hpx Resolved · high auto-curated

H37Rv Rv3171c · MTBC0 - · 299 aa · 3539846–3540745 (-) · RefSeq NP_217687.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)non-heme haloperoxidase Hpx
MTBC0 PGAP re-annotation
Revised (this work)Non-heme haloperoxidase Hpx. Pfam: Abhydrolase_1 (PF00561.27), Hydrolase_4 (PF12146.16), Abhydrolase_6 (PF12697.14), Abhydrolase_4 (PF08386.17).

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 O53321 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible non-heme haloperoxidase Hpx

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namehpx
eggNOG descriptionAlpha beta hydrolase
Orthologous groupCOG2267

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 0.473 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 5 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
Abhydrolase_1PF00561.27 5.0e-2422–272 alpha/beta hydrolase fold
Hydrolase_4PF12146.16 8.6e-1924–256 Serine aminopeptidase, S33
Abhydrolase_6PF12697.14 6.8e-1924–278 Alpha/beta hydrolase family
Abhydrolase_4PF08386.17 1.3e-04198–283 TAP-like protein

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

Closest characterised functional partner: bpoC (non-heme bromoperoxidase BpoC), high confidence from genomic context alone (score 728 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0554 bpoC non-heme bromoperoxidase BpoC 728 728 ctx cooccurence:728
Rv0134 ephF epoxide hydrolase EphF 697 698 ctx cooccurence:696
Rv3177 peroxidase 635 635 ctx cooccurence:633
Rv2296 dhmA1 haloalkane dehalogenase 545 546 ctx cooccurence:543
Rv1833c dhmA2 haloalkane dehalogenase 515 516 ctx cooccurence:514
Rv3172c hyp hypothetical protein 506 506 ctx neighborhood:504
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 529 501 experimental:441
Rv2940c mas multifunctional mycocerosic acid synthase 528 501 experimental:441
Rv1527c pks5 polyketide synthase 527 500 experimental:441
Rv2048c pks12 polyketide synthase 526 499 experimental:441
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 526 498 experimental:441
Rv1124 ephC epoxide hydrolase EphC 497 498 ctx cooccurence:495
Rv2946c pks1 polyketide synthase 486 455
Rv0125 pepA serine protease PepA 455 455
Rv0983 pepD serine protease PepD 451 451

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): non-heme haloperoxidase Hpx
  • Pfam (hmmscan --cut_ga): Abhydrolase_1 PF00561.27 (E=5e-24), Hydrolase_4 PF12146.16 (E=9e-19), Abhydrolase_6 PF12697.14 (E=7e-19), Abhydrolase_4 PF08386.17 (E=1e-04)
  • (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_217687.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Abhydrolase_1 (PF00561.27), Hydrolase_4 (PF12146.16), Abhydrolase_6 (PF12697.14), Abhydrolase_4 (PF08386.17)
  • 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 COG2267
  • Curated reference: UniProt O53321 (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 — 27 functional partner(s); context anchor bpoC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3171c|hpx
MTVRAADGTPLHTQVFGPPHGYPIVLTHGFVCAIRAWAYQIADLAGDYRVIAFDHRGHGRSGVPRRGAYSLNHLAADLDSVLDATLAPRERAVVAGHSMGGITIAAWSDRYRHKVRRRTDAVALINTTTGDLVRKVKLLSVPRELSPVRVLAGRSLVNTFGGFPLPGAARALSRHVISTLAVAADADPSATRLVYELFTQTSAAGRGGCAKMLVEEVGSAHLNLDGLTVPTLVIGGVRDRLTPISQSRRIARTAPNVVGLVELPGGHCSMLERHQEVNSHLRALAESVTRHVRDRRISS