Rv2818c Resolved · high auto-curated
H37Rv Rv2818c · MTBC0 - ·
382 aa · 3124996–3126144 (-) ·
RefSeq NP_217334.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | CRISPR-associated protein Csm6 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | CRISPR-associated protein Csm6. Pfam: Cas_Csm6_CARF (PF22208.2), Cas_Csm6_6H (PF22206.3), Cas_Csm6_HEPN (PF09659.17). |
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 |
P71635
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | CRISPR system endoribonuclease Csm6 |
| EC (curated) |
EC 3.1.-.-
|
| Curated function | CRISPR (clustered regularly interspaced short palindromic repeat) is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain spacers, sequences complementary to antecedent mobile elements, and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA). The type III-A Csm effector complex binds crRNA and acts as a crRNA-guided RNase, DNase and cyclic oligoadenylate synthase; binding of target RNA cognate to the crRNA is required for all activiti. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | csm6 |
| eggNOG description | Psort location Cytoplasmic, score |
| Orthologous group | 28K2E |
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) pseudogene candidate
| pN/pS | 1.005 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 5 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 11.45% of strains (16620) · 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 |
|---|---|---|---|---|
Cas_Csm6_CARF | PF22208.2 | 1.1e-45 | 30–137 | Cas_Csm6 CARF domain |
Cas_Csm6_6H | PF22206.3 | 2.4e-13 | 141–190 | CRISPR-associated protein Csm6 6H domain |
Cas_Csm6_HEPN | PF09659.17 | 1.8e-25 | 211–373 | Cas_Csm6 HEPN domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: csm5 (CRISPR type III-associated RAMP protein Csm5), high confidence from genomic context alone (score 944 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2819c csm5 |
CRISPR type III-associated RAMP protein Csm5 | 988 | 944 ctx | neighborhood:625 coexpression:857 textmining:803 |
Rv2820c csm4 |
CRISPR type III-associated RAMP protein Csm4 | 988 | 916 ctx | neighborhood:587 coexpression:806 textmining:870 |
Rv2821c csm3 |
CRISPR type III-associated RAMP protein Csm3 | 984 | 884 ctx | neighborhood:587 coexpression:730 textmining:876 |
Rv2822c csm2 |
CRISPR type III-associated protein Csm2 | 962 | 882 ctx | neighborhood:581 coexpression:731 textmining:693 |
Rv2817c cas1 |
CRISPR-associated endonuclease Cas1 | 777 | 777 ctx | neighborhood:775 |
Rv2816c cas2 |
CRISPR-associated endoribonuclease Cas2 | 925 | 775 ctx | neighborhood:775 textmining:680 |
Rv2823c cas10 |
CRISPR-associated protein Cas10/Csm1 | 963 | 709 ctx | neighborhood:587 textmining:880 |
Rv2824c cas6 |
CRISPR-associated endoribonuclease Cas6 | 917 | 589 ctx | neighborhood:569 textmining:808 |
Rv1682 hyp |
hypothetical protein | 647 | 87 | textmining:630 |
Rv0560c |
benzoquinone methyltransferase | 518 | 50 | textmining:514 |
Rv3096 hyp |
hypothetical protein | 514 | 47 | textmining:511 |
Rv1191 hyp |
hypothetical protein | 513 | 47 | textmining:510 |
Rv1636 TB15.3 |
iron-regulated universal stress protein | 451 | 46 | textmining:449 |
Rv1586c |
phage integrase | 443 | 46 | textmining:441 |
Rv3648c cspA |
cold shock protein A | 544 | 45 | textmining:543 |
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): CRISPR-associated protein Csm6
- Pfam (hmmscan --cut_ga): Cas_Csm6_CARF PF22208.2 (E=1e-45), Cas_Csm6_6H PF22206.3 (E=2e-13), Cas_Csm6_HEPN PF09659.17 (E=2e-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 NP_217334.1)
- Domains: Pfam-A via hmmscan --cut_ga — Cas_Csm6_CARF (PF22208.2), Cas_Csm6_6H (PF22206.3), Cas_Csm6_HEPN (PF09659.17)
- 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
28K2E - Curated reference: UniProt P71635 (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 —
24 functional partner(s); context anchor
csm5 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2818c| MLFLSAEIAAFENADRRYSAAITRLAPETDVRIVTYTNPSVHRFDLFVPVFRNHLVELSAEFPDRTILLNTSSGTPAMQAALVAINVFGIPRTTAVQVSTPARALSKPGDRESPDAYDLELMWDANDDNQPGAPNRCFEATSAALGALLERANLKQLIVSYDYSAAVTIAADSRLPDQVSNLIRGAMHRSRLEHLVAPKFFKDTAFTYDPANKVAEYISALALLAKREQWAEFARSATPAITIVLRAAVAKHLPEDRYLDDMGRVDRRKLEREPEIRCALKHPPKSPNAEWYLYTKDWLALLRQFAPDRVGALEVLGRFESRVRNTAAHEIVSISEDRITKDGGLLPEQLLKILARETGADLTLYDRLNDEIIRQIDMAPLG