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Overview

Uniprot ID	P51635
Protein Name	Aldo-keto reductase family 1 member A1
Gene Name	Akr1a1
Organism	Rattus norvegicus

Kla Sites from experimental identification

Position	Flanking peptide
127	RGDNPFPKNADGTVK
134	KNADGTVKYDSTHYK
153	ALEALVAKGLVKALG
68	KESVGAGKAVPREEL

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 (PubMed:22820017, PubMed:25152401). Plays an important role in ascorbic acid biosynthesis by catalyzing the reduction of D-glucuronic acid and D-glucurono-gamma-lactone (PubMed:22820017). 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 (PubMed:25152401, PubMed:8500767). Involved also in the detoxification of lipid-derived aldehydes like acrolein (PubMed:25152401). 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 (By similarity)

Protein Sequence

10 MTASSVLLHT 20 GQKMPLIGLG 30 TWKSEPGQVK 40 AAIKYALSVG 50 YRHIDCASVY 60 GNETEIGEAL 70 KESVGAGKAV 80 PREELFVTSK 90 LWNTKHHPED 100 VEPAVRKTLA 110 DLQLEYLDLY 120 LMHWPYAFER 130 GDNPFPKNAD 140 GTVKYDSTHY 150 KETWKALEAL 160 VAKGLVKALG 170 LSNFSSRQID 180 DVLSVASVRP 190 AVLQVECHPY 200 LAQNELIAHC 210 QARGLEVTAY 220 SPLGSSDRAW 230 RHPDEPVLLE 240 EPVVLALAEK 250 HGRSPAQILL 260 RWQVQRKVIC 270 IPKSITPSRI 280 LQNIQVFDFT 290 FSPEEMKQLD 300 ALNKNWRYIV 310 PMITVDGKRV 320 PRDAGHPLYP FNDPY

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0016324	apical plasma membrane
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0045202	synapse
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:0042840	D-glucuronate catabolic process
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:0019853	L-ascorbic acid biosynthetic process
Biological Process	GO:0006629	lipid metabolic process
Biological Process	GO:0043066	negative regulation of apoptotic process

Reference

[1] Yao Y, Bade R, Li G, Zhang A, Zhao H et al.. Global-Scale Profiling of Differential Expressed Lysine-Lactylated Proteins in the Cerebral Endothelium of Cerebral Ischemia-Reperfusion Injury Rats.. Cell Mol Neurobiol 43(5):1989-2004. 2023 Jul. PMID: 36030297.

[2] Sheng L, Xu H, Wang Y, Ni J, Xiang T et al.. Systematic analysis of lysine lactylation in nucleus pulposus cells.. iScience 27(11):111157. 2024 Nov 15. PMID: 39524337.

[3] Chen Y, Sun W, Sun Z, Zhao H, Wu T et al.. Effect of electroacupuncture on hippocampal protein lactylation in a rat model of vascular dementia.. Front Neurol 16:1629474. 2025. PMID: 40963935.