Rv2191 Family assigned · medium auto-curated

H37Rv Rv2191 · MTBC0 - · 645 aa · 2453819–2455756 (+) · RefSeq NP_216707.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains RNase_T (PF00929.32), UvrC_M (PF27096.1) domain(s); putative function inferred from the domain architecture.

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 P9WLJ1 SwissProt · reviewed · Evidence at protein level
UniProt namePutative bifunctional exonuclease/endonuclease protein Rv2191
EC (curated) EC 3.1.-.-

UniProt still lists this protein as Putative bifunctional exonuclease/endonuclease protein Rv2191; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred namednaQ
eggNOG descriptionDNA polymerase III, epsilon subunit
Orthologous groupCOG0322
EC number EC 2.7.7.7
KEGG orthology K02342
KEGG pathways map00230, map00240, map01100, map03030, map03430, map03440
KEGG modules M00260
Gene Ontology (26) GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006950, GO:0006974, GO:0008150, GO:0009380, GO:0009987 +14 more

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 1.495 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 12 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 1.00% of strains (1445) · 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
RNase_TPF00929.32 6.9e-3844–207 Exonuclease
UvrC_MPF27096.1 1.2e-08335–425 UvrC/Cho excinuclease, middle domain

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

Closest characterised functional partner: polA (DNA polymerase I), high confidence from genomic context alone (score 740 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1633 uvrB excinuclease ABC subunit UvrB 977 967 coexpression:670 experimental:772
Rv3644c DNA polymerase 971 961 experimental:474 database:900
Rv0002 dnaN DNA polymerase III subunit beta 967 954 experimental:481 database:900
Rv1547 dnaE1 DNA polymerase III subunit alpha 976 953 experimental:510 database:900 textmining:515
Rv3721c dnaZX DNA polymerase III subunit gamma/tau 963 949 experimental:474 database:900
Rv2413c hyp hypothetical protein 966 944 experimental:442 database:900 textmining:413
Rv3711c dnaQ DNA polymerase III subunit epsilon 932 902 database:900
Rv3202c adnA ATP-dependent DNA helicase 885 841 coexpression:810
Rv3297 nei endonuclease VIII 834 803 coexpression:797
Rv3296 lhr ATP-dependent helicase 767 750 coexpression:735
Rv3585 radA DNA repair protein RadA 812 741 coexpression:734
Rv1629 polA DNA polymerase I 927 740 ctx neighborhood:544 textmining:733
Rv3555c hyp hypothetical protein 730 731 coexpression:730
Rv0651 rplJ 50S ribosomal protein L10 732 723 database:588
Rv0722 rpmD 50S ribosomal protein L30 728 717 database:583

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): hypothetical protein
  • Pfam (hmmscan --cut_ga): RNase_T PF00929.32 (E=7e-38), UvrC_M PF27096.1 (E=1e-08)
  • (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_216707.1)
  • Domains: Pfam-A via hmmscan --cut_ga — RNase_T (PF00929.32), UvrC_M (PF27096.1)
  • 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 COG0322
  • Curated reference: UniProt P9WLJ1 (SwissProt, reviewed; 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 — 123 functional partner(s); context anchor polA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2191|
MQGPNVAAMGATGGTQLSFADLAHAQGAAWTPADEMSLRETTFVVVDLETTGGRTTGNDATPPDAITEIGAVKVCGGAVLGEFATLVNPQHSIPPQIVRLTGITTAMVGNAPTIDAVLPMFFEFAGDSVLVAHNAGFDIGFLRAAARRCDITWPQPQVLCTMRLARRVLSRDEAPSVRLAALARLFAVASNPTHRALDDARATVDVLHALIERVGNQGVHTYAELRSYLPNVTQAQRCKRVLAETLPHRPGVYLFRGPSGEVLYVGTAADLRRRVSQYFNGTDRRKRMTEMVMLASSIDHVECAHPLEAGVRELRMLSTHAPPYNRRSKFPYRWWWVALTDEAFPRLSVIRAPRHDRVVGPFRSRSKAAETAALLARCTGLRTCTTRLTRSARHGPACPELEVSACPAARDVTAAQYAEAVLRAAALIGGLDNAALAAAVQQVTELAERRRYESAARLRDHLATAIEALWHGQRLRALAALPELIAAKPDGPREGGYQLAVIRHGQLAAAGRAPRGVPPMPVVDAIRRGAQAILPTPAPLGGALVEEIALIARWLAEPGVRIVGVSNDAAGLASPVRSAGPWAAWAATARSAQLAGEQLSRGWQSDLPTEPHPSREQLFGRTGVDCRTGPPQPLLPGRQPFSTAG