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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

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

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
LigandNADP

Enzyme and pathway databases

BRENDAi1.1.1.2 2681
ReactomeiR-HSA-156590 Glutathione conjugation
R-HSA-5661270 Formation of xylulose-5-phosphate
SABIO-RKiP14550

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
ProteomicsDBi53058

2D gel databases

REPRODUCTION-2DPAGEiIPI00220271
P14550
SWISS-2DPAGEiP14550
UCD-2DPAGEiP14550

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 Expressed in 224 organ(s), highest expression level in nephron tubule
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

3D structure databases

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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5T621Q5T621_HUMAN
Alcohol dehydrogenase [NADP(+)]
AKR1A1
147Annotation score:
V9GYP9V9GYP9_HUMAN
Alcohol dehydrogenase [NADP(+)]
AKR1A1
140Annotation score:
V9GYG2V9GYG2_HUMAN
Alcohol dehydrogenase [NADP(+)]
AKR1A1
119Annotation score:

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

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
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

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...

Protein-protein interaction databases

BioGridi115610, 29 interactors
IntActiP14550, 5 interactors
STRINGi9606.ENSP00000312606

Chemistry databases

BindingDBiP14550
ChEMBLiCHEMBL2246
DrugBankiDB03461 2'-Monophosphoadenosine 5'-Diphosphoribose
DB00997 Doxorubicin
DB00898 Ethanol
DB00157 NADH
DB02383 Tolrestat

PTM databases

iPTMnetiP14550
PhosphoSitePlusiP14550
SwissPalmiP14550

Polymorphism and mutation databases

BioMutaiAKR1A1
DMDMi113600

2D gel databases

REPRODUCTION-2DPAGEiIPI00220271
P14550
SWISS-2DPAGEiP14550
UCD-2DPAGEiP14550

Proteomic databases

EPDiP14550
PaxDbiP14550
PeptideAtlasiP14550
PRIDEiP14550
ProteomicsDBi53058

Protocols and materials databases

DNASUi10327
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi10327
DisGeNETi10327
EuPathDBiHostDB:ENSG00000117448.13
GeneCardsiAKR1A1
HGNCiHGNC:380 AKR1A1
HPAiCAB006246
HPA017919
HPA019649
HPA027734
MIMi103830 gene
neXtProtiNX_P14550
OpenTargetsiENSG00000117448
PharmGKBiPA24674
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BRENDAi1.1.1.2 2681
ReactomeiR-HSA-156590 Glutathione conjugation
R-HSA-5661270 Formation of xylulose-5-phosphate
SABIO-RKiP14550

Miscellaneous databases

ChiTaRSiAKR1A1 human
EvolutionaryTraceiP14550
GeneWikiiAldo-keto_reductase_family_1,_member_A1
GenomeRNAii10327
PROiPR:P14550
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000117448 Expressed in 224 organ(s), highest expression level in nephron tubule
CleanExiHS_AKR1A1
ExpressionAtlasiP14550 baseline and differential
GenevisibleiP14550 HS

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
ProtoNetiSearch...

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: November 7, 2018
This is version 191 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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