Rv3254 Resolved · medium auto-curated

H37Rv Rv3254 · MTBC0 mtbc0_003462 · 462 aa · 3655818–3657206 (+) · RefSeq NP_217771.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationoxidoreductase
Revised (this work)Oxidoreductase.

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

Curated reference (UniProt)

UniProt O05897 SwissProt · reviewed · Evidence at protein level
UniProt nameProtein Rv3254

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
H Coenzyme transport and metabolism
eggNOG descriptionCOG0654 2-polyprenyl-6-methoxyphenol hydroxylase and related FAD-dependent oxidoreductases
Orthologous groupCOG0654
Gene Ontology (58) GO:0003674, GO:0005488, GO:0005506, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006725, GO:0006766 +46 more

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 0.413 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 6 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)

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

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

Closest characterised functional partner: Rv0538 (membrane protein), medium confidence from genomic context alone (score 643 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0538 membrane protein 642 643 ctx cooccurence:638
Rv0339c iniR transcriptional regulator 635 634 ctx cooccurence:623
Rv2164c hyp hypothetical protein 622 622 ctx cooccurence:620
Rv1814 erg3 membrane-bound C-5 sterol desaturase 641 613 coexpression:405
Rv1853 ureD urease accessory protein UreD 607 608 ctx cooccurence:600
Rv3732 hyp hypothetical protein 598 599 ctx cooccurence:595
Rv3253c cationic amino acid transport integral membrane protein 856 598 ctx neighborhood:553 textmining:658
Rv2264c hyp hypothetical protein 586 568 ctx cooccurence:504
Rv1963c mce3R transcriptional repressor Mce3R 535 534 ctx cooccurence:522
Rv2709 transmembrane protein 523 523 ctx cooccurence:520
Rv1666c cyp139 cytochrome P450 Cyp139 510 492
Rv3788 hyp hypothetical protein 492 492 ctx cooccurence:489
Rv0343 iniC iIsoniazid inductible protein IniC 471 471 ctx cooccurence:450
Rv0134 ephF epoxide hydrolase EphF 471 462 ctx fusion:446
Rv3835 hyp hypothetical protein 479 460 ctx cooccurence:441

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: oxidoreductase
  • (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_217771.1)
  • 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 COG0654
  • Curated reference: UniProt O05897 (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 — 50 functional partner(s); context anchor Rv0538
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003462|Rv3254|
MVIGASIAGLCAARVLSDFYSTVTVFERDELPEAPANRATVPQDRHLHMLMARGAQEFDSLFPGLLHDMVAAGVPMLENRPDCIYLGAAGHVLGTGHTLRKEFTAYVPSRPHLEWQLRRRVLQLSNVQIVRRLVTEPQFERRQQRVVGVLLDSPGSGQDREREEFIAADLVVDAAGRGTRLPVWLTQWGYRRPAEDTVDIGISYASHQFRIPDGLIAEKVVVAGASHDQSLGLGMLCYEDGTWVLTTFGVADAKPPPTFDEMRALADKLLPARFTAALAQAQPIGCPAFHAFPASRWRRYDKLERFPRGIVPFGDAVASFNPTFGQGMTMTSLQAGHLRRALKARNSAMKGDLAAELNRATAKTTYPVWMMNAIGDISFHHATAEPLPRWWRPAGSLFDQFLGAAETDPVLAEWFLRRFSLLDSLYMVPSVPIIGRAIAHNLRLWLKEQRERRQPVTTRRSP