Rv2885c Resolved · high auto-curated

H37Rv Rv2885c · MTBC0 - · 460 aa · 3194166–3195548 (-) · RefSeq NP_217401.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transposase
MTBC0 PGAP re-annotation
Revised (this work)Transposase. Pfam: HTH_OrfB_IS605 (PF12323.15), OrfB_IS605 (PF01385.26), Cas12f1-like_TNB (PF07282.19).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WL37 SwissProt · reviewed · Inferred from homology
UniProt namePutative RNA-guided DNA endonuclease Rv2885c
EC (curated) EC 3.1.21.-
Curated functionAn RNA-guided dsDNA endonuclease. When guided by an RNA derived from the right-end element of its insertion sequence element (IS), cleaves DNA downstream of the transposon-associated motif (TAM). Cleaves supercoiled and linear DNA in a staggered manner 15-21 bases from the TAM yielding 5'-overhangs. Binds reRNA, an approximately 150 nucleotide base sRNA derived from the 3' end of its own gene, the right end (RE) of the insertion sequence (IS) plus sequence downstream of the IS.

UniProt still lists this protein as Putative RNA-guided DNA endonuclease Rv2885c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
eggNOG descriptionTransposase
Orthologous groupCOG0675
KEGG orthology K07496
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) pseudogene candidate

pN/pS 0.705 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 12 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 49.03% of strains (71203) · 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
HTH_OrfB_IS605PF12323.15 3.7e-0814–49 Helix-turn-helix domain
OrfB_IS605PF01385.26 8.8e-28204–322 Probable transposase
Cas12f1-like_TNBPF07282.19 1.3e-15345–406 Cas12f1-like, TNB domain

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

Closest characterised functional partner: Rv2979c (resolvase), high confidence from genomic context alone (score 959 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2979c resolvase 960 959 ctx cooccurence:760 coexpression:831
Rv0605 IS1536 family serine type transposase 954 953 ctx cooccurence:761 coexpression:806
Rv2886c resolvase 948 947 ctx neighborhood:781 cooccurence:758
Rv3828c resolvase 894 891 ctx cooccurence:759 coexpression:553
Rv2978c tnpB transposase 861 861 coexpression:860
Rv2792c resolvase 850 847 ctx cooccurence:761
Rv0606 Possible transposase (fragment); Rv0606, (MTCY19H5.16c), len: 247 aa. Possible truncated transposase for IS_1536 element, highly similar to 816 817 coexpression:815
Rv3827c transposase 801 801 coexpression:799
Rv2977c thiL thiamine-monophosphate kinase 798 799 coexpression:798
Rv2791c tnpB transposase 782 782 coexpression:780
Rv0921 resolvase 777 771 ctx cooccurence:761
Rv1765c hyp hypothetical protein 731 731 coexpression:731
Rv0336 hyp hypothetical protein 731 731 coexpression:731
Rv2887 HTH-type transcriptional regulator 576 576 ctx neighborhood:572
Rv2015c hyp hypothetical protein 533 533 coexpression:533

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): transposase
  • Pfam (hmmscan --cut_ga): HTH_OrfB_IS605 PF12323.15 (E=4e-08), OrfB_IS605 PF01385.26 (E=9e-28), Cas12f1-like_TNB PF07282.19 (E=1e-15)
  • (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_217401.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HTH_OrfB_IS605 (PF12323.15), OrfB_IS605 (PF01385.26), Cas12f1-like_TNB (PF07282.19)
  • 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 COG0675
  • Curated reference: UniProt P9WL37 (SwissProt, reviewed; Inferred from homology)
  • 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 — 20 functional partner(s); context anchor Rv2979c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2885c|
MMARLKVPEGWCVQAFRFTLNPTQTQAASLARHFGARRKAFNWTVTALKADIKAWRADGTESAKPSLRVLRKRWNTVKDQVCVNAQTGQVWWPECSKEAYADGIAGAVDAYWNWQSCRAGKRAGKTVGVPRFKKKGRDADRVCFTTGAMRVEPDRRHLTLPVIGTIRTYENTRRVERLIAKGRARVLAITVRRNGTRLDASVRVLVQRPQQRRVALPDSRVGVDVGVRRLATVADAEGTVLEQVPNPRPLDAALRGLRRVSRARSRCTKGSRRYCERTTELSRLHRRVNDVRTHHLHVLTTRLAKTHGRIVVEGLDAAGMLRQKGLPGARARRRALSDAALATPRRHLSYKTGWYGSSLVVADRWFPSSKTCHACRHVQDIGWDEKWQCDGCSITHQRDDNAAINLARYEEPPSVVGPVGAAVKRGADRKTGPGPAGGREARKATGHPAGEQPRDGVQVK