phoH1 Resolved · high auto-curated

H37Rv Rv2368c · MTBC0 - · 352 aa · 2648916–2649974 (-) · RefSeq YP_177874.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)phosphate starvation-inducible protein PhoH
MTBC0 PGAP re-annotation
Revised (this work)Phosphate starvation-inducible protein PhoH. Pfam: PhoH (PF02562.23), AAA_30 (PF13604.13), AAA_19 (PF13245.13).

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 P9WIA3 SwissProt · reviewed · Evidence at protein level
UniProt namePhoH-like protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category T Signal transduction mechanisms
Preferred namephoH
eggNOG descriptionPhosphate starvation-inducible protein PhoH
Orthologous groupCOG1702
KEGG orthology K06217
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, 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 0.548 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 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
PhoHPF02562.23 1.5e-96126–328 PhoH-like protein
AAA_30PF13604.13 2.9e-08133–283 AAA domain
AAA_19PF13245.13 1.9e-07135–282 AAA domain

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

Closest characterised functional partner: ybeY (endoribonuclease), high confidence from genomic context alone (score 996 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2367c ybeY endoribonuclease 996 996 ctx neighborhood:881 coexpression:967
Rv2366c transmembrane protein 976 976 ctx neighborhood:881 coexpression:806
Rv2365c hyp hypothetical protein 944 944 ctx neighborhood:881 coexpression:548
Rv2364c era GTPase Era 917 910 ctx neighborhood:791 coexpression:519
Rv2362c recO DNA repair protein RecO 790 783 coexpression:730
Rv2369c hyp hypothetical protein 774 774 ctx neighborhood:773
Rv2370c hyp hypothetical protein 774 773 ctx neighborhood:773
Rv2420c rsfS hyp hypothetical protein 573 573 ctx cooccurence:546
Rv1712 cmk cytidylate kinase 573 573 ctx cooccurence:535
Rv2457c clpX ATP-dependent CLP protease ATP-binding subunit ClpX 550 550 coexpression:407
Rv1901 cinA competence damage-inducible protein CinA 523 524
Rv2372c rsmE rRNA small subunit methyltransferase E 517 517 ctx neighborhood:514
Rv2371 PE_PGRS40 PE-PGRS family protein PE_PGRS40 497 497 ctx neighborhood:497
Rv1407 fmu 16S rRNA m5C967 methyltransferase 477 477
Rv3752c tadA cytidine/deoxycytidylate deaminase 458 459 ctx cooccurence:456

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): phosphate starvation-inducible protein PhoH
  • Pfam (hmmscan --cut_ga): PhoH PF02562.23 (E=2e-96), AAA_30 PF13604.13 (E=3e-08), AAA_19 PF13245.13 (E=2e-07)
  • (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 YP_177874.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PhoH (PF02562.23), AAA_30 (PF13604.13), AAA_19 (PF13245.13)
  • 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 COG1702
  • Curated reference: UniProt P9WIA3 (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 — 25 functional partner(s); context anchor ybeY
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2368c|phoH1
MTSRETRAADAAGARQADAQVRSSIDVPPDLVVGLLGSADENLRALERTLSADLHVRGNAVTLCGEPADVALAERVISELIAIVASGQSLTPEVVRHSVAMLVGTGNESPAEVLTLDILSRRGKTIRPKTLNQKRYVDAIDANTIVFGIGPAGTGKTYLAMAKAVHALQTKQVTRIILTRPAVEAGERLGFLPGTLSEKIDPYLRPLYDALYDMMDPELIPKLMSAGVIEVAPLAYMRGRTLNDAFIVLDEAQNTTAEQMKMFLTRLGFGSKVVVTGDVTQIDLPGGARSGLRAAVDILEDIDDIHIAELTSVDVVRHRLVSEIVDAYARYEEPGSGLNRAARRASGARGRR