rphA Resolved · high auto-curated

H37Rv Rv1340 · MTBC0 mtbc0_001437 · 259 aa · 1517457–1518236 (+) · RefSeq NP_215856.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease PH
MTBC0 PGAP re-annotationribonuclease PH
Revised (this work)Ribonuclease PH. Pfam: RNase_PH (PF01138.28), RNase_PH_C (PF03725.21).

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

Curated reference (UniProt)

UniProt P9WGZ7 SwissProt · reviewed · Evidence at protein level
UniProt nameRibonuclease PH
EC (curated) EC 2.7.7.56
Curated functionPhosphorolytic 3'-5' exoribonuclease that plays an important role in tRNA 3'-end maturation. Removes nucleotide residues following the 3'-CCA terminus of tRNAs; can also add nucleotides to the ends of RNA molecules by using nucleoside diphosphates as substrates, but this may not be physiologically important. Probably plays a role in initiation of 16S rRNA degradation (leading to ribosome degradation) during starvation.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category J Translation, ribosomal structure and biogenesis
Preferred namerph
eggNOG descriptionPhosphorolytic exoribonuclease that removes nucleotide residues following the -CCA terminus of tRNA and adds nucleotides to the ends of RNA molecules by using nucleoside diphosphates as substrates
Orthologous groupCOG2123
EC number EC 2.7.7.56
KEGG orthology K00989
Gene Ontology (37) GO:0005575, GO:0005623, GO:0005886, GO:0006139, GO:0006401, GO:0006725, GO:0006807, GO:0008150, GO:0008152, GO:0009056, GO:0009057, GO:0009987 +25 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 1.089 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 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
RNase_PHPF01138.28 2.2e-3012–142 3' exoribonuclease family, domain 1
RNase_PH_CPF03725.21 8.4e-11161–225 3' exoribonuclease family, domain 2

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

Closest characterised functional partner: rdgB (non-canonical purine NTP pyrophosphatase), high confidence from genomic context alone (score 994 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1341 rdgB non-canonical purine NTP pyrophosphatase 993 994 ctx neighborhood:825 fusion:900 coexpression:678
Rv2681 hyp hypothetical protein 991 988 experimental:921 database:844
Rv1630 rpsA 30S ribosomal protein S1 904 903 experimental:434 database:806
Rv1339 hyp hypothetical protein 906 896 ctx neighborhood:861
Rv3458c rpsD 30S ribosomal protein S4 898 896 database:783
Rv3459c rpsK 30S ribosomal protein S11 856 849 database:746
Rv1336 cysM O-phosphoserine sulfhydrylase 835 835 ctx neighborhood:825
Rv2343c dnaG DNA primase 852 824 experimental:821
Rv1335 cysO sulfur carrier protein CysO 824 824 ctx neighborhood:821
Rv0721 rpsE 30S ribosomal protein S5 816 814 database:802
Rv1334 mec [CysO 816 809 ctx neighborhood:797
Rv1333 hydrolase 803 803 ctx neighborhood:797
Rv1332 transcriptional regulator 789 790 ctx neighborhood:783
Rv1331 clpS ATP-dependent Clp protease adapter protein ClpS 784 784 ctx neighborhood:783
Rv1338 murI glutamate racemase 743 743 ctx neighborhood:714

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: ribonuclease PH
  • MTBC0 PGAP product: ribonuclease PH
  • Pfam (hmmscan --cut_ga): RNase_PH PF01138.28 (E=2e-30), RNase_PH_C PF03725.21 (E=8e-11)
  • (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_215856.1)
  • Domains: Pfam-A via hmmscan --cut_ga — RNase_PH (PF01138.28), RNase_PH_C (PF03725.21)
  • 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 COG2123
  • Curated reference: UniProt P9WGZ7 (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 — 61 functional partner(s); context anchor rdgB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001437|Rv1340|rphA
MSKREDGRLDHELRPVIITRGFTENPAGSVLIEFGHTKVLCTASVTEGVPRWRKATGLGWLTAEYAMLPSATHSRSDRESVRGRLSGRTQEISRLIGRSLRACIDLAALGENTIAIDCDVLQADGGTRTAAITGAYVALADAVTYLSAAGKLSDPRPLSCAIAAVSVGVVDGRIRVDLPYEEDSRAEVDMNVVATDTGTLVEIQGTGEGATFARSTLDKLLDMALGACDTLFAAQRDALALPYPGVLPQGPPPPKAFGT