mmpL5 Resolved · high auto-curated
H37Rv Rv0676c · MTBC0 mtbc0_000715 ·
964 aa · 779672–782566 (-) ·
RefSeq NP_215190.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transmembrane transport protein MmpL5 |
|---|---|
| MTBC0 PGAP re-annotation | siderophore RND transporter MmpL5 |
| Revised (this work) | Siderophore RND transporter MmpL5. 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 |
P9WJV1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Siderophore exporter MmpL5 |
| Curated function | Part of an export system, which is required for biosynthesis and secretion of siderophores..; FUNCTION: Overexpression of the system confers non-target based resistance to azoles, clofazimine and bedaquiline, via an efflux mechanism. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | mmpL5 |
| eggNOG description | transport protein |
| Orthologous group | COG1033 |
| KEGG orthology |
K06994
|
| Gene Ontology (18) |
GO:0005575, GO:0005576, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0005887, GO:0016020, GO:0016021, GO:0031224, GO:0031226 +6 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) pseudogene candidate
| pN/pS | 1.142 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 13 missense, 1 nonsense, 2 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 1.34% of strains (1952) · 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 |
|---|---|---|---|---|
MMPL | PF03176.22 | 1.9e-122 | 63–393 | MMPL family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mmpS5 (membrane protein MmpS5), high confidence from genomic context alone (score 968 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0677c mmpS5 |
membrane protein MmpS5 | 998 | 968 ctx | neighborhood:801 coexpression:848 textmining:951 |
Rv0678 mmpR5 hyp |
hypothetical protein | 989 | 915 ctx | neighborhood:571 coexpression:810 textmining:883 |
Rv3160c |
TetR family transcriptional regulator | 799 | 800 | coexpression:799 |
Rv1598c hyp |
hypothetical protein | 724 | 725 ctx | cooccurence:724 |
Rv0290 eccD3 |
ESX-3 secretion system protein EccD | 745 | 695 ctx | cooccurence:693 |
Rv1303 hyp |
hypothetical protein | 665 | 665 ctx | cooccurence:664 |
Rv0283 eccB3 |
ESX-3 secretion system protein EccB3 | 648 | 578 ctx | cooccurence:560 |
Rv2945c lppX |
lipoprotein LppX | 672 | 566 ctx | cooccurence:566 |
Rv0466 hyp |
hypothetical protein | 544 | 544 ctx | cooccurence:544 |
Rv0128 |
transmembrane protein | 529 | 529 ctx | cooccurence:529 |
Rv1278 hyp |
hypothetical protein | 520 | 521 ctx | cooccurence:519 |
Rv0523c hyp |
hypothetical protein | 504 | 505 ctx | cooccurence:504 |
Rv3035 hyp |
hypothetical protein | 482 | 483 ctx | cooccurence:476 |
Rv0256c PPE2 |
PPE family protein PPE2 | 479 | 480 ctx | cooccurence:478 |
Rv1270c lprA |
lipoprotein LprA | 475 | 476 ctx | cooccurence:475 |
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 MmpL5
- MTBC0 PGAP product: siderophore RND transporter MmpL5
- Pfam (hmmscan --cut_ga): MMPL PF03176.22 (E=2e-122)
- (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_215190.1)
- 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
COG1033 - Curated reference: UniProt P9WJV1 (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 —
60 functional partner(s); context anchor
mmpS5 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000715|Rv0676c|mmpL5 MIVQRTAAPTGSVPPDRHAARPFIPRMIRTFAVPIILGWLVTIAVLNVTVPQLETVGQIQAVSMSPDAAPSMISMKHIGKVFEEGDSDSAAMIVLEGQRPLGDAAHAFYDQMIGRLQADTTHVQSLQDFWGDPLTATGAQSSDGKAAYVQVKLAGNQGESLANESVEAVKTIVERLAPPPGVKVYVTGSAALVADQQQAGDRSLQVIEAVTFTVIIVMLLLVYRSIITSAIMLTMVVLGLLATRGGVAFLGFHRIIGLSTFATNLLVVLAIAAATDYAIFLIGRYQEARGLGQDRESAYYTMFGGTAHVVLGSGLTIAGATFCLSFTRLPYFQTLGVPLAIGMVIVVAAALTLGPAIIAVTSRFGKLLEPKRMARVRGWRKVGAAIVRWPGPILVGAVALALVGLLTLPGYRTNYNDRNYLPADLPANEGYAAAERHFSQARMNPEVLMVESDHDMRNSADFLVINKIAKAIFAVEGISRVQAITRPDGKPIEHTSIPFLISMQGTSQKLTEKYNQDLTARMLEQVNDIQSNIDQMERMHSLTQQMADVTHEMVIQMTGMVVDVEELRNHIADFDDFFRPIRSYFYWEKHCYDIPVCWSLRSVFDTLDGIDVMTEDINNLLPLMQRLDTLMPQLTAMMPEMIQTMKSMKAQMLSMHSTQEGLQDQMAAMQEDSAAMGEAFDASRNDDSFYLPPEVFDNPDFQRGLEQFLSPDGHAVRFIISHEGDPMSQAGIARIAKIKTAAKEAIKGTPLEGSAIYLGGTAAMFKDLSDGNTYDLMIAGISALCLIFIIMLIITRSVVAAAVIVGTVVLSLGASFGLSVLIWQHILGIELHWLVLAMAVIILLAVGADYNLLLVARLKEEIHAGINTGIIRAMGGSGSVVTAAGLVFAFTMMSFAVSELTVMAQVGTTIGMGLLFDTLIVRSFMTPSIAALLGKWFWWPQVVRQRPVPQPWPSPASARTFALV