Rv2717c Family assigned · medium auto-curated

H37Rv Rv2717c · MTBC0 mtbc0_002891 · 164 aa · 3052282–3052776 (-) · RefSeq NP_217233.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationFABP family protein
Revised (this work)FABP family protein. Pfam: THAP4_heme-bd (PF08768.18).

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

Curated reference (UniProt)

UniProt P9WFG7 SwissProt · reviewed · Evidence at protein level
UniProt namePeroxynitrite isomerase 1
EC (curated) EC 5.99.-.-
Curated functionHeme-binding protein able to scavenge peroxynitrite and to protect free L-tyrosine against peroxynitrite-mediated nitration, by acting as a peroxynitrite isomerase that converts peroxynitrite to nitrate. Therefore, this protein likely plays a role in peroxynitrite sensing and in the detoxification of reactive nitrogen and oxygen species (RNS and ROS, respectively). In M.tuberculosis, could be part of the pool of proteins required to scavenge RNS and ROS produced by the host during the immunity response. Is able to bind nitric oxide (NO) in vitro, but may act as a sensor of peroxynitrite levels.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionMay play a role in the intracellular transport of hydrophobic ligands
Orthologous groupCOG4044

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 0.351 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 3 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.80% of strains (1162) · 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
THAP4_heme-bdPF08768.18 4.2e-499–162 THAP4-like, heme-binding beta-barrel domain

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

Closest characterised functional partner: nrdR (transcriptional regulator NrdR), high confidence from genomic context alone (score 724 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2718c nrdR transcriptional regulator NrdR 724 724 ctx neighborhood:720
Rv1158c hyp hypothetical protein 604 604 ctx cooccurence:604
Rv2719c chiZ membrane protein 606 564 ctx neighborhood:549
Rv1010 ksgA rRNA small subunit methyltransferase A 550 509 coexpression:492
Rv1988 erm(37) 23S rRNA (adenine(2058)-N(6))-methyltransferase Erm(37) 547 506 coexpression:489
Rv2126c PE_PGRS37 PE-PGRS family protein PE_PGRS37 506 506 ctx cooccurence:506
Rv2720 lexA repressor LexA 461 461 ctx neighborhood:454
Rv0819 mshD mycothiol acetyltransferase 446 446
Rv3829c dehydrogenase 435 435
Rv3775 lipE lipase LipE 403 403 ctx neighborhood:403

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: FABP family protein
  • Pfam (hmmscan --cut_ga): THAP4_heme-bd PF08768.18 (E=4e-49)
  • (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_217233.1)
  • Domains: Pfam-A via hmmscan --cut_ga — THAP4_heme-bd (PF08768.18)
  • 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 COG4044
  • Curated reference: UniProt P9WFG7 (SwissProt, reviewed; 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 — 10 functional partner(s); context anchor nrdR
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002891|Rv2717c|
MTRDLAPALQALSPLLGSWAGRGAGKYPTIRPFEYLEEVVFAHVGKPFLTYTQQTRAVADGKPLHSETGYLRVCRPGCVELVLAHPSGITEIEVGTYSVTGDVIELELSTRADGSIGLAPTAKEVTALDRSYRIDGDELSYSLQMRAVGQPLQDHLAAVLHRQR