clpP1 Family assigned · medium auto-curated
H37Rv Rv2461c · MTBC0 - ·
200 aa · 2763172–2763774 (-) ·
RefSeq YP_177883.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ATP-dependent CLP protease proteolytic subunit 1 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | ATP-dependent CLP protease proteolytic subunit 1. 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.
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 |
P9WPC5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | ATP-dependent Clp protease proteolytic subunit 1 |
| 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 ClpP2 and ClpX. 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, chaperonesU Intracellular trafficking, secretion and vesicular transport
|
|---|---|
| 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 (11) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0044424, GO:0044444, GO:0044464, GO:0071944
|
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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 0 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 | 4.6e-75 | 18–192 | Clp protease |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: clpP2 (ATP-dependent CLP protease proteolytic subunit 2), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2460c clpP2 |
ATP-dependent CLP protease proteolytic subunit 2 | 999 | 1000 ctx | neighborhood:882 coexpression:794 experimental:999 database:540 textmining:595 |
Rv2457c clpX |
ATP-dependent CLP protease ATP-binding subunit ClpX | 998 | 986 ctx | cooccurence:700 coexpression:652 experimental:829 textmining:917 |
Rv2462c tig |
trigger factor | 928 | 844 ctx | neighborhood:765 textmining:562 |
Rv3596c clpC1 |
ATP-dependent protease ATP-binding subunit ClpC | 997 | 829 | coexpression:487 experimental:529 textmining:984 |
Rv0384c clpB |
chaperone protein ClpB | 940 | 806 | coexpression:467 experimental:529 textmining:707 |
Rv3418c groES |
chaperonin GroES | 874 | 744 | experimental:420 textmining:530 |
Rv2667 clpC2 |
ATP-dependent protease ATP-binding subunit ClpC | 875 | 741 | coexpression:462 experimental:529 textmining:540 |
Rv0429c def |
polypeptide deformylase | 742 | 726 ctx | cooccurence:485 coexpression:460 |
Rv0781 ptrBa |
Rv0781, (MTCY369.25), len: 236 aa. Probable ptrBa,first part of protease II, equivalent to N-terminus of NP_302455.1|NC_002677 protease II f | 781 | 691 | coexpression:691 |
Rv0782 ptrBb |
Rv0782, (MTCY369.26), len: 552 aa. Probable ptrBb,second part of protease II, equivalent to C-terminus of NP_302455.1|NC_002677 protease II | 823 | 689 | coexpression:689 textmining:455 |
Rv2374c hrcA |
heat-inducible transcription repressor HrcA | 722 | 685 | coexpression:685 |
Rv3417c groEL1 |
chaperonin GroEL | 739 | 624 | coexpression:423 |
Rv0440 groEL2 |
molecular chaperone GroEL | 765 | 622 | coexpression:425 textmining:406 |
Rv0640 rplK |
50S ribosomal protein L11 | 777 | 619 ctx | cooccurence:545 textmining:440 |
Rv0351 grpE |
stress response protein GrpE | 797 | 601 | coexpression:483 textmining:514 |
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 CLP protease proteolytic subunit 1
- Pfam (hmmscan --cut_ga): CLP_protease PF00574.29 (E=5e-75)
- (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_177883.1)
- 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 P9WPC5 (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 —
111 functional partner(s); context anchor
clpP2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2461c|clpP1 MSQVTDMRSNSQGLSLTDSVYERLLSERIIFLGSEVNDEIANRLCAQILLLAAEDASKDISLYINSPGGSISAGMAIYDTMVLAPCDIATYAMGMAASMGEFLLAAGTKGKRYALPHARILMHQPLGGVTGSAADIAIQAEQFAVIKKEMFRLNAEFTGQPIERIEADSDRDRWFTAAEALEYGFVDHIITRAHVNGEAQ