC:3978; -. DR CTD; 10840; -. DR DisGeNET; 10840; -. DR GeneCards; ALDH1L1; -. DR HGNC; HGNC:3978; ALDH1L1. DR HPA; ENSG00000144908; Tissue enhanced (liver). DR MIM; 600249; gene. DR neXtProt; NX_O75891; -. DR OpenTargets; ENSG00000144908; -. DR PharmGKB; PA28393; -. DR VEuPathDB; HostDB:ENSG00000144908; -. DR eggNOG; KOG2452; Eukaryota. DR GeneTree; ENSGT00940000160913; -. DR HOGENOM; CLU_014974_1_0_1; -. DR InParanoid; O75891; -. DR OMA; FENGVWG; -. DR OrthoDB; 2291791at2759; -. DR PhylomeDB; O75891; -. DR TreeFam; TF354242; -. DR BioCyc; MetaCyc:HS07217-MONOMER; -. DR BRENDA; 1.5.1.6; 2681. DR PathwayCommons; O75891; -. DR Reactome; R-HSA-196757; Metabolism of folate and pterines. DR SignaLink; O75891; -. DR BioGRID-ORCS; 10840; 9 hits in 1152 CRISPR screens. DR ChiTaRS; ALDH1L1; human. DR EvolutionaryTrace; O75891; -. DR GeneWiki; ALDH1L1; -. DR GenomeRNAi; 10840; -. DR Pharos; O75891; Tbio. DR PRO; PR:O75891; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; O75891; Protein. DR Bgee; ENSG00000144908; Expressed in right lobe of liver and 180 other cell types or tissues. DR ExpressionAtlas; O75891; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IBA:GO_Central. DR GO; GO:0016155; F:formyltetrahydrofolate dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0009258; P:10-formyltetrahydrofolate catabolic process; IDA:UniProtKB. DR GO; GO:0009058; P:biosynthetic process; IEA:InterPro. DR GO; GO:0006740; P:NADPH regeneration; IDA:UniProtKB. DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW. DR CDD; cd07140; ALDH_F1L_FTFDH; 1. DR CDD; cd08703; FDH_Hydrolase_C; 1. DR CDD; cd08647; FMT_core_FDH_N; 1. DR Gene3D; 1.10.1200.10; ACP-like; 1. DR Gene3D; 3.10.25.10; Formyl transferase, C-terminal domain; 1. DR Gene3D; 3.40.50.170; Formyl transferase, N-terminal domain; 1. DR InterPro; IPR011407; 10_FTHF_DH. DR InterPro; IPR036736; ACP-like_sf. DR InterPro; IPR016161; Ald_DH/histidinol_DH. DR InterPro; IPR016163; Ald_DH_C. DR InterPro; IPR016160; Ald_DH_CS_CYS. DR InterPro; IPR029510; Ald_DH_CS_GLU. DR InterPro; IPR016162; Ald_DH_N. DR InterPro; IPR015590; Aldehyde_DH_dom. DR InterPro; IPR005793; Formyl_trans_C. DR InterPro; IPR037022; Formyl_trans_C_sf. DR InterPro; IPR002376; Formyl_transf_N. DR InterPro; IPR036477; Formyl_transf_N_sf. DR InterPro; IPR011034; Formyl_transferase-like_C_sf. DR InterPro; IPR001555; GART_AS. DR InterPro; IPR009081; PP-bd_ACP. DR PANTHER; PTHR11699; ALDEHYDE DEHYDROGENASE-RELATED; 1. DR PANTHER; PTHR11699:SF120; CYTOSOLIC 10-FORMYLTETRAHYDROFOLATE DEHYDROGENASE; 1. DR Pfam; PF00171; Aldedh; 1. DR Pfam; PF02911; Formyl_trans_C; 1. DR Pfam; PF00551; Formyl_trans_N; 1. DR Pfam; PF00550; PP-binding; 1. DR PIRSF; PIRSF036489; 10-FTHFDH; 1. DR SUPFAM; SSF47336; ACP-like; 1. DR SUPFAM; SSF53720; ALDH-like; 1. DR SUPFAM; SSF50486; FMT C-terminal domain-like; 1. DR SUPFAM; SSF53328; Formyltransferase; 1. DR PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1. DR PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1. DR PROSITE; PS50075; CARRIER; 1. DR PROSITE; PS00373; GART; 1. DR Genevisible; O75891; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; NADP; KW One-carbon metabolism; Oxidoreductase; Phosphopantetheine; Phosphoprotein; KW Reference proteome. FT CHAIN 1..902 FT /note="Cytosolic 10-formyltetrahydrofolate dehydrogenase" FT /id="PRO_0000199419" FT DOMAIN 318..395 FT /note="Carrier" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258" FT REGION 1..310 FT /note="Hydrolase domain" FT /evidence="ECO:0000250|UniProtKB:P28037" FT REGION 417..902 FT /note="Aldehyde dehydrogenase domain" FT /evidence="ECO:0000250|UniProtKB:P28037" FT ACT_SITE 106 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:P28037" FT ACT_SITE 673 FT /note="Proton acceptor" FT /evidence="ECO:0000250|UniProtKB:P28037" FT ACT_SITE 707 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:P28037" FT BINDING 88..90 FT /ligand="(6R)-10-formyltetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:195366" FT /evidence="ECO:0000305|PubMed:17057331, FT ECO:0007744|PDB:2CFI" FT BINDING 142 FT /ligand="(6R)-10-formyltetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:195366" FT /evidence="ECO:0000305|PubMed:17057331, FT ECO:0007744|PDB:2CFI" FT BINDING 571..573 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P28037" FT BINDING 597..600 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P28037" FT BINDING 630..635 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P28037" FT BINDING 650..651 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P28037" FT BINDING 673..674 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P28037" FT BINDING 757 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P28037" FT BINDING 804..806 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P28037" FT SITE 142 FT /note="Essential for catalytic activity" FT /evidence="ECO:0000250|UniProtKB:P28037" FT MOD_RES 9 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 38 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8R0Y6" FT MOD_RES 354 FT /note="O-(pantetheine 4'-phosphoryl)serine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258, FT ECO:0000269|PubMed:19933275" FT MOD_RES 629 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 631 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 660 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8K009" FT MOD_RES 767 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8R0Y6" FT MOD_RES 825 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 882 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q3SY69" FT VAR_SEQ 1 FT /note="M -> MAGPSNPPATM (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_047260" FT VAR_SEQ 118..218 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045569" FT VAR_SEQ 492..505 FT /note="LADLMEQHQEELAT -> APPSPSTRPDPTAT (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_057429" FT VAR_SEQ 506..902 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_057430" FT VARIANT 254 FT /note="L -> P (in dbSNP:rs3796191)" FT /id="VAR_052290" FT VARIANT 330 FT /note="V -> F (in dbSNP:rs2886059)" FT /id="VAR_052291" FT VARIANT 429 FT /note="E -> A (in dbSNP:rs9282691)" FT /id="VAR_052292" FT VARIANT 436 FT /note="A -> T (in dbSNP:rs9282692)" FT /id="VAR_052293" FT VARIANT 448 FT /note="S -> N (in dbSNP:rs9282697)" FT /id="VAR_052295" FT VARIANT 481 FT /note="S -> G (in dbSNP:rs2276724)" FT /id="VAR_052296" FT VARIANT 511 FT /note="A -> V (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs768309358)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036101" FT VARIANT 793 FT /note="D -> G (in dbSNP:rs1127717)" FT /id="VAR_052297" FT VARIANT 803 FT /note="E -> K (in dbSNP:rs9282689)" FT /id="VAR_052298" FT VARIANT 812 FT /note="I -> V (in dbSNP:rs4646750)" FT /id="VAR_052299" FT MUTAGEN 354 FT /note="S->A: Loss of phosphopantetheinylation by AASDHPPT. FT Loss of formyltetrahydrofolate dehydrogenase activity." FT /evidence="ECO:0000269|PubMed:19933275" FT CONFLICT 63 FT /note="G -> A (in Ref. 1; AAC35000)" FT /evidence="ECO:0000305" FT CONFLICT 85 FT /note="F -> S (in Ref. 1; AAC35000)" FT /evidence="ECO:0000305" FT CONFLICT 176 FT /note="M -> V (in Ref. 1; AAC35000)" FT /evidence="ECO:0000305" FT CONFLICT 195 FT /note="E -> K (in Ref. 1; AAC35000)" FT /evidence="ECO:0000305" FT CONFLICT 470 FT /note="D -> G (in Ref. 1; AAC35000)" FT /evidence="ECO:0000305" FT CONFLICT 472 FT /note="F -> L (in Ref. 2; BAG57647)" FT /evidence="ECO:0000305" FT CONFLICT 677 FT /note="K -> E (in Ref. 1; AAC35000)" FT /evidence="ECO:0000305" FT CONFLICT 680 FT /note="L -> F (in Ref. 1; AAC35000)" FT /evidence="ECO:0000305" FT CONFLICT 702 FT /note="N -> S (in Ref. 1; AAC35000)" FT /evidence="ECO:0000305" FT STRAND 2..6 FT /evidence="ECO:0007829|PDB:2BW0" FT HELIX 9..21 FT /evidence="ECO:0007829|PDB:2BW0" FT STRAND 25..31 FT /evidence="ECO:0007829|PDB:2BW0" FT HELIX 41..49 FT /evidence="ECO:0007829|PDB:2BW0" FT STRAND 53..55 FT /evidence="ECO:0007829|PDB:2BW0" FT HELIX 67..74 FT /evidence="ECO:0007829|PDB:2BW0" FT STRAND 79..85 FT /evidence="ECO:0007829|PDB:2BW0" FT HELIX 92..95 FT /evidence="ECO:0007829|PDB:2BW0" FT STRAND 102..108 FT /evidence="ECO:0007829|PDB:2BW0" FT TURN 110..113 FT /evidence="ECO:0007829|PDB:2BW0" FT STRAND 114..116 FT /evidence="ECO:0007829|PDB:2BW0" FT HELIX 118..124 FT /evidence="ECO:0007829|PDB:2BW0" FT STRAND 128..136 FT /evidence="ECO:0007829|PDB:2BW0" FT STRAND 139..142 FT /evidence="ECO:0007829|PDB:2BW0" FT STRAND 146..153 FT /evidence="ECO:0007829|PDB:2BW0" FT HELIX 160..166 FT /evidence="ECO:0007829|PDB:2BW0" FT TURN 167..169 FT /evidence="ECO:0007829|PDB:2BW0" FT HELIX 170..185 FT /evidence="ECO:0007829|PDB:2BW0" FT HELIX 206..209 FT /evidence="ECO:0007829|PDB:2BW0" FT HELIX 217..225 FT /evidence="ECO:0007829|PDB:2BW0" FT TURN 226..231 FT /evidence="ECO:0007829|PDB:2BW0" FT STRAND 234..237 FT /evidence="ECO:0007829|PDB:2BW0" FT STRAND 240..249 FT /evidence="ECO:0007829|PDB:2BW0" FT STRAND 258..261 FT /evidence="ECO:0007829|PDB:2BW0" FT STRAND 270..273 FT /evidence="ECO:0007829|PDB:2BW0" FT STRAND 276..280 FT /evidence="ECO:0007829|PDB:2BW0" FT STRAND 286..293 FT /evidence="ECO:0007829|PDB:2BW0" FT STRAND 299..301 FT /evidence="ECO:0007829|PDB:2BW0" FT HELIX 302..304 FT /evidence="ECO:0007829|PDB:2BW0" FT HELIX 320..334 FT /evidence="ECO:0007829|PDB:2CQ8" FT HELIX 347..351 FT /evidence="ECO:0007829|PDB:2CQ8" FT HELIX 356..367 FT /evidence="ECO:0007829|PDB:2CQ8" FT HELIX 375..380 FT /evidence="ECO:0007829|PDB:2CQ8" FT HELIX 384..397 FT /evidence="ECO:0007829|PDB:2CQ8" SQ SEQUENCE 902 AA; 98829 MW; D92CB2930617F7CF CRC64; MKIAVIGQSL FGQEVYCHLR KEGHEVVGVF TVPDKDGKAD PLGLEAEKDG VPVFKYSRWR AKGQALPDVV AKYQALGAEL NVLPFCSQFI PMEIISAPRH GSIIYHPSLL PRHRGASAIN WTLIHGDKKG GFSIFWADDG LDTGDLLLQK ECEVLPDDTV STLYNRFLFP EGIKGMVQAV RLIAEGKAPR LPQPEEGATY EGIQKKETAK INWDQPAEAI HNWIRGNDKV PGAWTEACEQ KLTFFNSTLN TSGLVPEGDA LPIPGAHRPG VVTKAGLILF GNDDKMLLVK NIQLEDGKMI LASNFFKGAA SSVLELTEAE LVTAEAVRSV WQRILPKVLE VEDSTDFFKS GAASVDVVRL VEEVKELCDG LELENEDVYM ASTFGDFIQL LVRKLRGDDE EGECSIDYVE MAVNKRTVRM PHQLFIGGEF VDAEGAKTSE TINPTDGSVI CQVSLAQVTD VDKAVAAAKD AFENGRWGKI SARDRGRLMY RLADLMEQHQ EELATIEALD AGAVYTLALK THVGMSIQTF RYFAGWCDKI QGSTIPINQA RPNRNLTLTR KEPVGVCGII IPWNYPLMML SWKTAACLAA GNTVVIKPAQ VTPLTALKFA ELTLKAGIPK GVVNVLPGSG SLVGQRLSDH PDVRKIGFTG STEVGKHIMK SCAISNVKKV SLELGGKSPL IIFADCDLNK AVQMGMSSVF FNKGENCIAA GRLFVEDSIH DEFVRRVVEE VRKMKVGNPL DRDTDHGPQN HHAHLVKLME YCQHGVKEGA TLVCGGNQVP RPGFFFEPTV FTDVEDHMFI AKEESFGPVM IISRFADGDL DAVLSRANAT EFGLASGVFT RDINKALYVS DKLQAGTVFV NTYNKTDVAA PFGGFKQSGF GKDLGEAALN EYLRVKTVTF EY //