Rv3529c Resolved · high auto-curated

H37Rv Rv3529c · MTBC0 mtbc0_003746 · 384 aa · 3989561–3990715 (-) · RefSeq NP_218046.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationTLR2-mediated response inhibitor
Revised (this work)TLR2-mediated response inhibitor. 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 I6YCC4 TrEMBL · unreviewed · Evidence at protein level
UniProt nameSulfotransferase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionSulfotransferase domain
Orthologous group2DBBP

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 0.275 · purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 4 missense, 2 nonsense, 0 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 5.93% of strains (8612) · 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 5.7e-0692–352 Sulfotransferase domain
Sulfotransfer_3PF13469.13 5.9e-6593–341 Sulfotransferase family

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

Closest characterised functional partner: Rv3530c (oxidoreductase), high confidence from genomic context alone (score 996 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3530c oxidoreductase 996 996 ctx neighborhood:881 fusion:487 cooccurence:630 coexpression:826
Rv3531c hyp hypothetical protein 975 975 ctx neighborhood:881 cooccurence:774
Rv2299c htpG chaperone protein HtpG 932 926 experimental:786 database:631
Rv2555c alaS alanine--tRNA ligase 925 920 experimental:775 database:644
Rv3457c rpoA DNA-directed RNA polymerase subunit alpha 877 870 experimental:668 database:607
Rv0696 mftF mycofactocin biosynthesis glycosyltransferase MftF 824 805 experimental:788
Rv1390 rpoZ DNA-directed RNA polymerase subunit omega 804 805 experimental:515 database:594
Rv3492c Mce associated protein 809 801 experimental:417 database:540
Rv3526 kshA 3-ketosteroid-9-alpha-monooxygenase oxygenase subunit 797 798 ctx cooccurence:765
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 810 790 experimental:476 database:592
Rv2919c glnB nitrogen regulatory protein P-II 807 789 experimental:787
Rv0310c hyp hypothetical protein 800 785 ctx cooccurence:756
Rv2264c hyp hypothetical protein 783 772 experimental:455 database:567
Rv3446c hyp hypothetical protein 782 770 experimental:455 database:567
Rv0312 hyp hypothetical protein 781 769 experimental:455 database:567

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: TLR2-mediated response inhibitor
  • Pfam (hmmscan --cut_ga): Sulfotransfer_1 PF00685.34 (E=6e-06), Sulfotransfer_3 PF13469.13 (E=6e-65)
  • (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_218046.1)
  • 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 2DBBP
  • Curated reference: UniProt I6YCC4 (TrEMBL, unreviewed; 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 — 151 functional partner(s); context anchor Rv3530c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003746|Rv3529c|
MTRRPDRKDVATVDELHASATKLVGLDDFGTDDDNYREALGVLLDAYQGEAGLTVLGSKMNRFFLRGALVARLLSQSAWKQYPEHVDVAIKRPIFVTGLVRTGTTALHRLLGADPAHQGLHMWLAEYPQPRPPRETWESNPLYRQLDAQFTQHHAENPGYTGLHFMAAYELEECWQLLRQSLHSVSYEALAHVPSYADWLSRQDWTPSYCRHRRNLQLIGLNDAEKRWVLKNPSHLFALDALMATYPDALVVQTHRPVETIMASMCSLAQHTTEGWSTKFVGAQIGADAMDTWSRGLERFNAARAKYDSAQFYDVDYHDLIADPLGTVADIYRHFGLTLSDEARQAMTTVHAESQSGARAPKHSYSLADYGLTVEMVKERFAGL