Rv2651c Family assigned · medium auto-curated

H37Rv Rv2651c · MTBC0 mtbc0_001684 · 177 aa · 1794033–1794566 (-) · RefSeq NP_217167.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)prophage protease
MTBC0 PGAP re-annotationHK97 family phage prohead protease
Revised (this work)HK97 family phage prohead protease. Pfam: Peptidase_S78 (PF04586.23).

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

Curated reference (UniProt)

UniProt I6XEX3 TrEMBL · unreviewed · Predicted
UniProt namePossible PhiRv2 prophage protease

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionCaudovirus prohead serine protease
Orthologous groupCOG3740
KEGG orthology K06904

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 0.372 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 2 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.15% of strains (212) · 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
Peptidase_S78PF04586.23 7.0e-2019–161 Caudovirus prohead serine protease

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

Closest characterised functional partner: Rv2650c (prophage protein), high confidence from genomic context alone (score 988 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2650c prophage protein 989 988 ctx neighborhood:787 cooccurence:686 coexpression:838
Rv1576c phage capsid protein 931 925 ctx cooccurence:648 coexpression:783
Rv1577c phage prohead protease 848 847 coexpression:846
Rv2652c prophage protein 636 617 ctx neighborhood:493
Rv1452c PE_PGRS28 PE-PGRS family protein PE_PGRS28 502 503 ctx cooccurence:496
Rv3350c PPE56 PPE family protein PPE56 479 479 ctx cooccurence:476
Rv3347c PPE55 PPE family protein PPE55 473 474 ctx cooccurence:469
Rv0355c PPE8 PPE family protein PPE8 471 471 ctx cooccurence:468
Rv2490c PE_PGRS43 PE-PGRS family protein PE_PGRS43 471 471 ctx cooccurence:464
Rv1749c integral membrane protein 458 459 ctx cooccurence:456
Rv1956 higA antitoxin HigA 446 446 ctx cooccurence:446
Rv0872c PE_PGRS15 PE-PGRS family protein PE_PGRS15 445 446 ctx cooccurence:438
Rv0304c PPE5 PPE family protein PPE5 443 444 ctx cooccurence:440
Rv2653c toxin 429 429 ctx neighborhood:426
Rv3343c PPE54 PPE family protein PPE54 426 426 ctx cooccurence:421

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: prophage protease
  • MTBC0 PGAP product: HK97 family phage prohead protease
  • Pfam (hmmscan --cut_ga): Peptidase_S78 PF04586.23 (E=7e-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_217167.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_S78 (PF04586.23)
  • 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 COG3740
  • Curated reference: UniProt I6XEX3 (TrEMBL, unreviewed; Predicted)
  • 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 — 25 functional partner(s); context anchor Rv2650c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001684|Rv2651c|
MSSILFRMAELRSGEGRTVHGTIVPYNEATTVRDFDGEFQEMFAPGAFRRSIAERGHKLKLLVSHDARTRYPVGRAVELREEPHGLFGAFEIADTPDGDEALANVKAGVVDSFSVGFRPIRDRREGDVLVRVEAALLEVSLTGVPAYSGAQIAGVRAESLTVVSRSTAEAWLSLLDW