mmpL4 Resolved · high auto-curated
H37Rv Rv0450c · MTBC0 - ·
967 aa · 538588–541491 (-) ·
RefSeq NP_214964.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transmembrane transport protein MmpL4 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Transmembrane transport protein MmpL4. Pfam: MMPL (PF03176.22). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WJV3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Siderophore exporter MmpL4 |
| Curated function | Part of an export system, which is required for biosynthesis and secretion of siderophores. Essential for normal replication during the active-growth phase of the murine tuberculosis model. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | mmpL4 |
| eggNOG description | transport protein |
| Orthologous group | COG1033 |
| KEGG orthology |
K06994
|
| Gene Ontology (18) |
GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0030312, GO:0040007, GO:0044110, GO:0044116, GO:0044117 +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)
| pN/pS | 0.182 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 16 synonymous, 9 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 | 1.4e-129 | 59–388 | MMPL family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mmpS4 (membrane protein MmpS4), high confidence from genomic context alone (score 909 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0451c mmpS4 |
membrane protein MmpS4 | 984 | 909 ctx | neighborhood:882 textmining:831 |
Rv1598c hyp |
hypothetical protein | 693 | 693 ctx | cooccurence:693 |
Rv0449c hyp |
hypothetical protein | 668 | 667 ctx | neighborhood:667 |
Rv0290 eccD3 |
ESX-3 secretion system protein EccD | 711 | 653 ctx | cooccurence:650 |
Rv1303 hyp |
hypothetical protein | 639 | 639 ctx | cooccurence:637 |
Rv2945c lppX |
lipoprotein LppX | 715 | 622 ctx | cooccurence:620 |
Rv0283 eccB3 |
ESX-3 secretion system protein EccB3 | 585 | 557 ctx | cooccurence:536 |
Rv0128 |
transmembrane protein | 551 | 551 ctx | cooccurence:551 |
Rv0448c hyp |
hypothetical protein | 538 | 538 ctx | neighborhood:538 |
Rv0447c ufaA1 |
cyclopropane-fatty-acyl-phospholipid synthase UfaA | 535 | 535 ctx | neighborhood:533 |
Rv0446c |
transmembrane protein | 534 | 534 ctx | neighborhood:533 |
Rv0452 |
transcriptional regulator | 620 | 520 ctx | neighborhood:514 |
Rv1145 mmpL13a |
transmembrane transport protein | 572 | 518 ctx | cooccurence:517 |
Rv1278 hyp |
hypothetical protein | 492 | 492 ctx | cooccurence:492 |
Rv0256c PPE2 |
PPE family protein PPE2 | 491 | 491 ctx | cooccurence:488 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): transmembrane transport protein MmpL4
- Pfam (hmmscan --cut_ga): MMPL PF03176.22 (E=1e-129)
- (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_214964.1)
- 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 P9WJV3 (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 —
44 functional partner(s); context anchor
mmpS4 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0450c|mmpL4 MSTKFANDSNTNARPEKPFIARMIHAFAVPIILGWLAVCVVVTVFVPSLEAVGQERSVSLSPKDAPSFEAMGRIGMVFKEGDSDSFAMVIIEGNQPLGDAAHKYYDGLVAQLRADKKHVQSVQDLWGDPLTAAGVQSNDGKAAYVQLSLAGNQGTPLANESVEAVRSIVESTPAPPGIKAYVTGPSALAADMHHSGDRSMARITMVTVAVIFIMLLLVYRSIITVVLLLITVGVELTAARGVVAVLGHSGAIGLTTFAVSLLTSLAIAAGTDYGIFIIGRYQEARQAGEDKEAAYYTMYRGTAHVILGSGLTIAGATFCLSFARMPYFQTLGIPCAVGMLVAVAVALTLGPAVLHVGSRFGLFDPKRLLKVRGWRRVGTVVVRWPLPVLVATCAIALVGLLALPGYKTSYNDRDYLPDFIPANQGYAAADRHFSQARMKPEILMIESDHDMRNPADFLVLDKLAKGIFRVPGISRVQAITRPEGTTMDHTSIPFQISMQNAGQLQTIKYQRDRANDMLKQADEMATTIAVLTRMHSLMAEMASTTHRMVGDTEEMKEITEELRDHVADFDDFWRPIRSYFYWEKHCYGIPICWSFRSIFDALDGIDKLSEQIGVLLGDLREMDRLMPQMVAQIPPQIEAMENMRTMILTMHSTMTGIFDQMLEMSDNATAMGKAFDAAKNDDSFYLPPEVFKNKDFQRAMKSFLSSDGHAARFIILHRGDPQSPEGIKSIDAIRTAAEESLKGTPLEDAKIYLAGTAAVFHDISEGAQWDLLIAAISSLCLIFIIMLIITRAFIAAAVIVGTVALSLGASFGLSVLLWQHILAIHLHWLVLAMSVIVLLAVGSDYNLLLVSRFKQEIGAGLKTGIIRSMGGTGKVVTNAGLVFAVTMASMAVSDLRVIGQVGTTIGLGLLFDTLIVRSFMTPSIAALLGRWFWWPLRVRSRPARTPTVPSETQPAGRPLAMSSDRLG