Rv2248 Family assigned · medium auto-curated

H37Rv Rv2248 · MTBC0 - · 271 aa · 2522360–2523175 (+) · RefSeq NP_216764.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains AbiEi_1 (PF09407.17) 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 P9WLG5 SwissProt · reviewed · Predicted
UniProt nameUncharacterized protein Rv2248

UniProt still lists this protein as Uncharacterized protein Rv2248; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein conserved in bacteria
Orthologous groupCOG2852
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 0.591 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 6 missense, 1 nonsense, 2 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 1.35% of strains (1964) · 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
AbiEi_1PF09407.17 1.6e-3345–158 AbiEi antitoxin C-terminal domain

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

Closest characterised functional partner: rsmA (anti-sigma-M factor RsmA), medium confidence from genomic context alone (score 630 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3912 rsmA anti-sigma-M factor RsmA 630 630 ctx cooccurence:628
Rv3779 transmembrane protein 589 589 ctx cooccurence:589
Rv0204c transmembrane protein 582 583 ctx cooccurence:581
Rv0955 integral membrane protein 540 540 ctx cooccurence:540
Rv1353c HTH-type transcriptional regulator 539 539 ctx cooccurence:538
Rv2246 kasB 3-oxoacyl-ACP synthase 2 539 538
Rv0048c membrane protein 525 525 ctx cooccurence:525
Rv3859c gltB glutamate synthase large subunit 522 522 coexpression:515
Rv0256c PPE2 PPE family protein PPE2 513 514 ctx cooccurence:505
Rv1060 hyp hypothetical protein 512 512 ctx cooccurence:512
Rv3773c hyp hypothetical protein 509 510 ctx cooccurence:507
Rv2378c mbtG L-lysine N6-monooxygenase 501 501 ctx cooccurence:494
Rv2247 accD6 acetyl-/propionyl-CoA carboxylase subunit beta 494 494 ctx neighborhood:451
Rv3594 hyp hypothetical protein 478 479 ctx cooccurence:471
Rv2687c antibiotic ABC transporter permease 473 474 ctx cooccurence:471

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): AbiEi_1 PF09407.17 (E=2e-33)
  • (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_216764.1)
  • Domains: Pfam-A via hmmscan --cut_ga — AbiEi_1 (PF09407.17)
  • 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 COG2852
  • Curated reference: UniProt P9WLG5 (SwissProt, reviewed; 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)
  • 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 rsmA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2248|
MTRQQLDVQVKNGGLVRVWYGVYAAQEPDLLGRLAALDVFMGGHAVACLGTAAALYGFDTENTVAIHMLDPGVRMRPTVGLMVHQRVGARLQRVSGRLATAPAWTAVEVARQLRRPRALATLDAALRSMRCARSEIENAVAEQRGRRGIVAARELLPFADGRAESAMESEARLVMIDHGLPLPELQYPIHGHGGEMWRVDFAWPDMRLAAEYESIEWHAGPAEMLRDKTRWAKLQELGWTIVPIVVDDVRREPGRLAARIARHLDRARMAG