Rv2621c Family assigned · medium auto-curated

H37Rv Rv2621c · MTBC0 mtbc0_002790 · 224 aa · 2971446–2972120 (-) · RefSeq NP_217137.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transcriptional regulator
MTBC0 PGAP re-annotationhelix-turn-helix domain-containing protein
Revised (this work)Helix-turn-helix domain-containing protein. Pfam: HTH_20 (PF12840.14).

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

Curated reference (UniProt)

UniProt I6Y187 TrEMBL · unreviewed · Predicted
UniProt namePossible transcriptional regulatory protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptionTranscriptional regulator
Orthologous groupCOG2345

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 3.364 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 9 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.22% of strains (320) · 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
HTH_20PF12840.14 1.1e-0817–58 Helix-turn-helix domain

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

Closest characterised functional partner: Rv2620c (transmembrane protein), high confidence from genomic context alone (score 920 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2620c transmembrane protein 920 920 ctx neighborhood:882
Rv2619c hyp hypothetical protein 908 908 ctx neighborhood:859
Rv3183 higA3 transcriptional regulator 824 824 coexpression:797
Rv3167c TetR family transcriptional regulator 780 780 coexpression:780
Rv0792c transcriptional regulator 791 778 coexpression:778
Rv1460 sufR transcriptional regulator 761 761 coexpression:761
Rv1776c transcriptional regulator 811 759 coexpression:759
Rv1674c transcriptional regulator 741 741 coexpression:739
Rv3060c GntR family transcriptional regulator 746 734 coexpression:734
Rv1359 transcriptional regulator 734 734 coexpression:734
Rv1985c lysG HTH-type transcriptional regulator 733 733 coexpression:733
Rv1167c transcriptional regulator 733 733 coexpression:733
Rv3263 DNA methylase 730 730 coexpression:730
Rv0038 hyp hypothetical protein 703 703 coexpression:703
Rv3855 ethR HTH-type transcriptional repressor EthR 703 703 coexpression:703

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 regulator
  • MTBC0 PGAP product: helix-turn-helix domain-containing protein
  • Pfam (hmmscan --cut_ga): HTH_20 PF12840.14 (E=1e-08)
  • (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_217137.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HTH_20 (PF12840.14)
  • 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 COG2345
  • Curated reference: UniProt I6Y187 (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 — 39 functional partner(s); context anchor Rv2620c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002790|Rv2621c|
MGVSVIIRSLQEPVGRRRAVLRALCASRVPMSIAAIAGKLGVHPNTVRFHLDNLVADGQVERVEPGRGRPGRPPLMFRAVRRTDSTGTRRYRLLAEILASGLAAERDSRAMALSAGRAWGRQLEAPPAGADTEETIDHLVAVLDDLGFAPERRASNGRQQVGLRHCPFLELAETQAGVVCPVHLGIMRGALQTWGAPVTVDRLDAFVEPDLCLAHFTPLEGAIR