Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | chaperone protein HtpG |
| MTBC0 PGAP re-annotation | molecular 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 name | Chaperone protein HtpG |
| Curated function | Molecular chaperone. Has ATPase activity. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
| Preferred name | htpG |
| eggNOG description | Molecular chaperone. Has ATPase activity |
| Orthologous group | COG0326 |
| 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)
| Pfam | Accession | i-Evalue | Residues | Description |
HATPase_c_3 | PF13589.13 |
3.2e-10 | 33–157 |
Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase |
HATPase_c | PF02518.32 |
5.4e-06 | 33–183 |
Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase |
HSP90 | PF00183.24 |
9.5e-135 | 235–645 |
Hsp90 protein |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥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
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