birA Resolved · high auto-curated
H37Rv Rv3279c · MTBC0 mtbc0_003487 ·
266 aa · 3683355–3684155 (-) ·
RefSeq NP_217796.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | bifunctional biotin operon repressor/biotin--[acetyl-CoA-carboxylase |
|---|---|
| MTBC0 PGAP re-annotation | biotin--[acetyl-CoA-carboxylase] ligase |
| Revised (this work) | Biotin--[acetyl-CoA-carboxylase] ligase. Pfam: BPL_LplA_LipB (PF03099.25), BPL_C (PF02237.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YFP0
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Biotin--[acetyl-CoA-carboxylase] ligase |
| EC (curated) |
EC 6.3.4.15
|
| Curated function | Catalyzes the transfer of biotin onto a conserved lysine residue of the biotin carboxyl carrier protein (BCCP) domain of acetyl-CoA carboxylase and converts it to active holo-BCCP. Forms an acyl-adenylate intermediate. Cannot use GTP or desthiobiotin. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | birA |
| eggNOG description | biotin lipoate A B protein ligase |
| Orthologous group | COG0340 |
| EC number |
EC 6.3.4.15
|
| KEGG orthology |
K03524
|
| KEGG pathways |
map00780, map01100
|
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 | 0.498 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 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 |
|---|---|---|---|---|
BPL_LplA_LipB | PF03099.25 | 9.1e-09 | 55–147 | Biotin/lipoate A/B protein ligase family |
BPL_C | PF02237.24 | 4.0e-13 | 218–264 | Biotin protein ligase C terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: accD5 (propionyl-CoA carboxylase subunit beta), high confidence from genomic context alone (score 936 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3280 accD5 |
propionyl-CoA carboxylase subunit beta | 959 | 936 ctx | neighborhood:788 database:622 |
Rv3285 accA3 |
bifunctional protein acetyl-/propionyl-CoA carboxylase subunit alpha AccA | 956 | 928 ctx | neighborhood:406 cooccurence:685 database:644 textmining:421 |
Rv1589 bioB |
biotin synthetase | 985 | 912 | database:900 textmining:840 |
Rv1442 bisC |
biotin sulfoxide reductase BisC | 904 | 902 | database:900 |
Rv2501c accA1 |
acetyl/propionyl-CoA carboxylase subuit alpha | 969 | 887 ctx | cooccurence:670 database:644 textmining:745 |
Rv1722 |
carboxylase | 954 | 884 | database:844 textmining:626 |
Rv0973c accA2 |
acetyl/propionyl-CoA carboxylase subuit alpha | 948 | 882 ctx | cooccurence:659 database:644 textmining:578 |
Rv3278c |
transmembrane protein | 822 | 823 ctx | neighborhood:822 |
Rv2967c pca |
pyruvate carboxylase | 822 | 799 | database:662 |
Rv3282 hyp |
hypothetical protein | 774 | 775 ctx | neighborhood:766 |
Rv3281 accE5 |
bifunctional protein acetyl-/propionyl-CoAcarboxylase subunit epsilon AccE | 864 | 767 ctx | neighborhood:766 textmining:441 |
Rv3799c accD4 |
propionyl-CoA carboxylase subunit beta AccD | 812 | 749 | database:622 |
Rv2247 accD6 |
acetyl-/propionyl-CoA carboxylase subunit beta | 766 | 720 | database:622 |
Rv2524c fas |
fatty acid synthase | 836 | 717 ctx | neighborhood:544 coexpression:404 textmining:448 |
Rv3221c TB7.3 |
acetyl-CoA carboxylase biotin carboxyl carrier protein subunit | 961 | 696 | database:662 textmining:878 |
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: bifunctional biotin operon repressor/biotin--[acetyl-CoA-carboxylase
- MTBC0 PGAP product: biotin--[acetyl-CoA-carboxylase] ligase
- Pfam (hmmscan --cut_ga): BPL_LplA_LipB PF03099.25 (E=9e-09), BPL_C PF02237.24 (E=4e-13)
- (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_217796.1)
- Domains: Pfam-A via hmmscan --cut_ga — BPL_LplA_LipB (PF03099.25), BPL_C (PF02237.24)
- 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
COG0340 - Curated reference: UniProt I6YFP0 (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 —
82 functional partner(s); context anchor
accD5 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003487|Rv3279c|birA MTDRDRLRPPLDERSLRDQLIGAGSGWRQLDVVAQTGSTNADLLARAASGADIDGVVLIAEHQTAGRGRHGRGWAATARAQIILSVGVRVVDVPVQAWGWLSLAAGLAVLDSVAPLIAVPPAETGLKWPNDVLARGGKLAGILAEVAQPFVVLGVGLNVTQAPEEVDPDATSLLDLGVAAPDRNRIASRLLRELEARIIQWRNANPQLAADYRARSLTIGSRVRVELPGGQDVVGIARDIDDQGRLCLDVGGRTVVVSAGDVVHLR