AL1L1_XENTR
ID AL1L1_XENTR Reviewed; 902 AA.
AC Q63ZT8; Q28CS4;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 117.
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; ORFNames=TNeu011l01.1;
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neurula;
RG Sanger Xenopus tropicalis EST/cDNA project;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tail bud;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (SEP-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 (By similarity).
CC Regulates reduced folate pools as well as glycine metabolism (By
CC similarity). {ECO:0000250|UniProtKB:P28037,
CC ECO:0000250|UniProtKB:Q8R0Y6}.
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; CR926185; CAJ82649.1; -; mRNA.
DR EMBL; CR926221; CAJ83333.1; -; mRNA.
DR EMBL; BC082822; AAH82822.1; -; mRNA.
DR RefSeq; NP_001011027.1; NM_001011027.1.
DR AlphaFoldDB; Q63ZT8; -.
DR SMR; Q63ZT8; -.
DR STRING; 8364.ENSXETP00000062653; -.
DR PRIDE; Q63ZT8; -.
DR DNASU; 496436; -.
DR Ensembl; ENSXETT00000084678; ENSXETP00000085727; ENSXETG00000011551.
DR GeneID; 496436; -.
DR KEGG; xtr:496436; -.
DR CTD; 10840; -.
DR Xenbase; XB-GENE-1016237; aldh1l1.
DR eggNOG; KOG2452; Eukaryota.
DR InParanoid; Q63ZT8; -.
DR OrthoDB; 153834at2759; -.
DR Reactome; R-XTR-196757; Metabolism of folate and pterines.
DR Proteomes; UP000008143; Chromosome 4.
DR Proteomes; UP000790000; Unplaced.
DR Bgee; ENSXETG00000011551; Expressed in neurula embryo and 8 other tissues.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IBA:GO_Central.
DR GO; GO:0016155; F:formyltetrahydrofolate dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0016787; F:hydrolase activity; IEA:Ensembl.
DR GO; GO:0016742; F:hydroxymethyl-, formyl- and related transferase activity; 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:0048703; P:embryonic viscerocranium morphogenesis; IEA:Ensembl.
DR GO; GO:0007369; P:gastrulation; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0006740; P:NADPH regeneration; ISS:UniProtKB.
DR GO; GO:0001755; P:neural crest cell migration; IEA:Ensembl.
DR GO; GO:0048885; P:neuromast deposition; IEA:Ensembl.
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_0000316000"
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; 99658 MW; 120CFF8CD10474BE CRC64;
MKIAVIGQSL FGREVYRELL KEGHQVVGVF TIPDKNGKAD PLGADAEKDG IPVFKFPRWR
VKGQAIPEVV EKYKALEAEL NVLPFCSQFI PMEVIDCPKH GSIIYHPSIL PRHRGASAIN
WTLMQGDKIG GFTIFWADDG LDTGDILLQR ECEVLPDDTV NTIYNRFLFP EGVKGMVEAV
RLIAEGNAPR IKQATEGATY DPMQKKENAK INWDQPAEAI HNFIRGNDKV PGAWTVVGDQ
QLTFFGSSFI SNGPAPDGQP LEIPGAFRPA VVTKTGLVLF GNDGQKLSVK NIQFEDGKMI
PASQYYKTAD SAALQLSDEE KKFSEEIRAA WKRILTNVSE IEDSTDFFKA GAASMDVVRL
VEEVKLKCNG LQLQNEDVYM ATKFEEFIQM VVRRLRGEDG EEELVVDYVE KEINNMTVKI
PHQLFINGQF IDAEGGKTYD TVNPTDGTAI CKVSLAQVSD IDRAVAAAKE AFENGEWGKM
NPRDRGRILY RLADIMEEHQ EELATIESID SGAVYTLALK THVGMSIQTF RYFAGWCDKI
QGSTIPINQA RPNRNLTFTR REPIGVCGIV IPWNYPLMML AWKTAACLAA GNTVVLKPAQ
VTPLTALKFA ELSVKAGIPK GVINILPGAG SLIGQRLSDH PDVRKIGFTG STPIGKHIMK
SCAVGNVKKV SLELGGKSPL IIFQDCDLDK AVRMGMSSVF FNKGENCIAA GRLFLEESIH
DEFVKRVVGE VKKMKIGDPL DRSTDHGPQN HKAHLDKLIE YCQTGVKEGA KLVYGGKQVE
RPGFFFEPTI FTDVTDEMFI AKEESFGPIM IISKFKDGDV DEVLKRANNT EFGLASGVFT
KDISKALYVS EKLQAGTVFV NTYNKTDVAA PFGGFKQSGF GKDLGEEALN EYLKTKAVTI
EY
