mmpL3 Resolved · high auto-curated
H37Rv Rv0206c · MTBC0 mtbc0_000220 ·
944 aa · 244836–247670 (-) ·
RefSeq NP_214720.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transmembrane transport protein MmpL3 |
|---|---|
| MTBC0 PGAP re-annotation | trehalose monomycolate RND transporter MmpL3 |
| Revised (this work) | Trehalose monomycolate RND transporter MmpL3. Pfam: MMPL (PF03176.22). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJV5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Trehalose monomycolate exporter MmpL3 |
| Curated function | Transports trehalose monomycolate (TMM) to the cell wall. Flips TMM across the inner membrane. Membrane potential is not required for this function. Transports probably phosphatidylethanolamine (PE) as well. Binds specifically both TMM and PE, but not trehalose dimycolate (TDM). Also binds diacylglycerol (DAG) and other phospholipids, including phosphatidylglycerol (PG), phosphatidylinositol (PI), and cardiolipin (CDL). Contributes to membrane potential, cell wall composition, antibiotic susceptibility and fitness (By similarity). Could also be part of a heme-iron acquisition system..; FUNCTIO. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | mmpL3 |
| eggNOG description | lipid transport |
| Orthologous group | COG2409 |
| KEGG orthology |
K06994, K20466, K20470
|
| Gene Ontology (33) |
GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0005886, GO:0005887, GO:0006810, GO:0006869, GO:0008150, GO:0009273, GO:0009987, GO:0010876 +21 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 | 0.443 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 11 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 |
|---|---|---|---|---|
MMPL | PF03176.22 | 4.4e-38 | 47–340 | MMPL family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: trmB (tRNA (guanine-N(7)-)-methyltransferase), high confidence from genomic context alone (score 837 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0207c hyp |
hypothetical protein | 874 | 850 ctx | neighborhood:798 |
Rv0208c trmB |
tRNA (guanine-N(7)-)-methyltransferase | 862 | 837 ctx | neighborhood:798 |
Rv0210 hyp |
hypothetical protein | 722 | 722 ctx | neighborhood:721 |
Rv3909 hyp |
hypothetical protein | 722 | 666 ctx | cooccurence:663 |
Rv3835 hyp |
hypothetical protein | 658 | 658 ctx | cooccurence:653 |
Rv2739c |
transferase | 640 | 640 ctx | cooccurence:638 |
Rv2843 hyp |
hypothetical protein | 588 | 588 ctx | cooccurence:588 |
Rv0007 |
membrane protein | 564 | 551 ctx | cooccurence:464 |
Rv1024 |
membrane protein | 507 | 507 ctx | cooccurence:501 |
Rv0209 hyp |
hypothetical protein | 487 | 487 ctx | neighborhood:485 |
Rv3755c hyp |
hypothetical protein | 448 | 448 ctx | cooccurence:440 |
Rv0444c rskA |
anti-sigma-K factor RskA | 437 | 438 ctx | cooccurence:433 |
Rv3668c |
protease | 430 | 431 ctx | cooccurence:429 |
Rv3494c mce4F |
Mce family protein Mce4 | 411 | 412 ctx | cooccurence:405 |
Rv3682 ponA2 |
bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase | 421 | 387 |
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: transmembrane transport protein MmpL3
- MTBC0 PGAP product: trehalose monomycolate RND transporter MmpL3
- Pfam (hmmscan --cut_ga): MMPL PF03176.22 (E=4e-38)
- (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_214720.1)
- Domains: Pfam-A via hmmscan --cut_ga — MMPL (PF03176.22)
- 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
COG2409 - Curated reference: UniProt P9WJV5 (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 —
41 functional partner(s); context anchor
trmB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000220|Rv0206c|mmpL3 MFAWWGRTVYRYRFIVIGVMVALCLGGGVFGLSLGKHVTQSGFYDDGSQSVQASVLGDQVYGRDRSGHIVAIFQAPAGKTVDDPAWSKKVVDELNRFQQDHPDQVLGWAGYLRASQATGMATADKKYTFVSIPLKGDDDDTILNNYKAIAPDLQRLDGGTVKLAGLQPVAEALTGTIATDQRRMEVLALPLVAVVLFFVFGGVIAAGLPVMVGGLCIAGALGIMRFLAIFGPVHYFAQPVVSLIGLGIAIDYGLFIVSRFREEIAEGYDTETAVRRTVITAGRTVTFSAVLIVASAIGLLLFPQGFLKSLTYATIASVMLSAILSITVLPACLGILGKHVDALGVRTLFRVPFLANWKISAAYLNWLADRLQRTKTREEVEAGFWGKLVNRVMKRPVLFAAPIVIIMILLIIPVGKLSLGGISEKYLPPTNSVRQAQEEFDKLFPGYRTNPLTLVIQTSNHQPVTDAQIADIRSKAMAIGGFIEPDNDPANMWQERAYAVGASKDPSVRVLQNGLINPADASKKLTELRAITPPKGITVLVGGTPALELDSIHGLFAKMPLMVVILLTTTIVLMFLAFGSVVLPIKATLMSALTLGSTMGILTWIFVDGHFSKWLNFTPTPLTAPVIGLIIALVFGLSTDYEVFLVSRMVEARERGMSTQEAIRIGTAATGRIITAAALIVAVVAGAFVFSDLVMMKYLAFGLMAALLLDATVVRMFLVPSVMKLLGDDCWWAPRWARRLQTRIGLGEIHLPDERKRPVSNGRPARPPVTAGLVAARAAGDPRPPHDPTHPLAESPRPARSSPASSPELTPALEATAAPAAPSGASTTRMQIGSSTEPPTTRLAAAGRSVQSPASTPPPTPTPPSAPSAGQTRAMPLAANRSTDAAGDPAEPTAALPIIRSDGDDSEAATEQLNARGTSDKTRQRRRGGGALSAQDLLRREGRL