mmpL8 Resolved · high auto-curated
H37Rv Rv3823c · MTBC0 mtbc0_004052 ·
1089 aa · 4312370–4315639 (-) ·
RefSeq NP_218340.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | integral membrane transport protein MmpL8 |
|---|---|
| MTBC0 PGAP re-annotation | sulfolipid-1 RND transporter MmpL8 |
| Revised (this work) | Sulfolipid-1 RND transporter MmpL8. Pfam: MMPL (PF03176.22), Sterol-sensing (PF12349.15). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJU5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Sulfolipid-1 exporter MmpL8 |
| Curated function | Required for the biosynthesis and the transport across the inner membrane of sulfolipid-1 (SL-1), which is a major cell wall lipid of pathogenic mycobacteria. Could also transport SL1278 (2-palmitoyl-3-(C43)-phthioceranyl-alpha, alpha'-D-trehalose-2'-sulfate), which is the precursor of SL-1. Required for virulence. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | mmpL10 |
| eggNOG description | transport protein |
| Orthologous group | COG1511 |
| KEGG orthology |
K06994
|
| Gene Ontology (30) |
GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006082, GO:0006629, GO:0006790, GO:0008150, GO:0008152, GO:0008610 +18 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 | 0.379 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 14 synonymous, 15 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 | 3.2e-107 | 75–401 | MMPL family |
Sterol-sensing | PF12349.15 | 2.6e-05 | 240–375 | Sterol-sensing domain of SREBP cleavage-activation |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: papA1 (acyltransferase), high confidence from genomic context alone (score 937 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3824c papA1 |
acyltransferase | 994 | 937 ctx | neighborhood:535 coexpression:803 textmining:915 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 969 | 862 ctx | neighborhood:436 coexpression:737 textmining:791 |
Rv1183 mmpL10 |
transmembrane transport protein MmpL10 | 813 | 808 | coexpression:803 |
Rv1598c hyp |
hypothetical protein | 562 | 562 ctx | cooccurence:562 |
Rv1303 hyp |
hypothetical protein | 507 | 507 ctx | cooccurence:507 |
Rv1145 mmpL13a |
transmembrane transport protein | 550 | 500 ctx | cooccurence:497 |
Rv1182 papA3 |
acyltransferase papA3 | 881 | 484 | textmining:779 |
Rv0523c hyp |
hypothetical protein | 407 | 408 ctx | cooccurence:406 |
Rv3826 fadD23 |
long-chain-fatty-acid--CoA ligase FadD23 | 665 | 380 | textmining:482 |
Rv3820c papA2 |
trehalose-2-sulfate acyltransferase | 813 | 368 | textmining:717 |
Rv2942 mmpL7 |
transmembrane transport protein MmpL7 | 455 | 323 | |
Rv0383c ttfA hyp |
hypothetical protein | 411 | 298 | |
Rv1184c chp2 hyp |
hypothetical protein | 414 | 293 | |
Rv0295c stf0 hyp |
hypothetical protein | 628 | 244 | textmining:528 |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 750 | 217 | textmining:695 |
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: integral membrane transport protein MmpL8
- MTBC0 PGAP product: sulfolipid-1 RND transporter MmpL8
- Pfam (hmmscan --cut_ga): MMPL PF03176.22 (E=3e-107), Sterol-sensing PF12349.15 (E=3e-05)
- (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_218340.1)
- Domains: Pfam-A via hmmscan --cut_ga — MMPL (PF03176.22), Sterol-sensing (PF12349.15)
- 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
COG1511 - Curated reference: UniProt P9WJU5 (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 —
23 functional partner(s); context anchor
papA1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_004052|Rv3823c|mmpL8 MCDVLMQPVRTPRPSTNLRSKPLRPTGDGGVFPRLGRLIVRRPWVVIAFWVALAGLLAPTVPSLDAISQRHPVAILPSDAPVLVSTRQMTAAFREAGLQSVAVVVLSDAKGLGAADERSYKELVDALRRDTRDVVMLQDFVTTPPLRELMTSKDNQAWILPVGLPGDLGSTQSKQAYARVADIVEHQVAGSTLTANLTGPAATVADLNLTGQRDRSRIEFAITILLLVILLIIYRNPITMVLPLITIGMSVVVAQRLVAIAGLAGLGIANQSIIFMSGMMVGAGTDYAVFLISRYHDYLRQGADSDQAVKKALTSIGKVIAASAATVAITFLGMVFTQLGILKTVGPMLGISVAVVFFAAVTLLPALMVLTGRRGWIAPRRDLTRRFWRSSGVHIVRRPKTHLLASALVLVILAGCAGLARYNYDDRKTLPASVESSIGYAALDKHFPSNLIIPEYLFIQSSTDLRTPKALADLEQMVQRVSQVPGVAMVRGITRPAGRSLEQARTSWQAGEVGSKLDEGSKQIAAHTGDIDKLAGGANLMASKLGDVRAQVNRAISTVGGLIDALAYLQDLLGGNRVLGELEGAEKLIGSMRALGDTIDADASFVANNTEWASPVLGALDSSPMCTADPACASARTELQRLVTARDDGTLAKISELARQLQATRAVQTLAATVSGLRGALATVIRAMGSLGMSSPGGVRSKINLVNKGVNDLADGSRQLAEGVQLLVDQVKKMGFGLGEASAFLLAMKDTATTPAMAGFYIPPELLSYATGESVKAETMPSEYRDLLGGLNVDQLKKVAAAFISPDGHSIRYLIQTDLNPFSTAAMDQIDAITAAARGAQPNTALADAKVSVVGLPVVLKDTRDYSDHDLRLIIAMTVCIVLLILIVLLRAIVAPLYLIGSVIVSYLAALGIGVIVFQFLLGQEMHWSIPGLTFVILVAVGADYNMLLISRLREEAVLGVRSGVIRTVASTGGVITAAGLIMAASMYGLVFASLGSVVQGAFVLGTGLLLDTFLVRTVTVPAIAVLVGQANWWLPSSWRPATWWPLGRRRGRAQRTKRKPLLPKEEEEQSPPDDDDLIGLWLHDGLRL