cmk Resolved · high auto-curated

H37Rv Rv1712 · MTBC0 mtbc0_001822 · 230 aa · 1951614–1952306 (+) · RefSeq NP_216228.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cytidylate kinase
MTBC0 PGAP re-annotation(d)CMP kinase
Revised (this work)(d)CMP kinase. Pfam: Cytidylate_kin2 (PF13189.13), Cytidylate_kin (PF02224.25), AAA_18 (PF13238.13).

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

Curated reference (UniProt)

UniProt P9WPA9 SwissProt · reviewed · Evidence at protein level
UniProt nameCytidylate kinase
EC (curated) EC 2.7.4.25

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namecmk
eggNOG descriptionBelongs to the cytidylate kinase family. Type 1 subfamily
Orthologous groupCOG0283
EC number EC 2.7.4.25
KEGG orthology K00945
KEGG pathways map00240, map01100
KEGG modules M00052
Gene Ontology (85) GO:0003674, GO:0003824, GO:0004127, GO:0004592, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006082, GO:0006139, GO:0006520 +73 more

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 0.126 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 1 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
Cytidylate_kin2PF13189.13 1.2e-068–161 Cytidylate kinase-like family
Cytidylate_kinPF02224.25 1.9e-839–223 Cytidylate kinase
AAA_18PF13238.13 1.5e-079–163 AAA domain

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

Closest characterised functional partner: engA (GTPase Der), high confidence from genomic context alone (score 999 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1713 engA GTPase Der 999 999 ctx neighborhood:881 fusion:887 coexpression:849 textmining:917
Rv1711 RNA pseudouridine synthase 997 995 ctx neighborhood:882 fusion:592 coexpression:886 textmining:489
Rv1710 scpB segregation and condensation protein ScpB 990 983 ctx neighborhood:881 coexpression:829 textmining:489
Rv1709 scpA segregation and condensation protein ScpA 983 970 ctx neighborhood:881 coexpression:761 textmining:479
Rv1630 rpsA 30S ribosomal protein S1 925 918 ctx fusion:897
Rv3227 aroA 3-phosphoshikimate 1-carboxyvinyltransferase 923 913 ctx fusion:896
Rv0570 nrdZ vitamin B12-dependent ribonucleoside-diphosphate reductase 922 913 database:900
Rv3051c nrdE ribonucleoside-diphosphate reductase subunit alpha 922 913 database:900
Rv2445c ndkA nucleoside diphosphate kinase 931 910 database:900
Rv3602c panC pantothenate synthetase 908 908 ctx fusion:900
Rv3048c nrdF2 ribonucleoside-diphosphate reductase subunit beta NrdF2 913 904 database:900
Rv0233 nrdB ribonucleoside-diphosphate reductase subunit beta NrdB 913 904 database:900
Rv1981c nrdF1 ribonucleoside-diphosphate reductase subunit beta NrdF1 912 903 database:900
Rv1708 initiation inhibitor protein 888 889 ctx neighborhood:881
Rv1707 transmembrane protein 743 744 ctx neighborhood:744

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: cytidylate kinase
  • MTBC0 PGAP product: (d)CMP kinase
  • Pfam (hmmscan --cut_ga): Cytidylate_kin2 PF13189.13 (E=1e-06), Cytidylate_kin PF02224.25 (E=2e-83), AAA_18 PF13238.13 (E=1e-07)
  • (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_216228.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Cytidylate_kin2 (PF13189.13), Cytidylate_kin (PF02224.25), AAA_18 (PF13238.13)
  • 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 COG0283
  • Curated reference: UniProt P9WPA9 (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 — 98 functional partner(s); context anchor engA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001822|Rv1712|cmk
MSRLSAAVVAIDGPAGTGKSSVSRRLARELGARFLDTGAMYRIVTLAVLRAGADPSDIAAVETIASTVQMSLGYDPDGDSCYLAGEDVSVEIRGDAVTRAVSAVSSVPAVRTRLVELQRTMAEGPGSIVVEGRDIGTVVFPDAPVKIFLTASAETRARRRNAQNVAAGLADDYDGVLADVRRRDHLDSTRAVSPLQAAGDAVIVDTSDMTEAEVVAHLLELVTRRSEAVR