AL1L1_XENLA
ID AL1L1_XENLA Reviewed; 902 AA.
AC Q6GNL7;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 97.
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;
GN Name=aldh1l1;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JUN-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}.
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DR EMBL; BC073490; AAH73490.1; -; mRNA.
DR RefSeq; NP_001085894.1; NM_001092425.2.
DR AlphaFoldDB; Q6GNL7; -.
DR SMR; Q6GNL7; -.
DR DNASU; 444321; -.
DR GeneID; 444321; -.
DR KEGG; xla:444321; -.
DR CTD; 444321; -.
DR Xenbase; XB-GENE-1016244; aldh1l1.L.
DR Proteomes; UP000186698; Chromosome 4L.
DR Bgee; 444321; Expressed in kidney and 15 other tissues.
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 PIRSF; PIRSF036489; 10-FTHFDH; 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 Cytoplasm; NADP; One-carbon metabolism; Oxidoreductase; Phosphopantetheine;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..902
FT /note="Cytosolic 10-formyltetrahydrofolate dehydrogenase"
FT /id="PRO_0000315999"
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 354
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000250|UniProtKB:P28037,
FT ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 902 AA; 99982 MW; C484728096D4C281 CRC64;
MKIAVIGQSL FGREVYRELL KEGHQVVGVF TIPDKNGKAD PLGADAEKDG IPVFKFPRWR
VKGQAIPEVV EKYKALEAEL NVLPFCSQFI PMEVIDCPKH GSIIYHPSIL PRHRGASAIN
WTLMQGDKIG GFTVFWADDG LDTGDILLQR QCEVLPDDTV NTIYNRFLFP EGVKGMVEAV
RLIAEGNAPR IKQPTEGATY DPMQKKENAK INWDQPAEDI HNFIRGNDKV PGAWTVVDDQ
QLTFFGSSFT RNGPAPDGQP LEIPGASRPA LVTKTGLVLF GNDGERLTVK NIQFEDGKMI
PASQYFKTAD SAALQLSEEE QKVSEEIRAA WRRILTNVSE IEDSTDFFKA GAASMDVVRL
VEEVKLKCNG LQLQNEDVYM ATKFEEFIQM VVRRMRGEDG EEELVIDYVE KEINNMTVKI
PHQLFINGQF MDAEGGKSYD TINPTDGTAI CKVSLAQISD IDRAVAAAKE AFENGEWGKM
NPRDRGRLLY RLADLMEEHQ EELATIESID SGAVYTLALK THVGMSIQTF RYFAGWCDKI
QGRTIPINQA RPNRNLTFTR REPIGVCGIV IPWNYPLMML AWKTAACLTA GNTVVLKPAQ
VTPLTALKFA ELSVKAGIPK GVINILPGAG SLIGQRLSDH PDVRKIGFTG STPIGKQIMK
SCAVSNVKKV SLELGGKSPL IIFHDCDLDK AVRMGMSSVF FNKGENCIAA GRLFLEESIH
DEFVKRVVEE VKKMKIGDPL DRSTDHGPQN HKAHLDKLIE YCQTGVKEGG KLVYGGKQVE
RPGFFFEPTI FTDVTDEMFI AKEESFGPVM IISKFNDGDI DGVLKRANDS EFGLASGVFT
KDINKALYVS EKLQAGTVFV NTYNKTDVAA PFGGFKQSGF GKDLGEEALN EYLKTKAVTI
EY
