Rv1870c Family assigned · low auto-curated · to review

H37Rv Rv1870c · MTBC0 - · 211 aa · 2120795–2121430 (-) · RefSeq NP_216386.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)No Pfam domain above threshold; Foldseek indicates a fold similar to 4uob-assembly1_A Crystal structure of Deinococcus radiodurans Endonuclease III-3 (prob 1.00, TM 0.56). Structure-based, putative.

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).

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 P95145 TrEMBL · unreviewed · Predicted
UniProt nameEndonuclease

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
eggNOG descriptionDNA repair enzyme that has both DNA N-glycosylase activity and AP-lyase activity. The DNA N-glycosylase activity releases various damaged pyrimidines from DNA by cleaving the N- glycosidic bond, leaving an AP (apurinic apyrimidinic) site. The AP-lyase activity cleaves the phosphodiester bond 3' to the AP site by a beta-elimination, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate
Orthologous groupCOG0177

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 1.834 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 5 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.42% of strains (615) · 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 95.2 (very high). A confident model makes the fold comparison meaningful.

Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.

TargetProbTME-valueDescription
4uob-assembly1_A 1.00 0.56 3.6e-03 sig 4uob-assembly1_A Crystal structure of Deinococcus radiodurans Endonuclease III-3
8a5g-assembly1_A 1.00 0.57 8.2e-03 sig 8a5g-assembly1_A Crystal structure of Deinococcus radiodurans Endonuclease III-3 double mutant
7ulc-assembly1_A 1.00 0.55 1.5e-02 7ulc-assembly1_A Crystal structure of queuine salvage enzyme DUF2419 mutant D231N, in complex with queuosine-5'-monophosphate
7u5a-assembly2_B 1.00 0.54 1.1e-02 7u5a-assembly2_B Crystal structure of queuine salvage enzyme DUF2419 mutant K199C, complexed with queuosine
7u1o-assembly1_A 1.00 0.54 2.1e-02 7u1o-assembly1_A Crystal structure of queuine salvage enzyme DUF2419 complexed with queuosine
7ayy-assembly4_DDD 1.00 0.47 1.0e-02 7ayy-assembly4_DDD Structure of the human 8-oxoguanine DNA Glycosylase hOGG1 in complex with activator TH10785
7ugk-assembly1_A 1.00 0.51 4.1e-02 7ugk-assembly1_A Crystal structure of the human queuine salvage enzyme DUF2419, wild-type apo form
4aia-assembly4_D 1.00 0.61 1.7e-01 4aia-assembly4_D The structural basis of 3-methyladenine recognition by 3- methyladenine DNA glycosylase I (TAG) from Staphylococcus aureus

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

Closest characterised functional partner: Rv1869c (reductase), high confidence from genomic context alone (score 783 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1297 rho transcription termination factor Rho 820 821 coexpression:796
Rv1871c hyp hypothetical protein 814 815 ctx neighborhood:799
Rv1631 coaE dephospho-CoA kinase CoaE 811 812 coexpression:801
Rv0427c xthA exodeoxyribonuclease III protein XthA 818 799 experimental:403 database:641
Rv3921c yidC membrane protein insertase YidC 788 789 coexpression:788
Rv1869c reductase 783 783 ctx neighborhood:773
Rv3920c hyp hypothetical protein 732 732 coexpression:732
Rv1872c lldD2 L-lactate dehydrogenase 611 611 ctx neighborhood:595
Rv1613 trpA tryptophan synthase subunit alpha 558 559 coexpression:554
Rv0670 end endonuclease IV 530 480 experimental:441
Rv2902c rnhB ribonuclease HII 512 467 coexpression:459
Rv1614 lgt prolipoprotein diacylglyceryl transferase 459 460 coexpression:441
Rv1873 hyp hypothetical protein 443 443 ctx neighborhood:441
Rv0797 insertion sequence element IS1547 transposase 441 442 ctx cooccurence:425
Rv0188 transmembrane protein 432 432 ctx cooccurence:432

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
  • Foldseek best: 4uob-assembly1_A Crystal structure of Deinococcus radiodurans Endonuclease III-3 (prob 1.00, E=4e-03, TM=0.56)
  • (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_216386.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG0177
  • Curated reference: UniProt P95145 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 95.2, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 30 functional partner(s); context anchor Rv1869c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1870c|
MPPRIAGMRLLVIKPEPLARRLLKLAGTTYAAEAGIRIRDKPMPLFQLLVLCMLASKPIGAATAARAARELFCSGLRTPKAVLSAERQTMISAFGRAHYVRYDESSATRLTAIAHRVRDEYSGDLRELAQRTRPDVSAAKRMLKTFNGIGDTGADIFLREVQDVWIWVRPYFDDRATAAAKQLGLPTDPKKLASVAPSSNALLAAALVRVA