Search Results

Overview

Uniprot IDP14550
Protein NameAldo-keto reductase family 1 member A1
Gene NameAKR1A1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
127 RGDNPFPKNADGTIC
13 VLLHTGQKMPLIGLG
141 CYDSTHYKETWKALE
294 KQLNALNKNWRYIVP
30 KSEPGQVKAAVKYAL
308 PMLTVDGKRVPRDAG
68 KEDVGPGKAVPREEL
80 EELFVTSKLWNTKHH
85 TSKLWNTKHHPEDVE

Function

Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols (PubMed:10510318, PubMed:30538128). 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 (PubMed:10510318, PubMed:30538128). Functions as a detoxifiying enzyme by reducing a range of toxic aldehydes (By similarity). Reduces methylglyoxal and 3-deoxyglucosone, which are present at elevated levels under hyperglycemic conditions and are cytotoxic (By similarity). 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, including the anthracyclines doxorubicin (DOX) and daunorubicin (DAUN) (PubMed:11306097, PubMed:18276838). 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 (PubMed:30538128). 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 (PubMed:31649033). Displays no reductase activity towards retinoids (By similarity)

Protein Sequence

10 MAASCVLLHT 20 GQKMPLIGLG 30 TWKSEPGQVK 40 AAVKYALSVG 50 YRHIDCAAIY 60 GNEPEIGEAL 70 KEDVGPGKAV 80 PREELFVTSK 90 LWNTKHHPED 100 VEPALRKTLA 110 DLQLEYLDLY 120 LMHWPYAFER 130 GDNPFPKNAD 140 GTICYDSTHY 150 KETWKALEAL 160 VAKGLVQALG 170 LSNFNSRQID 180 DILSVASVRP 190 AVLQVECHPY 200 LAQNELIAHC 210 QARGLEVTAY 220 SPLGSSDRAW 230 RDPDEPVLLE 240 EPVVLALAEK 250 YGRSPAQILL 260 RWQVQRKVIC 270 IPKSITPSRI 280 LQNIKVFDFT 290 FSPEEMKQLN 300 ALNKNWRYIV 310 PMLTVDGKRV 320 PRDAGHPLYP FNDPY

Gene Ontology

Classification GO ID Description
Cellular Component GO:0016324 apical plasma membrane
Biological Process GO:0043066 negative regulation of apoptotic process
Cellular Component GO:0005829 cytosol
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0005615 extracellular space
Cellular Component GO:0045202 synapse
Molecular Function GO:0008106 alcohol dehydrogenase (NADP+) activity
Molecular Function GO:0004032 aldose reductase (NADPH) activity
Molecular Function GO:0047655 allyl-alcohol dehydrogenase activity
Molecular Function GO:0047941 glucuronolactone reductase activity
Molecular Function GO:0047956 glycerol dehydrogenase (NADP+) activity
Molecular Function GO:0047939 L-glucuronate reductase activity
Molecular Function GO:1990002 methylglyoxal reductase (NADPH) (acetol producing) activity
Molecular Function GO:0080007 S-nitrosoglutathione reductase (NADH) activity
Molecular Function GO:0160163 S-nitrosoglutathione reductase (NADPH) activity
Biological Process GO:0046185 aldehyde catabolic process
Biological Process GO:0110095 cellular detoxification of aldehyde
Biological Process GO:0019640 D-glucuronate catabolic process to D-xylulose 5-phosphate
Biological Process GO:0044597 daunorubicin metabolic process
Biological Process GO:0044598 doxorubicin metabolic process
Biological Process GO:1901687 glutathione derivative biosynthetic process
Biological Process GO:0006629 lipid metabolic process

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.