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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 similarity

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)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei80 – 801NADP1 Publication
    Active sitei85 – 851Proton donor
    Sitei113 – 1131Lowers pKa of active site TyrBy similarity
    Binding sitei149 – 1491Substrate
    Binding sitei205 – 2051NADP1 Publication
    Binding sitei258 – 2581NADP1 Publication
    Binding sitei268 – 2681Substrate
    Binding sitei271 – 2711Substrate
    Binding sitei367 – 3671Substrate

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi179 – 1802NADP1 Publication
    Nucleotide bindingi234 – 24411NADP1 PublicationAdd
    BLAST
    Nucleotide bindingi326 – 3349NADP1 Publication

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Ligandi

    NADP

    Enzyme and pathway databases

    ReactomeiREACT_288150. 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
    ProteomesiUP000000589 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)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 367367Aflatoxin B1 aldehyde reductase member 2PRO_0000070376Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei136 – 1361N6-acetyllysine1 Publication
    Modified residuei244 – 2441N6-succinyllysine1 Publication

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiQ8CG76.
    PaxDbiQ8CG76.
    PRIDEiQ8CG76.

    2D gel databases

    REPRODUCTION-2DPAGEQ8CG76.

    PTM databases

    PhosphoSiteiQ8CG76.

    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

    BgeeiQ8CG76.
    GenevisibleiQ8CG76. MM.

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Protein-protein interaction databases

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

    Structurei

    Secondary structure

    1
    367
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi47 – 515Combined sources
    Turni56 – 583Combined sources
    Helixi61 – 7313Combined sources
    Beta strandi78 – 803Combined sources
    Helixi85 – 884Combined sources
    Helixi89 – 957Combined sources
    Beta strandi109 – 1146Combined sources
    Turni117 – 1204Combined sources
    Helixi124 – 13714Combined sources
    Beta strandi143 – 1486Combined sources
    Helixi157 – 16913Combined sources
    Beta strandi172 – 1809Combined sources
    Helixi183 – 19614Combined sources
    Beta strandi201 – 2077Combined sources
    Helixi214 – 2163Combined sources
    Helixi219 – 2268Combined sources
    Beta strandi229 – 2335Combined sources
    Helixi237 – 2426Combined sources
    Helixi247 – 2504Combined sources
    Turni251 – 2533Combined sources
    Beta strandi260 – 2623Combined sources
    Helixi265 – 2728Combined sources
    Helixi275 – 29218Combined sources
    Helixi293 – 2953Combined sources
    Helixi299 – 30911Combined sources
    Helixi315 – 3173Combined sources
    Beta strandi320 – 3234Combined sources
    Helixi328 – 33710Combined sources
    Helixi345 – 35814Combined sources
    Helixi359 – 3613Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2C91X-ray2.30A/B/C/D/E/F/G/H/I/J30-367[»]
    ProteinModelPortaliQ8CG76.
    SMRiQ8CG76. Positions 43-367.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8CG76.

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG0667.
    GeneTreeiENSGT00550000074567.
    HOGENOMiHOG000250286.
    HOVERGENiHBG050576.
    InParanoidiQ8CG76.
    KOiK15303.
    OMAiCTVKIAT.
    OrthoDBiEOG77127F.
    TreeFamiTF329173.

    Family and domain databases

    Gene3Di3.20.20.100. 1 hit.
    InterProiIPR001395. Aldo/ket_red.
    IPR023210. NADP_OxRdtase_dom.
    [Graphical view]
    PANTHERiPTHR11732. PTHR11732. 1 hit.
    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 AAH31857.1 differs from that shown. Reason: Erroneous initiation. Curated
    The sequence CAC81077.1 differs from that shown. Reason: Erroneous initiation. Curated
    The sequence CAC81078.1 differs from that shown. Reason: Erroneous initiation. Curated

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti5 – 51A → G in BAE25302 (PubMed:16141072).Curated
    Sequence conflicti9 – 91V → G in BAE25302 (PubMed:16141072).Curated
    Sequence conflicti12 – 121A → V in BAE25302 (PubMed:16141072).Curated
    Sequence conflicti17 – 171A → G in BAE25302 (PubMed:16141072).Curated
    Sequence conflicti127 – 1271I → V in AAH31857 (PubMed:15489334).Curated
    Sequence conflicti127 – 1271I → V in CAC81078 (PubMed:12879023).Curated
    Sequence conflicti162 – 1621R → C in AAO38437 (PubMed:12123834).Curated
    Sequence conflicti354 – 3541A → G in AAH31857 (PubMed:15489334).Curated

    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
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2C91X-ray2.30A/B/C/D/E/F/G/H/I/J30-367[»]
    ProteinModelPortaliQ8CG76.
    SMRiQ8CG76. Positions 43-367.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

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

    PTM databases

    PhosphoSiteiQ8CG76.

    2D gel databases

    REPRODUCTION-2DPAGEQ8CG76.

    Proteomic databases

    MaxQBiQ8CG76.
    PaxDbiQ8CG76.
    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

    eggNOGiCOG0667.
    GeneTreeiENSGT00550000074567.
    HOGENOMiHOG000250286.
    HOVERGENiHBG050576.
    InParanoidiQ8CG76.
    KOiK15303.
    OMAiCTVKIAT.
    OrthoDBiEOG77127F.
    TreeFamiTF329173.

    Enzyme and pathway databases

    ReactomeiREACT_288150. Aflatoxin activation and detoxification.
    SABIO-RKQ8CG76.

    Miscellaneous databases

    EvolutionaryTraceiQ8CG76.
    NextBioi363519.
    PROiQ8CG76.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ8CG76.
    GenevisibleiQ8CG76. MM.

    Family and domain databases

    Gene3Di3.20.20.100. 1 hit.
    InterProiIPR001395. Aldo/ket_red.
    IPR023210. NADP_OxRdtase_dom.
    [Graphical view]
    PANTHERiPTHR11732. PTHR11732. 1 hit.
    PfamiPF00248. Aldo_ket_red. 1 hit.
    [Graphical view]
    SUPFAMiSSF51430. SSF51430. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Eye.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-367.
      Strain: FVB/N.
      Tissue: LiverImported.
    4. "Aflatoxin B1 aldehyde reductase (AFAR) genes cluster at 1p35-1p36.1 in a region frequently altered in human tumour cells."
      Praml C., Savelyeva L., Schwab M.
      Oncogene 22:4765-4773(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 25-367.
      Strain: BALB/cImported.
    5. "Characterisation of a novel mouse liver aldo-keto reductase AKR7A5."
      Hinshelwood A., McGarvie G., Ellis E.
      FEBS Lett. 523:213-218(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 30-367, TISSUE SPECIFICITY.
      Strain: CD-1.
      Tissue: Liver.
    6. Ellis E.M., Hinshelwood A., McGarvie G.
      Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION TO 127 AND 162.
    7. "Novel homodimeric and heterodimeric rat gamma-hydroxybutyrate synthases that associate with the Golgi apparatus define a distinct subclass of aldo-keto reductase 7 family proteins."
      Kelly V.P., Sherratt P.J., Crouch D.H., Hayes J.D.
      Biochem. J. 366:847-861(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: GENE STRUCTURE.
    8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    9. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
      Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
      Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-244, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    10. "Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways."
      Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.
      Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-136, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    11. "Crystal structure of mouse succinic semialdehyde reductase AKR7A5: structural basis for substrate specificity."
      Zhu X., Lapthorn A.J., Ellis E.M.
      Biochemistry 45:1562-1570(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 30-367 IN COMPLEX WITH NADP AND THE INHIBITOR TARTRATE, ENZYME REGULATION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, SUBUNIT.

    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: June 24, 2015
    This is version 115 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

    External Data

    Dasty 3

    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 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.