AL1L1_PONAB
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 03-AUG-2022, entry version 99.
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=(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;
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 STRING; 9601.ENSPPYP00000015052; -.
DR GeneID; 100189626; -.
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:0016742; F:hydroxymethyl-, formyl- and related transferase activity; IEA:InterPro.
DR GO; GO:0016620; F:oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor; IEA:InterPro.
DR GO; GO:0009258; P:10-formyltetrahydrofolate catabolic process; ISS:UniProtKB.
DR GO; GO:0009058; P:biosynthetic process; IEA:InterPro.
DR GO; GO:0006740; P:NADPH regeneration; ISS: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 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="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
FT /evidence="ECO:0000250|UniProtKB:O75891"
FT BINDING 142
FT /ligand="(6S)-10-formyltetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57454"
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
