Rv3718c Family assigned · medium auto-curated

H37Rv Rv3718c · MTBC0 mtbc0_003941 · 147 aa · 4185936–4186379 (-) · RefSeq NP_218235.1

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 I6XI16 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

UniProt still lists this protein as Conserved protein; 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
Orthologous groupCOG3832

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 0.22 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 2 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)

PfamAccessioni-EvalueResiduesDescription
Polyketide_cyc2PF10604.16 8.1e-204–144 Polyketide cyclase / dehydrase and lipid transport

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

Closest characterised functional partner: Rv3720 (fatty acid synthase), high confidence from genomic context alone (score 774 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3720 fatty acid synthase 774 774 ctx neighborhood:773
Rv3719 hyp hypothetical protein 649 649 ctx neighborhood:646
Rv3120 hyp hypothetical protein 458 459 ctx cooccurence:451
Rv3249c TetR family transcriptional regulator 456 456 ctx cooccurence:456
Rv1636 TB15.3 iron-regulated universal stress protein 446 446 ctx cooccurence:443
Rv3839 hyp hypothetical protein 437 437 ctx cooccurence:437
Rv2214c ephD oxidoreductase EphD 431 432 ctx cooccurence:427
Rv3629c integral membrane protein 418 418 ctx cooccurence:417
Rv3484 cpsA hyp hypothetical protein 406 406 ctx cooccurence:406
Rv3207c hyp hypothetical protein 889 187 textmining:870
Rv2519 PE26 PE family protein PE26 772 105 textmining:756
Rv2270 lppN lipoprotein LppN 438 41 textmining:438

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=8e-20)
  • (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_218235.1)
  • 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 COG3832
  • Curated reference: UniProt I6XI16 (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 — 12 functional partner(s); context anchor Rv3720
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003941|Rv3718c|
MGQVSAASTILINAEPTATLDALADYETVRPKILSPHYSEYQVLEGGKGRGTVAKWRLQATQSRVRDVQVNVDVAGHTVIEKDMNSSMVTNWTVAPAGPGSSVTVKTTWTGAGGVKGFFEKTFAPLGLKKIQAEVLSNLKTELEGDA