Rv2640c Family assigned · medium auto-curated

H37Rv Rv2640c · MTBC0 mtbc0_002810 · 119 aa · 2989039–2989398 (-) · RefSeq NP_217156.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ArsR family transcriptional regulator
MTBC0 PGAP re-annotationRv2640c family ArsR-like transcriptional regulator
Revised (this work)Rv2640c family ArsR-like transcriptional regulator. Pfam: HTH_20 (PF12840.14), HTH_5 (PF01022.27).

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

Curated reference (UniProt)

UniProt I6Y1A7 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible transcriptional regulatory protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namearsR
eggNOG descriptionarsR family
Orthologous groupCOG0640
KEGG orthology K03892

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 0 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
HTH_20PF12840.14 2.2e-1039–88 Helix-turn-helix domain
HTH_5PF01022.27 3.8e-1541–89 Bacterial regulatory protein, arsR family

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

Closest characterised functional partner: cadI (cadmium inducible protein CadI), high confidence from genomic context alone (score 812 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2641 cadI cadmium inducible protein CadI 872 812 ctx neighborhood:665 cooccurence:453
Rv2643 arsC arsenic-transport integral membrane protein ArsC 851 802 ctx neighborhood:687
Rv2642 ArsR family transcriptional regulator 602 602 ctx neighborhood:532
Rv2639c integral membrane protein 564 549 ctx neighborhood:542
Rv0576 transcriptional regulator 505 505 ctx cooccurence:458
Rv1994c cmtR HTH-type transcriptional regulator CmtR 680 462 ctx cooccurence:454 textmining:431
Rv2034 ArsR family HTH-type transcriptional repressor 652 264 textmining:547
Rv1353c HTH-type transcriptional regulator 442 257
Rv3173c TetR/Acr family transcriptional regulator 569 227 textmining:466
Rv1674c transcriptional regulator 553 225 textmining:448
Rv3167c TetR family transcriptional regulator 425 202
Rv3744 nmtR HTH-type transcriptional regulator NmtR 590 83 textmining:572
Rv0827c kmtR HTH-type transcriptional regulator KmtR 450 78 textmining:428
Rv0662c vapB7 antitoxin VapB7 416 52 textmining:410
Rv1952 vapB14 antitoxin VapB14 439 41 textmining:439

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: ArsR family transcriptional regulator
  • MTBC0 PGAP product: Rv2640c family ArsR-like transcriptional regulator
  • Pfam (hmmscan --cut_ga): HTH_20 PF12840.14 (E=2e-10), HTH_5 PF01022.27 (E=4e-15)
  • (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_217156.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HTH_20 (PF12840.14), HTH_5 (PF01022.27)
  • 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 COG0640
  • Curated reference: UniProt I6Y1A7 (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 — 15 functional partner(s); context anchor cadI
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002810|Rv2640c|
MPKSLPVIDISAPVCCAPVAAGPMSDGDALAVALRLKALADPARVKIMSYLFSSPAGEQVSGQLAAALSLSDGTVSHHLAQLRKAGLVISDRRGMHVFHRVHPEALQALCTVLNPNCCA