csm4 Resolved · high auto-curated
H37Rv Rv2820c · MTBC0 mtbc0_002998 ·
302 aa · 3148021–3148929 (-) ·
RefSeq NP_217336.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | CRISPR type III-associated RAMP protein Csm4 |
|---|---|
| MTBC0 PGAP re-annotation | type III-A CRISPR-associated RAMP protein Csm4 |
| Revised (this work) | Type III-A CRISPR-associated RAMP protein Csm4. Pfam: RAMPs (PF03787.21), Csm4_C (PF17953.7). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJF7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | CRISPR system Cms protein Csm4 |
| 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 | csm4 |
| eggNOG description | CRISPR-associated RAMP protein, Csm4 family |
| Orthologous group | COG1567 |
| KEGG orthology |
K19139
|
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 | 1.23 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 7 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 |
|---|---|---|---|---|
RAMPs | PF03787.21 | 1.2e-04 | 85–192 | RAMP superfamily |
Csm4_C | PF17953.7 | 4.1e-25 | 209–296 | CRISPR Csm4 C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: csm3 (CRISPR type III-associated RAMP protein Csm3), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2821c csm3 |
CRISPR type III-associated RAMP protein Csm3 | 999 | 1000 ctx | neighborhood:882 cooccurence:772 coexpression:860 experimental:928 textmining:887 |
Rv2822c csm2 |
CRISPR type III-associated protein Csm2 | 999 | 1000 ctx | neighborhood:882 cooccurence:774 coexpression:826 experimental:911 textmining:852 |
Rv2819c csm5 |
CRISPR type III-associated RAMP protein Csm5 | 999 | 1000 ctx | neighborhood:801 fusion:448 cooccurence:774 coexpression:847 experimental:911 textmining:857 |
Rv2823c cas10 |
CRISPR-associated protein Cas10/Csm1 | 999 | 998 ctx | neighborhood:882 cooccurence:774 experimental:928 textmining:829 |
Rv2824c cas6 |
CRISPR-associated endoribonuclease Cas6 | 990 | 953 ctx | neighborhood:793 cooccurence:772 textmining:804 |
Rv2818c csm6 |
CRISPR-associated protein Csm6 | 988 | 916 ctx | neighborhood:587 coexpression:806 textmining:870 |
Rv2816c cas2 |
CRISPR-associated endoribonuclease Cas2 | 925 | 859 ctx | neighborhood:559 cooccurence:694 textmining:491 |
Rv2817c cas1 |
CRISPR-associated endonuclease Cas1 | 777 | 777 ctx | neighborhood:559 cooccurence:512 |
Rv1004c |
membrane protein | 738 | 738 ctx | cooccurence:737 |
Rv0355c PPE8 |
PPE family protein PPE8 | 720 | 721 ctx | cooccurence:719 |
Rv3347c PPE55 |
PPE family protein PPE55 | 710 | 711 ctx | cooccurence:710 |
Rv3350c PPE56 |
PPE family protein PPE56 | 709 | 710 ctx | cooccurence:709 |
Rv2209 |
integral membrane protein | 708 | 708 ctx | cooccurence:708 |
Rv1917c PPE34 |
PPE family protein PPE34 | 703 | 703 ctx | cooccurence:703 |
Rv2490c PE_PGRS43 |
PE-PGRS family protein PE_PGRS43 | 702 | 702 ctx | cooccurence:702 |
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 type III-associated RAMP protein Csm4
- MTBC0 PGAP product: type III-A CRISPR-associated RAMP protein Csm4
- Pfam (hmmscan --cut_ga): RAMPs PF03787.21 (E=1e-04), Csm4_C PF17953.7 (E=4e-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_217336.1)
- Domains: Pfam-A via hmmscan --cut_ga — RAMPs (PF03787.21), Csm4_C (PF17953.7)
- 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
COG1567 - Curated reference: UniProt P9WJF7 (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 —
78 functional partner(s); context anchor
csm3 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002998|Rv2820c|csm4 MNSRLFRFDFDRTHFGDHGLESSTISCPADTLYSALCVEALRMGGQQLLGELVACSTLRLTDLLPYVGPDYLVPKPLHSVRSDGSSMQKKLAKKIGFLPAAQLGSFLDGTADLKELAARQTKIGVHAVSAKAAIHNGKKDADPYRVGYFRFELDAGLWLLATGSESELGLLTRLLKGISALGGERTSGFGAFNLTESEAPAALTPTVDAASLMTLTTSLPTDDELEAALAGATYRLVKRSGFVASSTYADMPLRKRDIYKFAAGSVFSRPFQGGILDVSLGGNHPVYSYARPLFLALPESAA