mmpL6 Resolved · high auto-curated

H37Rv Rv1557 · MTBC0 - · 397 aa · 1761744–1762937 (+) · RefSeq NP_216073.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane transport protein MmpL6
MTBC0 PGAP re-annotation
Revised (this work)Transmembrane transport protein MmpL6. 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 P9WJU9 SwissProt · reviewed · Inferred from homology
UniProt nameProbable transport protein MmpL6

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namemmpL6
eggNOG descriptionMMPL family
Orthologous groupCOG2409
KEGG orthology K06994
Gene Ontology (4) GO:0008150, GO:0010033, GO:0042221, GO:0050896

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 2.451 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 7 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)

PfamAccessioni-EvalueResiduesDescription
MMPLPF03176.22 9.3e-10529–364 MMPL family

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: mmpL13a (transmembrane transport protein), medium confidence from genomic context alone (score 690 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1558 hyp hypothetical protein 868 868 ctx neighborhood:867
Rv1145 mmpL13a transmembrane transport protein 706 690 ctx cooccurence:687
Rv1559 ilvA threonine dehydratase IlvA 680 681 ctx neighborhood:676
Rv1556 HTH-type transcriptional regulator 572 572 ctx neighborhood:498
Rv1560 vapB11 antitoxin VapB11 561 561 ctx neighborhood:556
Rv1561 vapC11 ribonuclease VapC11 561 561 ctx neighborhood:556
Rv1598c hyp hypothetical protein 460 461 ctx cooccurence:459
Rv0290 eccD3 ESX-3 secretion system protein EccD 428 429 ctx cooccurence:427
Rv2147c sepF cell division protein SepF 400 372
Rv2945c lppX lipoprotein LppX 489 323
Rv0202c mmpL11 transmembrane transport protein MmpL11 446 310
Rv1551 plsB1 acyltransferase PlsB 405 233
Rv1856c oxidoreductase 430 196
Rv0078 transcriptional regulator 810 66 textmining:805
Rv1472 echA12 enoyl-CoA hydratase EchA12 439 52 textmining:433

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 MmpL6
  • Pfam (hmmscan --cut_ga): MMPL PF03176.22 (E=9e-105)
  • (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_216073.1)
  • 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 P9WJU9 (SwissProt, reviewed; Inferred from homology)
  • 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 — 19 functional partner(s); context anchor mmpL13a
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1557|mmpL6
MQGISVTGLVKRGWMVRSVFDTIDGIDQLGEQLASVTVTLDKLAAIQPQLVALLPDEIASQQINRELALANYATMSGIYAQTAALIENAAAMGQAFDAAKNDDSFYLPPEAFDNPDFQRGLKLFLSADGKAARMIISHEGDPATPEGISHIDAIKQAAHEAVKGTPMAGAGIYLAGTAATFKDIQDGATYDLLIAGIAALSLILLIMMIITRSLVAALVIVGTVALSLGASFGLSVLVWQHLLGIQLYWIVLALAVILLLAVGSDYNLLLISRFKEEIGAGLNTGIIRAMAGTGGVVTAAGLVFAATMSSFVFSDLRVLGQIGTTIGLGLLFDTLVVRAFMTPSIAVLLGRWFWWPQRVRPRPASRMLRPYGPRPVVRELLLREGNDDPRTQVATHR