clpC2 Family assigned · medium auto-curated
H37Rv Rv2667 · MTBC0 - ·
252 aa · 2983896–2984654 (+) ·
RefSeq YP_177897.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ATP-dependent protease ATP-binding subunit ClpC |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | ATP-dependent protease ATP-binding subunit ClpC. Pfam: Clp_N (PF02861.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WPC7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2667 |
UniProt still lists this protein as Uncharacterized protein Rv2667; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | clpC2 |
| eggNOG description | PFAM Clp N terminal domain protein |
| Orthologous group | COG0542 |
| Gene Ontology (8) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0044424, GO:0044444, GO:0044464
|
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 | 0.471 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 3 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.18% of strains (258) · 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 |
|---|---|---|---|---|
Clp_N | PF02861.26 | 5.9e-23 | 98–210 | Clp repeat (R) N-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2669 (GCN5-like N-acetyltransferase), high confidence from genomic context alone (score 760 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1331 clpS |
ATP-dependent Clp protease adapter protein ClpS | 903 | 849 | experimental:773 |
Rv2264c hyp |
hypothetical protein | 833 | 809 | coexpression:615 experimental:508 |
Rv3446c hyp |
hypothetical protein | 832 | 808 | coexpression:613 experimental:508 |
Rv0350 dnaK |
chaperone protein DnaK | 831 | 807 | coexpression:612 experimental:508 |
Rv0312 hyp |
hypothetical protein | 831 | 807 | coexpression:612 experimental:508 |
Rv2668 hyp |
hypothetical protein | 787 | 787 ctx | neighborhood:786 |
Rv0351 grpE |
stress response protein GrpE | 830 | 761 | coexpression:709 |
Rv2669 |
GCN5-like N-acetyltransferase | 768 | 760 ctx | neighborhood:758 |
Rv2461c clpP1 |
ATP-dependent CLP protease proteolytic subunit 1 | 875 | 741 | coexpression:462 experimental:529 textmining:540 |
Rv2460c clpP2 |
ATP-dependent CLP protease proteolytic subunit 2 | 816 | 741 | coexpression:462 experimental:529 |
Rv2666 |
Probable transposase for insertion sequence element IS1081 (fragment); Required for the transposition of the insertion element. | 715 | 715 ctx | neighborhood:715 |
Rv0251c hsp |
heat shock protein | 750 | 702 | coexpression:645 |
Rv2031c hspX |
alpha-crystallin | 719 | 701 | coexpression:644 |
Rv2299c htpG |
chaperone protein HtpG | 738 | 698 | coexpression:643 |
Rv0352 dnaJ1 |
chaperone protein DnaJ | 768 | 697 | coexpression:516 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): ATP-dependent protease ATP-binding subunit ClpC
- Pfam (hmmscan --cut_ga): Clp_N PF02861.26 (E=6e-23)
- (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 YP_177897.1)
- Domains: Pfam-A via hmmscan --cut_ga — Clp_N (PF02861.26)
- 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
COG0542 - Curated reference: UniProt P9WPC7 (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 —
38 functional partner(s); context anchor
Rv2669 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2667|clpC2 MPEPTPTAYPVRLDELINAIKRVHSDVLDQLSDAVLAAEHLGEIADHLIGHFVDQARRSGASWSDIGKSMGVTKQAAQKRFVPRAEATTLDSNQGFRRFTPRARNAVVAAQNAAHGAASSEITPDHLLLGVLTDPAALATALLQQQEIDIATLRTAVTLPPAVTEPPQPIPFSGPARKVLELTFREALRLGHNYIGTEHLLLALLELEDGDGPLHRSGVDKSRAEADLITTLASLTGANAAGATDAGATDAG