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Protein

Aflatoxin B1 aldehyde reductase member 2

Gene

Akr7a2

Organism
Rattus norvegicus (Rat)
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. Acts as a 2-carboxybenzaldehyde reductase.1 Publication

Miscellaneous

With 4-nitrobenzaldehyde as substrate, it exhibits a substantially greater specific activity with NADPH than with NADH. Conversely, it has a 1.8-fold higher activity towards succinic semialdehyde with NADH than with NADPH.

Catalytic activityi

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

Kineticsi

Has a low KM for succinic semialdehyde.

      Sites

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Binding sitei80NADPBy similarity1
      Active sitei85Proton donorBy similarity1
      Sitei113Lowers pKa of active site TyrBy similarity1
      Binding sitei149SubstrateBy similarity1
      Binding sitei205NADPBy similarity1
      Binding sitei258NADPBy similarity1
      Binding sitei268SubstrateBy similarity1
      Binding sitei271SubstrateBy similarity1
      Binding sitei367SubstrateBy similarity1

      Regions

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Nucleotide bindingi179 – 180NADPBy similarity2
      Nucleotide bindingi234 – 244NADPBy similarityAdd BLAST11
      Nucleotide bindingi326 – 334NADPBy similarity9

      GO - Molecular functioni

      • alditol:NADP+ 1-oxidoreductase activity Source: RGD
      • aldo-keto reductase (NADP) activity Source: RGD

      Keywordsi

      Molecular functionOxidoreductase
      LigandNADP

      Enzyme and pathway databases

      SABIO-RKiQ8CG45.

      Names & Taxonomyi

      Protein namesi
      Recommended name:
      Aflatoxin B1 aldehyde reductase member 2 (EC:1.1.1.n11)
      Short name:
      rAFAR2
      Alternative name(s):
      Succinic semialdehyde reductase
      Short name:
      SSA reductase
      Gene namesi
      Name:Akr7a2
      Synonyms:Afar2, Aiar
      OrganismiRattus norvegicus (Rat)
      Taxonomic identifieri10116 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
      Proteomesi
      • UP000002494 Componenti: Unplaced

      Organism-specific databases

      RGDi620311. Akr7a2.

      Subcellular locationi

      • Golgi apparatusGolgi stack 1 Publication
      • Cytoplasm 1 Publication

      • Note: Its association with the Golgi stack may facilitate secretion of GHB.

      GO - Cellular componenti

      • Golgi apparatus Source: RGD
      • Golgi stack Source: UniProtKB-SubCell

      Keywords - Cellular componenti

      Cytoplasm, Golgi apparatus

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      ChainiPRO_00000703771 – 367Aflatoxin B1 aldehyde reductase member 2Add BLAST367

      Amino acid modifications

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Modified residuei10PhosphoserineBy similarity1
      Modified residuei40PhosphoserineBy similarity1
      Modified residuei48PhosphothreonineBy similarity1
      Modified residuei121PhosphoserineBy similarity1
      Modified residuei136N6-acetyllysineBy similarity1
      Modified residuei244N6-succinyllysineBy similarity1
      Modified residuei263PhosphoserineCombined sources1

      Keywords - PTMi

      Acetylation, Phosphoprotein

      Proteomic databases

      PaxDbiQ8CG45.
      PRIDEiQ8CG45.

      PTM databases

      iPTMnetiQ8CG45.
      PhosphoSitePlusiQ8CG45.

      Expressioni

      Gene expression databases

      BgeeiENSRNOG00000017780.

      Interactioni

      Subunit structurei

      Homodimer. Heterodimer with AKR7A1.1 Publication

      Protein-protein interaction databases

      MINTiMINT-4567597.
      STRINGi10116.ENSRNOP00000024063.

      Structurei

      3D structure databases

      ProteinModelPortaliQ8CG45.
      SMRiQ8CG45.
      ModBaseiSearch...
      MobiDBiSearch...

      Family & Domainsi

      Sequence similaritiesi

      Phylogenomic databases

      eggNOGiENOG410IDYD. Eukaryota.
      COG0667. LUCA.
      HOGENOMiHOG000250286.
      HOVERGENiHBG050576.
      InParanoidiQ8CG45.
      KOiK15303.
      PhylomeDBiQ8CG45.
      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.
      PfamiView protein in Pfam
      PF00248. Aldo_ket_red. 1 hit.
      SUPFAMiSSF51430. SSF51430. 1 hit.

      Sequencei

      Sequence statusi: Complete.

      Q8CG45-1 [UniParc]FASTAAdd to basket

      « Hide

              10         20         30         40         50
      MLRAVSRAVS RAAVRCAWRS GPSVARPLAM SRSPAPRAVS GAPLRPGTVL
      60 70 80 90 100
      GTMEMGRRMD ASASAATVRA FLERGLNELD TAFMYCDGQS ESILGSLGLG
      110 120 130 140 150
      LGSGDCTVKI ATKANPWDGK SLKPDSVRSQ LETSLKRLQC PRVDLFYLHA
      160 170 180 190 200
      PDHGTPIVET LQACQQLHQE GKFVELGLSN YASWEVAEIY TLCKSNGWIL
      210 220 230 240 250
      PTVYQGMYNA TTRQVETELL PCLRYFGLRF YAYNPLAGGL LTGKYRYEDK
      260 270 280 290 300
      DGKQPEGRFF GNSWSETYRN RFWKEHHFEA IALVEKALKT TYGTSAPSMT
      310 320 330 340 350
      SAALRWMYHH SQLQGTRGDA VILGMSSLEQ LEQNLAATEE GPLEPAVVEA
      360
      FNQAWNVVAH ECPNYFR
      Length:367
      Mass (Da):40,675
      Last modified:December 15, 2003 - v2
      Checksum:iAA27A3FBB454FEC5
      GO

      Sequence cautioni

      The sequence AAH61816 differs from that shown. Reason: Erroneous initiation.Curated
      The sequence BAA90396 differs from that shown. Reason: Erroneous initiation.Curated
      The sequence CAC81080 differs from that shown. Reason: Erroneous initiation.Curated

      Experimental Info

      Feature keyPosition(s)DescriptionActionsGraphical viewLength
      Sequence conflicti136K → N in AAN03824 (PubMed:12071861).Curated1
      Sequence conflicti295S → D in AAN03824 (PubMed:12071861).Curated1
      Sequence conflicti299 – 300MT → ND in CAC81080 (PubMed:12879023).Curated2

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      AF503514 mRNA. Translation: AAN03824.1.
      BC061816 mRNA. Translation: AAH61816.1. Different initiation.
      AJ271883 mRNA. Translation: CAC81080.1. Different initiation.
      AB037424 mRNA. Translation: BAA90396.1. Different initiation.
      RefSeqiNP_599234.1. NM_134407.1.
      UniGeneiRn.8548.

      Genome annotation databases

      GeneIDi171445.
      KEGGirno:171445.
      UCSCiRGD:620311. rat.

      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.

      Entry informationi

      Entry nameiARK72_RAT
      AccessioniPrimary (citable) accession number: Q8CG45
      Secondary accession number(s): Q6P765, Q8K435, Q9JM82
      Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 2003
      Last sequence update: December 15, 2003
      Last modified: May 10, 2017
      This is version 115 of the entry and version 2 of the sequence. See complete history.
      Entry statusiReviewed (UniProtKB/Swiss-Prot)
      Annotation programChordata Protein Annotation Program

      Miscellaneousi

      Keywords - Technical termi

      Complete proteome, Direct protein sequencing, Reference proteome

      Documents

      1. SIMILARITY comments
        Index of protein domains and families