htpG Resolved · high auto-curated

H37Rv Rv2299c · MTBC0 mtbc0_002439 · 647 aa · 2594808–2596751 (-) · RefSeq NP_216815.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)chaperone protein HtpG
MTBC0 PGAP re-annotationmolecular chaperone HtpG
Revised (this work)Molecular chaperone HtpG. Pfam: HATPase_c_3 (PF13589.13), HATPase_c (PF02518.32), HSP90 (PF00183.24).

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

Curated reference (UniProt)

UniProt P9WMJ7 SwissProt · reviewed · Evidence at protein level
UniProt nameChaperone protein HtpG
Curated functionMolecular chaperone. Has ATPase activity.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
Preferred namehtpG
eggNOG descriptionMolecular chaperone. Has ATPase activity
Orthologous groupCOG0326
KEGG orthology K04079
KEGG pathways map04141, map04151, map04217, map04612, map04621, map04626, map04657, map04659, map04914, map04915, map05200, map05215, map05418
Gene Ontology (28) GO:0000302, GO:0000303, GO:0000305, GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0005886, GO:0006950, GO:0006979, GO:0008150, GO:0009987 +16 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) pseudogene candidate

pN/pS 0.779 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 4 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 1.08% of strains (1573) · clonal

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
HATPase_c_3PF13589.13 3.2e-1033–157 Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase
HATPase_cPF02518.32 5.4e-0633–183 Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase
HSP90PF00183.24 9.5e-135235–645 Hsp90 protein

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv0350 dnaK chaperone protein DnaK 993 970 coexpression:671 experimental:772 database:622 textmining:796
Rv2264c hyp hypothetical protein 977 969 coexpression:668 experimental:772 database:622
Rv0312 hyp hypothetical protein 977 969 coexpression:668 experimental:772 database:622
Rv3446c hyp hypothetical protein 977 969 coexpression:668 experimental:772 database:622
Rv2373c dnaJ2 chaperone protein DnaJ 971 958 coexpression:694 experimental:542 database:655
Rv0352 dnaJ1 chaperone protein DnaJ 965 950 coexpression:697 experimental:542 database:655
Rv1691 hyp hypothetical protein 933 926 experimental:786 database:631
Rv2267c stf3 hyp hypothetical protein 933 926 experimental:786 database:631
Rv3529c hyp hypothetical protein 932 926 experimental:786 database:631
Rv2582 ppiB peptidyl-prolyl cis-trans isomerase B 923 913 coexpression:492 experimental:465 database:655
Rv0009 ppiA iron-regulated peptidyl-prolyl cis-trans isomerase PpiA 886 872 experimental:465 database:655
Rv0440 groEL2 molecular chaperone GroEL 907 833 coexpression:720 experimental:416 textmining:471
Rv2357c glyS glycine--tRNA ligase 827 828 coexpression:806
Rv3417c groEL1 chaperonin GroEL 942 827 coexpression:715 experimental:416 textmining:681
Rv3418c groES chaperonin GroES 954 797 coexpression:769 textmining:785

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: chaperone protein HtpG
  • MTBC0 PGAP product: molecular chaperone HtpG
  • Pfam (hmmscan --cut_ga): HATPase_c_3 PF13589.13 (E=3e-10), HATPase_c PF02518.32 (E=5e-06), HSP90 PF00183.24 (E=1e-134)
  • (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_216815.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HATPase_c_3 (PF13589.13), HATPase_c (PF02518.32), HSP90 (PF00183.24)
  • 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 COG0326
  • Curated reference: UniProt P9WMJ7 (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 — 166 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002439|Rv2299c|htpG
MNAHVEQLEFQAEARQLLDLMVHSVYSNKDAFLRELISNASDALDKLRIEALRNKDLEVDTSDLHIEIDADKAARTLTVRDNGIGMAREEVVDLIGTLAKSGTAELRAQLREAKNAAASEELIGQFGIGFYSSFMVADKVQLLTRKAGESAATRWESSGEGTYTIESVEDAPQGTSVTLHLKPEDAEDDLHDYTSEWKIRNLVKKYSDFIAWPIRMDVERRTPASQEEGGEGGEETVTIETETLNSMKALWARPKEEVSEQEYKEFYKHVAHAWDDPLEIIAMKAEGTFEYQALLFIPSHAPFDLFDRDAHVGIQLYVKRVFIMGDCDQLMPEYLRFVKGVVDAQDMSLNVSREILQQDRQIKAIRRRLTKKVLSTIKDVQSSRPEDYRTFWTQFGRVLKEGLLSDIDNRETLLGISSFVSTYSEEEPTTLAEYVERMKDGQQQIFYATGETRQQLLKSPHLEAFKAKGYEVLLLTDPVDEVWVGMVPEFDGKPLQSVAKGEVDLSSEEDTSEAEREERQKEFADLLTWLQETLSDHVKEVRLSTRLTESPACLITDAFGMTPALARIYRASGQEVPVGKRILELNPSHPLVTGLRQAHQDRADDAEKSLAETAELLYGTALLAEGGALEDPARFAELLAERLARTL