Rv2762c Family assigned · low auto-curated

H37Rv Rv2762c · MTBC0 mtbc0_002939 · 139 aa · 3095052–3095471 (-) · RefSeq NP_217278.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationwinged helix-turn-helix domain-containing protein
Revised (this work)Winged helix-turn-helix domain-containing protein.

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

Curated reference (UniProt)

UniProt I6X5B0 TrEMBL · unreviewed · Predicted
UniProt nameWinged helix-turn-helix domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionWinged helix DNA-binding domain
Orthologous groupCOG3214
KEGG orthology K09927

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) pseudogene candidate

pN/pS 0.394 · purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 missense, 1 nonsense, 2 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 10.12% of strains (14697) · 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: hsdS (type I restriction/modification system specificity determinant HsdS), high confidence from genomic context alone (score 947 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2761c hsdS type I restriction/modification system specificity determinant HsdS 947 947 ctx neighborhood:800 coexpression:746
Rv2763c dfrA dihydrofolate reductase 937 827 ctx neighborhood:791 textmining:651
Rv2759c vapC42 ribonuclease VapC42 802 803 ctx neighborhood:800
Rv2760c vapB42 antitoxin VapB42 802 803 ctx neighborhood:800
Rv2756c hsdM type I restriction/modification system DNA methylase HsdM 745 745 ctx neighborhood:741
Rv2764c thyA thymidylate synthase ThyA 874 733 ctx neighborhood:730 textmining:548
Rv2757c vapC21 ribonuclease VapC21 960 711 ctx neighborhood:707 textmining:870
Rv2758c vapB21 antitoxin VapB21 710 710 ctx neighborhood:707
Rv2765 hydrolase 673 673 ctx neighborhood:673
Rv2754c thyX thymidylate synthase ThyX 755 669 ctx neighborhood:667
Rv2753c dapA 4-hydroxy-tetrahydrodipicolinate synthase 755 655 ctx neighborhood:643
Rv2752c rnj ribonuclease J 788 640 ctx neighborhood:635 textmining:436
Rv2755c hsdS.1 Rv2755c, (MTV002.20c), len: 91 aa. Possible hsdS.1,fragment of type I restriction/modification system specificity determinant (S protein), s 560 560 ctx neighborhood:557

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: winged helix-turn-helix domain-containing protein
  • (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_217278.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG3214
  • Curated reference: UniProt I6X5B0 (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 — 13 functional partner(s); context anchor hsdS
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002939|Rv2762c|
MSAATAAWDRRAAVVVGGVAEPGSAGPIAGADRKRLISRIQVRQLDSAAVAAKRRHLYYVRPLDGHPVARVDRKTDRAADSLPVAGVLGELDIPPVTVAEGLAGELASMASWLGLGGIAVSTRGDLAGELCAATKRTNG