prfA Resolved · high auto-curated

H37Rv Rv1299 · MTBC0 mtbc0_001391 · 357 aa · 1464534–1465607 (+) · RefSeq NP_215815.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)peptide chain release factor PrfA
MTBC0 PGAP re-annotationpeptide chain release factor 1
Revised (this work)Peptide chain release factor 1. Pfam: PCRF (PF03462.24), RF-1 (PF00472.27).

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

Curated reference (UniProt)

UniProt P9WHG3 SwissProt · reviewed · Evidence at protein level
UniProt namePeptide chain release factor 1
Curated functionPeptide chain release factor 1 directs the termination of translation in response to the peptide chain termination codons UAG and UAA.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category J Translation, ribosomal structure and biogenesis
Preferred nameprfA
eggNOG descriptionPeptide chain release factor 1 directs the termination of translation in response to the peptide chain termination codons UAG and UAA
Orthologous groupCOG0216
KEGG orthology K02835
Gene Ontology (2) GO:0008150, GO:0040007

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 0.674 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 3 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.38% of strains (548) · 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
PCRFPF03462.24 2.9e-6013–204 PCRF domain
RF-1PF00472.27 5.6e-41215–322 RF-1 domain

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

Closest characterised functional partner: hemK (release factor glutamine methyltransferase), high confidence from genomic context alone (score 999 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1300 hemK release factor glutamine methyltransferase 999 999 ctx neighborhood:881 coexpression:896 experimental:890 textmining:551
Rv3443c rplM 50S ribosomal protein L13 979 979 ctx cooccurence:683 experimental:908
Rv1643 rplT 50S ribosomal protein L20 979 977 ctx cooccurence:582 coexpression:411 experimental:913
Rv1298 rpmE 50S ribosomal protein L31 979 977 ctx neighborhood:778 coexpression:434 experimental:830
Rv2441c rpmA 50S ribosomal protein L27 978 973 ctx cooccurence:610 experimental:913
Rv0683 rpsG 30S ribosomal protein S7 976 969 ctx cooccurence:544 experimental:907
Rv0702 rplD 50S ribosomal protein L4 968 966 ctx cooccurence:567 experimental:908
Rv3442c rpsI 30S ribosomal protein S9 967 964 ctx cooccurence:501 experimental:907
Rv2785c rpsO 30S ribosomal protein S15 964 961 ctx cooccurence:555 experimental:907
Rv0701 rplC 50S ribosomal protein L3 964 960 ctx cooccurence:535 experimental:908
Rv3456c rplQ 50S ribosomal protein L17 964 959 ctx cooccurence:486 experimental:913
Rv0708 rplP 50S ribosomal protein L16 961 957 ctx cooccurence:521 experimental:908
Rv2890c rpsB 30S ribosomal protein S2 958 956 experimental:907
Rv2909c rpsP 30S ribosomal protein S16 950 946 experimental:907
Rv0682 rpsL 30S ribosomal protein S12 957 945 experimental:907

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: peptide chain release factor PrfA
  • MTBC0 PGAP product: peptide chain release factor 1
  • Pfam (hmmscan --cut_ga): PCRF PF03462.24 (E=3e-60), RF-1 PF00472.27 (E=6e-41)
  • (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_215815.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PCRF (PF03462.24), RF-1 (PF00472.27)
  • 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 COG0216
  • Curated reference: UniProt P9WHG3 (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 — 167 functional partner(s); context anchor hemK
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001391|Rv1299|prfA
MTQPVQTIDVLLAEHAELELALADPALHSNPAEARRVGRRFARLAPIVATHRKLTSARDDLETARELVASDESFAAEVAALEARVGELDAQLTDMLAPRDPHDADDIVLEVKSGEGGEESALFAADLARMYIRYAERHGWAVTVLDETTSDLGGYKDATLAIASKADTPDGVWSRMKFEGGVHRVQRVPVTESQGRVHTSAAGVLVYPEPEEVGQVQIDESDLRIDVFRSSGKGGQGVNTTDSAVRITHLPTGIVVTCQNERSQLQNKTRALQVLAARLQAMAEEQALADASADRASQIRTVDRSERIRTYNFPENRITDHRIGYKSHNLDQVLDGDLDALFDALSAADKQSRLRQS