Rv2267c Resolved · high auto-curated

H37Rv Rv2267c · MTBC0 mtbc0_002409 · 388 aa · 2567749–2568915 (-) · RefSeq NP_216783.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationsulfotransferase
Revised (this work)Sulfotransferase. Pfam: Sulfotransfer_1 (PF00685.34), Sulfotransfer_3 (PF13469.13).

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

Curated reference (UniProt)

UniProt P9WLG1 SwissProt · reviewed · Evidence at protein level
UniProt nameOmega-hydroxy-beta-dihydromenaquinone-9 sulfotransferase Stf3
EC (curated) EC 2.8.2.40
Curated functionInvolved in the biosynthesis of sulfomenaquinone (SMK, initially named S881 on the basis of its mass), which is localized in the outer envelope of M.tuberculosis and negatively regulates its virulence. Catalyzes the transfer of a sulfonate group from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to omega-hydroxy-beta-dihydromenaquinone-9, generating omega-sulfo-beta-dihydromenaquinone-9 (sulfomenaquinone).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionSulfotransferase domain
Orthologous groupCOG0446
Gene Ontology (29) GO:0003674, GO:0003824, GO:0005575, GO:0006082, GO:0006629, GO:0006790, GO:0008146, GO:0008150, GO:0008152, GO:0008610, GO:0009058, GO:0009987 +17 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 0.513 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 5 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.22% of strains (320) · 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
Sulfotransfer_1PF00685.34 2.2e-1180–324 Sulfotransferase domain
Sulfotransfer_3PF13469.13 4.5e-3782–324 Sulfotransferase family

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

Closest characterised functional partner: cyp128 (cytochrome P450 Cyp128), high confidence from genomic context alone (score 986 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2268c cyp128 cytochrome P450 Cyp128 998 986 ctx neighborhood:834 coexpression:821 database:500 textmining:875
Rv2299c htpG chaperone protein HtpG 933 926 experimental:786 database:631
Rv2555c alaS alanine--tRNA ligase 925 919 experimental:775 database:644
Rv3457c rpoA DNA-directed RNA polymerase subunit alpha 878 870 experimental:668 database:607
Rv0696 mftF mycofactocin biosynthesis glycosyltransferase MftF 823 805 experimental:788
Rv1390 rpoZ DNA-directed RNA polymerase subunit omega 804 805 experimental:515 database:594
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 810 790 experimental:476 database:592
Rv2919c glnB nitrogen regulatory protein P-II 806 788 experimental:787
Rv0312 hyp hypothetical protein 783 772 experimental:455 database:567
Rv3446c hyp hypothetical protein 783 771 experimental:455 database:567
Rv2264c hyp hypothetical protein 782 770 experimental:455 database:567
Rv0350 dnaK chaperone protein DnaK 781 769 experimental:455 database:567
Rv2269c hyp hypothetical protein 968 766 ctx neighborhood:765 textmining:870
Rv2328 PE23 PE family protein PE23 817 766 experimental:454 database:583
Rv3036c TB22.2 hyp hypothetical protein 778 766 experimental:454 database:583

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: sulfotransferase
  • Pfam (hmmscan --cut_ga): Sulfotransfer_1 PF00685.34 (E=2e-11), Sulfotransfer_3 PF13469.13 (E=5e-37)
  • (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_216783.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Sulfotransfer_1 (PF00685.34), Sulfotransfer_3 (PF13469.13)
  • 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 COG0446
  • Curated reference: UniProt P9WLG1 (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 — 127 functional partner(s); context anchor cyp128
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002409|Rv2267c|
MKALRSSSRLSRWREWAAPLWVGCNFSAWMRLLIRNRFAVHHSRWHFAVLYTFLSMVNSCLGLWQKIVFGRRVAETVIADPPIFIVGHWRTGTTLLHELLVVDDRHTGPTGYECLAPHHFLLTEWFAPYVEFLVSKHRAMDNMDLSLHHPQEDEFVWCMQGLPSPYLTIAFPNRPPQYEEYLDLEQVAPRELEIWKRTLFRFVQQVYFRRRKTVILKNPTHSFRIKVLLEVFPQAKFIHIVRDPYVVYPSTIHLHKALYRIHGLQQPTFDGLDDKVVSTYVDLYRKLDEGRELVDPTRFYELRYEDLIGDPEGQLRRLYQHLGLGDFECYLPRLRQYLADHADYKTNSYQLTVEQRAIVDEHWGEIIDRYGYDRHTPEPARLRPAVGG