P50578 · AK1A1_PIG
- ProteinAldo-keto reductase family 1 member A1
- GeneAKR1A1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids325 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosaccharides and bile acids, with a preference for negatively charged substrates, such as glucuronate and succinic semialdehyde (By similarity).
Plays an important role in ascorbic acid biosynthesis by catalyzing the reduction of D-glucuronic acid and D-glucurono-gamma-lactone (By similarity).
Functions as a detoxifiying enzyme by reducing a range of toxic aldehydes. Reduces methylglyoxal and 3-deoxyglucosone, which are present at elevated levels under hyperglycemic conditions and are cytotoxic. Involved also in the detoxification of lipid-derived aldehydes like acrolein (By similarity).
Plays a role in the activation of procarcinogens, such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the metabolism of various xenobiotics and drugs (By similarity).
Also acts as an inhibitor of protein S-nitrosylation by mediating degradation of S-nitroso-coenzyme A (S-nitroso-CoA), a cofactor required to S-nitrosylate proteins (By similarity).
S-nitroso-CoA reductase activity is involved in reprogramming intermediary metabolism in renal proximal tubules, notably by inhibiting protein S-nitrosylation of isoform 2 of PKM (PKM2) (By similarity).
Also acts as a S-nitroso-glutathione reductase by catalyzing the NADPH-dependent reduction of S-nitrosoglutathione (By similarity).
Displays no reductase activity towards retinoids (PubMed:12732097).
Plays an important role in ascorbic acid biosynthesis by catalyzing the reduction of D-glucuronic acid and D-glucurono-gamma-lactone (By similarity).
Functions as a detoxifiying enzyme by reducing a range of toxic aldehydes. Reduces methylglyoxal and 3-deoxyglucosone, which are present at elevated levels under hyperglycemic conditions and are cytotoxic. Involved also in the detoxification of lipid-derived aldehydes like acrolein (By similarity).
Plays a role in the activation of procarcinogens, such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the metabolism of various xenobiotics and drugs (By similarity).
Also acts as an inhibitor of protein S-nitrosylation by mediating degradation of S-nitroso-coenzyme A (S-nitroso-CoA), a cofactor required to S-nitrosylate proteins (By similarity).
S-nitroso-CoA reductase activity is involved in reprogramming intermediary metabolism in renal proximal tubules, notably by inhibiting protein S-nitrosylation of isoform 2 of PKM (PKM2) (By similarity).
Also acts as a S-nitroso-glutathione reductase by catalyzing the NADPH-dependent reduction of S-nitrosoglutathione (By similarity).
Displays no reductase activity towards retinoids (PubMed:12732097).
Catalytic activity
- a primary alcohol + NADP+ = an aldehyde + H+ + NADPH
- hydroxyacetone + NADP+ = H+ + methylglyoxal + NADPH
- 3-deoxyfructose + NADP+ = 3-deoxyglucosone + H+ + NADPH
- (R)-mevalonate + NADP+ = (R)-mevaldate + H+ + NADPH
- NADP+ + pyridine 3-methanol = H+ + NADPH + pyridine-3-carbaldehyde
- H+ + NADPH + S-nitroso-CoA = NADP+ + sulfinamide-CoAThis reaction proceeds in the forward direction.
- H+ + NADPH + S-nitrosoglutathione = NADP+ + S-(hydroxysulfenamide)glutathione
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
700 μM | pyridine-3-carbaldehyde | |||||
4600 μM | D,L-glyceraldehyde |
kcat is 11000 min-1 for pyridine-3-carbaldehyde as substrate. kcat is 2500 min-1 for D,L-glyceraldehyde as substrate.
Features
Showing features for binding site, active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 11-20 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: GQKMPLIGLG | ||||||
Binding site | 21 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 22 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 45 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Active site | 50 | Proton donor | ||||
Sequence: Y | ||||||
Site | 80 | Lowers pKa of active site Tyr | ||||
Sequence: K | ||||||
Binding site | 162 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 163 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 211 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 213 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 215 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 216 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 263 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 264 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 265 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 266 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 269 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 272 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 273 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: N |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | apical plasma membrane | |
Cellular Component | cytosol | |
Molecular Function | aldose reductase (NADPH) activity | |
Molecular Function | allyl-alcohol dehydrogenase activity | |
Molecular Function | glucuronolactone reductase activity | |
Molecular Function | glycerol dehydrogenase (NADP+) activity | |
Molecular Function | L-glucuronate reductase activity | |
Molecular Function | methylglyoxal reductase (NADPH) (acetol producing) activity | |
Molecular Function | S-nitrosoglutathione reductase (NADPH) activity | |
Biological Process | aldehyde catabolic process | |
Biological Process | cellular detoxification of aldehyde | |
Biological Process | D-glucuronate catabolic process | |
Biological Process | L-ascorbic acid biosynthetic process | |
Biological Process | lipid metabolic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAldo-keto reductase family 1 member A1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Suina > Suidae > Sus
Accessions
- Primary accessionP50578
- Secondary accessions
Proteomes
Subcellular Location
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 50 | Abolished aldo-keto reductase activity. | ||||
Sequence: Y → F |
Chemistry
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000124619 | 2-325 | Aldo-keto reductase family 1 member A1 | |||
Sequence: AASCVLLHTGQKMPLIGLGTWKSEPGQVKAAIKYALTVGYRHIDCAAIYGNELEIGEALQETVGPGKAVPREELFVTSKLWNTKHHPEDVEPALRKTLADLQLEYLDLYLMHWPYAFERGDNPFPKNADGTIRYDATHYKDTWKALEALVAKGLVRALGLSNFSSRQIDDVLSVASVRPAVLQVECHPYLAQNELIAHCQARGLEVTAYSPLGSSDRAWRDPNEPVLLEEPVVQALAEKYNRSPAQILLRWQVQRKVICIPKSVTPSRILQNIQVFDFTFSPEEMKQLDALNKNLRFIVPMLTVDGKRVPRDAGHPLYPFNDPY | ||||||
Modified residue | 4 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 127 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 127 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 145 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 211 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
Structure
Sequence
- Sequence statusComplete
- Length325
- Mass (Da)36,582
- Last updated2019-02-13 v3
- Checksum1572641AEA57043F
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 61 | in Ref. 1; AAB60266 | ||||
Sequence: Q → T | ||||||
Sequence conflict | 271 | in Ref. 1; AAB60266 | ||||
Sequence: L → P |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U46064 EMBL· GenBank· DDBJ | AAB60266.1 EMBL· GenBank· DDBJ | mRNA | ||
AEMK02000049 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |