Q8R0Y6 · AL1L1_MOUSE
- ProteinCytosolic 10-formyltetrahydrofolate dehydrogenase
- GeneAldh1l1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids902 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Cytosolic 10-formyltetrahydrofolate dehydrogenase that catalyzes the NADP+-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate and carbon dioxide (PubMed:31624291).
May also have an NADP+-dependent aldehyde dehydrogenase activity towards formaldehyde, acetaldehyde, propionaldehyde, and benzaldehyde (By similarity).
May also have an NADP+-dependent aldehyde dehydrogenase activity towards formaldehyde, acetaldehyde, propionaldehyde, and benzaldehyde (By similarity).
Catalytic activity
- (6R)-10-formyltetrahydrofolate + H2O + NADP+ = (6S)-5,6,7,8-tetrahydrofolate + CO2 + H+ + NADPHThis reaction proceeds in the forward direction.
Features
Showing features for binding site, active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 88-90 | (6R)-10-formyltetrahydrofolate (UniProtKB | ChEBI) | ||||
Sequence: QFI | ||||||
Active site | 106 | Proton donor | ||||
Sequence: H | ||||||
Binding site | 142 | (6R)-10-formyltetrahydrofolate (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Site | 142 | Essential for catalytic activity | ||||
Sequence: D | ||||||
Binding site | 571-573 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: IPW | ||||||
Binding site | 597-600 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: KPAQ | ||||||
Binding site | 630-635 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: GSLVGQ | ||||||
Binding site | 650-651 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: GS | ||||||
Active site | 673 | Proton acceptor | ||||
Sequence: E | ||||||
Binding site | 673-674 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: EL | ||||||
Active site | 707 | Proton donor | ||||
Sequence: C | ||||||
Binding site | 757 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 804-806 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: ESF |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | mitochondrion | |
Cellular Component | protein-containing complex | |
Molecular Function | aldehyde dehydrogenase (NAD+) activity | |
Molecular Function | aldehyde dehydrogenase (NADP+) activity | |
Molecular Function | aldehyde dehydrogenase [NAD(P)+] activity | |
Molecular Function | formyltetrahydrofolate dehydrogenase activity | |
Molecular Function | protein-containing complex binding | |
Biological Process | 10-formyltetrahydrofolate catabolic process | |
Biological Process | biosynthetic process | |
Biological Process | folic acid metabolic process | |
Biological Process | NADPH regeneration | |
Biological Process | one-carbon metabolic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCytosolic 10-formyltetrahydrofolate dehydrogenase
- EC number
- Short names10-FTHFDH; FDH
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8R0Y6
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Disruption phenotype
Homozygous knockout mice are viable, fertile, develop normally and do not display overt phenotype (PubMed:31624291).
However, they have metabolic signs of folate deficiency like the accumulation of formiminoglutamate (PubMed:31624291).
Mice show reduced hepatic folate pools with a strong accumulation of (6S)-10-formyltetrahydrofolate and a significant drop in tetrahydrofolate levels (PubMed:31624291).
This is associated with a strong decrease of glycine levels as well as levels of several glycine conjugates (PubMed:31624291).
However, they have metabolic signs of folate deficiency like the accumulation of formiminoglutamate (PubMed:31624291).
Mice show reduced hepatic folate pools with a strong accumulation of (6S)-10-formyltetrahydrofolate and a significant drop in tetrahydrofolate levels (PubMed:31624291).
This is associated with a strong decrease of glycine levels as well as levels of several glycine conjugates (PubMed:31624291).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 61 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000199420 | 1-902 | Cytosolic 10-formyltetrahydrofolate dehydrogenase | |||
Sequence: MKIAVIGQSLFGQEVYCQLRKEGHEVVGVFTIPDKDGKADPLGLEAEKDGVPVFKFPRWRARGQALPEVVAKYQALGAELNVLPFCSQFIPMEVINAPRHGSIIYHPSLLPRHRGASAINWTLIHGDKKGGFTIFWADDGLDTGDLLLQKECDVLPDDTVSTLYNRFLFPEGIKGMVQAVRLIAEGTAPRRPQPEEGATYEGIQKKETAMINWDQPAEAIHNWIRGNDKVPGAWTEACGQKLTFFNSTLNTSGLVAQGEALPIPGAHRPGLVTKAGLILFGNDDRMLLVKNIQLEDGKMMPASQFFKGSASSALELTEEELATAEAVRSSWMRILPNVPEVEDSTDFFKSGAASVDVVRLVEEVKELCDGLELENEDVYMATTFGDFIQLLVRKLRGEDGESECVINYVEKAVKKLTLQMPYQLFIGGEFVDAEGAKTYSTINPTDGSVICQVSLAQVSDVDKAVAAAKEAFENGLWGKINARDRGRLLYRLADLMEQHQEELATIEALDAGAVYTLALKTHVGMSIQTFRYFAGWCDKIQGATIPINQARPNRNLTLTKKEPVGVCGIVIPWNYPLMMLSWKTAACLAAGNTVVIKPAQVTPLTALKFAELTLKAGIPKGVVNILPGSGSLVGQRLSDHPDVRKIGFTGSTEVGKHIMKSCALSNVKKVSLELGGKSPLIIFADCDLNKAVQMGMSSVFFNKGENCIAAGRLFVEDSIHDQFVQKVVEEVGKMKIGNPLDRDTNHGPQNHEAHLRKLVEYCQRGVKEGATLVCGGNQVPRPGFFFQPTVFTDVEDHMYIAKEESFGPIMIISRFADGDVDAVLSRANATEFGLASGVFTRDINKALYVSDKLQAGTVFVNTYNKTDVAAPFGGFKQSGFGKDLGEAALNEYLRIKTVTFEY | ||||||
Modified residue | 9 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 38 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 354 | O-(pantetheine 4'-phosphoryl)serine | ||||
Sequence: S | ||||||
Modified residue | 629 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 631 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 660 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 767 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 825 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 882 | N6-acetyllysine | ||||
Sequence: K |
Post-translational modification
Phosphopantetheinylation at Ser-354 by AASDHPPT is required for the formyltetrahydrofolate dehydrogenase activity.
Keywords
- PTM
Proteomic databases
PTM databases
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-310 | Hydrolase domain | ||||
Sequence: MKIAVIGQSLFGQEVYCQLRKEGHEVVGVFTIPDKDGKADPLGLEAEKDGVPVFKFPRWRARGQALPEVVAKYQALGAELNVLPFCSQFIPMEVINAPRHGSIIYHPSLLPRHRGASAINWTLIHGDKKGGFTIFWADDGLDTGDLLLQKECDVLPDDTVSTLYNRFLFPEGIKGMVQAVRLIAEGTAPRRPQPEEGATYEGIQKKETAMINWDQPAEAIHNWIRGNDKVPGAWTEACGQKLTFFNSTLNTSGLVAQGEALPIPGAHRPGLVTKAGLILFGNDDRMLLVKNIQLEDGKMMPASQFFKGSA | ||||||
Domain | 318-395 | Carrier | ||||
Sequence: EEELATAEAVRSSWMRILPNVPEVEDSTDFFKSGAASVDVVRLVEEVKELCDGLELENEDVYMATTFGDFIQLLVRKL | ||||||
Region | 417-902 | Aldehyde dehydrogenase domain | ||||
Sequence: TLQMPYQLFIGGEFVDAEGAKTYSTINPTDGSVICQVSLAQVSDVDKAVAAAKEAFENGLWGKINARDRGRLLYRLADLMEQHQEELATIEALDAGAVYTLALKTHVGMSIQTFRYFAGWCDKIQGATIPINQARPNRNLTLTKKEPVGVCGIVIPWNYPLMMLSWKTAACLAAGNTVVIKPAQVTPLTALKFAELTLKAGIPKGVVNILPGSGSLVGQRLSDHPDVRKIGFTGSTEVGKHIMKSCALSNVKKVSLELGGKSPLIIFADCDLNKAVQMGMSSVFFNKGENCIAAGRLFVEDSIHDQFVQKVVEEVGKMKIGNPLDRDTNHGPQNHEAHLRKLVEYCQRGVKEGATLVCGGNQVPRPGFFFQPTVFTDVEDHMYIAKEESFGPIMIISRFADGDVDAVLSRANATEFGLASGVFTRDINKALYVSDKLQAGTVFVNTYNKTDVAAPFGGFKQSGFGKDLGEAALNEYLRIKTVTFEY |
Domain
The N-terminal hydrolase domain has an NADP-independent formyltetrahydrofolate hydrolase activity, releasing formate and tetrahydrofolate.
The C-terminal aldehyde dehydrogenase domain has an NADP-dependent dehydrogenase activity. It catalyzes the oxidation of formate, released by the hydrolysis of formyltetrahydrofolate, into CO2.
The carrier domain is phosphopantetheinylated and uses the 4'-phosphopantetheine/4'-PP swinging arm to transfer the formyl group released by the N-terminal formyltetrahydrofolate hydrolase activity to the C-terminal aldehyde dehydrogenase domain that catalyzes its NADP-dependent oxidation into CO2. The overall NADP-dependent physiological reaction requires the 3 domains (N-terminal hydrolase, C-terminal aldehyde dehydrogenase and carrier domains) to convert formyltetrahydrofolate into tetrahydrofolate and CO2.
Sequence similarities
In the N-terminal section; belongs to the GART family.
In the C-terminal section; belongs to the aldehyde dehydrogenase family. ALDH1L subfamily.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length902
- Mass (Da)98,709
- Last updated2002-06-01 v1
- Checksum9B5526A7FB41909E
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0N4SVT2 | A0A0N4SVT2_MOUSE | Aldh1l1 | 135 | ||
A0A0N4SW56 | A0A0N4SW56_MOUSE | Aldh1l1 | 359 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
BC025939 EMBL· GenBank· DDBJ | AAH25939.1 EMBL· GenBank· DDBJ | mRNA | ||
BC028817 EMBL· GenBank· DDBJ | AAH28817.1 EMBL· GenBank· DDBJ | mRNA | ||
BC030722 EMBL· GenBank· DDBJ | AAH30722.1 EMBL· GenBank· DDBJ | mRNA | ||
BC030723 EMBL· GenBank· DDBJ | AAH30723.1 EMBL· GenBank· DDBJ | mRNA | ||
BC030727 EMBL· GenBank· DDBJ | AAH30727.1 EMBL· GenBank· DDBJ | mRNA | ||
BC030730 EMBL· GenBank· DDBJ | AAH30730.1 EMBL· GenBank· DDBJ | mRNA |