Rv2415c Family assigned · medium auto-curated

H37Rv Rv2415c · MTBC0 mtbc0_002571 · 297 aa · 2737159–2738052 (-) · RefSeq NP_216931.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationComEA family DNA-binding protein
Revised (this work)ComEA family DNA-binding protein. Pfam: SLBB (PF10531.16), HHH_3 (PF12836.14), HHH (PF00633.30).

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

Curated reference (UniProt)

UniProt P71728 TrEMBL · unreviewed · Predicted
UniProt nameHelix-hairpin-helix DNA-binding motif class 1 domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred namecomEA
eggNOG descriptionTIGRFAM Competence protein ComEA, helix-hairpin-helix
Orthologous groupCOG1555
KEGG orthology K02237
KEGG modules M00429

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 1.369 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 7 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
SLBBPF10531.16 8.0e-09139–193 SLBB domain
HHH_3PF12836.14 7.7e-20234–296 Helix-hairpin-helix motif
HHHPF00633.30 2.7e-08238–263 Helix-hairpin-helix motif

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

Closest characterised functional partner: eis (enhanced intracellular survival protein), high confidence from genomic context alone (score 865 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2414c hyp hypothetical protein 922 898 ctx neighborhood:869
Rv2416c eis enhanced intracellular survival protein 865 865 ctx neighborhood:429 coexpression:774
Rv2413c hyp hypothetical protein 836 830 ctx neighborhood:829
Rv1988 erm(37) 23S rRNA (adenine(2058)-N(6))-methyltransferase Erm(37) 740 741 coexpression:732
Rv1257c oxidoreductase 732 733 coexpression:732
Rv2551c hyp hypothetical protein 729 646 coexpression:645
Rv2421c nadD nicotinate-nucleotide adenylyltransferase 543 543
Rv0017c rodA cell division protein RodA 521 503
Rv1258c tap multidrug-efflux transporter 474 474 coexpression:474
Rv2420c rsfS hyp hypothetical protein 467 467
Rv3840 transcriptional regulator 453 453 ctx cooccurence:414
Rv2478c hyp hypothetical protein 567 433 coexpression:417
Rv0648 alpha-mannosidase 430 430 coexpression:430
Rv2417c DegV domain-containing protein 424 425 ctx neighborhood:420
Rv0054 ssb single-strand DNA-binding protein 560 424 coexpression:408

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: ComEA family DNA-binding protein
  • Pfam (hmmscan --cut_ga): SLBB PF10531.16 (E=8e-09), HHH_3 PF12836.14 (E=8e-20), HHH PF00633.30 (E=3e-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_216931.1)
  • Domains: Pfam-A via hmmscan --cut_ga — SLBB (PF10531.16), HHH_3 (PF12836.14), HHH (PF00633.30)
  • 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 COG1555
  • Curated reference: UniProt P71728 (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 — 24 functional partner(s); context anchor eis
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002571|Rv2415c|
MRTELPAERLQRRLGAVPDIDSHAASAHLDPEPHDPTDDGPDHDEPRDDPNSLLPRWLPDTSRGQGWADRIRADPGRAGAVALAVIAALAVLVTVFTLIRDRTEPVMSAKLPPVEPVSPTNPRSSASPGSPDRSGLPVVVSVVGLVHTPGLVTLAPGARIADALQAAGGAVDGADTVGLNMARQLGDGEQIVVGLAPPSGQPRVLGSSVGAGTPGPAGTSGTATTGPKTAPKTAEVLDLNTATVEQLDALPGIGPVTAAAIVAWRQRNGRFTSVDQLADVDGIGPARLDKLRNLVRV