mce3F Family assigned · medium auto-curated

H37Rv Rv1971 · MTBC0 mtbc0_002087 · 437 aa · 2234374–2235687 (+) · RefSeq NP_216487.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)Mce family protein Mce3F
MTBC0 PGAP re-annotationMlaD family protein
Revised (this work)MlaD family protein. Pfam: MlaD (PF02470.26).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt O53972 TrEMBL · unreviewed · Predicted
UniProt nameMce-family protein Mce3F

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namemce3F
eggNOG descriptionVirulence factor Mce family protein
Orthologous groupCOG1463
KEGG orthology K02067
KEGG pathways map02010
KEGG modules M00210, M00669, M00670

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) pseudogene candidate

pN/pS 0.72 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 8 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 5.19% of strains (7539) · 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
MlaDPF02470.26 3.4e-1742–116 MlaD protein

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

Closest characterised functional partner: yrbE3A (integral membrane protein), high confidence from genomic context alone (score 996 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1964 yrbE3A integral membrane protein 997 996 ctx neighborhood:876 cooccurence:764 coexpression:815 textmining:412
Rv1965 yrbE3B integral membrane protein 995 995 ctx neighborhood:799 cooccurence:771 coexpression:849
Rv1972 Mce associated membrane protein 994 994 ctx neighborhood:851 cooccurence:755 coexpression:860
Rv1967 mce3B Mce family protein Mce3B 996 993 ctx neighborhood:795 cooccurence:774 coexpression:860 textmining:566
Rv1966 mce3A Mce family protein Mce3A 995 993 ctx neighborhood:787 cooccurence:774 coexpression:860 textmining:443
Rv1970 lprM Mce family lipoprotein LprM 994 993 ctx neighborhood:789 cooccurence:774 coexpression:860
Rv1969 mce3D Mce family protein Mce3D 998 992 ctx neighborhood:786 cooccurence:774 coexpression:857 textmining:778
Rv1968 mce3C Mce family protein Mce3C 990 988 ctx neighborhood:881 coexpression:860
Rv1973 Mce associated membrane protein 976 976 ctx neighborhood:721 cooccurence:608 coexpression:801
Rv1974 membrane protein 956 956 ctx neighborhood:839 coexpression:738
Rv0655 mkl ABC transporter ATP-binding protein 940 900 ctx cooccurence:759 experimental:431 textmining:424
Rv0168 yrbE1B membrane protein 907 881 ctx cooccurence:770
Rv3500c yrbE4B integral membrane protein 902 875 ctx cooccurence:772
Rv0588 yrbE2B hyp hypothetical protein 901 874 ctx cooccurence:770
Rv3501c yrbE4A integral membrane protein 874 872 ctx cooccurence:768

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: Mce family protein Mce3F
  • MTBC0 PGAP product: MlaD family protein
  • Pfam (hmmscan --cut_ga): MlaD PF02470.26 (E=3e-17)
  • (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_216487.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MlaD (PF02470.26)
  • 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 COG1463
  • Curated reference: UniProt O53972 (TrEMBL, unreviewed; Predicted)
  • 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 — 47 functional partner(s); context anchor yrbE3A
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002087|Rv1971|mce3F
MLHLPRRVIVQLAVFTVIAVGVLAITFLHFVRLPAMLFGVGRYTVTMELVEAGGLYRTGNVTYRGFEVGRVAAVRLTDTGVQAVLALKSGIDIPSDLKAEVHSHTAIGETYVELLPRNAASPPLKNGDVIALADTSVPPDINDLLSAANTALEAIPHENLQTVIDESYTAVAGLGLELSRLIKGSAELAIDARANLDPLVALIDRAGPVLDSQTHTSDAIAAWAAQLAAVTGQLQTHDSAVGDLIDRGGPALGETRQLLERLQPTVPILLANLVSVGQVALTYHNDIEQLLVVFPMAIAAEQAGILANLNTKQAYRGQYLSFNLNLNLPPPCTTGFLPAQQRRIPTFEDYPDRPAGDLYCRVPQDSPFNVRGARNIPCETVPGKRAPTVKLCESDEPYLPLNDGYNWKGDPNATVPGLGSGQDIPQTWQTMLLPPGS