AL1L1_HUMAN
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 03-AUG-2022, entry version 206.
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=(6S)-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:57454, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.5.1.6; Evidence={ECO:0000269|PubMed:19933275,
CC 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}.
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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 PDBsum; 2BW0; -.
DR PDBsum; 2CFI; -.
DR PDBsum; 2CQ8; -.
DR AlphaFoldDB; O75891; -.
DR SMR; O75891; -.
DR BioGRID; 116052; 26.
DR IntAct; O75891; 82.
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; O75891; -.
DR PeptideAtlas; O75891; -.
DR PRIDE; O75891; -.
DR ProteomicsDB; 19312; -.
DR ProteomicsDB; 50249; -. [O75891-1]
DR ProteomicsDB; 74038; -.
DR ABCD; O75891; 1 sequenced antibody.
DR Antibodypedia; 33051; 528 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 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; HMFVAQE; -.
DR PhylomeDB; O75891; -.
DR TreeFam; TF354242; -.
DR BioCyc; MetaCyc:HS07217-MON; -.
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; 8 hits in 1072 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 178 other tissues.
DR ExpressionAtlas; O75891; baseline and differential.
DR Genevisible; O75891; HS.
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:0016742; F:hydroxymethyl-, formyl- and related transferase activity; IEA:InterPro.
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 Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.25.10; -; 1.
DR Gene3D; 3.40.309.10; -; 1.
DR Gene3D; 3.40.605.10; -; 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 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; SSF47336; 1.
DR SUPFAM; SSF50486; SSF50486; 1.
DR SUPFAM; SSF53328; SSF53328; 1.
DR SUPFAM; SSF53720; SSF53720; 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.
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="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000305|PubMed:17057331,
FT ECO:0007744|PDB:2CFI"
FT BINDING 142
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
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
