mce2R Family assigned · medium auto-curated

H37Rv Rv0586 · MTBC0 mtbc0_000616 · 240 aa · 687961–688683 (+) · RefSeq NP_215100.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)HTH-type transcriptional regulator Mce2R
MTBC0 PGAP re-annotationFadR family transcriptional regulator Mce2R
Revised (this work)FadR family transcriptional regulator Mce2R. Pfam: GntR (PF00392.28), FCD (PF07729.18).

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

Curated reference (UniProt)

UniProt P9WMG5 SwissProt · reviewed · Evidence at protein level
UniProt nameHTH-type transcriptional regulator Mce2R
Curated functionNegatively regulates the expression of its operon as well as expression of end (endonuclease 4).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namemce2R
eggNOG descriptionGntR family
Orthologous groupCOG2186
Gene Ontology (59) GO:0003674, GO:0003676, GO:0003677, GO:0005488, GO:0005575, GO:0006355, GO:0008150, GO:0009605, GO:0009607, GO:0009889, GO:0009890, GO:0009892 +47 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 1.054 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 2 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.14% of strains (197) · 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
GntRPF00392.28 8.6e-2013–74 Bacterial regulatory proteins, gntR family
FCDPF07729.18 6.9e-10113–223 FCD domain

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

Closest characterised functional partner: mce2C (Mce family protein Mce2C), high confidence from genomic context alone (score 803 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0587 yrbE2A hyp hypothetical protein 985 889 ctx neighborhood:882 textmining:870
Rv0588 yrbE2B hyp hypothetical protein 958 886 ctx neighborhood:882 textmining:653
Rv0591 mce2C Mce family protein Mce2C 803 803 ctx neighborhood:801
Rv0589 mce2A Mce family protein Mce2A 957 789 ctx neighborhood:786 textmining:805
Rv0590 mce2B Mce-family protein Mce2B; Rv0590, (MTCY19H5.32c), len: 275 aa. Mce2B; belongs to 24-membered Mycobacterium tuberculosis Mce protein family ( 788 787 ctx neighborhood:785
Rv0590A Mce-family related protein; Rv0590A, len: 84 aa. Probable continuation of mce2B|Rv0590. Can find no frameshift to account for this. Possible 787 786 ctx neighborhood:785
Rv0594 mce2F Mce family protein Mce2F 820 782 ctx neighborhood:781
Rv0593 lprL Mce family lipoprotein LprL 782 782 ctx neighborhood:781
Rv0592 mce2D Mce family protein Mce2D 782 782 ctx neighborhood:781
Rv0585c integral membrane protein 566 545 ctx neighborhood:545
Rv0792c transcriptional regulator 534 516
Rv0043c HTH-type transcriptional regulator 561 503 ctx cooccurence:469
Rv0904c accD3 acetyl-CoAcarboxylase carboxyl transferase subunit beta 542 503 coexpression:431
Rv0165c mce1R transcriptional regulator Mce1R 829 456 ctx cooccurence:416 textmining:700
Rv1719 transcriptional regulator 429 399

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: HTH-type transcriptional regulator Mce2R
  • MTBC0 PGAP product: FadR family transcriptional regulator Mce2R
  • Pfam (hmmscan --cut_ga): GntR PF00392.28 (E=9e-20), FCD PF07729.18 (E=7e-10)
  • (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_215100.1)
  • Domains: Pfam-A via hmmscan --cut_ga — GntR (PF00392.28), FCD (PF07729.18)
  • 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 COG2186
  • Curated reference: UniProt P9WMG5 (SwissProt, reviewed; 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 — 21 functional partner(s); context anchor mce2C
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000616|Rv0586|mce2R
MALQPVTRRSVPEEVFEQIATDVLTGEMPPGEALPSERRLAELLGVSRPAVREALKRLSAAGLVEVRQGDVTTVRDFRRHAGLDLLPRLLFRNGELDISVVRSILEARLRNFPKVAELAAERNEPELAELLQDSLRALDTEEDPIVWQRHTLDFWDHVVDSAGSIVDRLMYNAFRAAYEPTLAALTTTMTAAAKRPSDYRKLADAICSGDPTGAKKAAQDLLELANTSLMAVLVSQASRQ