Rv3729 Resolved · high auto-curated

H37Rv Rv3729 · MTBC0 - · 776 aa · 4178285–4180615 (+) · RefSeq NP_218246.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transferase
MTBC0 PGAP re-annotation
Revised (this work)Transferase. Pfam: Zn_ribbon_HMPTM (PF23545.2), Radical_SAM (PF04055.28), Fer4_12 (PF13353.12), Methyltransf_23 (PF13489.13), Ubie_methyltran (PF01209.25), Methyltransf_31 (PF13847.13), Methyltransf_25 (PF13649.13), Methyltransf_11 (PF08241.19), Methyltransf_12 (PF08242.19).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt O69696 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible transferase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG description4Fe-4S single cluster domain
Orthologous groupCOG0500
KEGG orthology K06937

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 1.794 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 15 missense, 1 nonsense, 2 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 0.79% of strains (1152) · 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
Zn_ribbon_HMPTMPF23545.2 4.2e-172–45 HMPTM N-terminal zinc ribbon domain
Radical_SAMPF04055.28 6.8e-2195–259 Radical SAM superfamily
Fer4_12PF13353.12 4.0e-0599–183 4Fe-4S single cluster domain
Methyltransf_23PF13489.13 4.2e-10554–707 Methyltransferase domain
Ubie_methyltranPF01209.25 6.2e-09561–661 ubiE/COQ5 methyltransferase family
Methyltransf_31PF13847.13 7.9e-15564–679 Methyltransferase domain
Methyltransf_25PF13649.13 2.8e-19565–660 Methyltransferase domain
Methyltransf_11PF08241.19 7.1e-19567–661 Methyltransferase domain
Methyltransf_12PF08242.19 1.9e-10567–661 Methyltransferase domain

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

Closest characterised functional partner: Rv3728 (membrane protein), medium confidence from genomic context alone (score 458 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3728 membrane protein 469 458 ctx neighborhood:455
Rv3727 oxidoreductase 441 441
Rv0213c methyltransferase 442 421
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 415 415 ctx neighborhood:402
Rv3224 iron-regulated short-chain dehydrogenase/reductase 492 144 textmining:432
Rv2541 hyp hypothetical protein 870 42 textmining:870
Rv2012 hyp hypothetical protein 803 42 textmining:803
Rv0991c hyp hypothetical protein 641 42 textmining:641

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): transferase
  • Pfam (hmmscan --cut_ga): Zn_ribbon_HMPTM PF23545.2 (E=4e-17), Radical_SAM PF04055.28 (E=7e-21), Fer4_12 PF13353.12 (E=4e-05), Methyltransf_23 PF13489.13 (E=4e-10), Ubie_methyltran PF01209.25 (E=6e-09), Methyltransf_31 PF13847.13 (E=8e-15), Methyltransf_25 PF13649.13 (E=3e-19), Methyltransf_11 PF08241.19 (E=7e-19), Methyltransf_12 PF08242.19 (E=2e-10)
  • (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_218246.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Zn_ribbon_HMPTM (PF23545.2), Radical_SAM (PF04055.28), Fer4_12 (PF13353.12), Methyltransf_23 (PF13489.13), Ubie_methyltran (PF01209.25), Methyltransf_31 (PF13847.13), Methyltransf_25 (PF13649.13), Methyltransf_11 (PF08241.19), Methyltransf_12 (PF08242.19)
  • 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 COG0500
  • Curated reference: UniProt O69696 (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 — 8 functional partner(s); context anchor Rv3728
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3729|
MFVEYTKSICPVCKVVVDAQVNIRHDKVYLRKRCREHGSFEALVYGDAQMYLESARFNKPGTFPLRFQTEVRDGCPSDCGLCPDHKQHACLGLIEVNTHCNLDCPICFADSGHQPDGYAITAAQCERMLDTLVAAEGEPEVVMFSGGEPTIHKQLLEFVDAAQARPVKTVIINTNGIRLASDRRFVDQLATRNRPGHPVHIYLQFDGLDEATHRRIRGHDLRDVKQRALDNCAAAGLTVSLVAAVERGLNEHELGAVIRHGMAQPGVQPVVFQPVTHAGRHVQFDPLTRLTNSDIIACITAQLPEWFRPGDFFPVPCCFPSCRSITYLLTDGEHVVPIPRLLNVEDYLDYVSNRVIPDLAIREALENLWSASAVPGTDTMTAQLQRATAALNCAEGCGINLPEALTHLTDRVFAIVIQDFQDPYTLNVKQLMKCCVQQITPDGRLIPFCAYNSVGYREQVREQLTGVPVPDIVPNAIPLAGLLADAPHGSKQANTGGSIARLAGPTRGAPMALPPQQIKACCADAYSRDIVALLLGDSFHPGGATLTRRLADQLGLRSTGDPRRVADIAAGPGASARLLASDYGVAVDGVDISEINVKRAQAAVAQTGLTERVRFHLGDAESVPLPDDTFDALVCECAFCTFPDKNAAAQQFARILRPGGLAGITDVTVGDGGLPAELTPLAAWVACIADARTVTDYTDILEGAGLRTRHIESHDESLLDMIDRIDARITALHVAAPEILADNGIRHDSVRDFTALARAAVQTGRIGYTLMIAEKP