mce3R Family assigned · medium auto-curated

H37Rv Rv1963c · MTBC0 mtbc0_002079 · 406 aa · 2224698–2225918 (-) · RefSeq NP_216479.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transcriptional repressor Mce3R
MTBC0 PGAP re-annotationTetR family transcriptional regulator Mce3R
Revised (this work)TetR family transcriptional regulator Mce3R. Pfam: TetR_N (PF00440.30).

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

Curated reference (UniProt)

UniProt P95251 SwissProt · reviewed · Evidence at protein level
UniProt nameTranscriptional repressor Mce3R
Curated functionMce3R represses the transcription of mce3 operon and down-regulates its own expression, but does not affect the transcription of mce1, mce2 and mce4 operons.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namemce3R
eggNOG descriptionRegulatory
Orthologous groupCOG1309
Gene Ontology (59) GO:0000976, GO:0001067, GO:0003674, GO:0003676, GO:0003677, GO:0003690, GO:0003700, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737 +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 0.442 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 5 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)

PfamAccessioni-EvalueResiduesDescription
TetR_NPF00440.30 7.2e-1719–65 Bacterial regulatory proteins, tetR family

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

Closest characterised functional partner: iniR (transcriptional regulator), high confidence from genomic context alone (score 891 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0339c iniR transcriptional regulator 891 891 ctx cooccurence:608 coexpression:734
Rv1267c embR transcriptional regulator EmbR 870 868 coexpression:815
Rv0452 transcriptional regulator 826 826 coexpression:826
Rv1931c transcriptional regulator 803 803 coexpression:803
Rv0212c nadR transcriptional regulator NadR 810 801 coexpression:801
Rv3167c TetR family transcriptional regulator 800 800 coexpression:800
Rv3830c TetR family transcriptional regulator 804 799 coexpression:799
Rv3082c virS HTH-type transcriptional regulator VirS 802 799 coexpression:799
Rv1027c kdpE transcriptional regulator KdpE 799 798 coexpression:798
Rv2912c TetR family HTH-type transcriptional regulator 792 793 coexpression:751
Rv0494 HTH-type transcriptional regulator 797 791 coexpression:737
Rv1674c transcriptional regulator 793 785 coexpression:785
Rv1675c cmr HTH-type transcriptional regulator Cmr 783 783 coexpression:783
Rv1151c cobB NAD-dependent protein deacylase 784 776 coexpression:776
Rv2282c LysR family HTH-type transcriptional regulator 814 769 coexpression:740

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: transcriptional repressor Mce3R
  • MTBC0 PGAP product: TetR family transcriptional regulator Mce3R
  • Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (E=7e-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_216479.1)
  • Domains: Pfam-A via hmmscan --cut_ga — TetR_N (PF00440.30)
  • 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 COG1309
  • Curated reference: UniProt P95251 (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 — 86 functional partner(s); context anchor iniR
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002079|Rv1963c|mce3R
MASVAQPVRRRPKDRKKQILDQAVGLFIERGFHSVKLEDIAEAAGVTARALYRHYDNKQALLAEAIRTGQDQYQSARRLTEGETEPTPRPLNADLEDLIAAAVASRALTVLWQREARYLNEDDRTAVRRRINAIVAGMRDSVLLEVPDLSPQHSELRAWAVSSTLTSLGRHSLSLPGEELKKLLYQACMAAARTPPVCELPPLPAGDAARDEADVLFSRYETLLAAGARLFRAQGYPAVNTSEIGKGAGIAGPGLYRSFSSKQAILDALIRRLDEWRCLECIRALRANQQAAQRLRGLVQGHVRISLDAPDLVAVSVTELSHASVEVRDGYLRNQGDREAVWIDLIGKLVPATSVAQGRLLVAAAISFIEDVARTWHLTRYAGVADEISGLALAILTSGAGNLLRA