clpC1 Family assigned · medium auto-curated
H37Rv Rv3596c · MTBC0 - ·
848 aa · 4038158–4040704 (-) ·
RefSeq YP_177995.1
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), NBD_SMAX1 (PF23569.2), TniB (PF05621.18), AAA (PF00004.36), AAA_lid_9 (PF17871.8), UVR (PF02151.26), Sigma54_activat (PF00158.33), AAA_2 (PF07724.21), AAA_5 (PF07728.21), 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.
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 |
P9WPC9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | ATP-dependent Clp protease ATP-binding subunit ClpC1 |
| 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-E factor RseA in the presence of ClpP2. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | clpC |
| eggNOG description | with chaperone activity, ATP-binding subunit |
| Orthologous group | COG0542 |
| KEGG orthology |
K03696
|
| KEGG pathways |
map01100
|
| Gene Ontology (31) |
GO:0003674, GO:0003824, GO:0005488, GO:0005515, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006457 +19 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 | 0.023 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 43 synonymous, 3 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_N | PF02861.26 | 1.1e-37 | 4–126 | Clp repeat (R) N-terminal domain |
NBD_SMAX1 | PF23569.2 | 1.7e-07 | 195–293 | SMAX1 nucleotide binding domain |
TniB | PF05621.18 | 6.2e-05 | 196–347 | Bacterial TniB protein |
AAA | PF00004.36 | 1.1e-11 | 213–325 | ATPase family associated with various cellular activities (AAA) |
AAA_lid_9 | PF17871.8 | 6.9e-34 | 352–452 | AAA lid domain |
UVR | PF02151.26 | 4.3e-07 | 425–457 | UvrB/uvrC motif |
Sigma54_activat | PF00158.33 | 3.4e-07 | 531–649 | Sigma-54 interaction domain |
AAA_2 | PF07724.21 | 2.2e-64 | 544–716 | AAA domain (Cdc48 subfamily) |
AAA_5 | PF07728.21 | 2.2e-10 | 549–669 | AAA domain (dynein-related subfamily) |
ClpB_D2-small | PF10431.16 | 1.2e-25 | 722–802 | C-terminal, D2-small domain, of ClpB protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lsr2 (iron-regulated H-NS-like protein), high confidence from genomic context alone (score 724 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2460c clpP2 |
ATP-dependent CLP protease proteolytic subunit 2 | 996 | 907 | coexpression:478 experimental:754 textmining:963 |
Rv1331 clpS |
ATP-dependent Clp protease adapter protein ClpS | 955 | 851 | experimental:773 textmining:712 |
Rv2461c clpP1 |
ATP-dependent CLP protease proteolytic subunit 1 | 997 | 829 | coexpression:487 experimental:529 textmining:984 |
Rv0350 dnaK |
chaperone protein DnaK | 906 | 814 | coexpression:625 experimental:508 textmining:520 |
Rv0312 hyp |
hypothetical protein | 832 | 808 | coexpression:614 experimental:508 |
Rv3446c hyp |
hypothetical protein | 832 | 808 | coexpression:613 experimental:508 |
Rv2264c hyp |
hypothetical protein | 832 | 808 | coexpression:614 experimental:508 |
Rv0351 grpE |
stress response protein GrpE | 908 | 768 | coexpression:718 textmining:620 |
Rv3597c lsr2 |
iron-regulated H-NS-like protein | 724 | 724 ctx | neighborhood:721 |
Rv2373c dnaJ2 |
chaperone protein DnaJ | 779 | 711 | coexpression:539 |
Rv0352 dnaJ1 |
chaperone protein DnaJ | 789 | 705 | coexpression:530 |
Rv0251c hsp |
heat shock protein | 771 | 705 | coexpression:649 |
Rv2031c hspX |
alpha-crystallin | 720 | 702 | coexpression:646 |
Rv2299c htpG |
chaperone protein HtpG | 767 | 700 | coexpression:645 |
Rv3418c groES |
chaperonin GroES | 721 | 581 | coexpression: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 protease ATP-binding subunit ClpC
- Pfam (hmmscan --cut_ga): Clp_N PF02861.26 (E=1e-37), NBD_SMAX1 PF23569.2 (E=2e-07), TniB PF05621.18 (E=6e-05), AAA PF00004.36 (E=1e-11), AAA_lid_9 PF17871.8 (E=7e-34), UVR PF02151.26 (E=4e-07), Sigma54_activat PF00158.33 (E=3e-07), AAA_2 PF07724.21 (E=2e-64), AAA_5 PF07728.21 (E=2e-10), ClpB_D2-small PF10431.16 (E=1e-25)
- (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_177995.1)
- Domains: Pfam-A via hmmscan --cut_ga — Clp_N (PF02861.26), NBD_SMAX1 (PF23569.2), TniB (PF05621.18), AAA (PF00004.36), AAA_lid_9 (PF17871.8), UVR (PF02151.26), Sigma54_activat (PF00158.33), AAA_2 (PF07724.21), AAA_5 (PF07728.21), 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
COG0542 - Curated reference: UniProt P9WPC9 (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 —
71 functional partner(s); context anchor
lsr2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3596c|clpC1 MFERFTDRARRVVVLAQEEARMLNHNYIGTEHILLGLIHEGEGVAAKSLESLGISLEGVRSQVEEIIGQGQQAPSGHIPFTPRAKKVLELSLREALQLGHNYIGTEHILLGLIREGEGVAAQVLVKLGAELTRVRQQVIQLLSGYQGKEAAEAGTGGRGGESGSPSTSLVLDQFGRNLTAAAMEGKLDPVIGREKEIERVMQVLSRRTKNNPVLIGEPGVGKTAVVEGLAQAIVHGEVPETLKDKQLYTLDLGSLVAGSRYRGDFEERLKKVLKEINTRGDIILFIDELHTLVGAGAAEGAIDAASILKPKLARGELQTIGATTLDEYRKYIEKDAALERRFQPVQVGEPTVEHTIEILKGLRDRYEAHHRVSITDAAMVAAATLADRYINDRFLPDKAIDLIDEAGARMRIRRMTAPPDLREFDEKIAEARREKESAIDAQDFEKAASLRDREKTLVAQRAEREKQWRSGDLDVVAEVDDEQIAEVLGNWTGIPVFKLTEAETTRLLRMEEELHKRIIGQEDAVKAVSKAIRRTRAGLKDPKRPSGSFIFAGPSGVGKTELSKALANFLFGDDDALIQIDMGEFHDRFTASRLFGAPPGYVGYEEGGQLTEKVRRKPFSVVLFDEIEKAHQEIYNSLLQVLEDGRLTDGQGRTVDFKNTVLIFTSNLGTSDISKPVGLGFSKGGGENDYERMKQKVNDELKKHFRPEFLNRIDDIIVFHQLTREEIIRMVDLMISRVAGQLKSKDMALVLTDAAKALLAKRGFDPVLGARPLRRTIQREIEDQLSEKILFEEVGPGQVVTVDVDNWDGEGPGEDAVFTFTGTRKPPAEPDLAKAGAHSAGGPEPAAR