ccdA Resolved · medium auto-curated

H37Rv Rv0527 · MTBC0 - · 259 aa · 617493–618272 (+) · RefSeq YP_177735.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cytochrome C-type biogenesis protein CcdA
MTBC0 PGAP re-annotation
Revised (this work)Cytochrome C-type biogenesis protein CcdA.

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt L7N671 TrEMBL · unreviewed · Predicted
UniProt namePossible cytochrome C-type biogenesis protein CcdA

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
Preferred nameccdA
eggNOG descriptioncytochrome c biogenesis protein
Orthologous groupCOG0785
KEGG orthology K06196

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 0.826 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 2 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: Rv0526 (thioredoxin), high confidence from genomic context alone (score 991 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0526 thioredoxin 996 991 ctx neighborhood:882 cooccurence:464 coexpression:863 textmining:657
Rv0528 transmembrane protein 988 984 ctx neighborhood:833 coexpression:868
Rv0529 ccsA cytochrome C-type biogenesis protein CcsA 995 982 ctx neighborhood:833 coexpression:879 textmining:739
Rv0525 hyp hypothetical protein 933 934 ctx neighborhood:865 coexpression:530
Rv0524 hemL glutamate-1-semialdehyde 2,1-aminomutase 970 915 ctx neighborhood:865 textmining:661
Rv0511 hemD uroporphyrin-III C-methyltransferase 719 719 coexpression:651
Rv0530 hyp hypothetical protein 612 613 ctx neighborhood:609
Rv3673c membrane-anchored thioredoxin-like protein 711 535 textmining:404
Rv0523c hyp hypothetical protein 531 531 ctx neighborhood:531
Rv0514 transmembrane protein 493 494 coexpression:494
Rv0318c integral membrane protein 463 464 coexpression:462
Rv1677 dsbF lipoprotein DsbF 463 436
Rv2195 qcrA ubiquinol-cytochrome C reductase rieske iron-sulfur subunit 447 427
Rv2677c hemY protoporphyrinogen oxidase 591 426
Rv1586c phage integrase 425 425 coexpression:424

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): cytochrome C-type biogenesis protein CcdA
  • (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 YP_177735.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG0785
  • Curated reference: UniProt L7N671 (TrEMBL, unreviewed; Predicted)
  • 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 — 33 functional partner(s); context anchor Rv0526
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0527|ccdA
MTGFTEIAAVGPLLVAVGVCLLAGLVSFASPCVVPLVPGYLSYLAAVVGVDEQLPAGVVKPPVAARWRVAGSAALFVAGFTTVFVLGTVAVLGMTTTLITNQLLLQRVGGVLIVVMGLVFVGFIGALQRQARFTPRQLTSVAGAPVLGAVFALGWTPCLGPTLTGVITVASATEGASVARGIVLVIAYCLGLGIPFVLLAFGSAWAVAGLGWLRRHTRAIQIFGGALLIAVGAALVTGVWNDVVSWLRDAFVSDVRLPI