hemA Resolved · high auto-curated
H37Rv Rv0509 · MTBC0 mtbc0_000537 ·
468 aa · 603898–605304 (+) ·
RefSeq NP_215023.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | glutamyl-tRNA reductase |
|---|---|
| MTBC0 PGAP re-annotation | glutamyl-tRNA reductase |
| Revised (this work) | Glutamyl-tRNA reductase. Pfam: GlutR_N (PF05201.21), Shikimate_DH (PF01488.27), GlutR_dimer (PF00745.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMP7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Glutamyl-tRNA reductase |
| EC (curated) |
EC 1.2.1.70
|
| Curated function | Catalyzes the NADPH-dependent reduction of glutamyl-tRNA(Glu) to glutamate 1-semialdehyde (GSA). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | hemA |
| eggNOG description | Catalyzes the NADPH-dependent reduction of glutamyl- tRNA(Glu) to glutamate 1-semialdehyde (GSA) |
| Orthologous group | COG0373 |
| EC number |
EC 1.2.1.70
|
| KEGG orthology |
K02492
|
| KEGG pathways |
map00860, map01100, map01110, map01120
|
| KEGG modules |
M00121
|
| Gene Ontology (2) |
GO:0008150, GO:0040007
|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.275 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 3 missense, 0 nonsense, 0 frameshift |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
GlutR_N | PF05201.21 | 8.6e-50 | 7–156 | Glutamyl-tRNAGlu reductase, N-terminal domain |
Shikimate_DH | PF01488.27 | 7.6e-30 | 172–314 | Shikimate / quinate 5-dehydrogenase |
GlutR_dimer | PF00745.26 | 4.7e-25 | 328–426 | Glutamyl-tRNAGlu reductase, dimerisation domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hemC (porphobilinogen deaminase), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0510 hemC |
porphobilinogen deaminase | 999 | 998 ctx | neighborhood:876 fusion:742 cooccurence:768 coexpression:720 textmining:856 |
Rv0524 hemL |
glutamate-1-semialdehyde 2,1-aminomutase | 996 | 988 ctx | cooccurence:771 database:900 textmining:706 |
Rv0511 hemD |
uroporphyrin-III C-methyltransferase | 992 | 979 ctx | neighborhood:829 cooccurence:736 coexpression:563 textmining:669 |
Rv0512 hemB |
delta-aminolevulinic acid dehydratase | 984 | 953 ctx | neighborhood:748 cooccurence:763 textmining:693 |
Rv2992c gltS |
glutamate--tRNA ligase | 967 | 901 | database:900 textmining:686 |
Rv0508 hyp |
hypothetical protein | 818 | 812 ctx | neighborhood:811 |
Rv0513 |
transmembrane protein | 788 | 788 ctx | neighborhood:741 |
Rv0514 |
transmembrane protein | 756 | 756 ctx | neighborhood:741 |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 863 | 739 ctx | cooccurence:636 textmining:497 |
Rv0529 ccsA |
cytochrome C-type biogenesis protein CcsA | 753 | 655 | coexpression:434 |
Rv0506 mmpS2 |
membrane protein MmpS2 | 638 | 637 ctx | neighborhood:637 |
Rv0507 mmpL2 |
transmembrane transport protein MmpL2 | 637 | 637 ctx | neighborhood:637 |
Rv2678c hemE |
uroporphyrinogen decarboxylase | 853 | 617 ctx | cooccurence:446 textmining:633 |
Rv2677c hemY |
protoporphyrinogen oxidase | 737 | 576 ctx | cooccurence:449 textmining:405 |
Rv0505c serB1 |
phosphoserine phosphatase SerB | 534 | 534 ctx | neighborhood:531 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: glutamyl-tRNA reductase
- MTBC0 PGAP product: glutamyl-tRNA reductase
- Pfam (hmmscan --cut_ga): GlutR_N PF05201.21 (E=9e-50), Shikimate_DH PF01488.27 (E=8e-30), GlutR_dimer PF00745.26 (E=5e-25)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_215023.1)
- Domains: Pfam-A via hmmscan --cut_ga — GlutR_N (PF05201.21), Shikimate_DH (PF01488.27), GlutR_dimer (PF00745.26)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG0373 - Curated reference: UniProt P9WMP7 (SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
38 functional partner(s); context anchor
hemC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000537|Rv0509|hemA MSVLLFGVSHRSAPVVVLEQLSIDESDQVKIIDRVLASPLVTEAMVLSTCNRVEVYAVVDAFHGGLSVIGQVLAEHSGMSMGELTKYAYVRYSEAAVEHLFAVASGLDSAVIGEQQVLGQVRRAYAVAESNRTVGRVLHELAQRALSVGKRVHSETAIDAAGASVVSVALGMAERKLGSLAGTTAVVIGAGAMGALSAVHLTRAGVGHIQVLNRSLSRAQRLARRIRESGVPAEALALDRLANVLADADVVVSCTGAVRPVVSLADVHHALAAARRDEATRPLVICDLGMPRDVDPAVARLPCVWVVDVDSVQHEPSAHAAAADVEAARHIVAAEVASYLVGQRMAEVTPTVTALRQRAAEVVEAELLRLDNRLPGLQSVQREEVARTVRRVVDKLLHAPTVRIKQLASAPGGDSYAEALRELFELDQTAVDAVATAGELPVVPSGFDAESRRGGGDMQSSPKRSPSN