P64328 (HEM1_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutamyl-tRNA reductase
Short name=GluTR
EC=1.2.1.70

Gene names

Name:	hemA
Ordered Locus Names:	Rv0509, MT0530
ORF Names:	MTCY20G9.36

Organism

Mycobacterium tuberculosis [Reference proteome] [HAMAP]

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Actinobacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	468 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

General annotation (Comments)

Function	Catalyzes the NADPH-dependent reduction of glutamyl-tRNA(Glu) to glutamate 1-semialdehyde (GSA) By similarity. HAMAP-Rule MF_00087
Catalytic activity	L-glutamate 1-semialdehyde + NADP+ + tRNA(Glu) = L-glutamyl-tRNA(Glu) + NADPH. HAMAP-Rule MF_00087
Pathway	Porphyrin metabolism; protoporphyrin-IX biosynthesis; 5-aminolevulinate from L-glutamyl-tRNA(Glu): step 1/2. HAMAP-Rule MF_00087
Subunit structure	Homodimer By similarity.
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 By similarity. HAMAP-Rule MF_00087 Was identified as a high-confidence drug target. HAMAP-Rule MF_00087
Sequence similarities	Belongs to the glutamyl-tRNA reductase family.
Sequence caution	The sequence AAK44753.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Porphyrin biosynthesis
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chlorophyll biosynthetic process Inferred from electronic annotation. Source: HAMAP growth Inferred from mutant phenotype PubMed 12657046. Source: MTBBASE protoporphyrinogen IX biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway
Molecular_function	NADP binding Inferred from electronic annotation. Source: InterPro glutamyl-tRNA reductase activity Inferred from electronic annotation. Source: HAMAP
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 468	468	Glutamyl-tRNA reductase HAMAP-Rule MF_00087		PRO_0000114042
Regions
	Nucleotide binding	189 – 194	6	NADP By similarity
	Region	49 – 52	4	Substrate binding By similarity
	Region	114 – 116	3	Substrate binding By similarity
Sites
	Active site	50	1	Nucleophile By similarity
	Binding site	109	1	Substrate By similarity
	Binding site	120	1	Substrate By similarity
	Site	99	1	Important for activity By similarity

Sequences

	Sequence		Length	Mass (Da)
	P64328 [UniParc]. Last modified October 11, 2004. Version 1. Checksum: DDC257648FF6EAAB	FASTA	468	49,361
	10 20 30 40 50 60 MSVLLFGVSH RSAPVVVLEQ LSIDESDQVK IIDRVLASPL VTEAMVLSTC NRVEVYAVVD 70 80 90 100 110 120 AFHGGLSVIG QVLAEHSGMS MGELTKYAYV RYSEAAVEHL FAVASGLDSA VIGEQQVLGQ 130 140 150 160 170 180 VRRAYAVAES NRTVGRVLHE LAQRALSVGK RVHSETAIDA AGASVVSVAL GMAERKLGSL 190 200 210 220 230 240 AGTTAVVIGA GAMGALSAVH LTRAGVGHIQ VLNRSLSRAQ RLARRIRESG VPAEALALDR 250 260 270 280 290 300 LANVLADADV VVSCTGAVRP VVSLADVHHA LAAARRDEAT RPLVICDLGM PRDVDPAVAR 310 320 330 340 350 360 LPCVWVVDVD SVQHEPSAHA AAADVEAARH IVAAEVASYL VGQRMAEVTP TVTALRQRAA 370 380 390 400 410 420 EVVEAELLRL DNRLPGLQSV QREEVARTVR RVVDKLLHAP TVRIKQLASA PGGDSYAEAL 430 440 450 460 RELFELDQTA VDAVATAGEL PVVPSGFDAE SRRGGGDMQS SPKRSPSN

References

[1]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G. Nature 393:537-544(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. , Weidman J.F., Khouri H.M., Gill J., Mikula A., Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis." Raman K., Yeturu K., Chandra N. BMC Syst. Biol. 2:109-109(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases
EMBL GenBank DDBJ	BX842573 Genomic DNA. Translation: CAB00935.1. AE000516 Genomic DNA. Translation: AAK44753.1. Different initiation. AL123456 Genomic DNA. Translation: CCP43246.1.
PIR	H70746.
RefSeq	NP_215023.1. NC_000962.3. NP_334939.2. NC_002755.2. YP_006513842.1. NC_018143.1.
3D structure databases
ProteinModelPortal	P64328.
SMR	P64328. Positions 178-297.
ModBase	Search...
Protein-protein interaction databases
STRING	83332.Rv0509.
Proteomic databases
PRIDE	P64328.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblBacteria	AAK44753; AAK44753; MT0530.
GeneID	13318383. 887292. 924070.
KEGG	mtc:MT0530. mtu:Rv0509. mtv:RVBD_0509.
PATRIC	18122876. VBIMycTub22151_0572.
Organism-specific databases
TubercuList	Rv0509.
Phylogenomic databases
eggNOG	COG0373.
HOGENOM	HOG000109649.
KO	K02492.
OMA	GPILNRL.
ProtClustDB	PRK00045.
Enzyme and pathway databases
UniPathway	UPA00251; UER00316.
Family and domain databases
Gene3D	3.40.50.720. 1 hit.
HAMAP	MF_00087. Glu-tRNA_reductase.
InterPro	IPR000343. 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]
Pfam	PF00745. GlutR_dimer. 1 hit. PF05201. GlutR_N. 1 hit. PF01488. Shikimate_DH. 1 hit. [Graphical view]
PIRSF	PIRSF000445. 4pyrrol_synth_GluRdtase. 1 hit.
SUPFAM	SSF69075. 4pyrrol_synth_GluRdtase_C. 1 hit. SSF69742. GlutR. 1 hit.
TIGRFAMs	TIGR01035. hemA. 1 hit.
PROSITE	PS00747. GLUTR. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

HEM1_MYCTU

Accession

Primary (citable) accession number: P64328
Secondary accession number(s): L0T3Z5, Q11139

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	October 11, 2004
Last modified:	May 1, 2013
This is version 74 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program