dnaK Resolved · high auto-curated
H37Rv Rv0350 · MTBC0 mtbc0_000371 ·
625 aa · 423158–425035 (+) ·
RefSeq NP_214864.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | chaperone protein DnaK |
|---|---|
| MTBC0 PGAP re-annotation | molecular chaperone DnaK |
| Revised (this work) | Molecular chaperone DnaK. Pfam: HSP70 (PF00012.27), MreB_Mbl (PF06723.20). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMJ9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Chaperone protein DnaK |
| Curated function | Acts as a chaperone..; FUNCTION: Recombinant extracellular protein activates expression of NF-kappa-B in immortalized human dermal endothelial cells in a TLR2- and TLR4-dependent manner. Activation occurs via MYD88-dependent and -independent pathways and requires TIRAP, TRIF and TRAM (some experiments done in mouse cells, mice do not usually catch tuberculosis). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | dnaK |
| eggNOG description | Heat shock 70 kDa protein |
| Orthologous group | COG0443 |
| KEGG orthology |
K04043
|
| KEGG pathways |
map03018, map04212, map05152
|
| Gene Ontology (116) |
GO:0000302, GO:0000303, GO:0000305, GO:0001968, GO:0003674, GO:0005488, GO:0005515, GO:0005575, GO:0005576, GO:0005618, GO:0005622, GO:0005623 +104 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 | 0.197 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 3 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
HSP70 | PF00012.27 | 4.7e-248 | 4–583 | Hsp70 protein |
MreB_Mbl | PF06723.20 | 8.9e-16 | 4–349 | MreB/Mbl protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: dnaJ1 (chaperone protein DnaJ), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0384c clpB |
chaperone protein ClpB | 999 | 1000 | coexpression:965 experimental:999 textmining:937 |
Rv0352 dnaJ1 |
chaperone protein DnaJ | 999 | 1000 ctx | neighborhood:829 fusion:419 cooccurence:769 coexpression:942 experimental:476 database:601 textmining:948 |
Rv0351 grpE |
stress response protein GrpE | 999 | 999 ctx | neighborhood:882 coexpression:964 experimental:773 textmining:939 |
Rv2373c dnaJ2 |
chaperone protein DnaJ | 996 | 986 ctx | cooccurence:773 coexpression:633 experimental:476 database:601 textmining:773 |
Rv0353 hspR |
heat shock protein transcriptional repressor HspR | 997 | 979 ctx | neighborhood:829 coexpression:803 experimental:427 textmining:904 |
Rv2299c htpG |
chaperone protein HtpG | 993 | 970 | coexpression:671 experimental:772 database:622 textmining:796 |
Rv0440 groEL2 |
molecular chaperone GroEL | 996 | 893 | coexpression:718 experimental:410 textmining:965 |
Rv3417c groEL1 |
chaperonin GroEL | 988 | 868 | coexpression:648 experimental:410 textmining:917 |
Rv1349 irtB |
iron ABC transporter ATP-binding protein/permease IrtB | 824 | 816 ctx | cooccurence:677 |
Rv3596c clpC1 |
ATP-dependent protease ATP-binding subunit ClpC | 906 | 814 | coexpression:625 experimental:508 textmining:520 |
Rv3418c groES |
chaperonin GroES | 988 | 812 | coexpression:743 textmining:939 |
Rv2667 clpC2 |
ATP-dependent protease ATP-binding subunit ClpC | 831 | 807 | coexpression:612 experimental:508 |
Rv0733 adk |
adenylate kinase | 860 | 795 ctx | cooccurence:637 experimental:404 |
Rv2267c stf3 hyp |
hypothetical protein | 781 | 769 | experimental:455 database:567 |
Rv3529c hyp |
hypothetical protein | 781 | 769 | experimental:455 database:567 |
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 DnaK
- MTBC0 PGAP product: molecular chaperone DnaK
- Pfam (hmmscan --cut_ga): HSP70 PF00012.27 (E=5e-248), MreB_Mbl PF06723.20 (E=9e-16)
- (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_214864.1)
- Domains: Pfam-A via hmmscan --cut_ga — HSP70 (PF00012.27), MreB_Mbl (PF06723.20)
- 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
COG0443 - Curated reference: UniProt P9WMJ9 (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 —
212 functional partner(s); context anchor
dnaJ1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000371|Rv0350|dnaK MARAVGIDLGTTNSVVSVLEGGDPVVVANSEGSRTTPSIVAFARNGEVLVGQPAKNQAVTNVDRTVRSVKRHMGSDWSIEIDGKKYTAPEISARILMKLKRDAEAYLGEDITDAVITTPAYFNDAQRQATKDAGQIAGLNVLRIVNEPTAAALAYGLDKGEKEQRILVFDLGGGTFDVSLLEIGEGVVEVRATSGDNHLGGDDWDQRVVDWLVDKFKGTSGIDLTKDKMAMQRLREAAEKAKIELSSSQSTSINLPYITVDADKNPLFLDEQLTRAEFQRITQDLLDRTRKPFQSVIADTGISVSEIDHVVLVGGSTRMPAVTDLVKELTGGKEPNKGVNPDEVVAVGAALQAGVLKGEVKDVLLLDVTPLSLGIETKGGVMTRLIERNTTIPTKRSETFTTADDNQPSVQIQVYQGEREIAAHNKLLGSFELTGIPPAPRGIPQIEVTFDIDANGIVHVTAKDKGTGKENTIRIQEGSGLSKEDIDRMIKDAEAHAEEDRKRREEADVRNQAETLVYQTEKFVKEQREAEGGSKVPEDTLNKVDAAVAEAKAALGGSDISAIKSAMEKLGQESQALGQAIYEAAQAASQATGAAHPGGEPGGAHPGSADDVVDAEVVDDGREAK