Rv1546 Family assigned · medium auto-curated

H37Rv Rv1546 · MTBC0 mtbc0_001653 · 143 aa · 1757004–1757435 (+) · RefSeq NP_216062.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationSRPBCC family protein
Revised (this work)SRPBCC family protein. Pfam: Polyketide_cyc2 (PF10604.16).

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

Curated reference (UniProt)

UniProt P9WLU7 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv1546

UniProt still lists this protein as Uncharacterized protein Rv1546; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionPolyketide cyclase / dehydrase and lipid transport
Orthologous groupCOG3427
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944

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 0.044 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 8 synonymous, 1 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.13% of strains (192) · 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
Polyketide_cyc2PF10604.16 2.8e-271–141 Polyketide cyclase / dehydrase and lipid transport

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

Closest characterised functional partner: dnaE1 (DNA polymerase III subunit alpha), high confidence from genomic context alone (score 796 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1547 dnaE1 DNA polymerase III subunit alpha 796 796 ctx neighborhood:794
Rv1543 oxidoreductase 792 792 ctx neighborhood:685
Rv1544 ketoacyl reductase 791 791 ctx neighborhood:790
Rv3584 lpqE lipoprotein LpqE 731 731 ctx cooccurence:730
Rv0513 transmembrane protein 683 684 ctx cooccurence:679
Rv1545 hyp hypothetical protein 860 655 ctx neighborhood:641 textmining:613
Rv3217c integral membrane protein 585 585 ctx cooccurence:584
Rv3346c transmembrane protein 577 577 ctx cooccurence:571
Rv3527 hyp hypothetical protein 570 570 ctx cooccurence:569
Rv3415c hyp hypothetical protein 554 554 ctx cooccurence:553
Rv1368 lprF lipoprotein LprF 541 542 ctx cooccurence:536
Rv2418c octT hyp hypothetical protein 535 536 ctx cooccurence:530
Rv1871c hyp hypothetical protein 530 530 ctx cooccurence:526
Rv0826 hyp hypothetical protein 530 530 ctx cooccurence:530
Rv2001 hyp hypothetical protein 512 513 ctx cooccurence:511

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: SRPBCC family protein
  • Pfam (hmmscan --cut_ga): Polyketide_cyc2 PF10604.16 (E=3e-27)
  • (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_216062.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Polyketide_cyc2 (PF10604.16)
  • 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 COG3427
  • Curated reference: UniProt P9WLU7 (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 — 44 functional partner(s); context anchor dnaE1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001653|Rv1546|
MASVELSADVPISPQDTWDHVSELSELGEWLVIHEGWRSELPDQLGEGVQIVGVARAMGMRNRVTWRVTKWDPPHEVAMTGSGKGGTKYGVTLTVRPTKGGSALGLRLELGGRALFGPLGSAAARAVKGDVEKSLKQFAELYG