Rv2616 Family assigned · low auto-curated

H37Rv Rv2616 · MTBC0 mtbc0_002785 · 166 aa · 2968892–2969392 (+) · RefSeq NP_217132.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF1990 family protein
Revised (this work)DUF1990 family protein.

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

Curated reference (UniProt)

UniProt O06198 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionDomain of unknown function (DUF1990)
Orthologous groupCOG4762

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 0.551 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 5 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 5.95% of strains (8640) · 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
DUF1990PF09348.16 5.1e-5812–165 Domain of unknown function (DUF1990)

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

Closest characterised functional partner: blaR (sensor-transducer protein BlaR), medium confidence from genomic context alone (score 489 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0495c hyp hypothetical protein 660 661 ctx cooccurence:655
Rv1845c blaR sensor-transducer protein BlaR 488 489 ctx cooccurence:466
Rv2614c thrS threonine--tRNA ligase 455 455 ctx neighborhood:450
Rv2613c AP-4-A phosphorylase 442 443 ctx neighborhood:439
Rv2612c pgsA1 CDP-diacylglycerol--inositol 3-phosphatidyltransferase 427 427 ctx neighborhood:424
Rv1473 macrolide ABC transporter ATP-binding protein 657 65 textmining:649

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: DUF1990 family protein
  • Pfam (hmmscan --cut_ga): DUF1990 PF09348.16 (E=5e-58)
  • (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_217132.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF1990 (PF09348.16)
  • 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 COG4762
  • Curated reference: UniProt O06198 (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 — 6 functional partner(s); context anchor blaR
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002785|Rv2616|
MDLNALADLPLTYPEVGATATGRLPAGYNHLDVSTQIGTGRQRFEQAADAVMHWGMQRNAGLRVRASSETAVVSAVVLVGIAFLRAPCRVVYVIDEPDVRGFGYGTLPGHPVSGEERFAVRCDPMTSVVFAEVLSFSRPATWASKAAGPLGAVTQRFIAQRYLRAV