cas10 Resolved · high auto-curated

H37Rv Rv2823c · MTBC0 mtbc0_003001 · 812 aa · 3150001–3152439 (-) · RefSeq NP_217339.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)CRISPR-associated protein Cas10/Csm1
MTBC0 PGAP re-annotationtype III-A CRISPR-associated protein Cas10/Csm1
Revised (this work)Type III-A CRISPR-associated protein Cas10/Csm1. Pfam: HD (PF01966.29), Csm1_B (PF18211.8), Cas10-Cmr2_palm2 (PF22335.2), Cmr2_hel_dom2 (PF20824.3).

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

Curated reference (UniProt)

UniProt P71629 SwissProt · reviewed · Evidence at protein level
UniProt nameCRISPR system single-strand-specific deoxyribonuclease Cas10/Csm1
EC (curated) EC 2.7.7.-, EC 3.1.-.-
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 J Translation, ribosomal structure and biogenesis
Preferred namecsm1
eggNOG descriptioncrispr-associated protein
Orthologous groupCOG1353
KEGG orthology K07016
Gene Ontology (7) GO:0005575, GO:0005576, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944

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 0.558 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 9 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
HDPF01966.29 9.4e-057–108 HD domain
Csm1_BPF18211.8 1.0e-51265–423 Csm1 subunit domain B
Cas10-Cmr2_palm2PF22335.2 6.4e-35551–699 Cas10/Cmr2, second palm domain
Cmr2_hel_dom2PF20824.3 9.5e-29726–808 CRISPR RNA silencing complex Cmr2 subunit, second helical domain

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

Closest characterised functional partner: csm2 (CRISPR type III-associated protein Csm2), high confidence from genomic context alone (score 999 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2822c csm2 CRISPR type III-associated protein Csm2 999 999 ctx neighborhood:882 cooccurence:772 coexpression:553 experimental:927 textmining:878
Rv2820c csm4 CRISPR type III-associated RAMP protein Csm4 999 998 ctx neighborhood:882 cooccurence:774 experimental:928 textmining:829
Rv2821c csm3 CRISPR type III-associated RAMP protein Csm3 999 998 ctx neighborhood:882 cooccurence:774 experimental:928 textmining:891
Rv2819c csm5 CRISPR type III-associated RAMP protein Csm5 999 997 ctx neighborhood:801 cooccurence:772 experimental:919 textmining:830
Rv2824c cas6 CRISPR-associated endoribonuclease Cas6 996 970 ctx neighborhood:793 cooccurence:768 coexpression:423 textmining:876
Rv2816c cas2 CRISPR-associated endoribonuclease Cas2 972 874 ctx neighborhood:559 cooccurence:727 textmining:790
Rv2817c cas1 CRISPR-associated endonuclease Cas1 863 843 ctx neighborhood:559 cooccurence:647
Rv2818c csm6 CRISPR-associated protein Csm6 963 709 ctx neighborhood:587 textmining:880
Rv1004c membrane protein 637 637 ctx cooccurence:636
Rv2209 integral membrane protein 592 592 ctx cooccurence:592
Rv0355c PPE8 PPE family protein PPE8 588 589 ctx cooccurence:586
Rv3350c PPE56 PPE family protein PPE56 568 568 ctx cooccurence:568
Rv3347c PPE55 PPE family protein PPE55 567 567 ctx cooccurence:567
Rv2490c PE_PGRS43 PE-PGRS family protein PE_PGRS43 564 564 ctx cooccurence:564
Rv2082 hyp hypothetical protein 553 553 ctx cooccurence:552

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 protein Cas10/Csm1
  • MTBC0 PGAP product: type III-A CRISPR-associated protein Cas10/Csm1
  • Pfam (hmmscan --cut_ga): HD PF01966.29 (E=9e-05), Csm1_B PF18211.8 (E=1e-51), Cas10-Cmr2_palm2 PF22335.2 (E=6e-35), Cmr2_hel_dom2 PF20824.3 (E=1e-28)
  • (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_217339.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HD (PF01966.29), Csm1_B (PF18211.8), Cas10-Cmr2_palm2 (PF22335.2), Cmr2_hel_dom2 (PF20824.3)
  • 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 COG1353
  • Curated reference: UniProt P71629 (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 — 41 functional partner(s); context anchor csm2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003001|Rv2823c|cas10
MNPQLIEAIIGCLLHDIGKPVQRAALGYPGRHSAIGRAFMKKVWLRDSRNPSQFTDEVDEADIGVSDRRILDAISYHHSSALRTAAENGRLAADAPAYIAYIADNIAAGTDRRKADSDDGHGASTWDPDTPLYSMFNRFGSGTANLAFAPEMLDDRKPINIPSPRRIEFDKDRYAAIVNKLKAILVDLERSDTYLASLLNVLEATLSFVPSSTDASEVVDVSLFDHLKLTGALGACIWHYLQATGQSDFKSALFDKQDTFYNEKAFLLTTFDVSGIQDFIYTIHSSGAAKMLRARSFYLEMLTEHLIDELLARVGLSRANLNYSGGGHAYLLLPNTESARKSVEQFEREANDWLLENFATRLFIATGSVPLAANDLMRRPNESASQASNRALRYSGLYRELSEQLSAKKLARYSADQLRELNSRDHDGQKGDRECSVCHTVNRTVSADDEPKCSLCQALTAASSQIQSESRRFLLISDGATKGLPLPFGATLTFCSRADADKALQQPQTRRRYAKNKFFAGECLGTGLWVGDYVAQMEFGDYVKRASGIARLGVLRLDVDNLGQAFTHGFMEQGNGKFNTISRTAAFSRMLSLFFRQHINYVLARPKLRPITGDDPARPREATIIYSGGDDVFVVGAWDDVIEFGIELRERFHEFTQGKLTVSAGIGMFPDKYPISVMAREVGDLEDAAKSLPGKNGVALFDREFTFGWDELLSKVIEEKYRHIADYFSGNEERGMAFIYKLLELLAERDDRITKARWVYFLTRMRNPTGDTAPFQQFANRLHQWFQDPTDAKQLKTALHLYIYRTRKEESE