clpP2 Family assigned · medium auto-curated
H37Rv Rv2460c · MTBC0 mtbc0_002619 ·
214 aa · 2786779–2787423 (-) ·
RefSeq NP_216976.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ATP-dependent CLP protease proteolytic subunit 2 |
|---|---|
| MTBC0 PGAP re-annotation | ATP-dependent CLP protease proteolytic subunit ClpP2 |
| Revised (this work) | ATP-dependent CLP protease proteolytic subunit ClpP2. Pfam: CLP_protease (PF00574.29). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WPC3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | ATP-dependent Clp protease proteolytic subunit 2 |
| EC (curated) |
EC 3.4.21.92
|
| Curated function | Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins (By similarity). Degrades anti-sigma-D factor RsdA when present in a complex with ClpP1 and ClpX. Degrades anti-sigma-E factor RseA in the presence of ClpC1. Does not seem to act on anti-sigma-L factor RslA. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | clpP |
| eggNOG description | Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins |
| Orthologous group | COG0740 |
| EC number |
EC 3.4.21.92
|
| KEGG orthology |
K01358
|
| KEGG pathways |
map04112, map04212
|
| Gene Ontology (15) |
GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0008150, GO:0016020, GO:0030312, GO:0040007, GO:0044424 +3 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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 1 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 |
|---|---|---|---|---|
CLP_protease | PF00574.29 | 1.8e-74 | 30–206 | Clp protease |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: clpP1 (ATP-dependent CLP protease proteolytic subunit 1), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2461c clpP1 |
ATP-dependent CLP protease proteolytic subunit 1 | 999 | 1000 ctx | neighborhood:882 coexpression:794 experimental:999 database:540 textmining:595 |
Rv2457c clpX |
ATP-dependent CLP protease ATP-binding subunit ClpX | 996 | 986 ctx | cooccurence:699 coexpression:655 experimental:829 textmining:745 |
Rv3596c clpC1 |
ATP-dependent protease ATP-binding subunit ClpC | 996 | 907 | coexpression:478 experimental:754 textmining:963 |
Rv2462c tig |
trigger factor | 894 | 847 ctx | neighborhood:765 |
Rv0384c clpB |
chaperone protein ClpB | 916 | 809 | coexpression:470 experimental:529 textmining:583 |
Rv3716c hyp |
hypothetical protein | 809 | 777 | coexpression:770 |
Rv3195 hyp |
hypothetical protein | 807 | 776 | coexpression:776 |
Rv3418c groES |
chaperonin GroES | 870 | 761 ctx | cooccurence:434 experimental:420 textmining:481 |
Rv0429c def |
polypeptide deformylase | 765 | 750 ctx | cooccurence:531 coexpression:460 |
Rv2667 clpC2 |
ATP-dependent protease ATP-binding subunit ClpC | 816 | 741 | coexpression:462 experimental:529 |
Rv2374c hrcA |
heat-inducible transcription repressor HrcA | 757 | 682 | coexpression:682 |
Rv0440 groEL2 |
molecular chaperone GroEL | 740 | 633 | coexpression:425 |
Rv3417c groEL1 |
chaperonin GroEL | 739 | 631 | coexpression:423 |
Rv0640 rplK |
50S ribosomal protein L11 | 780 | 623 ctx | cooccurence:558 textmining:440 |
Rv0351 grpE |
stress response protein GrpE | 746 | 592 | coexpression:472 textmining:405 |
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: ATP-dependent CLP protease proteolytic subunit 2
- MTBC0 PGAP product: ATP-dependent CLP protease proteolytic subunit ClpP2
- Pfam (hmmscan --cut_ga): CLP_protease PF00574.29 (E=2e-74)
- (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_216976.1)
- Domains: Pfam-A via hmmscan --cut_ga — CLP_protease (PF00574.29)
- 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
COG0740 - Curated reference: UniProt P9WPC3 (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 —
101 functional partner(s); context anchor
clpP1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002619|Rv2460c|clpP2 MNSQNSQIQPQARYILPSFIEHSSFGVKESNPYNKLFEERIIFLGVQVDDASANDIMAQLLVLESLDPDRDITMYINSPGGGFTSLMAIYDTMQYVRADIQTVCLGQAASAAAVLLAAGTPGKRMALPNARVLIHQPSLSGVIQGQFSDLEIQAAEIERMRTLMETTLARHTGKDAGVIRKDTDRDKILTAEEAKDYGIIDTVLEYRKLSAQTA