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Protein

Aflatoxin B1 aldehyde reductase member 2

Gene

Akr7a2

Organism
Mus musculus (Mouse)
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. 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 (By similarity).By similarity1 Publication

Catalytic activityi

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

Enzyme regulationi

Inhibited by citrate, succinate and tartrate.1 Publication

Kineticsi

  1. KM=19.8 µM for succinic semialdehyde1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei80NADP1 Publication1
    Active sitei85Proton donor1
    Sitei113Lowers pKa of active site TyrBy similarity1
    Binding sitei149Substrate1
    Binding sitei205NADP1 Publication1
    Binding sitei258NADP1 Publication1
    Binding sitei268Substrate1
    Binding sitei271Substrate1
    Binding sitei367Substrate1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi179 – 180NADP1 Publication2
    Nucleotide bindingi234 – 244NADP1 PublicationAdd BLAST11
    Nucleotide bindingi326 – 334NADP1 Publication9

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Ligandi

    NADP

    Enzyme and pathway databases

    ReactomeiR-MMU-5423646. Aflatoxin activation and detoxification.
    SABIO-RKQ8CG76.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Aflatoxin B1 aldehyde reductase member 2 (EC:1.1.1.n11)
    Alternative name(s):
    Succinic semialdehyde reductase
    Short name:
    SSA reductase
    Gene namesi
    Name:Akr7a2By similarity
    Synonyms:AfarImported, Akr7a5Imported
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 4

    Organism-specific databases

    MGIiMGI:107796. Akr7a5.

    Subcellular locationi

    GO - Cellular componenti

    • extracellular exosome Source: MGI
    • Golgi apparatus Source: UniProtKB-SubCell
    • mitochondrion Source: MGI
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Golgi apparatus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000703761 – 367Aflatoxin B1 aldehyde reductase member 2Add BLAST367

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei40PhosphoserineCombined sources1
    Modified residuei48PhosphothreonineCombined sources1
    Modified residuei121PhosphoserineBy similarity1
    Modified residuei136N6-acetyllysineCombined sources1
    Modified residuei244N6-succinyllysineCombined sources1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiQ8CG76.
    MaxQBiQ8CG76.
    PaxDbiQ8CG76.
    PeptideAtlasiQ8CG76.
    PRIDEiQ8CG76.

    2D gel databases

    REPRODUCTION-2DPAGEQ8CG76.

    PTM databases

    iPTMnetiQ8CG76.
    PhosphoSitePlusiQ8CG76.
    SwissPalmiQ8CG76.

    Expressioni

    Tissue specificityi

    Expressed in liver, kidney, testis and brain with low levels in skeletal muscle, spleen, heart and lung.1 Publication

    Gene expression databases

    BgeeiENSMUSG00000028743.
    GenevisibleiQ8CG76. MM.

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Protein-protein interaction databases

    IntActiQ8CG76. 3 interactors.
    MINTiMINT-1869477.
    STRINGi10090.ENSMUSP00000073459.

    Structurei

    Secondary structure

    1367
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi47 – 51Combined sources5
    Turni56 – 58Combined sources3
    Helixi61 – 73Combined sources13
    Beta strandi78 – 80Combined sources3
    Helixi85 – 88Combined sources4
    Helixi89 – 95Combined sources7
    Beta strandi109 – 114Combined sources6
    Turni117 – 120Combined sources4
    Helixi124 – 137Combined sources14
    Beta strandi143 – 148Combined sources6
    Helixi157 – 169Combined sources13
    Beta strandi172 – 180Combined sources9
    Helixi183 – 196Combined sources14
    Beta strandi201 – 207Combined sources7
    Helixi214 – 216Combined sources3
    Helixi219 – 226Combined sources8
    Beta strandi229 – 233Combined sources5
    Helixi237 – 242Combined sources6
    Helixi247 – 250Combined sources4
    Turni251 – 253Combined sources3
    Beta strandi260 – 262Combined sources3
    Helixi265 – 272Combined sources8
    Helixi275 – 292Combined sources18
    Helixi293 – 295Combined sources3
    Helixi299 – 309Combined sources11
    Helixi315 – 317Combined sources3
    Beta strandi320 – 323Combined sources4
    Helixi328 – 337Combined sources10
    Helixi345 – 358Combined sources14
    Helixi359 – 361Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2C91X-ray2.30A/B/C/D/E/F/G/H/I/J30-367[»]
    ProteinModelPortaliQ8CG76.
    SMRiQ8CG76.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8CG76.

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiENOG410IDYD. Eukaryota.
    COG0667. LUCA.
    GeneTreeiENSGT00550000074567.
    HOGENOMiHOG000250286.
    HOVERGENiHBG050576.
    InParanoidiQ8CG76.
    KOiK15303.
    OMAiCTVKIAT.
    OrthoDBiEOG091G0BTK.
    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.

    Q8CG76-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MLRAASRAVG RAAVRSAQRS GTSVGRPLAM SRPPPPRAAS GAPLRPATVL
    60 70 80 90 100
    GTMEMGRRMD ASASAASVRA FLERGHSELD TAFMYCDGQS ENILGGLGLG
    110 120 130 140 150
    LGSGDCTVKI ATKANPWEGK SLKPDSIRSQ LETSLKRLQC PRVDLFYLHA
    160 170 180 190 200
    PDHSTPVEET LRACHQLHQE GKFVELGLSN YASWEVAEIC TLCKSNGWIL
    210 220 230 240 250
    PTVYQGMYNA TTRQVEAELL PCLRHFGLRF YAYNPLAGGL LTGKYKYEDK
    260 270 280 290 300
    DGKQPVGRFF GNNWAETYRN RFWKEHHFEA IALVEKALQT TYGTNAPRMT
    310 320 330 340 350
    SAALRWMYHH SQLQGTRGDA VILGMSSLEQ LEQNLAATEE GPLEPAVVEA
    360
    FDQAWNMVAH ECPNYFR
    Length:367
    Mass (Da):40,612
    Last modified:July 27, 2011 - v3
    Checksum:i1123BD7028D3FBDF
    GO

    Sequence cautioni

    The sequence AAH31857 differs from that shown. Reason: Erroneous initiation.Curated
    The sequence CAC81077 differs from that shown. Reason: Erroneous initiation.Curated
    The sequence CAC81078 differs from that shown. Reason: Erroneous initiation.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti5A → G in BAE25302 (PubMed:16141072).Curated1
    Sequence conflicti9V → G in BAE25302 (PubMed:16141072).Curated1
    Sequence conflicti12A → V in BAE25302 (PubMed:16141072).Curated1
    Sequence conflicti17A → G in BAE25302 (PubMed:16141072).Curated1
    Sequence conflicti127I → V in AAH31857 (PubMed:15489334).Curated1
    Sequence conflicti127I → V in CAC81078 (PubMed:12879023).Curated1
    Sequence conflicti162R → C in AAO38437 (PubMed:12123834).Curated1
    Sequence conflicti354A → G in AAH31857 (PubMed:15489334).Curated1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AK143203 mRNA. Translation: BAE25302.1.
    AL807811 Genomic DNA. Translation: CAM18543.1.
    BC031857 mRNA. Translation: AAH31857.1. Different initiation.
    AJ271800 mRNA. Translation: CAC81077.1. Different initiation.
    AJ271801 mRNA. Translation: CAC81078.1. Different initiation.
    AF525358 mRNA. Translation: AAO38437.2.
    BK000393 mRNA. Translation: DAA00087.1.
    CCDSiCCDS18844.1.
    RefSeqiNP_079613.3. NM_025337.3.
    UniGeneiMm.482154.

    Genome annotation databases

    EnsembliENSMUST00000073787; ENSMUSP00000073459; ENSMUSG00000028743.
    GeneIDi110198.
    KEGGimmu:110198.
    UCSCiuc008vmc.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AK143203 mRNA. Translation: BAE25302.1.
    AL807811 Genomic DNA. Translation: CAM18543.1.
    BC031857 mRNA. Translation: AAH31857.1. Different initiation.
    AJ271800 mRNA. Translation: CAC81077.1. Different initiation.
    AJ271801 mRNA. Translation: CAC81078.1. Different initiation.
    AF525358 mRNA. Translation: AAO38437.2.
    BK000393 mRNA. Translation: DAA00087.1.
    CCDSiCCDS18844.1.
    RefSeqiNP_079613.3. NM_025337.3.
    UniGeneiMm.482154.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2C91X-ray2.30A/B/C/D/E/F/G/H/I/J30-367[»]
    ProteinModelPortaliQ8CG76.
    SMRiQ8CG76.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiQ8CG76. 3 interactors.
    MINTiMINT-1869477.
    STRINGi10090.ENSMUSP00000073459.

    PTM databases

    iPTMnetiQ8CG76.
    PhosphoSitePlusiQ8CG76.
    SwissPalmiQ8CG76.

    2D gel databases

    REPRODUCTION-2DPAGEQ8CG76.

    Proteomic databases

    EPDiQ8CG76.
    MaxQBiQ8CG76.
    PaxDbiQ8CG76.
    PeptideAtlasiQ8CG76.
    PRIDEiQ8CG76.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000073787; ENSMUSP00000073459; ENSMUSG00000028743.
    GeneIDi110198.
    KEGGimmu:110198.
    UCSCiuc008vmc.2. mouse.

    Organism-specific databases

    CTDi110198.
    MGIiMGI:107796. Akr7a5.

    Phylogenomic databases

    eggNOGiENOG410IDYD. Eukaryota.
    COG0667. LUCA.
    GeneTreeiENSGT00550000074567.
    HOGENOMiHOG000250286.
    HOVERGENiHBG050576.
    InParanoidiQ8CG76.
    KOiK15303.
    OMAiCTVKIAT.
    OrthoDBiEOG091G0BTK.
    TreeFamiTF329173.

    Enzyme and pathway databases

    ReactomeiR-MMU-5423646. Aflatoxin activation and detoxification.
    SABIO-RKQ8CG76.

    Miscellaneous databases

    EvolutionaryTraceiQ8CG76.
    PROiQ8CG76.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSMUSG00000028743.
    GenevisibleiQ8CG76. MM.

    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_MOUSE
    AccessioniPrimary (citable) accession number: Q8CG76
    Secondary accession number(s): A2AMV3
    , Q3UPU2, Q8CG77, Q8JZQ8, Q9D157
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 15, 2003
    Last sequence update: July 27, 2011
    Last modified: November 30, 2016
    This is version 128 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. 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.