rpfA Resolved · high auto-curated

H37Rv Rv0867c · MTBC0 mtbc0_000922 · 407 aa · 967515–968738 (-) · RefSeq NP_215382.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)resuscitation-promoting factor RpfA
MTBC0 PGAP re-annotationresuscitation-promoting factor protein RpfA
Revised (this work)Resuscitation-promoting factor protein RpfA. Pfam: Transglycosylas (PF06737.20).

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

Curated reference (UniProt)

UniProt P9WG31 SwissProt · reviewed · Evidence at protein level
UniProt nameResuscitation-promoting factor RpfA
EC (curated) EC 3.-.-.-
Curated functionFactor that stimulates resuscitation of dormant cells. Has peptidoglycan (PG) hydrolytic activity. Active in the pM concentration range. Has little to no effect on actively-growing cells. PG fragments could either directly activate the resuscitation pathway of dormant bacteria or serve as a substrate for endogenous Rpf, resulting in low molecular weight products with resuscitation activity. Stimulates growth of stationary phase M.bovis (a slow-growing Mycobacterium), reduces the lag phase of diluted fast-growers M.smegmatis and Micrococcus luteus.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namerpfA
eggNOG descriptionTransglycosylase-like domain
Orthologous groupCOG1652
KEGG orthology K21687
CAZy family GH23
Gene Ontology (17) GO:0005575, GO:0005576, GO:0008150, GO:0009892, GO:0010468, GO:0010605, GO:0010629, GO:0019222, GO:0040008, GO:0040009, GO:0040010, GO:0045927 +5 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 0.425 · purifying
Polymorphic sites (≥ 0.1% of strains) 10 synonymous, 11 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
TransglycosylasPF06737.20 4.9e-3538–114 Transglycosylase-like domain

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

Closest characterised functional partner: Rv0316 (muconolactone isomerase), medium confidence from genomic context alone (score 465 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1954A Rv1954A, len: 100 aa. Hypothetical unknown protein. 870 870 coexpression:443 experimental:769
Rv0007 membrane protein 581 582 coexpression:501
Rv1651c PE_PGRS30 PE-PGRS family protein PE_PGRS30 474 475
Rv0316 muconolactone isomerase 464 465 ctx cooccurence:439
Rv3737 transmembrane protein 444 445 ctx cooccurence:428
Rv1230c membrane protein 444 445 ctx cooccurence:425
Rv3879c espK ESX-1 secretion-associated protein EspK 451 427
Rv3915 cwlM peptidoglycan hydrolase 583 425
Rv0925c hyp hypothetical protein 446 424 coexpression:424
Rv2771c hyp hypothetical protein 441 419 coexpression:419
Rv3372 otsB2 trehalose 6-phosphate phosphatase 446 417 coexpression:413
Rv2006 otsB1 trehalose-6-phosphate phosphatase OtsB 443 415 coexpression:409
Rv0194 multidrug ABC transporter ATPase/permease 412 413 ctx cooccurence:411
Rv0977 PE_PGRS16 PE-PGRS family protein PE_PGRS16 411 411
Rv0872c PE_PGRS15 PE-PGRS family protein PE_PGRS15 408 408

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: resuscitation-promoting factor RpfA
  • MTBC0 PGAP product: resuscitation-promoting factor protein RpfA
  • Pfam (hmmscan --cut_ga): Transglycosylas PF06737.20 (E=5e-35)
  • (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_215382.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Transglycosylas (PF06737.20)
  • 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 COG1652
  • Curated reference: UniProt P9WG31 (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 — 34 functional partner(s); context anchor Rv0316
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000922|Rv0867c|rpfA
MSGRHRKPTTSNVSVAKIAFTGAVLGGGGIAMAAQATAATDGEWDQVARCESGGNWSINTGNGYLGGLQFTQSTWAAHGGGEFAPSAQLASREQQIAVGERVLATQGRGAWPVCGRGLSNATPREVLPASAAMDAPLDAAAVNGEPAPLAPPPADPAPPVELAANDLPAPLGEPLPAAPADPAPPADLAPPAPADVAPPVELAVNDLPAPLGEPLPAAPADPAPPADLAPPAPADLAPPAPADLAPPAPADLAPPVELAVNDLPAPLGEPLPAAPAELAPPADLAPASADLAPPAPADLAPPAPAELAPPAPADLAPPAAVNEQTAPGDQPATAPGGPVGLATDLELPEPDPQPADAPPPGDVTEAPAETPQVSNIAYTKKLWQAIRAQDVCGNDALDSLAQPYVIG