Rv0939 Family assigned · medium auto-curated
H37Rv Rv0939 · MTBC0 mtbc0_000997 ·
644 aa · 1051629–1053563 (+) ·
RefSeq NP_215454.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | bifunctional 2-hydroxyhepta-2,4-diene-1,7-dioate isomerase/cyclase/dehydrase |
|---|---|
| MTBC0 PGAP re-annotation | fumarylacetoacetate hydrolase family protein |
| Revised (this work) | Fumarylacetoacetate hydrolase family protein. Pfam: FAA_hydrolase (PF01557.24), Lactamase_B (PF00753.34). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O86346
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible bifunctional enzyme: 2-hydroxyhepta-2,4-diene-1,7-dioate isomerase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| eggNOG description | Metallo-beta-lactamase superfamily |
| Orthologous group | COG0179 |
| KEGG orthology |
K05555
|
| KEGG pathways |
map01057, map01130
|
| KEGG modules |
M00778
|
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 | 0.469 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 7 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.10% of strains (148) · clonal |
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 |
|---|---|---|---|---|
FAA_hydrolase | PF01557.24 | 1.9e-45 | 75–300 | Fumarylacetoacetate (FAA) hydrolase C-terminal |
Lactamase_B | PF00753.34 | 1.9e-24 | 352–554 | Metallo-beta-lactamase superfamily |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ligD (multifunctional non-homologous end joining DNA repair protein/ATP dependent DNA ligase LigD), high confidence from genomic context alone (score 972 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0938 ligD |
multifunctional non-homologous end joining DNA repair protein/ATP dependent DNA ligase LigD | 973 | 972 ctx | neighborhood:882 coexpression:775 |
Rv0331 |
dehydrogenase/reductase | 702 | 668 | database:583 |
Rv0937c mku |
non-homologous end joining protein Ku | 597 | 597 ctx | neighborhood:591 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 702 | 515 | textmining:412 |
Rv2048c pks12 |
polyketide synthase | 700 | 512 | textmining:412 |
Rv1527c pks5 |
polyketide synthase | 700 | 511 | textmining:412 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 700 | 511 | textmining:412 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 700 | 511 | textmining:412 |
Rv2367c ybeY |
endoribonuclease | 519 | 496 | |
Rv3293 pcd |
piperideine-6-carboxylic acid dehydrogenase | 537 | 492 | coexpression:401 |
Rv0147 |
aldehyde dehydrogenase | 532 | 487 | |
Rv0458 |
aldehyde dehydrogenase | 532 | 487 | |
Rv0234c gabD1 |
succinate-semialdehyde dehydrogenase | 532 | 487 | |
Rv1731 gabD2 |
succinate-semialdehyde dehydrogenase | 530 | 485 | |
Rv0753c mmsA |
methylmalonate-semialdehyde dehydrogenase | 528 | 482 |
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 2-hydroxyhepta-2,4-diene-1,7-dioate isomerase/cyclase/dehydrase
- MTBC0 PGAP product: fumarylacetoacetate hydrolase family protein
- Pfam (hmmscan --cut_ga): FAA_hydrolase PF01557.24 (E=2e-45), Lactamase_B PF00753.34 (E=2e-24)
- (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_215454.1)
- Domains: Pfam-A via hmmscan --cut_ga — FAA_hydrolase (PF01557.24), Lactamase_B (PF00753.34)
- 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
COG0179 - Curated reference: UniProt O86346 (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 —
52 functional partner(s); context anchor
ligD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000997|Rv0939| MKWVTYRSDHGERTGVLSGDAIYAMPPDVSLLDLVGRGADGLRTAGERAVRSPAAVVALDEVTLAAPIPRPPSIRDSLCFLDHMRNCQEAMGGGRVLMDTWYRIPAFYFACPSTVLGPYDDAPTAPGSAWQDFELEIAAVIGTSGKDLTVEQAERSIIGYTIFNDWSARDLQMLEGQLRIGQAKGKDSGITLGPYLVTPDELEPYCRGGKLSLRVIALVNGTVIGSGSTAQMDWSFGEVIAYASRGVTLTPGDVFGSGTVPTCTLVEHLRPPESFPGWLHDGDVVTLQVEGLGETRQTVRTSGTPFPLALRPNPDAEPDRRGVNPAPTRVPFTRGLHEVADRVWAWTLPDGGYGFSNAGLVAGDGASLLVDTLFDLALTREMLAAMKPVTERAPITDALITHSNGDHTHGTQLLDRSVRIIAAKGTSEEIEHGPAPEMLARIQTADLGPVATRYLRDRFGHFDFSGIKLRNADLTFDRDLAIELGGRRVDLLNLGPAHTTADSVVHVADAGVLFAGDLLFIGCTPIVWAGPIANWVAACDAMIALDAPTVVPGHGPVTGPDGIRAVRGYLAHIAEQAEAAYRKGLSLPEAVETIDLGEYASWLDSERVVVNVYQRYRELDPDTPRQDLLALLVMQAEWAARHCT