MTBC Gene Atlas

mmpA Resolved · high

H37Rv Rv0226c · MTBC0 mtbc0_000240 · 576 aa · 270215–271945 (-) · RefSeq NP_214740.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)MmpA, a conserved inner-membrane protein required for efficient surface transport of trehalose mycolates in Corynebacterineae. RefSeq leaves it 'membrane protein'. Deletion of the ortholog (C. glutamicum NCgl2761 / Rv0226c) abolishes acetylation of trehalose monohydroxycorynomycolate (hTMCM), causing hTMCM accumulation in the inner membrane and reduced outer-membrane h2TDCM; MmpA acts with MtrP and TmaT to drive acetylation-dependent mycolate transport (Cashmore 2021). Named mmpA.

Curated reference (UniProt)

UniProt P96408 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable conserved transmembrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group28HIC

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 2.276 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 11 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: Rv0227c (membrane protein), high confidence from genomic context alone (score 973 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0227c membrane protein 996 973 ctx neighborhood:881 cooccurence:772 textmining:871
Rv0236c aftD alpha-(1->3)-arabinofuranosyltransferase 977 799 ctx cooccurence:764 textmining:895
Rv0228 acyltransferase 831 773 ctx neighborhood:582 cooccurence:466
Rv0224c methyltransferase 749 749 ctx cooccurence:743
Rv1476 membrane protein 745 746 ctx cooccurence:744
Rv3635 transmembrane protein 730 730 ctx cooccurence:687
Rv2673 aftC alpha-(1->3)-arabinofuranosyltransferase 714 714 ctx cooccurence:710
Rv0225 hyp hypothetical protein 719 705 ctx cooccurence:692
Rv3346c transmembrane protein 695 696 ctx cooccurence:694
Rv3802c membrane protein 692 677 ctx cooccurence:677
Rv3668c protease 671 671 ctx cooccurence:660
Rv3805c aftB terminal beta-(1->2)-arabinofuranosyltransferase 667 646 ctx cooccurence:615
Rv0885 hyp hypothetical protein 621 621 ctx cooccurence:621
Rv1274 lprB lipoprotein LprB 614 614 ctx cooccurence:613
Rv2342 hyp hypothetical protein 609 609 ctx cooccurence:609

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

  • Required for acetylation-dependent membrane transport of trehalose mycolates (hTMCM->AcTMCM) (Cashmore 2021, PMID 34944401)
  • Acts with MtrP and TmaT; ΔmmpA shifts global membrane lipid composition
  • Named mmpA
  • Curated from the literature crible (project 'Still unknown gene function', 2026-06-09)

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_214740.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 28HIC
  • Curated reference: UniProt P96408 (TrEMBL, unreviewed; 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 — 42 functional partner(s); context anchor Rv0227c
  • Primary literature: Cashmore TJ, Klatt S, Brammananth R, Rainczuk AK, Crellin PK, McConville MJ, Coppel RL (2021). MmpA, a Conserved Membrane Protein Required for Efficient Surface Transport of Trehalose Lipids in Corynebacterineae Biomolecules 11(12):1760. doi:10.3390/biom11121760 PMID:34944401

Ancestral MTBC0 protein sequence

>mtbc0_000240|Rv0226c|mmpA
MRWFRPGYALVLVLLLAAPLLRPGYLLLRDAVSTPRSYVSANALGLTSAPRATPQDFAVALASHLVDGGVVVKALLLLGLWLAGWGAARLVATALPAAGAAGQFVAITLAIWNPYVAERLLQGHWSLLVGYGCLPWVATAMLTMRTTVGAGWFGLFGLAFWVALAGLTPSGLLLAATVAVVCVAMPGAGRPRWQCGVAALGSALVGALPWLTASALGSSLTSHTAANQLGVTAFAPRAEPGLGTLGSLASLGGIWNGEAVPSSRTTLFAVASAVVLLAMVAIGLPTVARRPVAVPLLTLAAVSVMVPAVLATGPGLHALRVVVDAAPGLGVLRDGQKWVALAVPGYTLSGAGTVLTLRRWLRPATAAVVCCLALVLTLPDLAWGVWGKVAPVHYPSGWAAVAAAINADPRTVAVLPAGTMRRFSWSGSAPVLDPLPRWVRADVLTTGDLVISGVTVPGEDAHARAVQELLLTGPHPSTLAAAGVGWLVVESDSAGDMGAAARTLGRLAAAHRDDELALYRVGGQTSGASSARLKATMLAHWAWLSMLLVGGAGAAGYWVRRHLHHCEDTPASRAQD