ttfA Resolved · high auto-curated
H37Rv Rv0383c · MTBC0 mtbc0_000403 ·
284 aa · 461823–462677 (-) ·
RefSeq NP_214897.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | trehalose monomycolate transport factor TtfA |
| Revised (this work) | Trehalose monomycolate transport factor TtfA. Pfam: Treh_trans_TtfA (PF28092.1). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53718
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Trehalose monomycolate transport factor A |
| Curated function | Required for MmpL3-dependent trehalose monomycolate (TMM) transport to the cell wall (By similarity). The extramembranous domain possesses non-specific DNA-binding ability. TtfA may have additional roles in organizing DNA in the cytosol. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2DEM0 |
|---|
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 | 0.703 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 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 |
|---|---|---|---|---|
Treh_trans_TtfA | PF28092.1 | 2.3e-162 | 1–283 | Trehalose monomycolate transport factor TtfA |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0385 (monooxygenase), high confidence from genomic context alone (score 846 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) |
|---|---|---|---|---|
Rv0385 |
monooxygenase | 859 | 846 ctx | neighborhood:427 coexpression:669 |
Rv1125 hyp |
hypothetical protein | 807 | 798 ctx | cooccurence:764 |
Rv0382c pyrE |
orotate phosphoribosyltransferase | 785 | 786 ctx | neighborhood:786 |
Rv2139 pyrD |
dihydroorotate dehydrogenase | 839 | 779 | coexpression:730 |
Rv1384 carB |
carbamoyl-phosphate synthase large subunit | 801 | 775 | coexpression:730 |
Rv0381c hyp |
hypothetical protein | 773 | 774 ctx | neighborhood:774 |
Rv0817c lmeA hyp |
hypothetical protein | 773 | 773 ctx | cooccurence:773 |
Rv1275 lprC |
lipoprotein LprC | 772 | 772 ctx | cooccurence:763 |
Rv0475 hbhA |
heparin binding hemagglutinin HbhA | 772 | 772 ctx | cooccurence:772 |
Rv1274 lprB |
lipoprotein LprB | 771 | 771 ctx | cooccurence:761 |
Rv0996 |
transmembrane protein | 770 | 770 ctx | cooccurence:770 |
Rv3850 hyp |
hypothetical protein | 767 | 767 ctx | cooccurence:767 |
Rv0556 |
transmembrane protein | 766 | 766 ctx | cooccurence:766 |
Rv2732c |
transmembrane protein | 766 | 766 ctx | cooccurence:766 |
Rv3212 hyp |
hypothetical protein | 773 | 764 ctx | cooccurence:764 |
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: trehalose monomycolate transport factor TtfA
- Pfam (hmmscan --cut_ga): Treh_trans_TtfA PF28092.1 (E=2e-162)
- (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_214897.1)
- Domains: Pfam-A via hmmscan --cut_ga — Treh_trans_TtfA (PF28092.1)
- 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
2DEM0 - Curated reference: UniProt O53718 (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 —
195 functional partner(s); context anchor
Rv0385 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000403|Rv0383c|ttfA MVPLWFTLSALCFVGAVVLLYVDIDRRRGRSRRRKSWARSHGFDYERESTEILKRWTRGVMSTVGDVAAHNVVLGQIRGEAVYIFDLEEVATVIALHRKVGTNVVVDLRLKGLKEPRESDIWLLGAIGPRMVYSTNLDAARRACDRRMVTFAHTAPDCAEIMWNEQNWTLVSMPIASTRAQWDEGLRTVRQFNDLLRVLPPLPQEMPQQTGVGPRGAAPGRPVAPGGPAELPPRRAQPDPATTVLPDPARRAPEPIRRDEGRSEGVRRPPPAGRNGQQATNYQH