ccsA Resolved · high auto-curated
H37Rv Rv0529 · MTBC0 mtbc0_000557 ·
324 aa · 623348–624322 (+) ·
RefSeq NP_215041.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cytochrome C-type biogenesis protein CcsA |
|---|---|
| MTBC0 PGAP re-annotation | c-type cytochrome biogenesis protein CcsB |
| Revised (this work) | C-type cytochrome biogenesis protein CcsB. Pfam: Cytochrom_C_asm (PF01578.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O06393
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible cytochrome C-type biogenesis protein CcsA |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | ccsB |
| eggNOG description | Cytochrome C assembly protein |
| Orthologous group | COG0755 |
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 | 0.774 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 4 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Cytochrom_C_asm | PF01578.26 | 6.9e-45 | 107–318 | Cytochrome C assembly protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0528 (transmembrane protein), high confidence from genomic context alone (score 997 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0528 |
transmembrane protein | 997 | 997 ctx | neighborhood:882 cooccurence:754 coexpression:904 |
Rv0526 |
thioredoxin | 995 | 990 ctx | neighborhood:833 coexpression:937 textmining:584 |
Rv0527 ccdA |
cytochrome C-type biogenesis protein CcdA | 995 | 982 ctx | neighborhood:833 coexpression:879 textmining:739 |
Rv0524 hemL |
glutamate-1-semialdehyde 2,1-aminomutase | 935 | 909 ctx | neighborhood:820 coexpression:412 |
Rv0525 hyp |
hypothetical protein | 896 | 897 ctx | neighborhood:820 coexpression:449 |
Rv0511 hemD |
uroporphyrin-III C-methyltransferase | 876 | 876 | coexpression:822 |
Rv0530 hyp |
hypothetical protein | 751 | 751 ctx | neighborhood:736 |
Rv2874 dipZ |
integral membrane C-type cytochrome biogenesis protein DipZ | 914 | 666 | coexpression:619 textmining:754 |
Rv0509 hemA |
glutamyl-tRNA reductase | 753 | 655 | coexpression:434 |
Rv2196 qcrB |
ubiquinol-cytochrome C reductase cytochrome subunit B | 669 | 568 ctx | cooccurence:431 |
Rv0510 hemC |
porphobilinogen deaminase | 550 | 527 | coexpression:449 |
Rv0260c |
transcriptional regulator | 495 | 476 | |
Rv1607 chaA |
ionic transporter integral membrane protein ChaA | 474 | 474 | coexpression:474 |
Rv2093c tatC |
Sec-independent protein translocase transmembrane protein TatC | 532 | 471 ctx | cooccurence:427 |
Rv2195 qcrA |
ubiquinol-cytochrome C reductase rieske iron-sulfur subunit | 461 | 462 |
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: cytochrome C-type biogenesis protein CcsA
- MTBC0 PGAP product: c-type cytochrome biogenesis protein CcsB
- Pfam (hmmscan --cut_ga): Cytochrom_C_asm PF01578.26 (E=7e-45)
- (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_215041.2)
- Domains: Pfam-A via hmmscan --cut_ga — Cytochrom_C_asm (PF01578.26)
- 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
COG0755 - Curated reference: UniProt O06393 (TrEMBL, unreviewed; 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 —
43 functional partner(s); context anchor
Rv0528 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000557|Rv0529|ccsA MNTLHVNVGLARYSDWAFTSAVVALVVALLLLAFEFAQVRGRGLAPLAVPAGSVATDSATPGIVADQRHRPFDERVGRGGLAVAYLGIGLLLACVVLRGLATQRVPWGNMYEFINLTCLSGLIAGAVVLRRARYRPLWVFLLVPVLILLTVSGRWLYANAAPVMPALQSYWLPIHVSVVSLGSGVFLVAGVASILFLVRTSRLGEPTGEGALAGMVRRLPDAQTLDGIAYRTTIFAFPVFGFGVIFGAIWAEEAWGRYWGWDPKETVSFVAWVVYAAYLHARSTAGWRDRKAAWINVAGFVAMVFNLFFVNLVTVGLHSYAGVG