cstA Family assigned · medium auto-curated
H37Rv Rv3063 · MTBC0 mtbc0_003255 ·
758 aa · 3448607–3450883 (+) ·
RefSeq NP_217579.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | carbon starvation protein A |
|---|---|
| MTBC0 PGAP re-annotation | carbon starvation CstA family protein |
| Revised (this work) | Carbon starvation CstA family protein. Pfam: CstA (PF02554.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WP47
SwissProt · reviewed
· Inferred from homology
|
|---|---|
| UniProt name | Peptide transporter CstA |
| Curated function | Involved in peptide utilization. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | cstA |
| eggNOG description | Carbon starvation protein |
| Orthologous group | COG1966 |
| KEGG orthology |
K06200
|
| Gene Ontology (23) |
GO:0005575, GO:0005623, GO:0005886, GO:0005887, GO:0007154, GO:0008150, GO:0009605, GO:0009987, GO:0009991, GO:0016020, GO:0016021, GO:0031224 +11 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 | 0.525 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 13 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 |
|---|---|---|---|---|
CstA | PF02554.21 | 2.4e-249 | 68–633 | Carbon starvation protein CstA |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ligB (DNA ligase), high confidence from genomic context alone (score 758 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3062 ligB |
DNA ligase | 787 | 758 ctx | neighborhood:756 |
Rv3667 acs |
acetyl-CoAsynthetase | 695 | 683 | coexpression:681 |
Rv2443 dctA |
C4-dicarboxylate-transport transmembrane protein DctA | 585 | 559 | coexpression:410 |
Rv1188 |
proline dehydrogenase | 560 | 542 | coexpression:542 |
Rv3061c fadE22 |
acyl-CoA dehydrogenase FadE22 | 485 | 485 ctx | neighborhood:476 |
Rv1249c |
membrane protein | 469 | 470 | coexpression:460 |
Rv0887c hyp |
hypothetical protein | 459 | 460 | coexpression:453 |
Rv3293 pcd |
piperideine-6-carboxylic acid dehydrogenase | 424 | 425 | coexpression:425 |
Rv0409 ackA |
acetate kinase | 421 | 421 | coexpression:421 |
Rv0223c |
aldehyde dehydrogenase | 419 | 420 | coexpression:420 |
Rv2858c aldC |
aldehyde dehydrogenase AldC | 419 | 420 | coexpression:420 |
Rv0768 aldA |
aldehyde dehydrogenase AldA | 419 | 420 | coexpression:420 |
Rv1187 rocA |
pyrroline-5-carboxylate dehydrogenase RocA | 419 | 420 | coexpression:420 |
Rv1731 gabD2 |
succinate-semialdehyde dehydrogenase | 418 | 418 | coexpression:418 |
Rv0147 |
aldehyde dehydrogenase | 417 | 418 | coexpression:418 |
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: carbon starvation protein A
- MTBC0 PGAP product: carbon starvation CstA family protein
- Pfam (hmmscan --cut_ga): CstA PF02554.21 (E=2e-249)
- (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_217579.1)
- Domains: Pfam-A via hmmscan --cut_ga — CstA (PF02554.21)
- 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
COG1966 - Curated reference: UniProt P9WP47 (SwissProt, reviewed; Inferred from homology)
- 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 —
26 functional partner(s); context anchor
ligB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003255|Rv3063|cstA MAAPTPSNRIEERSGHASCVRADADLPPVAILGRSPITLRHKIFFVAVAVIGALAWTVVAFFRNEPVNAVWIVVAAGCTYIIGFRFYARLIEMKVVRPRDDHATPAEILDDGTDYVPTDRRVVFGHHFAAIAGAGPLVGPVLATQMGYLPSSIWIVVGAVLAGCVQDYLVLWISVRRRGRSLGQMVRDELGATAGVAALVGIPVIITIVIAVLALVVVRALAKSPWGVFSIAMTIPIAIFMGCYLRFLRPGRVSEVSLIGIGLLLLAVVSGDWVAHTSWGAAWFSLSPVTLCWLLISYGFAASVLPVWLLLAPRDYLSTFMKVGTIALLAIGVCAAHPIIEAPAVSKFAGSGNGPVFAGSLFPFLFITIACGALSGFHALICSGTTPKMLEKEGQMRVIGYGGMMTESFVAVIALLTAAILDQHLYFTLNAPSLHTHDSAATAAKYVNGLGLTGSPVTPDHISQAAASVGEQTIVSRTGGAPTLAFGMAEMLHRVVGGVGLKAFWYHFAIMFEALFILTTVDAGTRAARFMISDALGNFGGVLRKLQNPSWRPGAWACSLVVVAAWGSILLLGVTDPLGGINTLFPLFGIANQLLAGIALTVITVVVIKKGRLKWAWIPGIPLLWDLAVTLTASWQKIFSADPSVGYWTQHAHYAAAQHAGETAFGSATNADEINDVVRNTFVQGTLSIVFVVVVVLVVVAGVIVALKTIRGRGIPLAEDDPAPSTLFAPAGLIPTAAERKLQRRLGAPASASVAAPD