clpX Family assigned · medium auto-curated
H37Rv Rv2457c · MTBC0 mtbc0_002616 ·
426 aa · 2782456–2783736 (-) ·
RefSeq NP_216973.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ATP-dependent CLP protease ATP-binding subunit ClpX |
|---|---|
| MTBC0 PGAP re-annotation | ATP-dependent Clp protease ATP-binding subunit ClpX |
| Revised (this work) | ATP-dependent Clp protease ATP-binding subunit ClpX. Pfam: zf-C4_ClpX (PF06689.20), AAA_2 (PF07724.21), AAA_5 (PF07728.21), AAA (PF00004.36), ClpB_D2-small (PF10431.16). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WPB9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | ATP-dependent Clp protease ATP-binding subunit ClpX |
| Curated function | ATP-dependent specificity component of the Clp protease. It directs the protease to specific substrates. Can perform chaperone functions in the absence of ClpP (By similarity). Degrades anti-sigma-D factor RsdA when present in a complex with ClpP1 and ClpP2. 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 | clpX |
| eggNOG description | ATP-dependent specificity component of the Clp protease. It directs the protease to specific substrates. Can perform chaperone functions in the absence of ClpP |
| Orthologous group | COG1219 |
| KEGG orthology |
K03544
|
| KEGG pathways |
map04112
|
| Gene Ontology (65) |
GO:0000166, GO:0003674, GO:0003824, GO:0004176, GO:0005488, GO:0005524, GO:0005575, GO:0005618, GO:0005623, GO:0006508, GO:0006807, GO:0008144 +53 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 | 0.208 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 2 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 |
|---|---|---|---|---|
zf-C4_ClpX | PF06689.20 | 2.2e-20 | 12–48 | ClpX C4-type zinc finger |
AAA_2 | PF07724.21 | 6.5e-35 | 114–310 | AAA domain (Cdc48 subfamily) |
AAA_5 | PF07728.21 | 3.5e-06 | 116–193 | AAA domain (dynein-related subfamily) |
AAA | PF00004.36 | 8.6e-17 | 117–246 | ATPase family associated with various cellular activities (AAA) |
ClpB_D2-small | PF10431.16 | 2.7e-12 | 317–395 | C-terminal, D2-small domain, of ClpB protein |
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 986 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2461c clpP1 |
ATP-dependent CLP protease proteolytic subunit 1 | 998 | 986 ctx | cooccurence:700 coexpression:652 experimental:829 textmining:917 |
Rv2460c clpP2 |
ATP-dependent CLP protease proteolytic subunit 2 | 996 | 986 ctx | cooccurence:699 coexpression:655 experimental:829 textmining:745 |
Rv2456c |
MFS-type transporter | 912 | 821 ctx | neighborhood:812 textmining:530 |
Rv2453c mobA |
molybdenum cofactor guanylyltransferase | 722 | 722 ctx | neighborhood:721 |
Rv2458 mmuM |
homocysteine S-methyltransferase MmuM | 721 | 721 ctx | neighborhood:721 |
Rv3610c ftsH |
zinc metalloprotease FtsH | 879 | 717 | coexpression:712 textmining:592 |
Rv1310 atpD |
ATP synthase subunit beta | 730 | 647 ctx | fusion:626 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA | 599 | 574 ctx | neighborhood:570 |
Rv1630 rpsA |
30S ribosomal protein S1 | 598 | 559 | |
Rv2368c phoH1 |
phosphate starvation-inducible protein PhoH | 550 | 550 | coexpression:407 |
Rv1641 infC |
initiation factor IF-3 | 525 | 525 | coexpression:430 |
Rv2454c korB |
2-oxoglutarate oxidoreductase subunit KorB | 491 | 491 ctx | neighborhood:488 |
Rv2674 msrB |
peptide methionine sulfoxide reductase MsrB | 530 | 463 | |
Rv2462c tig |
trigger factor | 709 | 446 | textmining:496 |
Rv0014c pknB |
serine/threonine-protein kinase PknB | 464 | 444 | coexpression:426 |
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 ATP-binding subunit ClpX
- MTBC0 PGAP product: ATP-dependent Clp protease ATP-binding subunit ClpX
- Pfam (hmmscan --cut_ga): zf-C4_ClpX PF06689.20 (E=2e-20), AAA_2 PF07724.21 (E=6e-35), AAA_5 PF07728.21 (E=3e-06), AAA PF00004.36 (E=9e-17), ClpB_D2-small PF10431.16 (E=3e-12)
- (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_216973.1)
- Domains: Pfam-A via hmmscan --cut_ga — zf-C4_ClpX (PF06689.20), AAA_2 (PF07724.21), AAA_5 (PF07728.21), AAA (PF00004.36), ClpB_D2-small (PF10431.16)
- 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
COG1219 - Curated reference: UniProt P9WPB9 (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 —
66 functional partner(s); context anchor
clpP1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002616|Rv2457c|clpX MARIGDGGDLLKCSFCGKSQKQVKKLIAGPGVYICDECIDLCNEIIEEELADADDVKLDELPKPAEIREFLEGYVIGQDTAKRTLAVAVYNHYKRIQAGEKGRDSRCEPVELTKSNILMLGPTGCGKTYLAQTLAKMLNVPFAIADATALTEAGYVGEDVENILLKLIQAADYDVKRAETGIIYIDEVDKIARKSENPSITRDVSGEGVQQALLKILEGTQASVPPQGGRKHPHQEFIQIDTTNVLFIVAGAFAGLEKIIYERVGKRGLGFGAEVRSKAEIDTTDHFADVMPEDLIKFGLIPEFIGRLPVVASVTNLDKESLVKILSEPKNALVKQYIRLFEMDGVELEFTDDALEAIADQAIHRGTGARGLRAIMEEVLLPVMYDIPSRDDVAKVVVTKETVQDNVLPTIVPRKPSRSERRDKSA