Rv2515c Family assigned · medium auto-curated

H37Rv Rv2515c · MTBC0 mtbc0_002678 · 415 aa · 2854234–2855481 (-) · RefSeq NP_217031.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationXRE family transcriptional regulator
Revised (this work)XRE family transcriptional regulator. Pfam: HTH_3 (PF01381.29), Peptidase_M78 (PF06114.20).

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

Curated reference (UniProt)

UniProt I6XEH5 TrEMBL · unreviewed · Inferred from homology
UniProt nameHTH cro/C1-type domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
eggNOG descriptionIrrE N-terminal-like domain
Orthologous groupCOG1396

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 0.121 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 20 synonymous, 7 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.11% of strains (156) · 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_3PF01381.29 4.8e-0829–82 Helix-turn-helix
Peptidase_M78PF06114.20 8.0e-22190–325 IrrE N-terminal-like domain

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

Closest characterised functional partner: Rv1371 (membrane protein), medium confidence from genomic context alone (score 698 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2514c hyp hypothetical protein 998 994 ctx neighborhood:882 cooccurence:774 coexpression:802 textmining:803
Rv0332 hyp hypothetical protein 936 927 experimental:916
Rv1371 membrane protein 846 698 ctx cooccurence:695 textmining:511
Rv2608 PPE42 PPE family protein PPE42 651 651 ctx cooccurence:650
Rv2939 papA5 phthiocerol/phthiodiolone dimycocerosyl transferase 592 592 ctx cooccurence:590
Rv2516c hyp hypothetical protein 578 578 ctx neighborhood:566
Rv2517c hyp hypothetical protein 515 516 ctx neighborhood:513
Rv2017 transcriptional regulator 636 484
Rv2942 mmpL7 transmembrane transport protein MmpL7 447 447 ctx cooccurence:447
Rv3190c hyp hypothetical protein 654 437 textmining:412
Rv0878c PPE13 PPE family protein PPE13 437 437 ctx cooccurence:437
Rv1917c PPE34 PPE family protein PPE34 433 433 ctx cooccurence:425
Rv1959c parE1 toxin ParE1 416 417
Rv2021c higA2 transcriptional regulator 400 312
Rv0341 iniB isoniazid inducible protein IniB 403 276

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: hypothetical protein
  • MTBC0 PGAP product: XRE family transcriptional regulator
  • Pfam (hmmscan --cut_ga): HTH_3 PF01381.29 (E=5e-08), Peptidase_M78 PF06114.20 (E=8e-22)
  • (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_217031.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HTH_3 (PF01381.29), Peptidase_M78 (PF06114.20)
  • 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 COG1396
  • Curated reference: UniProt I6XEH5 (TrEMBL, unreviewed; Inferred from homology)
  • 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 — 38 functional partner(s); context anchor Rv1371
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002678|Rv2515c|
MGIGHPMWVGWCIIIAMRSIPASVESSVLRWARESCGLTEVAAARKLGLPDDRVAAWEVGEVVPTIAQLRKAAEVYKRSLAVFFLSEPPEGFDTLRDFRRLDGAASGQWTPGLHEEFRRAHTQRDFALELADAEDREIPGAWRLPLSGDEADADIAARIRKALIEVSPLPIPVASVDPYEHLNAWVSAIETSGVLVLATRGGKVAIDEMRGMCLYFDELPVIVLNGSDHPRPRLFSLLHEFVHVVLHTEGLCDVIADAHPSTQDRSLEARCNAIAAAVLMPADVVRARPEVIVRSETPSSWDYESLRPVAAHFGVSAEAFLRRLSTLGIVPVEVYRQRRAEFIAAHEDEAERARSAGGGNWYRNTVRDLGKGYVRAVTDAHRRRVIDSNTAAIYLDAKVSQIPKLAESAELRSVV