pflA Resolved · high auto-curated
H37Rv Rv3138 · MTBC0 mtbc0_003336 ·
362 aa · 3526897–3527985 (+) ·
RefSeq NP_217654.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | pyruvate formate lyase activating protein PflA |
|---|---|
| MTBC0 PGAP re-annotation | AmmeMemoRadiSam system radical SAM enzyme |
| Revised (this work) | AmmeMemoRadiSam system radical SAM enzyme. Pfam: Radical_SAM (PF04055.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P95188
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Probable pyruvate formate lyase activating protein PflA |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | pflA |
| eggNOG description | Radical SAM superfamily |
| Orthologous group | COG1180 |
| EC number |
EC 1.97.1.4
|
| KEGG orthology |
K04069
|
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 | 0.621 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 8 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.10% of strains (149) · clonal |
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 |
|---|---|---|---|---|
Radical_SAM | PF04055.28 | 3.9e-19 | 84–236 | Radical SAM superfamily |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hisN (histidinol-phosphatase), high confidence from genomic context alone (score 888 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3137 hisN |
histidinol-phosphatase | 937 | 888 ctx | neighborhood:855 textmining:462 |
Rv3139 fadE24 |
acyl-CoA dehydrogenase | 829 | 788 ctx | neighborhood:785 |
Rv3136A hyp |
hypothetical protein | 748 | 749 ctx | neighborhood:749 |
Rv3140 fadE23 |
acyl-CoA dehydrogenase FadE23 | 676 | 606 ctx | neighborhood:600 |
Rv0252 nirB |
nitrite reductase large subunit NirB | 464 | 432 | coexpression:419 |
Rv1869c |
reductase | 461 | 430 | coexpression:417 |
Rv3818 hyp |
hypothetical protein | 453 | 430 | coexpression:412 |
Rv0688 |
ferredoxin reductase | 460 | 429 | coexpression:416 |
Rv0253 nirD |
nitrite reductase small subunit NirD | 439 | 415 | coexpression:414 |
Rv0729 xylB |
D-xylulose kinase XylB | 413 | 414 | coexpression:414 |
Rv2633c hyp |
hypothetical protein | 435 | 411 | coexpression:410 |
Rv0254c cobU |
bifunctional cobinamide kinase/cobinamide phosphate guanylyltransferase | 410 | 411 | coexpression:411 |
Rv1213 glgC |
glucose-1-phosphate adenylyltransferase | 428 | 406 | coexpression:406 |
Rv3141 fadB4 |
NADPH quinone oxidoreductase FadB | 873 | 385 | textmining:803 |
Rv0711 atsA |
arylsulfatase AtsA | 687 | 336 | textmining:549 |
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: pyruvate formate lyase activating protein PflA
- MTBC0 PGAP product: AmmeMemoRadiSam system radical SAM enzyme
- Pfam (hmmscan --cut_ga): Radical_SAM PF04055.28 (E=4e-19)
- (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_217654.1)
- Domains: Pfam-A via hmmscan --cut_ga — Radical_SAM (PF04055.28)
- 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
COG1180 - Curated reference: UniProt P95188 (TrEMBL, unreviewed; Predicted)
- 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 —
29 functional partner(s); context anchor
hisN - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003336|Rv3138|pflA MSDPFTIATKHWHRLHDSRIQCDVCPRACKLHEGQRGLCFVRGRFDDQVKLTSYGRSSGFCVDPIEKKPLNHFLPGSATLSFGTAGCNLACKFCQNWDISKSREIDVLASRAAPADIARTAHELGCRSVAFTYNDPTIFWEYAADVADACHDQGIKAVAVTAGYMCPEPRAEFYRRVDAANVDLKAFTEDFYRKVCVSHLRNVLDTLAYLRHQTNVWLEITTLLIPGRNDSDAEVAAECRWIRENLGVDVPVHFTAFHPDYKMMDTPATPPATLTRAREIGIGEGLRFVYTGNVHDAVGGSTSCPGCRATVIVRDWYSIRHYALTEDGRCQACGYQMPGVYDGPAGHWGQRRLPLLTSLSRM