ID AL1L1_PONAB Reviewed; 902 AA. AC Q5RFM9; DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot. DT 21-DEC-2004, sequence version 1. DT 02-SEP-2026, entry version 108. DE RecName: Full=Cytosolic 10-formyltetrahydrofolate dehydrogenase {ECO:0000305}; DE Short=10-FTHFDH; DE Short=FDH; DE EC=1.5.1.6 {ECO:0000250|UniProtKB:P28037}; DE AltName: Full=Aldehyde dehydrogenase family 1 member L1 {ECO:0000250|UniProtKB:O75891}; GN Name=ALDH1L1 {ECO:0000250|UniProtKB:O75891}; Synonyms=FTHFD; OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Pongo. OX NCBI_TaxID=9601; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Kidney; RG The German cDNA consortium; RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Cytosolic 10-formyltetrahydrofolate dehydrogenase that CC catalyzes the NADP(+)-dependent conversion of 10-formyltetrahydrofolate CC to tetrahydrofolate and carbon dioxide. May also have an NADP(+)- CC dependent aldehyde dehydrogenase activity towards formaldehyde, CC acetaldehyde, propionaldehyde, and benzaldehyde. CC {ECO:0000250|UniProtKB:P28037}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(6R)-10-formyltetrahydrofolate + NADP(+) + H2O = (6S)-5,6,7,8- CC tetrahydrofolate + CO2 + NADPH + H(+); 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:0000250|UniProtKB:P28037}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10181; CC Evidence={ECO:0000250|UniProtKB:P28037}; CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P28037}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:P28037}. 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:0000250|UniProtKB:P28037}. 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; CR857124; CAH89428.1; -; mRNA. DR RefSeq; NP_001128736.1; NM_001135264.1. DR AlphaFoldDB; Q5RFM9; -. DR SMR; Q5RFM9; -. DR FunCoup; Q5RFM9; 503. DR STRING; 9601.ENSPPYP00000015052; -. DR GeneID; 100172380; -. DR CTD; 10840; -. DR eggNOG; KOG2452; Eukaryota. DR InParanoid; Q5RFM9; -. DR Proteomes; UP000001595; Unplaced. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0016155; F:formyltetrahydrofolate dehydrogenase activity; ISS:UniProtKB. DR GO; GO:0009258; P:10-formyltetrahydrofolate catabolic process; ISS:UniProtKB. DR GO; GO:0006740; P:NADPH regeneration; ISS:UniProtKB. DR GO; GO:0006730; P:one-carbon metabolic process; IEA:InterPro. DR CDD; cd07140; ALDH_F1L_FTFDH; 1. DR CDD; cd08703; FDH_Hydrolase_C; 1. DR CDD; cd08647; FMT_core_FDH_N; 1. DR FunFam; 1.10.1200.10:FF:000002; 10-formyltetrahydrofolate dehydrogenase; 1. DR FunFam; 3.10.25.10:FF:000002; 10-formyltetrahydrofolate dehydrogenase; 1. DR FunFam; 3.40.50.170:FF:000002; 10-formyltetrahydrofolate dehydrogenase; 1. DR FunFam; 3.40.605.10:FF:000026; Aldehyde dehydrogenase, putative; 1. DR FunFam; 3.40.309.10:FF:000008; Cytosolic 10-formyltetrahydrofolate dehydrogenase; 1. DR FunFam; 3.40.605.10:FF:000009; Cytosolic 10-formyltetrahydrofolate dehydrogenase; 1. DR Gene3D; 1.10.1200.10; ACP-like; 1. DR Gene3D; 3.40.605.10; Aldehyde Dehydrogenase, Chain A, domain 1; 1. DR Gene3D; 3.40.309.10; Aldehyde Dehydrogenase, Chain A, domain 2; 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 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. PE 2: Evidence at transcript level; KW Acetylation; Cytoplasm; NADP; One-carbon metabolism; Oxidoreductase; KW Phosphopantetheine; Phosphoprotein; Reference proteome. FT CHAIN 1..902 FT /note="Cytosolic 10-formyltetrahydrofolate dehydrogenase" FT /id="PRO_0000199421" 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:0000250|UniProtKB:O75891" FT BINDING 142 FT /ligand="(6R)-10-formyltetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:195366" FT /evidence="ECO:0000250|UniProtKB:O75891" 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:0000250|UniProtKB:O75891" 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:0000250|UniProtKB:P28037, FT ECO:0000255|PROSITE-ProRule:PRU00258" FT MOD_RES 629 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O75891" FT MOD_RES 631 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O75891" 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:0000250|UniProtKB:O75891" FT MOD_RES 882 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q3SY69" SQ SEQUENCE 902 AA; 98850 MW; C15ED0836C4CC789 CRC64; MKIAVIGQSL FGQEVYCHLR KEGHEVVGGF TVPDKDGKAD PLGLEAEKDG VPVFKFSRWR AKGQALPDVV AKYQALGAEL NVLPFCSQFI PMEIINAPQH GSIIYHPSLL PRHRGASAIN WTLIHGDKKG GFSIFWADDG LDTGDLLLQK ECEVLPDDTV STLYNRFLFP EGIKGMVQAV RLIAEGKAPR LPQPEEGATY EGIQKKETAK INWDQPAEAI HNWIRGNDKV PGAWTEACEQ KLTFFNSTLN TSGLVPEGDA LPIPGAHRPG VVTKAGLILF GNDDKMLLVK NIQLEDGKMI LASNFFKGAA SSALELTEAE LVTAEAVRSV WQRILPNVLE VEDSTDFFKS GAASVDVVRL VEEVKELCDG LELENEDVYM ASTFGDFIQL LVRKLRGDDE EGECSIDYVE MAVNKRTIRI PHQLFIGGEF VDAEGAKTYE TINPTDGSVI CQVSLAQVTD VDKAVAAAKD AFENGRWGKI SARDRGRLLY RLADLMEQHQ EELATIEALD AGAVYTLALK THVGMSIQTF RYFAGWCDKI QGSTIPINQA RPNRNLTLTR KEPVGVCGII IPWNYPLMML SWKTAACLAA GNTVVIKPAQ VTPLTALKFA ELTLKAGIPK GVVNVLPGSG SLVGQRLSDH PDVRKIGFTG STEVGKHIMK SCAISNVKKV SLELGGKSPL IIFADCDLNK AVQMGMSSVF FNKGENCIAA GRLFVEDSIH DEFVRRVVEE VRKMKVGDPL DRDTDHGPQN HHAHLMKLME YCQRGVKEGA TLVCGGNQVP RPGFFFEPTV FTDVEDHMFI AKEESFGPVM IISRFADGDV DTVLSRANAT EFGLASGVFT RDINKALYVS DKLQAGTVFV NTYNKTDVAA PFGGFKQSGF GKDLGEAALN EYLRVKTVTF EY //