hrp1 Resolved · high auto-curated

H37Rv Rv2626c · MTBC0 mtbc0_002795 · 143 aa · 2976124–2976555 (-) · RefSeq NP_217142.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypoxic response protein
MTBC0 PGAP re-annotationhypoxic response protein Hrp1
Revised (this work)Hypoxic response protein Hrp1. Pfam: CBS (PF00571.34).

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

Curated reference (UniProt)

UniProt P9WJA3 SwissProt · reviewed · Evidence at protein level
UniProt nameHypoxic response protein 1
Curated functionUnlike some other CBS-domain containing proteins does not seem to bind AMP.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionCBS domain
Orthologous groupCOG0517
Gene Ontology (40) GO:0001666, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006950, GO:0008150, GO:0009605, GO:0009607 +28 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 0.103 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 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
CBSPF00571.34 1.0e-124–55 CBS domain

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

Closest characterised functional partner: rip3 (zinc metalloprotease Rip3), high confidence from genomic context alone (score 920 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2625c rip3 zinc metalloprotease Rip3 920 920 ctx neighborhood:609 coexpression:805
Rv2624c universal stress protein 920 908 ctx neighborhood:586 coexpression:788
Rv2030c hyp hypothetical protein 939 901 coexpression:860 textmining:412
Rv2031c hspX alpha-crystallin 950 863 coexpression:859 textmining:654
Rv2623 TB31.7 universal stress protein 949 862 coexpression:860 textmining:648
Rv1733c transmembrane protein 950 861 coexpression:860 textmining:659
Rv2032 acg NAD(P)H nitroreductase 929 861 coexpression:860 textmining:513
Rv2627c hyp hypothetical protein 860 861 coexpression:860
Rv1996 universal stress protein 870 856 coexpression:853
Rv1737c narK2 nitrate/nitrite transporter 906 853 coexpression:853
Rv3134c universal stress protein 881 851 coexpression:848
Rv3127 hyp hypothetical protein 863 840 coexpression:839
Rv2007c fdxA ferredoxin 902 834 coexpression:834 textmining:434
Rv1997 ctpF cation transporter ATPase F 860 830 coexpression:804
Rv3131 NAD(P)H nitroreductase 893 818 coexpression:817 textmining:439

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: hypoxic response protein
  • MTBC0 PGAP product: hypoxic response protein Hrp1
  • Pfam (hmmscan --cut_ga): CBS PF00571.34 (E=1e-12)
  • (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_217142.1)
  • Domains: Pfam-A via hmmscan --cut_ga — CBS (PF00571.34)
  • 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 COG0517
  • Curated reference: UniProt P9WJA3 (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 — 39 functional partner(s); context anchor rip3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002795|Rv2626c|hrp1
MTTARDIMNAGVTCVGEHETLTAAAQYMREHDIGALPICGDDDRLHGMLTDRDIVIKGLAAGLDPNTATAGELARDSIYYVDANASIQEMLNVMEEHQVRRVPVISEHRLVGIVTEADIARHLPEHAIVQFVKAICSPMALAS