Rv2696c Still unknown · low auto-curated

H37Rv Rv2696c · MTBC0 mtbc0_002870 · 259 aa · 3035244–3036023 (-) · RefSeq NP_217212.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF3710 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF3710. Function unknown.

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

Curated reference (UniProt)

UniProt I6XF31 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved alanine and glycine and valine rich protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF3710)
Orthologous group28J4D

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 0.349 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 5 missense, 0 nonsense, 0 frameshift

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
DUF3710PF12502.14 2.1e-5452–221 Protein of unknown function (DUF3710)

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

Closest characterised functional partner: Rv2698 (transmembrane protein), high confidence from genomic context alone (score 800 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2698 transmembrane protein 800 800 ctx neighborhood:727
Rv2697c dut deoxyuridine 5'-triphosphate nucleotidohydrolase 793 793 ctx neighborhood:790
Rv2050 rbpA RNA polymerase-binding protein RbpA 721 721 ctx cooccurence:718
Rv2413c hyp hypothetical protein 699 700 ctx cooccurence:699
Rv1830 HTH-type transcriptional regulator 689 690 ctx cooccurence:688
Rv2708c hyp hypothetical protein 686 686 ctx cooccurence:685
Rv2219 transmembrane protein 682 683 ctx cooccurence:673
Rv1440 secG protein-export membrane protein SecG 672 672 ctx cooccurence:669
Rv2206 transmembrane protein 668 668 ctx cooccurence:666
Rv2699c hyp hypothetical protein 646 647 ctx cooccurence:585
Rv0807 hyp hypothetical protein 627 627 ctx cooccurence:625
Rv2731 hyp hypothetical protein 622 622 ctx cooccurence:620
Rv0383c ttfA hyp hypothetical protein 594 594 ctx cooccurence:594
Rv1390 rpoZ DNA-directed RNA polymerase subunit omega 589 590 ctx cooccurence:587
Rv3195 hyp hypothetical protein 705 588 ctx cooccurence:588

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: hypothetical protein
  • MTBC0 PGAP product: DUF3710 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF3710 PF12502.14 (E=2e-54)
  • (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_217212.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF3710 (PF12502.14)
  • 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 28J4D
  • Curated reference: UniProt I6XF31 (TrEMBL, unreviewed; 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 — 44 functional partner(s); context anchor Rv2698
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002870|Rv2696c|
MAFGRRTGKDGGKRKAGHAPVQPADEHVRPEDTVVASAAAASGVEDQEELQGPFDIDDFDDPSVAVLARLDLGSVLIPMPAAGQVQVELTESGVPSAVWVITPNGRYSIAAYAAPKTGGLWREVAGELADSLRKDSAKVSIKDGPWGREVIGIAAGVVRFIGVDGYRWMIRCVVNGPQETVDALTEEAREALADTVVRRGDTPLPVRTPLPVHLPEPMAAQLREAAAAQADTQRQAAAGVARRGAQGSAMQQLRSTTGG