Rv2295 Family assigned · low auto-curated

H37Rv Rv2295 · MTBC0 mtbc0_002435 · 212 aa · 2591521–2592159 (+) · RefSeq NP_216811.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationCbrC family protein
Revised (this work)CbrC 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 P9WFL7 SwissProt · reviewed · Evidence at protein level
UniProt nameUPF0167 protein Rv2295
Curated functionProbably plays a role in host phagosome maturation arrest.

UniProt still lists this protein as UPF0167 protein Rv2295; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionUncharacterised protein family (UPF0167)
Orthologous groupCOG3196
KEGG orthology K09925
Gene Ontology (48) GO:0002682, GO:0002683, GO:0008150, GO:0009605, GO:0009607, GO:0031347, GO:0031348, GO:0035821, GO:0043207, GO:0044003, GO:0044403, GO:0044413 +36 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 0.507 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 3 missense, 2 nonsense, 0 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.29% of strains (422) · 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
UPF0167PF03691.19 8.4e-6737–211 Uncharacterised protein family (UPF0167)

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

Closest characterised functional partner: PPE8 (PPE family protein PPE8), medium confidence from genomic context alone (score 676 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0355c PPE8 PPE family protein PPE8 675 676 ctx cooccurence:674
Rv2209 integral membrane protein 673 674 ctx cooccurence:669
Rv3350c PPE56 PPE family protein PPE56 667 667 ctx cooccurence:667
Rv3347c PPE55 PPE family protein PPE55 667 667 ctx cooccurence:665
Rv3343c PPE54 PPE family protein PPE54 649 649 ctx cooccurence:647
Rv0304c PPE5 PPE family protein PPE5 648 648 ctx cooccurence:646
Rv1917c PPE34 PPE family protein PPE34 646 647 ctx cooccurence:644
Rv2490c PE_PGRS43 PE-PGRS family protein PE_PGRS43 645 645 ctx cooccurence:645
Rv1452c PE_PGRS28 PE-PGRS family protein PE_PGRS28 643 643 ctx cooccurence:643
Rv1004c membrane protein 643 643 ctx cooccurence:642
Rv0330c hyp hypothetical protein 621 622 ctx cooccurence:620
Rv0442c PPE10 PPE family protein PPE10 611 611 ctx cooccurence:609
Rv1651c PE_PGRS30 PE-PGRS family protein PE_PGRS30 606 606 ctx cooccurence:606
Rv2082 hyp hypothetical protein 603 603 ctx cooccurence:601
Rv0305c PPE6 PPE family protein PPE6 598 599 ctx cooccurence:597

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: CbrC family protein
  • Pfam (hmmscan --cut_ga): UPF0167 PF03691.19 (E=8e-67)
  • (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_216811.1)
  • Domains: Pfam-A via hmmscan --cut_ga — UPF0167 (PF03691.19)
  • 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 COG3196
  • Curated reference: UniProt P9WFL7 (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 — 59 functional partner(s); context anchor PPE8
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002435|Rv2295|
MDQSANHACLPTPLASTTGRGQDHEMPVEETSTPQKLPQFRYHPDPVGTGSIVADEVSCVSCEQRRPYTYTGPVYAEEELNEAICPWCIADGSAASRFDATFTDAMWAVPDDVPEDVTEEVLCRTPGFTGWLQEEWLHHCGDAAAFLGPVGASEVADLPDALDALRNEYRGYDWPADKIEEFILTLDRNGLATAYLFRCLSCGVHLAYADFA