carD Resolved · high auto-curated

H37Rv Rv3583c · MTBC0 mtbc0_003802 · 162 aa · 4048733–4049221 (-) · RefSeq NP_218100.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)RNA polymerase-binding transcription factor CarD
MTBC0 PGAP re-annotationRNA polymerase-binding transcription factor CarD
Revised (this work)RNA polymerase-binding transcription factor CarD. Pfam: CarD_TRCF_RID (PF02559.23), CarD_C (PF21095.4).

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

Curated reference (UniProt)

UniProt P9WJG3 SwissProt · reviewed · Evidence at protein level
UniProt nameRNA polymerase-binding transcription factor CarD
Curated functionControls rRNA transcription by binding to the RNA polymerase (RNAP). Required for replication and persistence during infection of mice.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namecarD
eggNOG descriptiontranscription factor CarD
Orthologous groupCOG1329
KEGG orthology K07736
Gene Ontology (20) GO:0006950, GO:0007154, GO:0008150, GO:0009267, GO:0009405, GO:0009605, GO:0009987, GO:0009991, GO:0015968, GO:0031667, GO:0031668, GO:0031669 +8 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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 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
CarD_TRCF_RIDPF02559.23 2.9e-163–60 CarD-like/TRCF RID domain
CarD_CPF21095.4 1.3e-3769–155 CarD, C-terminal domain

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

Closest characterised functional partner: ispD (2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase), high confidence from genomic context alone (score 887 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 999 999 experimental:999
Rv3457c rpoA DNA-directed RNA polymerase subunit alpha 982 979 experimental:974
Rv0668 rpoC DNA-directed RNA polymerase subunit beta' 990 975 experimental:974 textmining:617
Rv1390 rpoZ DNA-directed RNA polymerase subunit omega 976 974 experimental:960
Rv2703 sigA RNA polymerase sigma factor SigA 974 973 experimental:971
Rv3197A whiB7 transcriptional regulator WhiB7 898 898 experimental:898
Rv2050 rbpA RNA polymerase-binding protein RbpA 992 897 experimental:895 textmining:930
Rv3582c ispD 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase 955 887 ctx neighborhood:865 textmining:622
Rv3581c ispF 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase 877 871 ctx neighborhood:865
Rv1872c lldD2 L-lactate dehydrogenase 820 820 coexpression:820
Rv1871c hyp hypothetical protein 800 800 coexpression:800
Rv3579c rlmB 23S rRNA (guanosine(2251)-2'-O)-methyltransferase RlmB 789 790 ctx neighborhood:788
Rv3580c cysS1 cysteine--tRNA ligase 788 789 ctx neighborhood:788
Rv2710 sigB RNA polymerase sigma factor SigB 802 781 experimental:765
Rv1398c vapB10 antitoxin VapB10 740 740 coexpression:740

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: RNA polymerase-binding transcription factor CarD
  • MTBC0 PGAP product: RNA polymerase-binding transcription factor CarD
  • Pfam (hmmscan --cut_ga): CarD_TRCF_RID PF02559.23 (E=3e-16), CarD_C PF21095.4 (E=1e-37)
  • (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_218100.1)
  • Domains: Pfam-A via hmmscan --cut_ga — CarD_TRCF_RID (PF02559.23), CarD_C (PF21095.4)
  • 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 COG1329
  • Curated reference: UniProt P9WJG3 (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 — 25 functional partner(s); context anchor ispD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003802|Rv3583c|carD
MIFKVGDTVVYPHHGAALVEAIETRTIKGEQKEYLVLKVAQGDLTVRVPAENAEYVGVRDVVGQEGLDKVFQVLRAPHTEEPTNWSRRYKANLEKLASGDVNKVAEVVRDLWRRDQERGLSAGEKRMLAKARQILVGELALAESTDDAKAETILDEVLAAAS