groEL1 Resolved · high auto-curated

H37Rv Rv3417c · MTBC0 mtbc0_003631 · 539 aa · 3860711–3862330 (-) · RefSeq NP_217934.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)chaperonin GroEL
MTBC0 PGAP re-annotationchaperonin GroEL
Revised (this work)Chaperonin GroEL. Pfam: Cpn60_TCP1 (PF00118.30).

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

Curated reference (UniProt)

UniProt P9WPE9 SwissProt · reviewed · Evidence at protein level
UniProt nameChaperonin GroEL 1
EC (curated) EC 5.6.1.7
Curated functionPrevents aggregation of substrate proteins and promotes their refolding. In vitro, activity may be independent of the presence or absence of the GroES co-chaperonin or ATP. Shows weak ATPase activity..; FUNCTION: Involved in copper homeostasis. Binds copper and may help maintaining copper homeostasis when copper is present in excess, notably in the macrophage phagosome, by acting as a metal storage protein. Could be involved in copper resistance during mycobacterial biofilm formation. Protects from copper stress in vitro. Can also bind other metals, but binds copper with relatively higher affi.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
Preferred namegroL2
eggNOG descriptionPrevents misfolding and promotes the refolding and proper assembly of unfolded polypeptides generated under stress conditions
Orthologous groupCOG0459
KEGG orthology K04077
KEGG pathways map03018, map04212, map04940, map05134, map05152
Gene Ontology (80) GO:0003674, GO:0003676, GO:0003677, GO:0003697, GO:0005488, GO:0005515, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829 +68 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 0.439 · 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
Cpn60_TCP1PF00118.30 2.7e-7122–525 TCP-1/cpn60 chaperonin family

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

Closest characterised functional partner: groES (chaperonin GroES), high confidence from genomic context alone (score 998 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3418c groES chaperonin GroES 999 998 ctx neighborhood:776 cooccurence:772 coexpression:831 experimental:829 textmining:953
Rv0440 groEL2 molecular chaperone GroEL 982 982 coexpression:825 database:900
Rv0087 hycE formate hydrogenase HycE 966 965 experimental:965
Rv0351 grpE stress response protein GrpE 981 929 coexpression:747 experimental:437 database:455 textmining:753
Rv0350 dnaK chaperone protein DnaK 988 868 coexpression:648 experimental:410 textmining:917
Rv0352 dnaJ1 chaperone protein DnaJ 973 862 coexpression:613 database:493 textmining:815
Rv2373c dnaJ2 chaperone protein DnaJ 940 846 coexpression:555 database:493 textmining:626
Rv2264c hyp hypothetical protein 853 829 coexpression:629 experimental:410
Rv0312 hyp hypothetical protein 851 828 coexpression:627 experimental:410
Rv2299c htpG chaperone protein HtpG 942 827 coexpression:715 experimental:416 textmining:681
Rv3446c hyp hypothetical protein 829 802 coexpression:627 experimental:410
Rv3433c nnr bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase 734 735 coexpression:648
Rv1310 atpD ATP synthase subunit beta 806 694 database:551
Rv3610c ftsH zinc metalloprotease FtsH 760 636 database:404
Rv2460c clpP2 ATP-dependent CLP protease proteolytic subunit 2 739 631 coexpression:423

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: chaperonin GroEL
  • MTBC0 PGAP product: chaperonin GroEL
  • Pfam (hmmscan --cut_ga): Cpn60_TCP1 PF00118.30 (E=3e-71)
  • (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_217934.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Cpn60_TCP1 (PF00118.30)
  • 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 COG0459
  • Curated reference: UniProt P9WPE9 (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 — 164 functional partner(s); context anchor groES
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003631|Rv3417c|groEL1
MSKLIEYDETARRAMEVGMDKLADTVRVTLGPRGRHVVLAKAFGGPTVTNDGVTVAREIELEDPFEDLGAQLVKSVATKTNDVAGDGTTTATILAQALIKGGLRLVAAGVNPIALGVGIGKAADAVSEALLASATPVSGKTGIAQVATVSSRDEQIGDLVGEAMSKVGHDGVVSVEESSTLGTELEFTEGIGFDKGFLSAYFVTDFDNQQAVLEDALILLHQDKISSLPDLLPLLEKVAGTGKPLLIVAEDVEGEALATLVVNAIRKTLKAVAVKGPYFGDRRKAFLEDLAVVTGGQVVNPDAGMVLREVGLEVLGSARRVVVSKDDTVIVDGGGTAEAVANRAKHLRAEIDKSDSDWDREKLGERLAKLAGGVAVIKVGAATETALKERKESVEDAVAAAKAAVEEGIVPGGGASLIHQARKALTELRASLTGDEVLGVDVFSEALAAPLFWIAANAGLDGSVVVNKVSELPAGHGLNVNTLSYGDLAADGVIDPVKVTRSAVLNASSVARMVLTTETVVVDKPAKAEDHDHHHGHAH