mmpL12 Resolved · high auto-curated

H37Rv Rv1522c · MTBC0 mtbc0_001629 · 1146 aa · 1723981–1727421 (-) · RefSeq NP_216038.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane transport protein MmpL12
MTBC0 PGAP re-annotationRND transporter MmpL12
Revised (this work)RND transporter MmpL12. 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 P9WJT7 SwissProt · reviewed · Inferred from homology
UniProt nameProbable transport protein MmpL12
Curated functionMay be involved in glycolipid transport.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namemmpL8
eggNOG descriptiontransport protein
Orthologous groupCOG1033
KEGG orthology K06994
Gene Ontology (26) GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0008150, GO:0009605, GO:0009607, GO:0030312, GO:0043207, GO:0044403 +14 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 0.821 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 8 synonymous, 18 missense, 1 nonsense, 3 frameshift
Disruption 4 distinct premature-stop/frameshift site(s); most common in 11.95% of strains (17354) · convergent

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 9.4e-10657–383 MMPL family

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

Closest characterised functional partner: Rv1523 (methyltransferase), medium confidence from genomic context alone (score 575 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1523 methyltransferase 833 575 ctx neighborhood:567 textmining:624
Rv1598c hyp hypothetical protein 514 515 ctx cooccurence:512
Rv1524 glycosyltransferase 526 509 ctx neighborhood:497
Rv1145 mmpL13a transmembrane transport protein 503 485 ctx cooccurence:483
Rv1303 hyp hypothetical protein 441 442 ctx cooccurence:440
Rv1525 wbbL2 rhamnosyl transferase WbbL 661 422 ctx neighborhood:411 textmining:438
Rv3824c papA1 acyltransferase 483 312
Rv3820c papA2 trehalose-2-sulfate acyltransferase 465 298
Rv1182 papA3 acyltransferase papA3 490 294
Rv1527c pks5 polyketide synthase 448 196
Rv1518 hyp hypothetical protein 650 108 textmining:624
Rv1505c hyp hypothetical protein 550 67 textmining:538
Rv3322c methyltransferase 804 47 textmining:803
Rv2813 hyp hypothetical protein 441 42 textmining:441
Rv1895 zinc-binding alcohol dehydrogenase 803 41 textmining:803

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 MmpL12
  • MTBC0 PGAP product: RND transporter MmpL12
  • Pfam (hmmscan --cut_ga): MMPL PF03176.22 (E=9e-106)
  • (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_216038.1)
  • 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 P9WJT7 (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 — 18 functional partner(s); context anchor Rv1523
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001629|Rv1522c|mmpL12
MARHDEAKAGGLFDRIGNFVVRWPLIVIGCWIAVAAALTLLLPTLQAQAAKREQAPLPPGAPSMVLQKEMSAAFQEKIETSALLLVLLTNENGLGPADEAVYRKLIENLRADTQDKISVQDFLAVPEMKELLASKDNKAWNLPITFAGDAASPETQAAFKRVAAIVKQTVAGTSLTVHLSGPIATVADLTELGEKDVRIIEIGTAVSVLIILILVYRNLVTMLVPLATIGASVVTAQGTLSGLAEFGLAVNMQAIVFMSAVMIGAGTDYAVFLISRYHDYVRHGEKSDMAVKKALMSIGKVITASAATVAVTFLAMVFTKLEVFSAVGPAIAVAITVSLLGAVTLLPAILTLTGRRGWIKPRRDLTSRMWRRSGVRIVRRPTIHLVGSLIVLVALAGCTLLIRFNYDDLKTVPQHVESVKGYEAMNRHFPMNAMTPMVLFIKSPRDLRTPGALADIEMMSREIAELPNIVMVRGLTRPNGEPLKETKVSFQAGEVGGKLDEATTLLEEHGGELDQLTGGAHQLADALAQIRNEINGAVASSSGIVNTLQAMMDLMGGDKTIRQLENASQYVGRMRALGDNLSGTVTDAEQIATWASPMVNALNSSPVCNSDPACRTSRAQLAAIVQAQDDGLLRSIRALAVTLQQTQEYQTLARTVSTLDGQLKQVVSTLKAVDGLPTKLAQMQQGANALADGSAALAAGVQELVDQVKKMGSGLNEAADFLLGIKRDADKPSMAGFNIPPQIFSRDEFKKGAQIFLSADGHAARYFVQSALNPATTEAMDQVNDILRVADSARPNTELEDATIGLAGVPTALRDIRDYYNSDMKFIVIATIVIVFLILVILLRALVAPIYLIGSVLISYLSALGIGTLVFQLILGQEMHWSLPGLSFILLVAIGADYNMLLISRIRDESPHGIRIGVIRTVGSTGGVITSAGLIFAASMFGLVGASINTMAQAGFTIGIGIVLDTFLVRTVTVPALTTMIGRANWWPSELGRDPSTPPTKADRWLRRVKGHRRKAPIPAPKPPHTKVVRNTNGHASKAATKSVPNGKPADLAEGNGEYLIDHLRRHSLPLFGYAAMPAYDVVDGVSKPNGDGAHIGKEPVDHLLGHSLPLFGLAGLPSYDRWDDTSIGEPAVGHAGSKPDAKLST