bioD Resolved · high auto-curated
H37Rv Rv1570 · MTBC0 mtbc0_001678 ·
226 aa · 1789823–1790503 (+) ·
RefSeq NP_216086.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ATP-dependent dethiobiotin synthetase BioD |
|---|---|
| MTBC0 PGAP re-annotation | dethiobiotin synthase |
| Revised (this work) | Dethiobiotin synthase. Pfam: AAA_26 (PF13500.13), CbiA (PF01656.30). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WPQ5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Dethiobiotin synthetase BioD |
| EC (curated) |
EC 6.3.3.3
|
| Curated function | Catalyzes a mechanistically unusual reaction, the ATP-dependent insertion of CO2 between the N7 and N8 nitrogen atoms of 7,8-diaminopelargonic acid (DAPA, also called 7,8-diammoniononanoate) to form a ureido ring. Can use a range of NTPs; has highest affinity for CTP (KD is measured as 17.2 uM or 0.160 uM in 2 different papers) while KD for ATP is 331 uM or 75 uM in the same papers. Gly-169 plays a role in NTP discrimination. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | bioD |
| eggNOG description | Catalyzes a mechanistically unusual reaction, the ATP- dependent insertion of CO2 between the N7 and N8 nitrogen atoms of 7,8-diaminopelargonic acid (DAPA) to form an ureido ring |
| Orthologous group | COG0132 |
| EC number |
EC 6.3.3.3
|
| KEGG orthology |
K01935
|
| KEGG pathways |
map00780, map01100
|
| KEGG modules |
M00123, M00573, M00577
|
| Gene Ontology (75) |
GO:0000166, GO:0000287, GO:0003674, GO:0003824, GO:0004141, GO:0005488, GO:0005524, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829 +63 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 | 0.529 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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 |
|---|---|---|---|---|
AAA_26 | PF13500.13 | 4.2e-27 | 4–187 | AAA domain |
CbiA | PF01656.30 | 3.6e-07 | 4–99 | CobQ/CobB/MinD/ParA nucleotide binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: bioA (adenosylmethionine--8-amino-7-oxononanoate aminotransferase BioA), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1568 bioA |
adenosylmethionine--8-amino-7-oxononanoate aminotransferase BioA | 999 | 999 ctx | neighborhood:881 cooccurence:762 coexpression:695 database:900 textmining:965 |
Rv1589 bioB |
biotin synthetase | 999 | 997 ctx | cooccurence:770 coexpression:856 database:900 textmining:954 |
Rv1569 bioF1 |
8-amino-7-oxononanoate synthase | 999 | 990 ctx | neighborhood:882 cooccurence:711 coexpression:723 textmining:964 |
Rv1571 hyp |
hypothetical protein | 990 | 953 ctx | neighborhood:882 coexpression:615 textmining:806 |
Rv0032 bioF2 |
8-amino-7-oxononanoate synthase | 931 | 869 ctx | cooccurence:513 coexpression:709 textmining:500 |
Rv2208 cobS |
adenosylcobinamide-GDP ribazoletransferase | 776 | 747 | coexpression:746 |
Rv1567c |
membrane protein | 741 | 741 ctx | neighborhood:741 |
Rv3329 |
aminotransferase | 743 | 710 | coexpression:693 |
Rv1563c treY |
maltooligosyl trehalose synthase | 626 | 626 ctx | neighborhood:623 |
Rv2524c fas |
fatty acid synthase | 678 | 546 ctx | neighborhood:544 |
Rv1590 hyp |
hypothetical protein | 521 | 500 | |
Rv1286 cysC |
adenylyl-sulfate kinase | 447 | 448 | coexpression:441 |
Rv1596 nadC |
nicotinate-nucleotide pyrophosphatase | 547 | 426 | |
Rv2392 cysH |
phosphoadenosine phosphosulfate reductase | 401 | 402 | coexpression:402 |
Rv1505c hyp |
hypothetical protein | 430 | 401 | coexpression:401 |
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: ATP-dependent dethiobiotin synthetase BioD
- MTBC0 PGAP product: dethiobiotin synthase
- Pfam (hmmscan --cut_ga): AAA_26 PF13500.13 (E=4e-27), CbiA PF01656.30 (E=4e-07)
- (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_216086.1)
- Domains: Pfam-A via hmmscan --cut_ga — AAA_26 (PF13500.13), CbiA (PF01656.30)
- 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
COG0132 - Curated reference: UniProt P9WPQ5 (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 —
30 functional partner(s); context anchor
bioA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001678|Rv1570|bioD MTILVVTGTGTGVGKTVVCAALASAARQAGIDVAVCKPVQTGTARGDDDLAEVGRLAGVTQLAGLARYPQPMAPAAAAEHAGMALPARDQIVRLIADLDRPGRLTLVEGAGGLLVELAEPGVTLRDVAVDVAAAALVVVTADLGTLNHTKLTLEALAAQQVSCAGLVIGSWPDPPGLVAASNRSALARIATVRAALPAGAASLDAGDFAAMSAAAFDRNWVAGLVG