UniProtKB - P14550 (AK1A1_HUMAN)
Aldo-keto reductase family 1 member A1
AKR1A1
Functioni
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 (PubMed:10510318).
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, including the anthracyclines doxorubicin (DOX) and daunorubicin (DAUN) (PubMed:18276838, PubMed:11306097).
Displays no reductase activity towards retinoids (By similarity).
By similarity3 PublicationsCatalytic activityi
- EC:1.1.1.21 Publication
- EC:1.1.1.541 Publication
- EC:1.1.1.3721 Publication
- EC:1.1.1.3721 Publication
- EC:1.1.1.191 Publication
- EC:1.1.1.20By similarity
Kineticsi
- Vmax=1426 nmol/min/mg enzyme for 4-hydroxynonenal1 Publication
- Vmax=268 nmol/min/mg enzyme for acrolein1 Publication
- Vmax=3460 nmol/min/mg enzyme for pyridine-3-carbaldehyde1 Publication
- Vmax=4273 nmol/min/mg enzyme for methylglyoxal1 Publication
- Vmax=1263 nmol/min/mg enzyme for D,L-glyceraldehyde1 Publication
- Vmax=5562 nmol/min/mg enzyme for D-glucuronic acid1 Publication
- Vmax=4983 nmol/min/mg enzyme for succinic semialdehyde1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 45 | NADPBy similarity | 1 | |
Active sitei | 50 | Proton donor1 Publication | 1 | |
Sitei | 80 | Lowers pKa of active site Tyr1 Publication | 1 | |
Binding sitei | 113 | Substrate1 Publication | 1 | |
Binding sitei | 184 | NADPBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 21 – 23 | NADPBy similarity | 3 | |
Nucleotide bindingi | 162 – 163 | NADPBy similarity | 2 | |
Nucleotide bindingi | 210 – 217 | NADPBy similarity | 8 | |
Nucleotide bindingi | 261 – 273 | NADPBy similarityAdd BLAST | 13 |
GO - Molecular functioni
- alditol:NADP+ 1-oxidoreductase activity Source: GO_Central
- aldo-keto reductase (NADP) activity Source: Reactome
- allyl-alcohol dehydrogenase activity Source: UniProtKB-EC
- glucuronolactone reductase activity Source: UniProtKB
- glycerol dehydrogenase [NADP+] activity Source: RHEA
- L-glucuronate reductase activity Source: UniProtKB
- methylglyoxal reductase (NADPH-dependent, acetol producing) Source: RHEA
GO - Biological processi
- aldehyde catabolic process Source: Ensembl
- cellular detoxification of aldehyde Source: UniProtKB
- daunorubicin metabolic process Source: UniProtKB
- D-glucuronate catabolic process Source: Ensembl
- doxorubicin metabolic process Source: UniProtKB
- glucuronate catabolic process to xylulose 5-phosphate Source: Reactome
- glutathione derivative biosynthetic process Source: Reactome
- L-ascorbic acid biosynthetic process Source: Ensembl
- lipid metabolic process Source: UniProtKB-KW
Keywordsi
Molecular function | Oxidoreductase |
Biological process | Lipid metabolism |
Ligand | NADP |
Enzyme and pathway databases
BRENDAi | 1.1.1.2, 2681 |
PathwayCommonsi | P14550 |
Reactomei | R-HSA-156590, Glutathione conjugation R-HSA-5661270, Formation of xylulose-5-phosphate |
SABIO-RKi | P14550 |
SignaLinki | P14550 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:AKR1A1 Synonyms:ALDR1, ALR |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:380, AKR1A1 |
MIMi | 103830, gene |
neXtProti | NX_P14550 |
VEuPathDBi | HostDB:ENSG00000117448 |
Subcellular locationi
Cytoplasm and Cytosol
- cytosol By similarity
Plasma membrane
- Apical cell membrane By similarity
Cytosol
- cytosol Source: UniProtKB
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular space Source: UniProtKB
Plasma Membrane
- apical plasma membrane Source: UniProtKB
Other locations
- synapse Source: Ensembl
Keywords - Cellular componenti
Cell membrane, Cytoplasm, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 50 | Y → F: Complete loss of enzymatic activity. 1 Publication | 1 | |
Mutagenesisi | 50 | Y → H: Complete loss of enzymatic activity. 1 Publication | 1 | |
Mutagenesisi | 80 | K → M: Complete loss of enzymatic activity. 1 Publication | 1 | |
Mutagenesisi | 113 | H → Q: Strong decrease in enzymatic activity. 1 Publication | 1 | |
Mutagenesisi | 299 | I → A: No change in enzymatic activity. 1 Publication | 1 | |
Mutagenesisi | 299 | I → C: No change in enzymatic activity. 1 Publication | 1 | |
Mutagenesisi | 300 | V → C: No change in enzymatic activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 10327 |
OpenTargetsi | ENSG00000117448 |
PharmGKBi | PA24674 |
Miscellaneous databases
Pharosi | P14550, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2246 |
DrugBanki | DB08904, Certolizumab pegol DB09130, Copper DB00997, Doxorubicin DB00898, Ethanol DB06077, Lumateperone DB00157, NADH DB03461, Nicotinamide adenine dinucleotide phosphate DB06207, Silodosin DB02383, Tolrestat |
DrugCentrali | P14550 |
Genetic variation databases
BioMutai | AKR1A1 |
DMDMi | 113600 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources1 Publication | |||
ChainiPRO_0000124617 | 2 – 325 | Aldo-keto reductase family 1 member A1Add BLAST | 324 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 4 | PhosphoserineBy similarity | 1 | |
Modified residuei | 38 | PhosphoserineCombined sources | 1 | |
Modified residuei | 127 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 127 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 145 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 211 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
CPTACi | CPTAC-10 CPTAC-9 |
EPDi | P14550 |
jPOSTi | P14550 |
MassIVEi | P14550 |
PaxDbi | P14550 |
PeptideAtlasi | P14550 |
PRIDEi | P14550 |
ProteomicsDBi | 53058 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00220271 P14550 |
SWISS-2DPAGEi | P14550 |
UCD-2DPAGEi | P14550 |
PTM databases
GlyGeni | P14550, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P14550 |
MetOSitei | P14550 |
PhosphoSitePlusi | P14550 |
SwissPalmi | P14550 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000117448, Expressed in nephron tubule and 239 other tissues |
ExpressionAtlasi | P14550, baseline and differential |
Genevisiblei | P14550, HS |
Organism-specific databases
HPAi | ENSG00000117448, Low tissue specificity |
Interactioni
Subunit structurei
Monomer.
By similarityBinary interactionsi
P14550
With | #Exp. | IntAct |
---|---|---|
HTT [P42858] | 6 | EBI-372388,EBI-466029 |
TERF2IP [Q9NYB0] | 2 | EBI-372388,EBI-750109 |
WFS1 [O76024] | 3 | EBI-372388,EBI-720609 |
Protein-protein interaction databases
BioGRIDi | 115610, 44 interactors |
IntActi | P14550, 14 interactors |
MINTi | P14550 |
STRINGi | 9606.ENSP00000361140 |
Chemistry databases
BindingDBi | P14550 |
Miscellaneous databases
RNActi | P14550, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P14550 |
SMRi | P14550 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P14550 |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1577, Eukaryota |
GeneTreei | ENSGT00940000156539 |
HOGENOMi | CLU_023205_0_0_1 |
InParanoidi | P14550 |
OMAi | WRHPDEP |
OrthoDBi | 1016440at2759 |
PhylomeDBi | P14550 |
TreeFami | TF106492 |
Family and domain databases
CDDi | cd19106, AKR_AKR1A1-4, 1 hit |
Gene3Di | 3.20.20.100, 1 hit |
InterProi | View protein in InterPro IPR020471, AKR IPR044481, AKR1A IPR018170, Aldo/ket_reductase_CS IPR023210, NADP_OxRdtase_dom IPR036812, NADP_OxRdtase_dom_sf |
Pfami | View protein in Pfam PF00248, Aldo_ket_red, 1 hit |
PIRSFi | PIRSF000097, AKR, 1 hit |
PRINTSi | PR00069, ALDKETRDTASE |
SUPFAMi | SSF51430, SSF51430, 1 hit |
PROSITEi | View protein in PROSITE PS00798, ALDOKETO_REDUCTASE_1, 1 hit PS00062, ALDOKETO_REDUCTASE_2, 1 hit PS00063, ALDOKETO_REDUCTASE_3, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MAASCVLLHT GQKMPLIGLG TWKSEPGQVK AAVKYALSVG YRHIDCAAIY
60 70 80 90 100
GNEPEIGEAL KEDVGPGKAV PREELFVTSK LWNTKHHPED VEPALRKTLA
110 120 130 140 150
DLQLEYLDLY LMHWPYAFER GDNPFPKNAD GTICYDSTHY KETWKALEAL
160 170 180 190 200
VAKGLVQALG LSNFNSRQID DILSVASVRP AVLQVECHPY LAQNELIAHC
210 220 230 240 250
QARGLEVTAY SPLGSSDRAW RDPDEPVLLE EPVVLALAEK YGRSPAQILL
260 270 280 290 300
RWQVQRKVIC IPKSITPSRI LQNIKVFDFT FSPEEMKQLN ALNKNWRYIV
310 320
PMLTVDGKRV PRDAGHPLYP FNDPY
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ5T621 | Q5T621_HUMAN | Aldo-keto reductase family 1 member... | AKR1A1 | 147 | Annotation score: | ||
V9GYG2 | V9GYG2_HUMAN | Aldo-keto reductase family 1 member... | AKR1A1 | 119 | Annotation score: | ||
V9GYP9 | V9GYP9_HUMAN | Aldo-keto reductase family 1 member... | AKR1A1 | 140 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 305 | V → A in BAF85772 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_048212 | 52 | N → S Reduced activity towards daunorubicin. 1 PublicationCorresponds to variant dbSNP:rs2229540Ensembl. | 1 | |
Natural variantiVAR_058909 | 55 | E → D Reduced activity towards daunorubicin. 1 PublicationCorresponds to variant dbSNP:rs6690497Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J04794 mRNA Translation: AAA51711.1 AF036683 , AF036680, AF036681, AF036682 Genomic DNA Translation: AAB92369.1 AF112485, AF112484 Genomic DNA Translation: AAF01260.1 AK293083 mRNA Translation: BAF85772.1 CR457010 mRNA Translation: CAG33291.1 BT007003 mRNA Translation: AAP35649.1 AL355480 Genomic DNA No translation available. CH471059 Genomic DNA Translation: EAX06970.1 CH471059 Genomic DNA Translation: EAX06971.1 CH471059 Genomic DNA Translation: EAX06972.1 CH471059 Genomic DNA Translation: EAX06974.1 BC000670 mRNA Translation: AAH00670.1 BC005394 mRNA Translation: AAH05394.1 |
CCDSi | CCDS523.1 |
PIRi | A33851 |
RefSeqi | NP_001189342.1, NM_001202413.1 NP_001189343.1, NM_001202414.1 NP_006057.1, NM_006066.3 NP_697021.1, NM_153326.2 |
Genome annotation databases
Ensembli | ENST00000351829.9; ENSP00000312606.4; ENSG00000117448.14 ENST00000372070.7; ENSP00000361140.3; ENSG00000117448.14 ENST00000621846.4; ENSP00000480713.1; ENSG00000117448.14 |
GeneIDi | 10327 |
KEGGi | hsa:10327 |
MANE-Selecti | ENST00000351829.9; ENSP00000312606.4; NM_153326.3; NP_697021.1 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J04794 mRNA Translation: AAA51711.1 AF036683 , AF036680, AF036681, AF036682 Genomic DNA Translation: AAB92369.1 AF112485, AF112484 Genomic DNA Translation: AAF01260.1 AK293083 mRNA Translation: BAF85772.1 CR457010 mRNA Translation: CAG33291.1 BT007003 mRNA Translation: AAP35649.1 AL355480 Genomic DNA No translation available. CH471059 Genomic DNA Translation: EAX06970.1 CH471059 Genomic DNA Translation: EAX06971.1 CH471059 Genomic DNA Translation: EAX06972.1 CH471059 Genomic DNA Translation: EAX06974.1 BC000670 mRNA Translation: AAH00670.1 BC005394 mRNA Translation: AAH05394.1 |
CCDSi | CCDS523.1 |
PIRi | A33851 |
RefSeqi | NP_001189342.1, NM_001202413.1 NP_001189343.1, NM_001202414.1 NP_006057.1, NM_006066.3 NP_697021.1, NM_153326.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2ALR | X-ray | 2.48 | A | 2-325 | [»] | |
AlphaFoldDBi | P14550 | |||||
SMRi | P14550 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 115610, 44 interactors |
IntActi | P14550, 14 interactors |
MINTi | P14550 |
STRINGi | 9606.ENSP00000361140 |
Chemistry databases
BindingDBi | P14550 |
ChEMBLi | CHEMBL2246 |
DrugBanki | DB08904, Certolizumab pegol DB09130, Copper DB00997, Doxorubicin DB00898, Ethanol DB06077, Lumateperone DB00157, NADH DB03461, Nicotinamide adenine dinucleotide phosphate DB06207, Silodosin DB02383, Tolrestat |
DrugCentrali | P14550 |
PTM databases
GlyGeni | P14550, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P14550 |
MetOSitei | P14550 |
PhosphoSitePlusi | P14550 |
SwissPalmi | P14550 |
Genetic variation databases
BioMutai | AKR1A1 |
DMDMi | 113600 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00220271 P14550 |
SWISS-2DPAGEi | P14550 |
UCD-2DPAGEi | P14550 |
Proteomic databases
CPTACi | CPTAC-10 CPTAC-9 |
EPDi | P14550 |
jPOSTi | P14550 |
MassIVEi | P14550 |
PaxDbi | P14550 |
PeptideAtlasi | P14550 |
PRIDEi | P14550 |
ProteomicsDBi | 53058 |
Protocols and materials databases
Antibodypediai | 3338, 574 antibodies from 37 providers |
DNASUi | 10327 |
Genome annotation databases
Ensembli | ENST00000351829.9; ENSP00000312606.4; ENSG00000117448.14 ENST00000372070.7; ENSP00000361140.3; ENSG00000117448.14 ENST00000621846.4; ENSP00000480713.1; ENSG00000117448.14 |
GeneIDi | 10327 |
KEGGi | hsa:10327 |
MANE-Selecti | ENST00000351829.9; ENSP00000312606.4; NM_153326.3; NP_697021.1 |
Organism-specific databases
CTDi | 10327 |
DisGeNETi | 10327 |
GeneCardsi | AKR1A1 |
HGNCi | HGNC:380, AKR1A1 |
HPAi | ENSG00000117448, Low tissue specificity |
MIMi | 103830, gene |
neXtProti | NX_P14550 |
OpenTargetsi | ENSG00000117448 |
PharmGKBi | PA24674 |
VEuPathDBi | HostDB:ENSG00000117448 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1577, Eukaryota |
GeneTreei | ENSGT00940000156539 |
HOGENOMi | CLU_023205_0_0_1 |
InParanoidi | P14550 |
OMAi | WRHPDEP |
OrthoDBi | 1016440at2759 |
PhylomeDBi | P14550 |
TreeFami | TF106492 |
Enzyme and pathway databases
BRENDAi | 1.1.1.2, 2681 |
PathwayCommonsi | P14550 |
Reactomei | R-HSA-156590, Glutathione conjugation R-HSA-5661270, Formation of xylulose-5-phosphate |
SABIO-RKi | P14550 |
SignaLinki | P14550 |
Miscellaneous databases
BioGRID-ORCSi | 10327, 13 hits in 1080 CRISPR screens |
ChiTaRSi | AKR1A1, human |
EvolutionaryTracei | P14550 |
GeneWikii | Aldo-keto_reductase_family_1,_member_A1 |
GenomeRNAii | 10327 |
Pharosi | P14550, Tchem |
PROi | PR:P14550 |
RNActi | P14550, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000117448, Expressed in nephron tubule and 239 other tissues |
ExpressionAtlasi | P14550, baseline and differential |
Genevisiblei | P14550, HS |
Family and domain databases
CDDi | cd19106, AKR_AKR1A1-4, 1 hit |
Gene3Di | 3.20.20.100, 1 hit |
InterProi | View protein in InterPro IPR020471, AKR IPR044481, AKR1A IPR018170, Aldo/ket_reductase_CS IPR023210, NADP_OxRdtase_dom IPR036812, NADP_OxRdtase_dom_sf |
Pfami | View protein in Pfam PF00248, Aldo_ket_red, 1 hit |
PIRSFi | PIRSF000097, AKR, 1 hit |
PRINTSi | PR00069, ALDKETRDTASE |
SUPFAMi | SSF51430, SSF51430, 1 hit |
PROSITEi | View protein in PROSITE PS00798, ALDOKETO_REDUCTASE_1, 1 hit PS00062, ALDOKETO_REDUCTASE_2, 1 hit PS00063, ALDOKETO_REDUCTASE_3, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | AK1A1_HUMAN | |
Accessioni | P14550Primary (citable) accession number: P14550 Secondary accession number(s): A8KAL8, D3DQ04, Q6IAZ4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 1, 1990 |
Last sequence update: | January 23, 2007 | |
Last modified: | May 25, 2022 | |
This is version 212 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families