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Protein

Alcohol dehydrogenase [NADP(+)]

Gene

AKR1A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the NADPH-dependent reduction of a variety of aromatic and aliphatic aldehydes to their corresponding alcohols. Catalyzes the reduction of mevaldate to mevalonic acid and of glyceraldehyde to glycerol. Has broad substrate specificity. In vitro substrates include succinic semialdehyde, 4-nitrobenzaldehyde, 1,2-naphthoquinone, methylglyoxal, and D-glucuronic acid. 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).3 Publications

Catalytic activityi

An alcohol + NADP+ = an aldehyde + NADPH.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei45NADPBy similarity1
Active sitei50Proton donor1 Publication1
Sitei80Lowers pKa of active site Tyr1 Publication1
Binding sitei113Substrate1 Publication1
Binding sitei184NADPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi21 – 23NADPBy similarity3
Nucleotide bindingi162 – 163NADPBy similarity2
Nucleotide bindingi210 – 217NADPBy similarity8
Nucleotide bindingi261 – 273NADPBy similarityAdd BLAST13

GO - Molecular functioni

  • alditol:NADP+ 1-oxidoreductase activity Source: ProtInc
  • aldo-keto reductase (NADP) activity Source: Reactome
  • electron transfer activity Source: UniProtKB
  • L-glucuronate reductase activity Source: Reactome

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
LigandNADP

Enzyme and pathway databases

BRENDAi1.1.1.2 2681
ReactomeiR-HSA-156590 Glutathione conjugation
R-HSA-5661270 Catabolism of glucuronate to xylulose-5-phosphate
SABIO-RKP14550

Names & Taxonomyi

Protein namesi
Recommended name:
Alcohol dehydrogenase [NADP(+)] (EC:1.1.1.2)
Alternative name(s):
Aldehyde reductase
Aldo-keto reductase family 1 member A1
Gene namesi
Name:AKR1A1
Synonyms:ALDR1, ALR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000117448.13
HGNCiHGNC:380 AKR1A1
MIMi103830 gene
neXtProtiNX_P14550

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi50Y → F: Complete loss of enzymatic activity. 1 Publication1
Mutagenesisi50Y → H: Complete loss of enzymatic activity. 1 Publication1
Mutagenesisi80K → M: Complete loss of enzymatic activity. 1 Publication1
Mutagenesisi113H → Q: Strong decrease in enzymatic activity. 1 Publication1
Mutagenesisi299I → A: No change in enzymatic activity. 1 Publication1
Mutagenesisi299I → C: No change in enzymatic activity. 1 Publication1
Mutagenesisi300V → C: No change in enzymatic activity. 1 Publication1

Organism-specific databases

DisGeNETi10327
OpenTargetsiENSG00000117448
PharmGKBiPA24674

Chemistry databases

ChEMBLiCHEMBL2246
DrugBankiDB03461 2'-Monophosphoadenosine 5'-Diphosphoribose
DB00997 Doxorubicin
DB00898 Ethanol
DB00157 NADH
DB02383 Tolrestat

Polymorphism and mutation databases

BioMutaiAKR1A1
DMDMi113600

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001246172 – 325Alcohol dehydrogenase [NADP(+)]Add BLAST324

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei4PhosphoserineBy similarity1
Modified residuei38PhosphoserineCombined sources1
Modified residuei127N6-acetyllysine; alternateBy similarity1
Modified residuei127N6-succinyllysine; alternateBy similarity1
Modified residuei145N6-succinyllysineBy similarity1
Modified residuei211PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP14550
PaxDbiP14550
PeptideAtlasiP14550
PRIDEiP14550

2D gel databases

REPRODUCTION-2DPAGEIPI00220271
P14550
SWISS-2DPAGEP14550
UCD-2DPAGEP14550

PTM databases

iPTMnetiP14550
PhosphoSitePlusiP14550
SwissPalmiP14550

Expressioni

Tissue specificityi

Widely expressed. Highly expressed in kidney, salivary gland and liver. Detected in trachea, stomach, brain, lung, prostate, placenta, mammary gland, small intestine and lung.2 Publications

Gene expression databases

BgeeiENSG00000117448
CleanExiHS_AKR1A1
ExpressionAtlasiP14550 baseline and differential
GenevisibleiP14550 HS

Organism-specific databases

HPAiCAB006246
HPA017919
HPA019649
HPA027734

Interactioni

Subunit structurei

Monomer.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
TERF2IPQ9NYB02EBI-372388,EBI-750109

Protein-protein interaction databases

BioGridi115610, 29 interactors
IntActiP14550, 5 interactors
STRINGi9606.ENSP00000312606

Chemistry databases

BindingDBiP14550

Structurei

Secondary structure

1325
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 7Combined sources3
Beta strandi13 – 17Combined sources5
Helixi26 – 39Combined sources14
Beta strandi43 – 45Combined sources3
Helixi48 – 50Combined sources3
Helixi53 – 63Combined sources11
Beta strandi68 – 70Combined sources3
Helixi72 – 74Combined sources3
Beta strandi76 – 81Combined sources6
Helixi83 – 85Combined sources3
Helixi88 – 102Combined sources15
Beta strandi107 – 113Combined sources7
Beta strandi115 – 118Combined sources4
Beta strandi120 – 122Combined sources3
Helixi140 – 153Combined sources14
Beta strandi155 – 163Combined sources9
Helixi166 – 173Combined sources8
Beta strandi182 – 186Combined sources5
Helixi194 – 203Combined sources10
Beta strandi206 – 210Combined sources5
Helixi232 – 241Combined sources10
Helixi245 – 255Combined sources11
Helixi267 – 274Combined sources8
Helixi283 – 290Combined sources8
Beta strandi302 – 305Combined sources4
Beta strandi308 – 313Combined sources6
Beta strandi320 – 323Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ALRX-ray2.48A2-325[»]
ProteinModelPortaliP14550
SMRiP14550
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP14550

Family & Domainsi

Sequence similaritiesi

Belongs to the aldo/keto reductase family.Curated

Phylogenomic databases

eggNOGiKOG1577 Eukaryota
COG0656 LUCA
GeneTreeiENSGT00760000119041
HOGENOMiHOG000250272
HOVERGENiHBG000020
InParanoidiP14550
KOiK00002
OMAiIVPMITV
OrthoDBiEOG091G0D69
PhylomeDBiP14550
TreeFamiTF106492

Family and domain databases

CDDicd06660 Aldo_ket_red, 1 hit
Gene3Di3.20.20.100, 1 hit
InterProiView protein in InterPro
IPR018170 Aldo/ket_reductase_CS
IPR020471 Aldo/keto_reductase
IPR023210 NADP_OxRdtase_dom
IPR036812 NADP_OxRdtase_dom_sf
PANTHERiPTHR11732 PTHR11732, 1 hit
PfamiView protein in Pfam
PF00248 Aldo_ket_red, 1 hit
PIRSFiPIRSF000097 AKR, 1 hit
PRINTSiPR00069 ALDKETRDTASE
SUPFAMiSSF51430 SSF51430, 1 hit
PROSITEiView protein in PROSITE
PS00798 ALDOKETO_REDUCTASE_1, 1 hit
PS00062 ALDOKETO_REDUCTASE_2, 1 hit
PS00063 ALDOKETO_REDUCTASE_3, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P14550-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:325
Mass (Da):36,573
Last modified:January 23, 2007 - v3
Checksum:iF6B27517EB754E37
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti305V → A in BAF85772 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04821252N → S Reduced activity towards daunorubicin. 1 PublicationCorresponds to variant dbSNP:rs2229540Ensembl.1
Natural variantiVAR_05890955E → 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
CCDSiCCDS523.1
PIRiA33851
RefSeqiNP_001189342.1, NM_001202413.1
NP_001189343.1, NM_001202414.1
NP_006057.1, NM_006066.3
NP_697021.1, NM_153326.2
UniGeneiHs.474584
Hs.721160

Genome annotation databases

EnsembliENST00000351829; ENSP00000312606; ENSG00000117448
ENST00000372070; ENSP00000361140; ENSG00000117448
ENST00000621846; ENSP00000480713; ENSG00000117448
GeneIDi10327
KEGGihsa:10327

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiAK1A1_HUMAN
AccessioniPrimary (citable) accession number: P14550
Secondary accession number(s): A8KAL8, D3DQ04, Q6IAZ4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 23, 2007
Last modified: March 28, 2018
This is version 187 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Direct protein sequencing, Reference proteome

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