csm2 Resolved · high auto-curated

H37Rv Rv2822c · MTBC0 mtbc0_003000 · 124 aa · 3149630–3150004 (-) · RefSeq NP_217338.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)CRISPR type III-associated protein Csm2
MTBC0 PGAP re-annotationtype III-A CRISPR-associated protein Csm2
Revised (this work)Type III-A CRISPR-associated protein Csm2. Pfam: Csm2_III-A (PF03750.19).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WJG1 SwissProt · reviewed · Evidence at protein level
UniProt nameCRISPR system Cms protein Csm2
Curated functionCRISPR (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 namecsm2
eggNOG descriptionCsm2 Type III-A
Orthologous groupCOG1421
KEGG orthology K19138

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 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)

PfamAccessioni-EvalueResiduesDescription
Csm2_III-APF03750.19 4.2e-109–120 Csm2 Type III-A

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: csm4 (CRISPR type III-associated RAMP protein Csm4), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2820c csm4 CRISPR type III-associated RAMP protein Csm4 999 1000 ctx neighborhood:882 cooccurence:774 coexpression:826 experimental:911 textmining:852
Rv2821c csm3 CRISPR type III-associated RAMP protein Csm3 999 1000 ctx neighborhood:882 cooccurence:722 coexpression:841 experimental:927 textmining:888
Rv2823c cas10 CRISPR-associated protein Cas10/Csm1 999 999 ctx neighborhood:882 cooccurence:772 coexpression:553 experimental:927 textmining:878
Rv2819c csm5 CRISPR type III-associated RAMP protein Csm5 999 999 ctx neighborhood:801 cooccurence:774 coexpression:806 experimental:927 textmining:852
Rv2824c cas6 CRISPR-associated endoribonuclease Cas6 987 953 ctx neighborhood:790 cooccurence:774 textmining:756
Rv2818c csm6 CRISPR-associated protein Csm6 962 882 ctx neighborhood:581 coexpression:731 textmining:693
Rv2816c cas2 CRISPR-associated endoribonuclease Cas2 961 848 ctx neighborhood:559 cooccurence:670 textmining:759
Rv1004c membrane protein 748 748 ctx cooccurence:748
Rv0355c PPE8 PPE family protein PPE8 744 744 ctx cooccurence:742
Rv3350c PPE56 PPE family protein PPE56 738 738 ctx cooccurence:737
Rv3347c PPE55 PPE family protein PPE55 736 737 ctx cooccurence:736
Rv2209 integral membrane protein 730 730 ctx cooccurence:730
Rv1452c PE_PGRS28 PE-PGRS family protein PE_PGRS28 728 728 ctx cooccurence:728
Rv2490c PE_PGRS43 PE-PGRS family protein PE_PGRS43 728 728 ctx cooccurence:728
Rv1917c PPE34 PPE family protein PPE34 728 728 ctx cooccurence:727

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 protein Csm2
  • MTBC0 PGAP product: type III-A CRISPR-associated protein Csm2
  • Pfam (hmmscan --cut_ga): Csm2_III-A PF03750.19 (E=4e-10)
  • (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_217338.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Csm2_III-A (PF03750.19)
  • 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 COG1421
  • Curated reference: UniProt P9WJG1 (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 csm4
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003000|Rv2822c|csm2
MSVIQDDYVKQAEVIRGLPKKKNGFELTTTQLRVLLSLTAQLFDEAQQSANPTLPRQLKEKVQYLRVRFVYQSGREDAVKTFVRNAKLLEALEGIGDSRDGLLRFCRYMEALAAYKKYLDPKDK