pafC Family assigned · medium auto-curated

H37Rv Rv2095c · MTBC0 mtbc0_002229 · 316 aa · 2381989–2382939 (-) · RefSeq NP_216611.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)proteasome accessory factor C
MTBC0 PGAP re-annotationYafY family protein
Revised (this work)YafY family protein. Pfam: HTH_PafC (PF19187.7), WYL (PF13280.13), WCX (PF25583.2).

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

Curated reference (UniProt)

UniProt P9WIL9 SwissProt · reviewed · Evidence at protein level
UniProt nameProtein PafC
Curated functionPart of the pafABC operon, but PafC does not seem to be involved in pupylation or substrate degradation. Appears to play at least a small role in resistance to reactive nitrogen intermediates (RNI) in vitro.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namepafC
eggNOG descriptionWYL domain
Orthologous groupCOG2378
KEGG orthology K13573
Gene Ontology (6) GO:0005575, GO:0005618, GO:0005623, GO:0030312, 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)

pN/pS 0.494 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 4 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
HTH_PafCPF19187.7 1.7e-416–119 PafC helix-turn-helix domain
WYLPF13280.13 8.2e-18140–204 WYL domain
WCXPF25583.2 6.7e-19235–307 WCX domain

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

Closest characterised functional partner: pafB (proteasome accessory factor B), high confidence from genomic context alone (score 997 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2096c pafB proteasome accessory factor B 999 997 ctx neighborhood:882 fusion:899 cooccurence:760 textmining:907
Rv2050 rbpA RNA polymerase-binding protein RbpA 928 897 experimental:870
Rv1390 rpoZ DNA-directed RNA polymerase subunit omega 892 893 experimental:870
Rv2097c pafA proteasome accessory factor PafA 980 886 ctx neighborhood:881 textmining:839
Rv2703 sigA RNA polymerase sigma factor SigA 871 871 experimental:870
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 877 870 experimental:870
Rv3457c rpoA DNA-directed RNA polymerase subunit alpha 870 870 experimental:870
Rv0668 rpoC DNA-directed RNA polymerase subunit beta' 870 870 experimental:870
Rv2094c tatA Sec-independent protein translocase membrane-bound protein TatA 807 797 ctx neighborhood:796
Rv2092c helY ATP-dependent DNA helicase HelY 735 735 ctx neighborhood:722
Rv2099c PE21 Rv2099c, (MTCY49.39c), len: 58 aa. PE21, Member of the Mycobacterium tuberculosis PE family (see Brennan and Delogu, 2002); 5'-end of Rv2098 622 622 ctx neighborhood:622
Rv2098c PE_PGRS36 PE-PGRS family protein PE_PGRS36; Rv2098c, (MTCY49.38c), len: 434 aa. PE_PGRS36,Member of the Mycobacterium tuberculosis PE family, PGRS sub 622 622 ctx neighborhood:622
Rv2093c tatC Sec-independent protein translocase transmembrane protein TatC 616 617 ctx neighborhood:611
Rv2710 sigB RNA polymerase sigma factor SigB 573 574 experimental:571
Rv2199c ctaF cytochrome c oxidase polypeptide 4 438 439 ctx cooccurence:437

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: proteasome accessory factor C
  • MTBC0 PGAP product: YafY family protein
  • Pfam (hmmscan --cut_ga): HTH_PafC PF19187.7 (E=2e-41), WYL PF13280.13 (E=8e-18), WCX PF25583.2 (E=7e-19)
  • (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_216611.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HTH_PafC (PF19187.7), WYL (PF13280.13), WCX (PF25583.2)
  • 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 COG2378
  • Curated reference: UniProt P9WIL9 (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 — 31 functional partner(s); context anchor pafB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002229|Rv2095c|pafC
MSALSTRLVRLLNMVPYFQANPRITRAEAAAELGVTAKQLEEDLNQLWMCGLPGYSPGDLIDFEFCGDTIEVTFSAGIDRPLKLTSPEATGLLVALRALADIPGVVDPQAARSAIAKIAAAAGAVAAVAEQAPTESPAAAAVRAAVRNSRALTIDYYAASHDTLTTRIVDPIRVLLIGGHSYLEAWSREAEGVRLFRFDRIVDAAELGEPAVPPESARQAPPDTSLFDGDLSLPSATLRVAPSASWMLEYYPIRELRQLPDGSCEVAMTYASEDWMTRLLLGFGSDVRVLAPESLAQRVRDAATAALDAYQAAAPP