Rv1146 Resolved · high auto-curated

H37Rv Rv1146 · MTBC0 - · 470 aa · 1273355–1274767 (+) · RefSeq NP_215662.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane transport protein
MTBC0 PGAP re-annotation
Revised (this work)Transmembrane transport protein. 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 O06546 TrEMBL · unreviewed · Inferred from homology
UniProt nameProbable conserved transmembrane transport protein MmpL13b

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namemmpL13
eggNOG descriptionMmpL family
Orthologous groupCOG2409
KEGG orthology K06994, K20466, K20470
Gene Ontology (38) GO:0005575, GO:0005576, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0005887, GO:0006810, GO:0006869, GO:0008150 +26 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 0.186 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 3 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.24% of strains (351) · clonal

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 6.2e-23202–422 MMPL family

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

Closest characterised functional partner: mmpL13a (transmembrane transport protein), high confidence from genomic context alone (score 999 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1145 mmpL13a transmembrane transport protein 999 999 ctx neighborhood:709 fusion:900 cooccurence:774 coexpression:805 textmining:650
Rv1147 hyp hypothetical protein 857 857 ctx neighborhood:490 coexpression:732
Rv0736 rslA anti-sigma-L factor RslA 746 746 coexpression:746
Rv2714 hyp hypothetical protein 425 426 ctx cooccurence:425
Rv0202c mmpL11 transmembrane transport protein MmpL11 443 307
Rv1091 PE_PGRS22 PE-PGRS family protein PE_PGRS22 528 71 textmining:513
Rv3595c PE_PGRS59 PE-PGRS family protein PE_PGRS59 525 71 textmining:510
Rv1396c PE_PGRS25 PE-PGRS family protein PE_PGRS25 453 71 textmining:436
Rv1089A celA2a Rv1089A, len: 34 aa. Probable celA2a, first part of cellulase (endoglucanase), similar to N-terminus of others. This region is a possible MT 560 70 textmining:547
Rv1090 celA2b Rv1090, (MTV017.43), len: 151 aa. Probable celA2b,second part of cellulase (endoglucanase), similar to C-terminus of others e.g. O08468 cell 527 50 textmining:523
Rv3566A hyp hypothetical protein 549 47 textmining:547
Rv0388c PPE9 Rv0388c, (MTV036.23c), len: 180 aa. PPE9, Member of the Mycobacterium tuberculosis PPE family, highly similar to others e.g. MTCY10G2_10|Z92 434 47 textmining:431
Rv0304c PPE5 PPE family protein PPE5 441 46 textmining:439
Rv3233c Rv3233c, (MTCY20B11.08c), len: 196 aa. Possible triacylglycerol synthase (See Daniel et al., 2004), similar to C-terminus of Q9RIU8|SCM11.13 436 46 textmining:434
Rv0305c PPE6 PPE family protein PPE6 438 45 textmining:436

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
  • Pfam (hmmscan --cut_ga): MMPL PF03176.22 (E=6e-23)
  • (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_215662.1)
  • 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 O06546 (TrEMBL, unreviewed; 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 — 20 functional partner(s); context anchor mmpL13a
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1146|
MATVAFVATASIVITPAAIVLLGPRLDALDVRRLVRRLLGRPDPVHKPVKQLFWYRSSKFVMRRWLPVGTAVVALLVLLGLPFLSVKWGFPDDRVLPRSASARQVGDILRDDFGHDPATQIPIVVPDARGLGPVELDSYAAELSRVPDVSAVAAPTGTFVDGSWVGTPRGATGLAEGSAFLTVSSTAPLFSRASDIQLKRLHQVAGPAGRSVVMAGVAQVNRDSVDAVTDRLPMVLGLIAAITYVLLFLLTGSVVLPAKALVCNVLSLTAAFGALVWIFQEGHFGALGTTPSGTLVANMPVLLFCIAFGLSMDYEVFLVSRIREYWLESGAARPARRSVAEVHAANDESVALGVARTGRVITAAALVMSMSFAALIAAHVSFMRMFGLGLTLAVAADATLVRMVVVPAFMHVTGRWNWWAPRPLAWLHERFGVSEAAEPVSRRRSHAGGLGKIAGRSDGQTIPASLTRNG