Rv3863 Family assigned · medium auto-curated

H37Rv Rv3863 · MTBC0 - · 392 aa · 4338849–4340027 (+) · RefSeq NP_218380.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains MSMEG_6518_N (PF27182.1) 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 P96214 TrEMBL · unreviewed · Evidence at protein level
UniProt nameFHA domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category T Signal transduction mechanisms
eggNOG descriptionATPase activity
Orthologous groupCOG1716

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 0.418 · purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 8 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
MSMEG_6518_NPF27182.1 5.6e-30267–337 MSMEG_6518 N-terminal domain

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

Closest characterised functional partner: espE (ESX-1 secretion-associated protein EspE), medium confidence from genomic context alone (score 500 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3864 espE ESX-1 secretion-associated protein EspE 870 500 ctx neighborhood:493 textmining:751
Rv3866 espG1 ESX-1 secretion-associated protein EspG 482 456 ctx neighborhood:444
Rv3869 eccB1 ESX-1 secretion system protein EccB 452 449 ctx neighborhood:438
Rv3865 espF ESX-1 secretion-associated protein EspF 800 408 ctx neighborhood:402 textmining:677
Rv3862c whiB6 transcriptional regulator WhiB6 408 408
Rv3868 eccA1 ESX-1 secretion system protein EccA1 838 382 textmining:749
Rv3867 espH ESX-1 secretion-associated protein EspH 791 361 textmining:687
Rv3004 cfp6 low molecular weight protein antigen 6 431 41 textmining:431

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): MSMEG_6518_N PF27182.1 (E=6e-30)
  • (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_218380.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MSMEG_6518_N (PF27182.1)
  • 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 COG1716
  • Curated reference: UniProt P96214 (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 — 8 functional partner(s); context anchor espE
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3863|
MAGERKVCPPSRLVPANKGSTQMSKAGSTVGPAPLVACSGGTSDVIEPRRGVAIIGHSCRVGTQIDDSRISQTHLRAVSDDGRWRIVGNIPRGMFVGGRRGSSVTVSDKTLIRFGDPPGGKALTFEVVRPSDSAAQHGRVQPSADLSDDPAHNAAPVAPDPGVVRAGAAAAARRRELDISQRSLAADGIINAGALIAFEKGRSWPRERTRAKLEEVLQWPAGTIARIRRGEPTEPATNPDASPGLRPADGPASLIAQAVTAAVDGCSLAIAALPATEDPEFTERAAPILADLRQLEAIAVQATRISRITPELIKALGAVRRHHDELMRLGATAPGATLAQRLYAARRRANLSTLETAQAAGVAEEMIVGAEAEEELPAEATEAIEALIRQIN