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P0A6X1 (HEM1_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 89. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glutamyl-tRNA reductase

Short name=GluTR
EC=1.2.1.70
Gene names
Name:hemA
Ordered Locus Names:b1210, JW1201
OrganismEscherichia coli (strain K12) [Reference proteome] [HAMAP]
Taxonomic identifier83333 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia

Protein attributes

Sequence length418 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.9 Ref.10

Catalytic activity

L-glutamate 1-semialdehyde + NADP+ + tRNA(Glu) = L-glutamyl-tRNA(Glu) + NADPH. Ref.9

Enzyme regulation

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. Ref.9

Pathway

Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; 5-aminolevulinate from L-glutamyl-tRNA(Glu): step 1/2. HAMAP-Rule MF_00087

Subunit structure

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. Ref.9 Ref.11

Domain

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. HAMAP-Rule MF_00087

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.

Sequence similarities

Belongs to the glutamyl-tRNA reductase family.

Biophysicochemical properties

Kinetic parameters:

KM=24 µM for L-glutamyl-tRNA(Glu) Ref.9

KM=39 µM for NADPH

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 418418Glutamyl-tRNA reductase HAMAP-Rule MF_00087
PRO_0000114023

Regions

Nucleotide binding189 – 1946NADP Probable
Region49 – 524Substrate binding Probable
Region114 – 1163Substrate binding Probable

Sites

Active site501Nucleophile
Binding site1091Substrate Probable
Binding site1201Substrate By similarity
Site991Important for activity

Experimental info

Mutagenesis71G → D: Loss of activity. Ref.9
Mutagenesis491T → V: 10% and 5% of wild-type reductase and esterase activity, respectively. Ref.12
Mutagenesis501C → S: Loss of activity. Ref.9
Mutagenesis521R → K: 5% and 4% of wild-type reductase and esterase activity, respectively. Ref.12
Mutagenesis521R → Q: Loss of activity. Ref.12
Mutagenesis541E → K: 6% and 2% of wild-type reductase and esterase activity, respectively. Ref.12
Mutagenesis741C → S: No effect. Ref.9
Mutagenesis991H → N: 5% and 4% of wild-type reductase and esterase activity, respectively. Ref.12
Mutagenesis1061G → N: Loss of activity. Ref.9
Mutagenesis1091S → A: 28% and 25% of wild-type reductase and esterase activity, respectively. Ref.12
Mutagenesis1141E → K: Loss of activity. Ref.9
Mutagenesis1161Q → L: Loss of reductase activity. 30% of wild-type esterase activity. Ref.12
Mutagenesis1451S → F: Loss of activity. Ref.9
Mutagenesis1701C → S: No effect. Ref.9
Mutagenesis1911G → D: Loss of reductase activity. Retains esterase activity. Ref.9
Mutagenesis3141R → C: Loss of activity. Ref.9
Sequence conflict151 – 16818RVRTE…SVAFA → PFALKQISVPALCLSLLP in CAA35476. Ref.3
Sequence conflict1721L → V in CAA35476. Ref.3
Sequence conflict2401L → M in CAA35476. Ref.3
Sequence conflict2431A → R Ref.1
Sequence conflict2431A → R Ref.4
Sequence conflict3651A → R in CAA35476. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P0A6X1 [UniParc].

Last modified March 29, 2005. Version 1.
Checksum: 3CEE59AC53610A88

FASTA41846,307
        10         20         30         40         50         60 
MTLLALGINH KTAPVSLRER VSFSPDKLDQ ALDSLLAQPM VQGGVVLSTC NRTELYLSVE 

        70         80         90        100        110        120 
EQDNLQEALI RWLCDYHNLN EEDLRKSLYW HQDNDAVSHL MRVASGLDSL VLGEPQILGQ 

       130        140        150        160        170        180 
VKKAFADSQK GHMKASELER MFQKSFSVAK RVRTETDIGA SAVSVAFAAC TLARQIFESL 

       190        200        210        220        230        240 
STVTVLLVGA GETIELVARH LREHKVQKMI IANRTRERAQ ILADEVGAEV IALSDIDERL 

       250        260        270        280        290        300 
READIIISST ASPLPIIGKG MVERALKSRR NQPMLLVDIA VPRDVEPEVG KLANAYLYSV 

       310        320        330        340        350        360 
DDLQSIISHN LAQRKAAAVE AETIVAQETS EFMAWLRAQS ASETIREYRS QAEQVRDELT 

       370        380        390        400        410 
AKALAALEQG GDAQAIMQDL AWKLTNRLIH APTKSLQQAA RDGDNERLNI LRDSLGLE 

« Hide

References

« Hide 'large scale' references
[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]"A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map."
Oshima T., Aiba H., Baba T., Fujita K., Hayashi K., Honjo A., Ikemoto K., Inada T., Itoh T., Kajihara M., Kanai K., Kashimoto K., Kimura S., Kitagawa M., Makino K., Masuda S., Miki T., Mizobuchi K. expand/collapse author list , Mori H., Motomura K., Nakamura Y., Nashimoto H., Nishio Y., Saito N., Sampei G., Seki Y., Tagami H., Takemoto K., Wada C., Yamamoto Y., Yano M., Horiuchi T.
DNA Res. 3:137-155(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[6]"The complete genome sequence of Escherichia coli K-12."
Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y.
Science 277:1453-1462(1997) [PubMed] [Europe PMC] [Abstract]
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]"Escherichia coli glutamyl-tRNA reductase. Trapping the thioester intermediate."
Schauer S., Chaturvedi S., Randau L., Moser J., Kitabatake M., Lorenz S., Verkamp E., Schubert W.-D., Nakayashiki T., Murai M., Wall K., Thomann H.-U., Heinz D.W., Inokuchi H., Soell D., Jahn D.
J. Biol. Chem. 277:48657-48663(2002) [PubMed] [Europe PMC] [Abstract]
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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRBVECHA. A45918.
RefSeqNP_415728.1. NC_000913.3.
YP_489477.1. NC_007779.1.

3D structure databases

ProteinModelPortalP0A6X1.
SMRP0A6X1. Positions 3-398.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-9877N.
IntActP0A6X1. 1 interaction.
STRING511145.b1210.

Proteomic databases

PaxDbP0A6X1.
PRIDEP0A6X1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAC74294; AAC74294; b1210.
BAA36068; BAA36068; BAA36068.
GeneID12931822.
945777.
KEGGecj:Y75_p1182.
eco:b1210.
PATRIC32117672. VBIEscCol129921_1258.

Organism-specific databases

EchoBASEEB0422.
EcoGeneEG10427. hemA.

Phylogenomic databases

eggNOGCOG0373.
HOGENOMHOG000109650.
KOK02492.
OMARTEIYCA.
OrthoDBEOG6MWNBM.
PhylomeDBP0A6X1.
ProtClustDBPRK00045.

Enzyme and pathway databases

BioCycEcoCyc:GLUTRNAREDUCT-MONOMER.
ECOL316407:JW1201-MONOMER.
MetaCyc:GLUTRNAREDUCT-MONOMER.
SABIO-RKP0A6X1.
UniPathwayUPA00251; UER00316.

Gene expression databases

GenevestigatorP0A6X1.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
HAMAPMF_00087. Glu_tRNA_reductase.
InterProIPR000343. 4pyrrol_synth_GluRdtase.
IPR015896. 4pyrrol_synth_GluRdtase_dimer.
IPR015895. 4pyrrol_synth_GluRdtase_N.
IPR016040. NAD(P)-bd_dom.
IPR018214. Pyrrol_synth_GluRdtase_CS.
IPR006151. Shikm_DH/Glu-tRNA_Rdtase.
[Graphical view]
PfamPF00745. GlutR_dimer. 1 hit.
PF05201. GlutR_N. 1 hit.
PF01488. Shikimate_DH. 1 hit.
[Graphical view]
PIRSFPIRSF000445. 4pyrrol_synth_GluRdtase. 1 hit.
SUPFAMSSF69075. SSF69075. 1 hit.
SSF69742. SSF69742. 1 hit.
TIGRFAMsTIGR01035. hemA. 1 hit.
PROSITEPS00747. GLUTR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

PROP0A6X1.

Entry information

Entry nameHEM1_ECOLI
AccessionPrimary (citable) accession number: P0A6X1
Secondary accession number(s): P13580, Q59405
Entry history
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: March 29, 2005
Last modified: April 16, 2014
This is version 89 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

Escherichia coli

Escherichia coli (strain K12): entries and cross-references to EcoGene