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Protein

Glutamyl-tRNA reductase

Gene

hemA

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the NADPH-dependent reduction of glutamyl-tRNA(Glu) to glutamate 1-semialdehyde (GSA). In the absence of NADPH, exhibits substrate esterase activity, leading to the release of glutamate from tRNA.2 Publications

Catalytic activityi

L-glutamate 1-semialdehyde + NADP+ + tRNA(Glu) = L-glutamyl-tRNA(Glu) + NADPH.1 Publication

Enzyme regulationi

Activated by Mg2+ ions. Inhibited by metal-chelating agents such as EDTA, EGTA, 1,10-phenanthroline, 2,2'-dipyridyl, and by PtCl4 and KPdCl4 as well as Ni2+ and Co2+. Also inhibited by iodoacetamide, N-tosyl-L-phenylalanine chloromethyl ketone, and 5,5'-dithiobis(2-nitrobenzoic acid), as well as glutamycin.1 Publication

Kineticsi

  1. KM=24 µM for L-glutamyl-tRNA(Glu)1 Publication
  2. KM=39 µM for NADPH1 Publication

    Pathway:iprotoporphyrin-IX biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes 5-aminolevulinate from L-glutamyl-tRNA(Glu).
    Proteins known to be involved in the 2 steps of the subpathway in this organism are:
    1. Glutamyl-tRNA reductase (hemA)
    2. Glutamate-1-semialdehyde 2,1-aminomutase (hemL)
    This subpathway is part of the pathway protoporphyrin-IX biosynthesis, which is itself part of Porphyrin-containing compound metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes 5-aminolevulinate from L-glutamyl-tRNA(Glu), the pathway protoporphyrin-IX biosynthesis and in Porphyrin-containing compound metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei50 – 501Nucleophile
    Sitei99 – 991Important for activity
    Binding sitei109 – 1091SubstrateCurated
    Binding sitei120 – 1201SubstrateBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi189 – 1946NADPCurated

    GO - Molecular functioni

    • glutamyl-tRNA reductase activity Source: EcoCyc
    • identical protein binding Source: EcoCyc
    • NADP binding Source: InterPro

    GO - Biological processi

    • protoporphyrinogen IX biosynthetic process from glutamate Source: EcoCyc
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Porphyrin biosynthesis

    Keywords - Ligandi

    NADP

    Enzyme and pathway databases

    BioCyciEcoCyc:GLUTRNAREDUCT-MONOMER.
    ECOL316407:JW1201-MONOMER.
    MetaCyc:GLUTRNAREDUCT-MONOMER.
    BRENDAi1.2.1.70. 2026.
    SABIO-RKP0A6X1.
    UniPathwayiUPA00251; UER00316.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Glutamyl-tRNA reductase (EC:1.2.1.70)
    Short name:
    GluTR
    Gene namesi
    Name:hemA
    Ordered Locus Names:b1210, JW1201
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
    ProteomesiUP000000318 Componenti: Chromosome UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG10427. hemA.

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi7 – 71G → D: Loss of activity. 1 Publication
    Mutagenesisi49 – 491T → V: 10% and 5% of wild-type reductase and esterase activity, respectively. 1 Publication
    Mutagenesisi50 – 501C → S: Loss of activity. 1 Publication
    Mutagenesisi52 – 521R → K: 5% and 4% of wild-type reductase and esterase activity, respectively. 1 Publication
    Mutagenesisi52 – 521R → Q: Loss of activity. 1 Publication
    Mutagenesisi54 – 541E → K: 6% and 2% of wild-type reductase and esterase activity, respectively. 1 Publication
    Mutagenesisi74 – 741C → S: No effect. 1 Publication
    Mutagenesisi99 – 991H → N: 5% and 4% of wild-type reductase and esterase activity, respectively. 1 Publication
    Mutagenesisi106 – 1061G → N: Loss of activity. 1 Publication
    Mutagenesisi109 – 1091S → A: 28% and 25% of wild-type reductase and esterase activity, respectively. 1 Publication
    Mutagenesisi114 – 1141E → K: Loss of activity. 1 Publication
    Mutagenesisi116 – 1161Q → L: Loss of reductase activity. 30% of wild-type esterase activity. 1 Publication
    Mutagenesisi145 – 1451S → F: Loss of activity. 1 Publication
    Mutagenesisi170 – 1701C → S: No effect. 1 Publication
    Mutagenesisi191 – 1911G → D: Loss of reductase activity. Retains esterase activity. 1 Publication
    Mutagenesisi314 – 3141R → C: Loss of activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 418418Glutamyl-tRNA reductasePRO_0000114023Add
    BLAST

    Proteomic databases

    PaxDbiP0A6X1.
    PRIDEiP0A6X1.

    Interactioni

    Subunit structurei

    Homodimer. Interacts with glutamate-1-semialdehyde 2,1-aminomutase (GSA-AM), which forms a metabolic channeling between both enzymes to protect the reactive aldehyde species GSA.2 Publications

    Protein-protein interaction databases

    DIPiDIP-9877N.
    IntActiP0A6X1. 1 interaction.
    STRINGi511145.b1210.

    Structurei

    3D structure databases

    ProteinModelPortaliP0A6X1.
    SMRiP0A6X1. Positions 3-398.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni49 – 524Substrate bindingCurated
    Regioni114 – 1163Substrate bindingCurated

    Domaini

    Possesses an unusual extended V-shaped dimeric structure with each monomer consisting of three distinct domains arranged along a curved 'spinal' alpha-helix. The N-terminal catalytic domain specifically recognizes the glutamate moiety of the substrate. The second domain is the NADPH-binding domain, and the third C-terminal domain is responsible for dimerization (By similarity).By similarity

    Sequence similaritiesi

    Belongs to the glutamyl-tRNA reductase family.Curated

    Phylogenomic databases

    eggNOGiCOG0373.
    HOGENOMiHOG000109650.
    InParanoidiP0A6X1.
    KOiK02492.
    OMAiNHCPNIK.
    OrthoDBiEOG6MWNBM.
    PhylomeDBiP0A6X1.

    Family and domain databases

    Gene3Di3.40.50.720. 1 hit.
    HAMAPiMF_00087. Glu_tRNA_reductase.
    InterProiIPR000343. 4pyrrol_synth_GluRdtase.
    IPR015896. 4pyrrol_synth_GluRdtase_dimer.
    IPR015895. 4pyrrol_synth_GluRdtase_N.
    IPR018214. GluRdtase_CS.
    IPR016040. NAD(P)-bd_dom.
    IPR006151. Shikm_DH/Glu-tRNA_Rdtase.
    [Graphical view]
    PfamiPF00745. GlutR_dimer. 1 hit.
    PF05201. GlutR_N. 1 hit.
    PF01488. Shikimate_DH. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000445. 4pyrrol_synth_GluRdtase. 1 hit.
    SUPFAMiSSF69075. SSF69075. 1 hit.
    SSF69742. SSF69742. 1 hit.
    TIGRFAMsiTIGR01035. hemA. 1 hit.
    PROSITEiPS00747. GLUTR. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P0A6X1-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MTLLALGINH KTAPVSLRER VSFSPDKLDQ ALDSLLAQPM VQGGVVLSTC
    60 70 80 90 100
    NRTELYLSVE EQDNLQEALI RWLCDYHNLN EEDLRKSLYW HQDNDAVSHL
    110 120 130 140 150
    MRVASGLDSL VLGEPQILGQ VKKAFADSQK GHMKASELER MFQKSFSVAK
    160 170 180 190 200
    RVRTETDIGA SAVSVAFAAC TLARQIFESL STVTVLLVGA GETIELVARH
    210 220 230 240 250
    LREHKVQKMI IANRTRERAQ ILADEVGAEV IALSDIDERL READIIISST
    260 270 280 290 300
    ASPLPIIGKG MVERALKSRR NQPMLLVDIA VPRDVEPEVG KLANAYLYSV
    310 320 330 340 350
    DDLQSIISHN LAQRKAAAVE AETIVAQETS EFMAWLRAQS ASETIREYRS
    360 370 380 390 400
    QAEQVRDELT AKALAALEQG GDAQAIMQDL AWKLTNRLIH APTKSLQQAA
    410
    RDGDNERLNI LRDSLGLE
    Length:418
    Mass (Da):46,307
    Last modified:March 29, 2005 - v1
    Checksum:i3CEE59AC53610A88
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti151 – 16818RVRTE…SVAFA → PFALKQISVPALCLSLLP in CAA35476 (PubMed:2664455).CuratedAdd
    BLAST
    Sequence conflicti172 – 1721L → V in CAA35476 (PubMed:2664455).Curated
    Sequence conflicti240 – 2401L → M in CAA35476 (PubMed:2664455).Curated
    Sequence conflicti243 – 2431A → R (PubMed:2684779).Curated
    Sequence conflicti243 – 2431A → R (PubMed:7543480).Curated
    Sequence conflicti365 – 3651A → R in CAA35476 (PubMed:2664455).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M30785 Genomic DNA. Translation: AAA23953.1.
    M25323 Genomic DNA. Translation: AAA23954.1.
    X17434 Genomic DNA. Translation: CAA35476.1.
    U18555 Genomic DNA. Translation: AAC43436.1.
    U00096 Genomic DNA. Translation: AAC74294.1.
    AP009048 Genomic DNA. Translation: BAA36068.1.
    D10264 Genomic DNA. Translation: BAA20969.1.
    PIRiA45918. BVECHA.
    RefSeqiNP_415728.1. NC_000913.3.
    WP_001299679.1. NZ_CP010445.1.

    Genome annotation databases

    EnsemblBacteriaiAAC74294; AAC74294; b1210.
    BAA36068; BAA36068; BAA36068.
    GeneIDi945777.
    KEGGieco:b1210.
    PATRICi32117672. VBIEscCol129921_1258.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M30785 Genomic DNA. Translation: AAA23953.1.
    M25323 Genomic DNA. Translation: AAA23954.1.
    X17434 Genomic DNA. Translation: CAA35476.1.
    U18555 Genomic DNA. Translation: AAC43436.1.
    U00096 Genomic DNA. Translation: AAC74294.1.
    AP009048 Genomic DNA. Translation: BAA36068.1.
    D10264 Genomic DNA. Translation: BAA20969.1.
    PIRiA45918. BVECHA.
    RefSeqiNP_415728.1. NC_000913.3.
    WP_001299679.1. NZ_CP010445.1.

    3D structure databases

    ProteinModelPortaliP0A6X1.
    SMRiP0A6X1. Positions 3-398.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    DIPiDIP-9877N.
    IntActiP0A6X1. 1 interaction.
    STRINGi511145.b1210.

    Proteomic databases

    PaxDbiP0A6X1.
    PRIDEiP0A6X1.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC74294; AAC74294; b1210.
    BAA36068; BAA36068; BAA36068.
    GeneIDi945777.
    KEGGieco:b1210.
    PATRICi32117672. VBIEscCol129921_1258.

    Organism-specific databases

    EchoBASEiEB0422.
    EcoGeneiEG10427. hemA.

    Phylogenomic databases

    eggNOGiCOG0373.
    HOGENOMiHOG000109650.
    InParanoidiP0A6X1.
    KOiK02492.
    OMAiNHCPNIK.
    OrthoDBiEOG6MWNBM.
    PhylomeDBiP0A6X1.

    Enzyme and pathway databases

    UniPathwayiUPA00251; UER00316.
    BioCyciEcoCyc:GLUTRNAREDUCT-MONOMER.
    ECOL316407:JW1201-MONOMER.
    MetaCyc:GLUTRNAREDUCT-MONOMER.
    BRENDAi1.2.1.70. 2026.
    SABIO-RKP0A6X1.

    Miscellaneous databases

    PROiP0A6X1.

    Family and domain databases

    Gene3Di3.40.50.720. 1 hit.
    HAMAPiMF_00087. Glu_tRNA_reductase.
    InterProiIPR000343. 4pyrrol_synth_GluRdtase.
    IPR015896. 4pyrrol_synth_GluRdtase_dimer.
    IPR015895. 4pyrrol_synth_GluRdtase_N.
    IPR018214. GluRdtase_CS.
    IPR016040. NAD(P)-bd_dom.
    IPR006151. Shikm_DH/Glu-tRNA_Rdtase.
    [Graphical view]
    PfamiPF00745. GlutR_dimer. 1 hit.
    PF05201. GlutR_N. 1 hit.
    PF01488. Shikimate_DH. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000445. 4pyrrol_synth_GluRdtase. 1 hit.
    SUPFAMiSSF69075. SSF69075. 1 hit.
    SSF69742. SSF69742. 1 hit.
    TIGRFAMsiTIGR01035. hemA. 1 hit.
    PROSITEiPS00747. GLUTR. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Cloning and structure of the hem A gene of Escherichia coli K-12."
      Li J.-M., Russell C.S., Cosloy S.D.
      Gene 82:209-217(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: K12.
    2. "Isolation, nucleotide sequence, and preliminary characterization of the Escherichia coli K-12 hemA gene."
      Verkamp E., Chelm B.K.
      J. Bacteriol. 171:4728-4735(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: K12.
    3. "Isolation and nucleotide sequence of the hemA gene of Escherichia coli K12."
      Drolet M., Peloquin L., Echelard Y., Cousineau L., Sasarman A.
      Mol. Gen. Genet. 216:347-352(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: K12.
    4. "Expression of genes kdsA and kdsB involved in 3-deoxy-D-manno-octulosonic acid metabolism and biosynthesis of enterobacterial lipopolysaccharide is growth phase regulated primarily at the transcriptional level in Escherichia coli K-12."
      Strohmaier H., Remler P., Renner W., Hoegenauer G.
      J. Bacteriol. 177:4488-4500(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: K12.
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    7. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
      Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
      Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    8. "Cloning and characterization of genes involved in the biosynthesis of delta-aminolevulinic acid in Escherichia coli."
      Ikemi M., Murakami K., Hashimoto M., Murooka Y.
      Gene 121:127-132(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-49.
    9. Cited for: PROTEIN SEQUENCE OF 1-15, FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION, ENZYME REGULATION, IDENTIFICATION BY MASS SPECTROMETRY, SUBUNIT, KINETIC PARAMETERS, CATALYTIC MECHANISM, MUTAGENESIS OF GLY-7; CYS-50; CYS-74; GLY-106; GLU-114; SER-145; CYS-170; GLY-191 AND ARG-314.
    10. "Glutamyl-tRNA reductase from Escherichia coli and Synechocystis 6803. Gene structure and expression."
      Verkamp E., Jahn M., Jahn D., Kumar A.M., Soell D.
      J. Biol. Chem. 267:8275-8280(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    11. "Complex formation between glutamyl-tRNA reductase and glutamate-1-semialdehyde 2,1-aminomutase in Escherichia coli during the initial reactions of porphyrin biosynthesis."
      Lueer C., Schauer S., Moebius K., Schulze J., Schubert W.-D., Heinz D.W., Jahn D., Moser J.
      J. Biol. Chem. 280:18568-18572(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GSA-AM.
    12. "Glutamate recognition and hydride transfer by Escherichia coli glutamyl-tRNA reductase."
      Lueer C., Schauer S., Virus S., Schubert W.-D., Heinz D.W., Moser J., Jahn D.
      FEBS J. 274:4609-4614(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF THR-49; ARG-52; GLU-54; HIS-99; SER-109 AND GLN-116.

    Entry informationi

    Entry nameiHEM1_ECOLI
    AccessioniPrimary (citable) accession number: P0A6X1
    Secondary accession number(s): P13580, Q59405
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 29, 2005
    Last sequence update: March 29, 2005
    Last modified: July 22, 2015
    This is version 99 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    During catalysis, the active site Cys acts as a nucleophile attacking the alpha-carbonyl group of tRNA-bound glutamate with the formation of a thioester intermediate between enzyme and glutamate, and the concomitant release of tRNA(Glu). The thioester intermediate is finally reduced by direct hydride transfer from NADPH, to form the product GSA.

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    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.