Rv2824c Resolved · high auto-curated
H37Rv Rv2824c · MTBC0 - ·
314 aa · 3131770–3132714 (-) ·
RefSeq NP_217340.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | CRISPR-associated endoribonuclease Cas6 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | CRISPR-associated endoribonuclease Cas6. Pfam: CRISPR_Cas6 (PF10040.15). |
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 |
P9WPJ1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | CRISPR-associated endoribonuclease Cas6 |
| 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 sequences complementary to antecedent mobile elements (spacers) 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 |
L Replication, recombination and repair
|
|---|---|
| eggNOG description | CRISPR-associated endoribonuclease Cas6 |
| Orthologous group | COG5551 |
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 | 3.907 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 11 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 |
|---|---|---|---|---|
CRISPR_Cas6 | PF10040.15 | 1.6e-18 | 184–299 | CRISPR-associated endoribonuclease Cas6 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cas10 (CRISPR-associated protein Cas10/Csm1), high confidence from genomic context alone (score 970 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2823c cas10 |
CRISPR-associated protein Cas10/Csm1 | 996 | 970 ctx | neighborhood:793 cooccurence:768 coexpression:423 textmining:876 |
Rv2820c csm4 |
CRISPR type III-associated RAMP protein Csm4 | 990 | 953 ctx | neighborhood:793 cooccurence:772 textmining:804 |
Rv2819c csm5 |
CRISPR type III-associated RAMP protein Csm5 | 990 | 953 ctx | neighborhood:793 cooccurence:774 textmining:803 |
Rv2822c csm2 |
CRISPR type III-associated protein Csm2 | 987 | 953 ctx | neighborhood:790 cooccurence:774 textmining:756 |
Rv2821c csm3 |
CRISPR type III-associated RAMP protein Csm3 | 991 | 935 ctx | neighborhood:793 cooccurence:681 textmining:876 |
Rv2816c cas2 |
CRISPR-associated endoribonuclease Cas2 | 969 | 851 ctx | neighborhood:570 cooccurence:668 textmining:806 |
Rv2817c cas1 |
CRISPR-associated endonuclease Cas1 | 795 | 757 ctx | neighborhood:559 cooccurence:447 |
Rv1004c |
membrane protein | 756 | 757 ctx | cooccurence:755 |
Rv0355c PPE8 |
PPE family protein PPE8 | 756 | 756 ctx | cooccurence:756 |
Rv2209 |
integral membrane protein | 753 | 754 ctx | cooccurence:753 |
Rv3350c PPE56 |
PPE family protein PPE56 | 752 | 752 ctx | cooccurence:752 |
Rv3347c PPE55 |
PPE family protein PPE55 | 752 | 752 ctx | cooccurence:752 |
Rv2490c PE_PGRS43 |
PE-PGRS family protein PE_PGRS43 | 746 | 746 ctx | cooccurence:746 |
Rv0304c PPE5 |
PPE family protein PPE5 | 746 | 746 ctx | cooccurence:746 |
Rv1917c PPE34 |
PPE family protein PPE34 | 745 | 746 ctx | cooccurence:745 |
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 endoribonuclease Cas6
- Pfam (hmmscan --cut_ga): CRISPR_Cas6 PF10040.15 (E=2e-18)
- (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_217340.1)
- Domains: Pfam-A via hmmscan --cut_ga — CRISPR_Cas6 (PF10040.15)
- 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
COG5551 - Curated reference: UniProt P9WPJ1 (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 —
82 functional partner(s); context anchor
cas10 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2824c| MAARRGGIRRTDLLRRSGQPRGRHRASAAESGLTWISPTLILVGFSHRGDRRMTEHLSRLTLTLEVDAPLERARVATLGPHLHGVLMESIPADYVQTLHTVPVNPYSQYALARSTTSLEWKISTLTNEARQQIVGPINDAAFAGFRLRASGIATQVTSRSLEQNPLSQFARIFYARPETRKFRVEFLTPTAFKQSGEYVFWPDPRLVFQSLAQKYGAIVDGEEPDPGLIAEFGQSVRLSAFRVASAPFAVGAARVPGFTGSATFTVRGVDTFASYIAALLWFGEFSGCGIKASMGMGAIRVQPLAPREKCVPKP