dfp Resolved · high auto-curated
H37Rv Rv1391 · MTBC0 mtbc0_001492 ·
418 aa · 1574785–1576041 (+) ·
RefSeq NP_215907.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | bifunctional phosphopantothenoylcysteine decarboxylase/phosphopantothenate--cysteine ligase |
|---|---|
| MTBC0 PGAP re-annotation | bifunctional phosphopantothenoylcysteine decarboxylase/phosphopantothenate--cysteine ligase CoaBC |
| Revised (this work) | Bifunctional phosphopantothenoylcysteine decarboxylase/phosphopantothenate--cysteine ligase CoaBC. Pfam: Flavoprotein (PF02441.25), DFP (PF04127.23). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNZ1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Coenzyme A biosynthesis bifunctional protein CoaBC |
| EC (curated) |
EC 4.1.1.36, EC 6.3.2.5
|
| Curated function | Catalyzes two sequential steps in the biosynthesis of coenzyme A. In the first step cysteine is conjugated to 4'-phosphopantothenate to form 4-phosphopantothenoylcysteine. In the second step the latter compound is decarboxylated to form 4'-phosphopantotheine (By similarity). Required for growth and persistence in mice. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | coaBC |
| eggNOG description | Catalyzes two steps in the biosynthesis of coenzyme A. In the first step cysteine is conjugated to 4'-phosphopantothenate to form 4-phosphopantothenoylcysteine, in the latter compound is decarboxylated to form 4'-phosphopantotheine |
| Orthologous group | COG0452 |
| EC number |
EC 4.1.1.36, EC 6.3.2.5
|
| KEGG orthology |
K13038
|
| KEGG pathways |
map00770, map01100
|
| KEGG modules |
M00120
|
| Gene Ontology (69) |
GO:0003674, GO:0003824, GO:0004633, GO:0005575, GO:0005623, GO:0005886, GO:0006139, GO:0006163, GO:0006164, GO:0006725, GO:0006732, GO:0006753 +57 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 | 0.301 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 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 |
|---|---|---|---|---|
Flavoprotein | PF02441.25 | 4.5e-28 | 9–173 | Flavoprotein |
DFP | PF04127.23 | 1.6e-69 | 191–411 | DNA/pantothenate metabolism flavoprotein C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rpoZ (DNA-directed RNA polymerase subunit omega), high confidence from genomic context alone (score 894 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2965c kdtB |
phosphopantetheine adenylyltransferase | 994 | 930 | database:900 textmining:930 |
Rv3600c coaX |
type III pantothenate kinase | 935 | 926 | database:900 |
Rv1092c coaA |
pantothenate kinase | 963 | 904 | database:900 textmining:640 |
Rv1390 rpoZ |
DNA-directed RNA polymerase subunit omega | 894 | 894 ctx | neighborhood:863 |
Rv1389 gmk |
guanylate kinase | 940 | 877 ctx | neighborhood:783 textmining:538 |
Rv3602c panC |
pantothenate synthetase | 927 | 866 | database:800 textmining:480 |
Rv2334 cysK1 |
O-acetylserine sulfhydrylase | 817 | 818 | database:800 |
Rv3684 |
lyase | 809 | 809 | database:800 |
Rv0075 |
aminotransferase | 806 | 807 | database:800 |
Rv2294 |
cystathionine beta-lyase | 804 | 805 | database:800 |
Rv1392 metK |
S-adenosylmethionine synthetase | 773 | 751 ctx | neighborhood:593 |
Rv1388 mihF |
integration host factor MihF | 746 | 747 ctx | neighborhood:698 |
Rv1402 priA |
primosomal protein N' | 716 | 717 | coexpression:648 |
Rv2697c dut |
deoxyuridine 5'-triphosphate nucleotidohydrolase | 716 | 699 | coexpression:674 |
Rv3211 rhlE |
ATP-dependent RNA helicase RhlE | 693 | 680 | database:491 |
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 phosphopantothenoylcysteine decarboxylase/phosphopantothenate--cysteine ligase
- MTBC0 PGAP product: bifunctional phosphopantothenoylcysteine decarboxylase/phosphopantothenate--cysteine ligase CoaBC
- Pfam (hmmscan --cut_ga): Flavoprotein PF02441.25 (E=4e-28), DFP PF04127.23 (E=2e-69)
- (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_215907.1)
- Domains: Pfam-A via hmmscan --cut_ga — Flavoprotein (PF02441.25), DFP (PF04127.23)
- 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
COG0452 - Curated reference: UniProt P9WNZ1 (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 —
63 functional partner(s); context anchor
rpoZ - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001492|Rv1391|dfp MVDHKRIPKQVIVGVSGGIAAYKACTVVRQLTEASHRVRVIPTESALRFVGAATFEALSGEPVCTDVFADVPAVPHVHLGQQADLVVVAPATADLLARAAAGRADDLLTATLLTARCPVLFAPAMHTEMWLHPATVDNVATLRRRGAVVLEPATGRLTGADSGAGRLPEAEEITTLAQLLLERHDALPYDLAGRKLLVTAGGTREPIDPVRFIGNRSSGKQGYAVARVAAQRGADVTLIAGHTAGLVDPAGVEVVHVSSAQQLADAVSKHAPTADVLVMAAAVADFRPAQVATAKIKKGVEGPPTIELLRNDDVLAGVVRARAHGQLPNMRAIVGFAAETGDANGDVLFHARAKLRRKGCDLLVVNAVGEGRAFEVDSNDGWLLASDGTESALQHGSKTLMASRIVDAIVTFLAGCSS