mfpA Resolved · high auto-curated
H37Rv Rv3361c · MTBC0 mtbc0_003576 ·
183 aa · 3799724–3800275 (-) ·
RefSeq NP_217878.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | pentapeptide repeat protein MfpA |
| Revised (this work) | Pentapeptide repeat protein MfpA. Pfam: Pentapeptide_3 (PF13576.13), Pentapeptide (PF00805.29). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YBX3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Pentapeptide repeat protein MfpA |
| Curated function | Might be involved in fluoroquinolone resistance. Inhibits ATP-independent DNA relaxation, ATP-dependent DNA supercoiling and ATP-dependent decatenation by endogenous gyrase, 50% inhibition occurs at 2 uM; inhibition is abolished if GyrA is mutated (Asp-87 to Gly or His). Also inhibits fluoroquinolone-promoted dsDNA cleavage. Increases fluoroquinolone (ciprofloxacin or moxifloxacin) inhibition of gyrase supercoiling activity in a concentration-dependent manner. Inhibits DNA relaxation and supercoiling by E.coli gyrase. Forms a structure that exhibits size, shape and electrostatic similarity to . |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | mfpA |
| eggNOG description | Pentapeptide repeat |
| Orthologous group | COG1357 |
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 | 0.169 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 1 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 |
|---|---|---|---|---|
Pentapeptide_3 | PF13576.13 | 3.5e-07 | 29–69 | Pentapeptide repeats (9 copies) |
Pentapeptide | PF00805.29 | 2.7e-07 | 88–126 | Pentapeptide repeats (8 copies) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3362c (ATP/GTP-binding protein), high confidence from genomic context alone (score 933 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0005 gyrB |
DNA gyrase subunit B | 997 | 997 | experimental:997 |
Rv3363c hyp |
hypothetical protein | 995 | 967 ctx | neighborhood:882 coexpression:735 textmining:870 |
Rv3362c |
ATP/GTP-binding protein | 987 | 933 ctx | neighborhood:882 coexpression:458 textmining:822 |
Rv3365c hyp |
hypothetical protein | 963 | 888 ctx | neighborhood:882 textmining:691 |
Rv3364c hyp |
hypothetical protein | 984 | 887 ctx | neighborhood:882 textmining:870 |
Rv3366 spoU |
tRNA/rRNA methylase SpoU | 547 | 548 ctx | neighborhood:541 |
Rv2719c chiZ |
membrane protein | 564 | 537 | |
Rv1288 hyp |
hypothetical protein | 522 | 493 | |
Rv0210 hyp |
hypothetical protein | 436 | 437 ctx | cooccurence:418 |
Rv0899 arfA |
peptidoglycan-binding protein ArfA | 440 | 413 | |
Rv1754c hyp |
hypothetical protein | 440 | 413 | |
Rv3668c |
protease | 438 | 403 | |
Rv1988 erm(37) |
23S rRNA (adenine(2058)-N(6))-methyltransferase Erm(37) | 480 | 119 | textmining:434 |
Rv3671c marP |
serine protease | 522 | 66 | textmining:510 |
Rv2201 asnB |
asparagine synthetase | 633 | 56 | textmining:628 |
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: hypothetical protein
- MTBC0 PGAP product: pentapeptide repeat protein MfpA
- Pfam (hmmscan --cut_ga): Pentapeptide_3 PF13576.13 (E=3e-07), Pentapeptide PF00805.29 (E=3e-07)
- (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_217878.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pentapeptide_3 (PF13576.13), Pentapeptide (PF00805.29)
- 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
COG1357 - Curated reference: UniProt I6YBX3 (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 —
17 functional partner(s); context anchor
Rv3362c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003576|Rv3361c|mfpA MQQWVDCEFTGRDFRDEDLSRLHTERAMFSECDFSGVNLAESQHRGSAFRNCTFERTTLWHSTFAQCSMLGSVFVACRLRPLTLDDVDFTLAVLGGNDLRGLNLTGCRLRETSLVDTDLRKCVLRGADLSGARTTGARLDDADLRGATVDPVLWRTASLVGARVDVDQAVAFAAAHGLCLAGG