proA Resolved · high auto-curated
H37Rv Rv2427c · MTBC0 mtbc0_002584 ·
415 aa · 2748478–2749725 (-) ·
RefSeq NP_216943.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | gamma-glutamyl phosphate reductase |
|---|---|
| MTBC0 PGAP re-annotation | glutamate-5-semialdehyde dehydrogenase |
| Revised (this work) | Glutamate-5-semialdehyde dehydrogenase. Pfam: Aldedh (PF00171.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHV1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Gamma-glutamyl phosphate reductase |
| EC (curated) |
EC 1.2.1.41
|
| Curated function | Catalyzes the NADPH-dependent reduction of L-glutamate 5-phosphate into L-glutamate 5-semialdehyde and phosphate. The product spontaneously undergoes cyclization to form 1-pyrroline-5-carboxylate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | proA |
| eggNOG description | Catalyzes the NADPH-dependent reduction of L-glutamate 5-phosphate into L-glutamate 5-semialdehyde and phosphate. The product spontaneously undergoes cyclization to form 1-pyrroline-5- carboxylate |
| Orthologous group | COG0014 |
| EC number |
EC 1.2.1.41
|
| KEGG orthology |
K00147
|
| KEGG pathways |
map00330, map00332, map01100, map01110, map01130, map01230
|
| KEGG modules |
M00015
|
| Gene Ontology (20) |
GO:0003674, GO:0003824, GO:0004350, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0008150, GO:0008152, GO:0016020 +8 more
|
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 | 0.282 · 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 |
|---|---|---|---|---|
Aldedh | PF00171.28 | 2.5e-13 | 12–302 | Aldehyde dehydrogenase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: proB (glutamate 5-kinase protein), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2439c proB |
glutamate 5-kinase protein | 999 | 1000 ctx | fusion:900 cooccurence:774 coexpression:806 database:900 textmining:705 |
Rv1187 rocA |
pyrroline-5-carboxylate dehydrogenase RocA | 907 | 901 | database:900 |
Rv0788 purQ |
phosphoribosylformylglycinamidine synthase | 869 | 851 | database:800 |
Rv1308 atpA |
ATP synthase subunit alpha | 850 | 841 ctx | fusion:840 |
Rv2426c hyp |
hypothetical protein | 826 | 826 ctx | neighborhood:817 |
Rv3432c gadB |
glutamate decarboxylase GadB | 831 | 823 | database:800 |
Rv2425c hyp |
hypothetical protein | 822 | 822 ctx | neighborhood:817 |
Rv3859c gltB |
glutamate synthase large subunit | 917 | 807 | database:800 textmining:591 |
Rv2860c glnA4 |
glutamine synthetase | 910 | 807 | database:800 textmining:556 |
Rv2222c glnA2 |
glutamine synthetase | 911 | 806 | database:800 textmining:561 |
Rv3858c gltD |
glutamate synthase small subunit | 815 | 806 | database:800 |
Rv2220 glnA1 |
glutamine synthetase | 867 | 805 | database:800 |
Rv1878 glnA3 |
glutamine synthetase GlnA | 895 | 804 | database:800 textmining:488 |
Rv0500 proC |
pyrroline-5-carboxylate reductase | 936 | 802 ctx | cooccurence:676 textmining:695 |
Rv2476c gdh |
NAD-dependent glutamate dehydrogenase | 801 | 802 | database:800 |
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: gamma-glutamyl phosphate reductase
- MTBC0 PGAP product: glutamate-5-semialdehyde dehydrogenase
- Pfam (hmmscan --cut_ga): Aldedh PF00171.28 (E=2e-13)
- (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_216943.1)
- Domains: Pfam-A via hmmscan --cut_ga — Aldedh (PF00171.28)
- 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
COG0014 - Curated reference: UniProt P9WHV1 (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 —
51 functional partner(s); context anchor
proB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002584|Rv2427c|proA MTVPAPSQLDLRQEVHDAARRARVAARRLASLPTTVKDRALHAAADELLAHRDQILAANAEDLNAAREADTPAAMLDRLSLNPQRVDGIAAGLRQVAGLRDPVGEVLRGYTLPNGLQLRQQRVPLGVVGMIYEGRPNVTVDAFGLTLKSGNAALLRGSSSAAKSNEALVAVLRTALVGLELPADAVQLLSAADRATVTHLIQARGLVDVVIPRGGAGLIEAVVRDAQVPTIETGVGNCHVYVHQAADLDVAERILLNSKTRRPSVCNAAETLLVDAAIAETALPRLLAALQHAGVTVHLDPDEADLRREYLSLDIAVAVVDGVDAAIAHINEYGTGHTEAIVTTNLDAAQRFTEQIDAAAVMVNASTAFTDGEQFGFGAEIGISTQKLHARGPMGLPELTSTKWIAWGAGHTRPA