MTBC Gene Atlas

phoP Resolved · high auto-curated

H37Rv Rv0757 · MTBC0 mtbc0_000806 · 247 aa · 856033–856776 (+) · RefSeq NP_215271.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)two component system response transcriptional positive regulator PhoP
MTBC0 PGAP re-annotationtwo-component system response regulator PhoP
Revised (this work)Two-component system response regulator PhoP. Pfam: Response_reg (PF00072.31), Trans_reg_C (PF00486.35).

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

Curated reference (UniProt)

UniProt P71814 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible two component system response transcriptional positive regulator PhoP

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
T Signal transduction mechanisms
Preferred namephoP
eggNOG descriptionresponse regulator
Orthologous groupCOG0745
KEGG orthology K02483

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 0.089 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 1 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
Response_regPF00072.31 3.3e-2823–132 Response regulator receiver domain
Trans_reg_CPF00486.35 9.0e-24169–243 Transcriptional regulatory protein, C terminal

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

Closest characterised functional partner: phoR (two component system response sensor kinase PhoR), high confidence from genomic context alone (score 975 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0758 phoR two component system response sensor kinase PhoR 999 975 ctx neighborhood:817 cooccurence:772 textmining:978
Rv0600c two component sensor kinase HK1 895 891 ctx cooccurence:753
Rv0902c prrB two component sensor histidine kinase PrrB 963 878 ctx cooccurence:718 textmining:711
Rv1032c trcS two component sensor histidine kinase TrcS 896 878 ctx cooccurence:720
Rv3764c tcrY two component sensor kinase TcrY 881 871 ctx cooccurence:702
Rv0490 senX3 two component sensor histidine kinase SenX3 918 853 ctx cooccurence:731 textmining:467
Rv0982 mprB two component histidine-protein kinase/phosphatase MprB 843 837 ctx cooccurence:620
Rv0756c hyp hypothetical protein 783 774 ctx neighborhood:773
Rv3245c mtrB two component sensory histidine kinase MtrB 809 733 ctx cooccurence:531
Rv0601c two component sensor kinase HK2 727 717
Rv2998A Rv2998A, len: 67 aa. Probable conserved hypothetical protein, (possibly gene fragment), highly similar to central part of two-component sens 649 636
Rv2374c hrcA heat-inducible transcription repressor HrcA 648 618 experimental:550
Rv3365c hyp hypothetical protein 590 575
Rv0353 hspR heat shock protein transcriptional repressor HspR 651 565 experimental:558
Rv3645 transmembrane protein 549 521

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: two component system response transcriptional positive regulator PhoP
  • MTBC0 PGAP product: two-component system response regulator PhoP
  • Pfam (hmmscan --cut_ga): Response_reg PF00072.31 (E=3e-28), Trans_reg_C PF00486.35 (E=9e-24)
  • (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_215271.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Response_reg (PF00072.31), Trans_reg_C (PF00486.35)
  • 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 COG0745
  • Curated reference: UniProt P71814 (TrEMBL, unreviewed; 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 — 75 functional partner(s); context anchor phoR
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000806|Rv0757|phoP
MRKGVDLVTAGTPGENTTPEARVLVVDDEANIVELLSVSLKFQGFEVYTATNGAQALDRARETRPDAVILDVMMPGMDGFGVLRRLRADGIDAPALFLTARDSLQDKIAGLTLGGDDYVTKPFSLEEVVARLRVILRRAGKGNKEPRNVRLTFADIELDEETHEVWKAGQPVSLSPTEFTLLRYFVINAGTVLSKPKILDHVWRYDFGGDVNVVESYVSYLRRKIDTGEKRLLHTLRGVGYVLREPR