Rv2778c Family assigned · medium auto-curated

H37Rv Rv2778c · MTBC0 mtbc0_002957 · 156 aa · 3108128–3108598 (-) · RefSeq NP_217294.1

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 I6Y1P2 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 / dehydrase and lipid transport
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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 0 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.26% of strains (379) · 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 1.4e-208–154 Polyketide cyclase / dehydrase and lipid transport

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

Closest characterised functional partner: Rv2779c (Lrp/AsnC family transcriptional regulator), 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)
Rv2779c Lrp/AsnC family transcriptional regulator 774 774 ctx neighborhood:765
Rv0385 monooxygenase 760 732 coexpression:713
Rv2638 hyp hypothetical protein 601 602 ctx cooccurence:599
Rv2912c TetR family HTH-type transcriptional regulator 582 582 ctx cooccurence:578
Rv2777c hyp hypothetical protein 560 560 ctx neighborhood:471
Rv2776c oxidoreductase 612 556
Rv3912 rsmA anti-sigma-M factor RsmA 540 540 ctx cooccurence:540
Rv1904 hyp hypothetical protein 526 527 ctx cooccurence:505
Rv0036c hyp hypothetical protein 524 524 ctx cooccurence:515
Rv2780 ald L-alanine dehydrogenase 513 514 ctx neighborhood:512
Rv1365c rsfA anti-sigma-F factor antagonist RsfA 502 503 ctx cooccurence:500
Rv0901 arfC membrane protein 476 476 ctx cooccurence:473
Rv1060 hyp hypothetical protein 461 462 ctx cooccurence:459
Rv2181 alpha-(1-2)-phosphatidylinositol mannoside mannosyltransferase 443 443 ctx cooccurence:443
Rv0172 mce1D Mce family protein Mce1D 414 414 ctx cooccurence:406

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=1e-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_217294.1)
  • 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 I6Y1P2 (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 — 18 functional partner(s); context anchor Rv2779c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002957|Rv2778c|
MPDPDGPSVTVTVEIDANPDLVYGLITDLPTLASLAEEVVAMQLRKGDDVRKGAVFVGRNENGGRRWTTTCTVTDADPGRVFAFDVRSGIIPISRWQYGIVATEHGCRVTESTWDRRPSWFRAVARMATGVKDRASVNTEHIRRTLQRLKDRAEAG