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Protein

Aflatoxin B1 aldehyde reductase member 2

Gene

AKR7A2

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 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

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

    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
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Ligandi

    NADP

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000053371-MONOMER.
    ReactomeiR-HSA-5423646. Aflatoxin activation and detoxification.
    SABIO-RKO43488.

    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

    HGNCiHGNC:389. AKR7A2.

    Subcellular locationi

    • Golgi apparatus By similarity
    • Cytoplasm 1 Publication

    GO - Cellular componenti

    • cytosol Source: Reactome
    • extracellular exosome Source: UniProtKB
    • Golgi apparatus Source: UniProtKB-SubCell
    • mitochondrion Source: Ensembl
    Complete GO annotation...

    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 residuei10PhosphoserineBy similarity1
    Modified residuei113PhosphoserineBy similarity1
    Modified residuei128N6-acetyllysineBy similarity1
    Modified residuei236N6-succinyllysineBy similarity1
    Modified residuei255PhosphoserineCombined sources1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiO43488.
    PaxDbiO43488.
    PeptideAtlasiO43488.
    PRIDEiO43488.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00305978.
    O43488.
    UCD-2DPAGEO43488.

    PTM databases

    iPTMnetiO43488.
    PhosphoSitePlusiO43488.
    SwissPalmiO43488.

    Miscellaneous databases

    PMAP-CutDBO43488.

    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.

    Interactioni

    Subunit structurei

    Homodimer.2 Publications

    Binary interactionsi

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

    Protein-protein interaction databases

    BioGridi114142. 34 interactors.
    IntActiO43488. 30 interactors.
    MINTiMINT-5002225.
    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

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2BP1X-ray2.40A/B/C/D30-359[»]
    ProteinModelPortaliO43488.
    SMRiO43488.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO43488.

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

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

    Family and domain databases

    CDDicd06660. Aldo_ket_red. 1 hit.
    Gene3Di3.20.20.100. 1 hit.
    InterProiIPR001395. Aldo/ket_red/Kv-b.
    IPR023210. NADP_OxRdtase_dom.
    [Graphical view]
    PANTHERiPTHR11732. PTHR11732. 2 hits.
    PfamiPF00248. Aldo_ket_red. 1 hit.
    [Graphical view]
    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 rs6670759dbSNPEnsembl.1
    Natural variantiVAR_017413142A → T.2 PublicationsCorresponds to variant rs1043657dbSNPEnsembl.1
    Natural variantiVAR_017414157Q → H.1 PublicationCorresponds to variant rs859208dbSNPEnsembl.1
    Natural variantiVAR_060222180E → K.Corresponds to variant rs859210dbSNPEnsembl.1
    Natural variantiVAR_048210198G → S.Corresponds to variant rs2231200dbSNPEnsembl.1
    Natural variantiVAR_017415214C → Y.Corresponds to variant rs2235794dbSNPEnsembl.1
    Natural variantiVAR_048211255S → N.Corresponds to variant rs2231203dbSNPEnsembl.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

    Cross-referencesi

    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.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2BP1X-ray2.40A/B/C/D30-359[»]
    ProteinModelPortaliO43488.
    SMRiO43488.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi114142. 34 interactors.
    IntActiO43488. 30 interactors.
    MINTiMINT-5002225.
    STRINGi9606.ENSP00000235835.

    PTM databases

    iPTMnetiO43488.
    PhosphoSitePlusiO43488.
    SwissPalmiO43488.

    Polymorphism and mutation databases

    BioMutaiAKR7A2.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00305978.
    O43488.
    UCD-2DPAGEO43488.

    Proteomic databases

    EPDiO43488.
    PaxDbiO43488.
    PeptideAtlasiO43488.
    PRIDEiO43488.

    Protocols and materials databases

    DNASUi8574.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000235835; ENSP00000235835; ENSG00000053371.
    GeneIDi8574.
    KEGGihsa:8574.

    Organism-specific databases

    CTDi8574.
    DisGeNETi8574.
    GeneCardsiAKR7A2.
    H-InvDBHIX0000198.
    HGNCiHGNC:389. AKR7A2.
    HPAiCAB032587.
    CAB032841.
    MIMi603418. gene.
    neXtProtiNX_O43488.
    OpenTargetsiENSG00000053371.
    PharmGKBiPA24682.
    GenAtlasiSearch...

    Phylogenomic databases

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

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000053371-MONOMER.
    ReactomeiR-HSA-5423646. Aflatoxin activation and detoxification.
    SABIO-RKO43488.

    Miscellaneous databases

    EvolutionaryTraceiO43488.
    GeneWikiiAKR7A2.
    GenomeRNAii8574.
    PMAP-CutDBO43488.
    PROiO43488.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000053371.
    CleanExiHS_AKR7A2.
    ExpressionAtlasiO43488. baseline and differential.
    GenevisibleiO43488. HS.

    Family and domain databases

    CDDicd06660. Aldo_ket_red. 1 hit.
    Gene3Di3.20.20.100. 1 hit.
    InterProiIPR001395. Aldo/ket_red/Kv-b.
    IPR023210. NADP_OxRdtase_dom.
    [Graphical view]
    PANTHERiPTHR11732. PTHR11732. 2 hits.
    PfamiPF00248. Aldo_ket_red. 1 hit.
    [Graphical view]
    SUPFAMiSSF51430. SSF51430. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiARK72_HUMAN
    AccessioniPrimary (citable) accession number: O43488
    Secondary accession number(s): O75749, Q5TG63
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: November 14, 2003
    Last modified: November 30, 2016
    This is version 164 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

    Caution

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

    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.