cas2 Resolved · high auto-curated
H37Rv Rv2816c · MTBC0 mtbc0_002994 ·
113 aa · 3144282–3144623 (-) ·
RefSeq NP_217332.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | CRISPR-associated endoribonuclease Cas2 |
|---|---|
| MTBC0 PGAP re-annotation | CRISPR-associated endonuclease Cas2 |
| Revised (this work) | CRISPR-associated endonuclease Cas2. Pfam: CRISPR_Cas2 (PF09827.15). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WPJ3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | CRISPR-associated endoribonuclease Cas2 |
| 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 |
L Replication, recombination and repair
|
|---|---|
| Preferred name | cas2 |
| eggNOG description | 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 and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA). Functions as a ssRNA-specific endoribonuclease. Involved in the integration of spacer DNA into the CRISPR cassette |
| Orthologous group | COG1343 |
| KEGG orthology |
K09951
|
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 | 0.617 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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 |
|---|---|---|---|---|
CRISPR_Cas2 | PF09827.15 | 7.3e-18 | 26–91 | CRISPR associated protein Cas2 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cas1 (CRISPR-associated endonuclease Cas1), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2817c cas1 |
CRISPR-associated endonuclease Cas1 | 999 | 1000 ctx | neighborhood:882 cooccurence:646 coexpression:865 experimental:928 |
Rv2823c cas10 |
CRISPR-associated protein Cas10/Csm1 | 972 | 874 ctx | neighborhood:559 cooccurence:727 textmining:790 |
Rv2821c csm3 |
CRISPR type III-associated RAMP protein Csm3 | 933 | 862 ctx | neighborhood:559 cooccurence:699 textmining:538 |
Rv2820c csm4 |
CRISPR type III-associated RAMP protein Csm4 | 925 | 859 ctx | neighborhood:559 cooccurence:694 textmining:491 |
Rv2824c cas6 |
CRISPR-associated endoribonuclease Cas6 | 969 | 851 ctx | neighborhood:570 cooccurence:668 textmining:806 |
Rv2819c csm5 |
CRISPR type III-associated RAMP protein Csm5 | 920 | 851 ctx | neighborhood:559 cooccurence:675 textmining:489 |
Rv2822c csm2 |
CRISPR type III-associated protein Csm2 | 961 | 848 ctx | neighborhood:559 cooccurence:670 textmining:759 |
Rv0071 |
maturase | 819 | 806 | experimental:790 |
Rv2818c csm6 |
CRISPR-associated protein Csm6 | 925 | 775 ctx | neighborhood:775 textmining:680 |
Rv2825c hyp |
hypothetical protein | 464 | 463 | |
Rv2949c |
chorismate pyruvate-lyase | 456 | 457 ctx | cooccurence:454 |
Rv2986c hupB |
DNA-binding protein HU | 447 | 425 | experimental:420 |
Rv2337c hyp |
hypothetical protein | 416 | 416 ctx | cooccurence:407 |
Rv0355c PPE8 |
PPE family protein PPE8 | 415 | 416 ctx | cooccurence:414 |
Rv3403c hyp |
hypothetical protein | 414 | 414 ctx | cooccurence:414 |
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: CRISPR-associated endoribonuclease Cas2
- MTBC0 PGAP product: CRISPR-associated endonuclease Cas2
- Pfam (hmmscan --cut_ga): CRISPR_Cas2 PF09827.15 (E=7e-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_217332.1)
- Domains: Pfam-A via hmmscan --cut_ga — CRISPR_Cas2 (PF09827.15)
- 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
COG1343 - Curated reference: UniProt P9WPJ3 (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 —
25 functional partner(s); context anchor
cas1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002994|Rv2816c|cas2 MPTRSREEYFNLPLKVDESSGTIGKMFVLVIYDISDNRRRASLAKILAGFGYRVQESAFEAMLTKGQLAKLVARIDRFAIDCDNIRIYKIRGVAAVTFYGRGRLVSAEEFVFF