cas1 Resolved · high auto-curated

H37Rv Rv2817c · MTBC0 mtbc0_002995 · 338 aa · 3144624–3145640 (-) · RefSeq NP_217333.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)CRISPR-associated endonuclease Cas1
MTBC0 PGAP re-annotationCRISPR-associated endonuclease Cas1
Revised (this work)CRISPR-associated endonuclease Cas1. Pfam: Cas_Cas1 (PF01867.22).

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

Curated reference (UniProt)

UniProt P9WPJ5 SwissProt · reviewed · Evidence at protein level
UniProt nameCRISPR-associated endonuclease Cas1
EC (curated) 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 L Replication, recombination and repair
Preferred namecas1
eggNOG descriptionCRISPR (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). Acts as a dsDNA endonuclease. Involved in the integration of spacer DNA into the CRISPR cassette
Orthologous groupCOG1518
KEGG orthology K15342
Gene Ontology (8) GO:0005575, GO:0005618, GO:0005623, GO:0008150, GO:0030312, GO:0040007, 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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 5 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
Cas_Cas1PF01867.22 1.3e-754–283 CRISPR associated protein Cas1

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

Closest characterised functional partner: cas2 (CRISPR-associated endoribonuclease Cas2), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2816c cas2 CRISPR-associated endoribonuclease Cas2 999 1000 ctx neighborhood:882 cooccurence:646 coexpression:865 experimental:928
Rv2821c csm3 CRISPR type III-associated RAMP protein Csm3 859 859 ctx neighborhood:559 cooccurence:692
Rv2823c cas10 CRISPR-associated protein Cas10/Csm1 863 843 ctx neighborhood:559 cooccurence:647
Rv2818c csm6 CRISPR-associated protein Csm6 777 777 ctx neighborhood:775
Rv2820c csm4 CRISPR type III-associated RAMP protein Csm4 777 777 ctx neighborhood:559 cooccurence:512
Rv2824c cas6 CRISPR-associated endoribonuclease Cas6 795 757 ctx neighborhood:559 cooccurence:447
Rv2819c csm5 CRISPR type III-associated RAMP protein Csm5 731 731 ctx neighborhood:559 cooccurence:411
Rv2822c csm2 CRISPR type III-associated protein Csm2 719 719 ctx neighborhood:559
Rv1752 hyp hypothetical protein 557 518 coexpression:408
Rv2986c hupB DNA-binding protein HU 470 471 experimental:465
Rv1343c lprD lipoprotein LprD 404 404 coexpression:404
Rv1213 glgC glucose-1-phosphate adenylyltransferase 404 404 coexpression:404
Rv1525 wbbL2 rhamnosyl transferase WbbL 400 401
Rv2515c hyp hypothetical protein 504 193 textmining:411

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 endonuclease Cas1
  • MTBC0 PGAP product: CRISPR-associated endonuclease Cas1
  • Pfam (hmmscan --cut_ga): Cas_Cas1 PF01867.22 (E=1e-75)
  • (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_217333.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Cas_Cas1 (PF01867.22)
  • 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 COG1518
  • Curated reference: UniProt P9WPJ5 (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 — 14 functional partner(s); context anchor cas2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002995|Rv2817c|cas1
MVQLYVSDSVSRISFADGRVIVWSEELGESQYPIETLDGITLFGRPTMTTPFIVEMLKRERDIQLFTTDGHYQGRISTPDVSYAPRLRQQVHRTDDPAFCLSLSKRIVSRKILNQQALIRAHTSGQDVAESIRTMKHSLAWVDRSGSLAELNGFEGNAAKAYFTALGHLVPQEFAFQGRSTRPPLDAFNSMVSLGYSLLYKNIIGAIERHSLNAYIGFLHQDSRGHATLASDLMEVWRAPIIDDTVLRLIADGVVDTRAFSKNSDTGAVFATREATRSIARAFGNRIARTATYIKGDPHRYTFQYALDLQLQSLVRVIEAGHPSRLVDIDITSEPSGA