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Protein

Aflatoxin B1 aldehyde reductase member 2

Gene

AKR7A2

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

Functioni

Catalyzes the NADPH-dependent reduction of succinic semialdehyde to gamma-hydroxybutyrate. May have an important role in producing the neuromodulator gamma-hydroxybutyrate (GHB). Has broad substrate specificity. Has NADPH-dependent aldehyde reductase activity towards 2-carboxybenzaldehyde, 2-nitrobenzaldehyde and pyridine-2-aldehyde (in vitro). Can reduce 1,2-naphthoquinone and 9,10-phenanthrenequinone (in vitro). Can reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. May be involved in protection of liver against the toxic and carcinogenic effects of AFB1, a potent hepatocarcinogen.2 Publications

Caution

It is uncertain whether Met-1 or Met-30 is the initiator.Curated

Catalytic activityi

4-hydroxybutanoate + NADP+ = succinate semialdehyde + NADPH.1 Publication

Kineticsi

  1. KM=20 µM for succinic semialdehyde1 Publication
  2. KM=17 µM for 2-carboxybenzaldehyde1 Publication
  3. KM=8 µM for 9,10-phenanthrenequinone1 Publication
  4. KM=102 µM for 1,2-naphthoquinone1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei72NADP1 Publication1
    Active sitei77Proton donorBy similarity1
    Sitei105Lowers pKa of active site TyrBy similarity1
    Binding sitei141SubstrateBy similarity1
    Binding sitei197NADP1 Publication1
    Binding sitei250NADP1 Publication1
    Binding sitei260SubstrateBy similarity1
    Binding sitei263SubstrateBy similarity1
    Binding sitei359SubstrateBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi171 – 172NADP1 Publication2
    Nucleotide bindingi226 – 236NADP1 PublicationAdd BLAST11
    Nucleotide bindingi318 – 326NADP1 Publication9

    GO - Molecular functioni

    • alditol:NADP+ 1-oxidoreductase activity Source: ProtInc
    • aldo-keto reductase (NADP) activity Source: Reactome
    • electron transfer activity Source: UniProtKB
    • phenanthrene-9,10-epoxide hydrolase activity Source: UniProtKB

    GO - Biological processi

    • carbohydrate metabolic process Source: ProtInc
    • cellular aldehyde metabolic process Source: ProtInc
    • daunorubicin metabolic process Source: UniProtKB
    • doxorubicin metabolic process Source: UniProtKB
    • xenobiotic metabolic process Source: Reactome

    Keywordsi

    Molecular functionOxidoreductase
    LigandNADP

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000053371-MONOMER
    ReactomeiR-HSA-5423646 Aflatoxin activation and detoxification
    SABIO-RKiO43488

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Aflatoxin B1 aldehyde reductase member 2 (EC:1.1.1.n11)
    Alternative name(s):
    AFB1 aldehyde reductase 1
    Short name:
    AFB1-AR 1
    Aldoketoreductase 7
    Succinic semialdehyde reductase
    Short name:
    SSA reductase
    Gene namesi
    Name:AKR7A2
    Synonyms:AFAR, AFAR1, AKR7
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 1

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000053371.12
    HGNCiHGNC:389 AKR7A2
    MIMi603418 gene
    neXtProtiNX_O43488

    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

    Keywords - Cellular componenti

    Cytoplasm, Golgi apparatus

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi8574
    OpenTargetsiENSG00000053371
    PharmGKBiPA24682

    Polymorphism and mutation databases

    BioMutaiAKR7A2

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000703751 – 359Aflatoxin B1 aldehyde reductase member 2Add BLAST359

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei40PhosphoserineBy similarity1
    Modified residuei128N6-acetyllysineBy similarity1
    Modified residuei236N6-succinyllysineBy similarity1
    Modified residuei255PhosphoserineCombined sources1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiO43488
    PaxDbiO43488
    PeptideAtlasiO43488
    PRIDEiO43488
    ProteomicsDBi48966

    2D gel databases

    REPRODUCTION-2DPAGEiIPI00305978
    O43488
    UCD-2DPAGEiO43488

    PTM databases

    iPTMnetiO43488
    PhosphoSitePlusiO43488
    SwissPalmiO43488

    Miscellaneous databases

    PMAP-CutDBiO43488

    Expressioni

    Tissue specificityi

    Detected in brain, liver, small intestine and testis, and at lower levels in heart, prostate, skeletal muscle and spleen. Detected in kidney proximal and distal tubules, endothelial cells lining the Bowman's capsules and some cysts. Detected at low levels in lung and pancreas (at protein level). Widely expressed.2 Publications

    Gene expression databases

    BgeeiENSG00000053371
    CleanExiHS_AKR7A2
    ExpressionAtlasiO43488 baseline and differential
    GenevisibleiO43488 HS

    Organism-specific databases

    HPAiCAB032587
    CAB032841
    HPA064638

    Interactioni

    Subunit structurei

    Homodimer.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    AKR7A3O951543EBI-748855,EBI-748869

    Protein-protein interaction databases

    BioGridi114142, 41 interactors
    IntActiO43488, 32 interactors
    STRINGi9606.ENSP00000235835

    Structurei

    Secondary structure

    1359
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi39 – 43Combined sources5
    Turni48 – 50Combined sources3
    Helixi53 – 65Combined sources13
    Beta strandi70 – 72Combined sources3
    Helixi77 – 80Combined sources4
    Helixi81 – 87Combined sources7
    Beta strandi101 – 106Combined sources6
    Helixi116 – 130Combined sources15
    Beta strandi135 – 140Combined sources6
    Helixi149 – 161Combined sources13
    Beta strandi164 – 172Combined sources9
    Helixi175 – 188Combined sources14
    Beta strandi193 – 199Combined sources7
    Helixi206 – 208Combined sources3
    Helixi211 – 218Combined sources8
    Beta strandi221 – 225Combined sources5
    Helixi229 – 234Combined sources6
    Helixi239 – 242Combined sources4
    Turni243 – 245Combined sources3
    Beta strandi252 – 254Combined sources3
    Helixi257 – 264Combined sources8
    Helixi267 – 284Combined sources18
    Helixi285 – 287Combined sources3
    Helixi291 – 302Combined sources12
    Helixi307 – 309Combined sources3
    Beta strandi312 – 315Combined sources4
    Helixi320 – 330Combined sources11
    Helixi337 – 350Combined sources14
    Helixi351 – 353Combined sources3

    3D structure databases

    ProteinModelPortaliO43488
    SMRiO43488
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO43488

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiENOG410IDYD Eukaryota
    COG0667 LUCA
    GeneTreeiENSGT00550000074567
    HOGENOMiHOG000250286
    HOVERGENiHBG050576
    InParanoidiO43488
    KOiK15303
    OMAiHHFEAIA
    OrthoDBiEOG091G0BTK
    PhylomeDBiO43488
    TreeFamiTF329173

    Family and domain databases

    CDDicd06660 Aldo_ket_red, 1 hit
    Gene3Di3.20.20.100, 1 hit
    InterProiView protein in InterPro
    IPR023210 NADP_OxRdtase_dom
    IPR036812 NADP_OxRdtase_dom_sf
    PfamiView protein in Pfam
    PF00248 Aldo_ket_red, 1 hit
    SUPFAMiSSF51430 SSF51430, 1 hit

    Sequencei

    Sequence statusi: Complete.

    O43488-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MLSAASRVVS RAAVHCALRS PPPEARALAM SRPPPPRVAS VLGTMEMGRR
    60 70 80 90 100
    MDAPASAAAV RAFLERGHTE LDTAFMYSDG QSETILGGLG LGLGGGDCRV
    110 120 130 140 150
    KIATKANPWD GKSLKPDSVR SQLETSLKRL QCPQVDLFYL HAPDHGTPVE
    160 170 180 190 200
    ETLHACQRLH QEGKFVELGL SNYASWEVAE ICTLCKSNGW ILPTVYQGMY
    210 220 230 240 250
    NATTRQVETE LFPCLRHFGL RFYAYNPLAG GLLTGKYKYE DKDGKQPVGR
    260 270 280 290 300
    FFGNSWAETY RNRFWKEHHF EAIALVEKAL QAAYGASAPS VTSAALRWMY
    310 320 330 340 350
    HHSQLQGAHG DAVILGMSSL EQLEQNLAAT EEGPLEPAVV DAFNQAWHLV

    AHECPNYFR
    Length:359
    Mass (Da):39,589
    Last modified:November 14, 2003 - v3
    Checksum:i2C9775FE4B977D2A
    GO

    Sequence cautioni

    The sequence AAC52104 differs from that shown. Reason: Erroneous initiation.Curated
    The sequence AAH04111 differs from that shown. Reason: Erroneous initiation.Curated
    The sequence AAH10852 differs from that shown. Reason: Erroneous initiation.Curated
    The sequence AAH11586 differs from that shown. Reason: Erroneous initiation.Curated
    The sequence AAH12171 differs from that shown. Reason: Erroneous initiation.Curated
    The sequence AAH13996 differs from that shown. Reason: Erroneous initiation.Curated
    The sequence AAP36011 differs from that shown. Reason: Erroneous initiation.Curated
    The sequence CAA76347 differs from that shown. Reason: Erroneous initiation.Curated
    The sequence CAB72321 differs from that shown. Reason: Erroneous initiation.Curated

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_048209135V → M. Corresponds to variant dbSNP:rs6670759Ensembl.1
    Natural variantiVAR_017413142A → T2 PublicationsCorresponds to variant dbSNP:rs1043657Ensembl.1
    Natural variantiVAR_017414157Q → H1 PublicationCorresponds to variant dbSNP:rs859208Ensembl.1
    Natural variantiVAR_060222180E → K. Corresponds to variant dbSNP:rs859210Ensembl.1
    Natural variantiVAR_048210198G → S. Corresponds to variant dbSNP:rs2231200Ensembl.1
    Natural variantiVAR_017415214C → Y. Corresponds to variant dbSNP:rs2235794Ensembl.1
    Natural variantiVAR_048211255S → N. Corresponds to variant dbSNP:rs2231203Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL035413 Genomic DNA Translation: CAB72321.1 Different initiation.
    BC004111 mRNA Translation: AAH04111.3 Different initiation.
    BC007352 mRNA Translation: AAH07352.2
    BC010852 mRNA Translation: AAH10852.1 Different initiation.
    BC011586 mRNA Translation: AAH11586.1 Different initiation.
    BC012171 mRNA Translation: AAH12171.1 Different initiation.
    BC013996 mRNA Translation: AAH13996.1 Different initiation.
    AF026947 mRNA Translation: AAC52104.1 Different initiation.
    Y16675 mRNA Translation: CAA76347.1 Different initiation.
    BT007347 mRNA Translation: AAP36011.1 Different initiation.
    BK000395 mRNA Translation: DAA00088.1
    CCDSiCCDS194.1
    RefSeqiNP_003680.2, NM_003689.3
    UniGeneiHs.571886

    Genome annotation databases

    EnsembliENST00000235835; ENSP00000235835; ENSG00000053371
    GeneIDi8574
    KEGGihsa:8574

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiARK72_HUMAN
    AccessioniPrimary (citable) accession number: O43488
    Secondary accession number(s): O75749, Q5TG63
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: November 14, 2003
    Last modified: July 18, 2018
    This is version 177 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. 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

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