Rv2646 Resolved · high auto-curated

H37Rv Rv2646 · MTBC0 mtbc0_002821 · 332 aa · 2994112–2995110 (+) · RefSeq NP_217162.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)integrase
MTBC0 PGAP re-annotationtyrosine-type recombinase/integrase
Revised (this work)Tyrosine-type recombinase/integrase. Pfam: Phage_integrase (PF00589.28).

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

Curated reference (UniProt)

UniProt I6XEU5 TrEMBL · unreviewed · Predicted
UniProt nameProbable integrase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
eggNOG descriptionto the 'phage' integrase family
Orthologous groupCOG0582

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 0.357 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 5 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.82% of strains (1194) · 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
Phage_integrasePF00589.28 2.2e-22186–319 Phage integrase family

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

Closest characterised functional partner: xerC (tyrosine recombinase XerC), high confidence from genomic context alone (score 798 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2645 hyp hypothetical protein 952 953 ctx neighborhood:774 coexpression:799
Rv2647 hyp hypothetical protein 872 866 ctx neighborhood:520 coexpression:732
Rv2894c xerC tyrosine recombinase XerC 798 798 ctx cooccurence:773
Rv2748c ftsK DNA translocase FtsK 682 553 ctx cooccurence:549
Rv3754 tyrA prephenate dehydrogenase TyrA 495 496 coexpression:434
Rv3242c hyp hypothetical protein 467 468 coexpression:466
Rv2584c apt adenine phosphoribosyltransferase 459 460 coexpression:458
Rv1708 initiation inhibitor protein 470 444
Rv3918c parA chromosome partitioning protein ParA 470 444 ctx cooccurence:420
Rv3226c hyp hypothetical protein 456 436 coexpression:436
Rv1423 whiA transcriptional regulator WhiA 434 434 coexpression:434
Rv3917c parB chromosome partitioning protein ParB 448 419 ctx cooccurence:412
Rv3781 rfbE O-antigen/lipopolysaccharide ABC transporter ATP-binding protein RfbE 416 416 coexpression:416
Rv3213c SOJ/ParA-like protein 435 408
Rv0186 bglS beta-glucosidase BglS 811 98 textmining:800

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: integrase
  • MTBC0 PGAP product: tyrosine-type recombinase/integrase
  • Pfam (hmmscan --cut_ga): Phage_integrase PF00589.28 (E=2e-22)
  • (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_217162.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Phage_integrase (PF00589.28)
  • 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 COG0582
  • Curated reference: UniProt I6XEU5 (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 — 16 functional partner(s); context anchor xerC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002821|Rv2646|
MNTATRVRLARKRADRLNLKLIKNGHHFRLRDADEITLAVGHLGVVEAFLAAAKSQNKPPGPPPSLHAPPSWRRDIDDYLLNLNAAGQRPATIRLRKTVLCAAAHGLGRPPADVTAEHLLDWLGKQQHLSPEGRKTYRSTLRGFFVWAYEMDRVRDYVADSLPKVRCPKQPPRPAGDDVWQAALAKADRRTELMIRLAGEAGLRRAEAAQAHTGDLMDGGLLLVHGKGGKRRIVPISDYLAALIRDTPHGYLFPNGTGGHLTAEHVGKLVSRALPGDATMHTLRHRYATRAYRGSHNLRAVQQLLGHASIVTTERYTALCDDEVRAAAAAAW