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Protein

Alcohol dehydrogenase [NADP(+)]

Gene

AKR1A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 carrier activity Source: UniProtKB
  • L-glucuronate reductase activity Source: Reactome

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

NADP

Enzyme and pathway databases

BioCyciZFISH:HS04133-MONOMER.
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

HGNCiHGNC:380. AKR1A1.

Subcellular locationi

GO - Cellular componenti

  • apical plasma membrane Source: Ensembl
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extracellular space Source: UniProtKB
Complete GO annotation...

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.
DrugBankiDB00997. Doxorubicin.
DB00898. Ethanol.

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. 28 interactors.
IntActiP14550. 4 interactors.
MINTiMINT-5001699.
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.
OMAiWDALEKI.
OrthoDBiEOG091G0D69.
PhylomeDBiP14550.
TreeFamiTF106492.

Family and domain databases

CDDicd06660. Aldo_ket_red. 1 hit.
Gene3Di3.20.20.100. 1 hit.
InterProiIPR001395. Aldo/ket_red/Kv-b.
IPR018170. Aldo/ket_reductase_CS.
IPR020471. Aldo/keto_reductase.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]
PANTHERiPTHR11732. PTHR11732. 2 hits.
PfamiPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
PIRSFiPIRSF000097. AKR. 1 hit.
PRINTSiPR00069. ALDKETRDTASE.
SUPFAMiSSF51430. SSF51430. 1 hit.
PROSITEiPS00798. ALDOKETO_REDUCTASE_1. 1 hit.
PS00062. ALDOKETO_REDUCTASE_2. 1 hit.
PS00063. ALDOKETO_REDUCTASE_3. 1 hit.
[Graphical view]

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 rs2229540dbSNPEnsembl.1
Natural variantiVAR_05890955E → D Reduced activity towards daunorubicin. 1 PublicationCorresponds to variant rs6690497dbSNPEnsembl.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. Translation: CAI22459.1.
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

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. Translation: CAI22459.1.
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. 28 interactors.
IntActiP14550. 4 interactors.
MINTiMINT-5001699.
STRINGi9606.ENSP00000312606.

Chemistry databases

BindingDBiP14550.
ChEMBLiCHEMBL2246.
DrugBankiDB00997. Doxorubicin.
DB00898. Ethanol.

PTM databases

iPTMnetiP14550.
PhosphoSitePlusiP14550.
SwissPalmiP14550.

Polymorphism and mutation databases

BioMutaiAKR1A1.
DMDMi113600.

2D gel databases

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

Proteomic databases

EPDiP14550.
PaxDbiP14550.
PeptideAtlasiP14550.
PRIDEiP14550.

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.
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.
OMAiWDALEKI.
OrthoDBiEOG091G0D69.
PhylomeDBiP14550.
TreeFamiTF106492.

Enzyme and pathway databases

BioCyciZFISH:HS04133-MONOMER.
BRENDAi1.1.1.2. 2681.
ReactomeiR-HSA-156590. Glutathione conjugation.
R-HSA-5661270. Catabolism of glucuronate to xylulose-5-phosphate.
SABIO-RKP14550.

Miscellaneous databases

ChiTaRSiAKR1A1. human.
EvolutionaryTraceiP14550.
GeneWikiiAldo-keto_reductase_family_1,_member_A1.
GenomeRNAii10327.
PROiP14550.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000117448.
CleanExiHS_AKR1A1.
ExpressionAtlasiP14550. baseline and differential.
GenevisibleiP14550. HS.

Family and domain databases

CDDicd06660. Aldo_ket_red. 1 hit.
Gene3Di3.20.20.100. 1 hit.
InterProiIPR001395. Aldo/ket_red/Kv-b.
IPR018170. Aldo/ket_reductase_CS.
IPR020471. Aldo/keto_reductase.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]
PANTHERiPTHR11732. PTHR11732. 2 hits.
PfamiPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
PIRSFiPIRSF000097. AKR. 1 hit.
PRINTSiPR00069. ALDKETRDTASE.
SUPFAMiSSF51430. SSF51430. 1 hit.
PROSITEiPS00798. ALDOKETO_REDUCTASE_1. 1 hit.
PS00062. ALDOKETO_REDUCTASE_2. 1 hit.
PS00063. ALDOKETO_REDUCTASE_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAK1A1_HUMAN
AccessioniPrimary (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: November 2, 2016
This is version 177 of the entry and version 3 of the sequence. [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. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.