mhuD Resolved · high auto-curated
H37Rv Rv3592 · MTBC0 mtbc0_003811 ·
105 aa · 4057734–4058051 (+) ·
RefSeq NP_218109.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | heme-degrading monooxygenase |
|---|---|
| MTBC0 PGAP re-annotation | mycobilin-forming heme oxygenase MhuD |
| Revised (this work) | Mycobilin-forming heme oxygenase MhuD. Pfam: ABM (PF03992.23). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKH3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Heme oxygenase |
| EC (curated) |
EC 1.14.99.57
|
| Curated function | Catalyzes the oxidative degradation of the heme macrocyclic porphyrin ring in the presence of a suitable electron donor such as ascorbate or NADPH--cytochrome P450 reductase, with subsequent release of free iron. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | mhuD |
| eggNOG description | Antibiotic biosynthesis monooxygenase |
| Orthologous group | COG2329 |
| EC number |
EC 1.14.99.57
|
| KEGG orthology |
K21481
|
| Gene Ontology (49) |
GO:0003674, GO:0003824, GO:0004392, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006725, GO:0006778, GO:0006787, GO:0006807 +37 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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 1 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 |
|---|---|---|---|---|
ABM | PF03992.23 | 4.8e-20 | 2–75 | Antibiotic biosynthesis monooxygenase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lpqF (lipoprotein LpqF), high confidence from genomic context alone (score 884 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3593 lpqF |
lipoprotein LpqF | 984 | 884 ctx | neighborhood:881 textmining:870 |
Rv3591c |
hydrolase | 791 | 791 ctx | neighborhood:791 |
Rv0087 hycE |
formate hydrogenase HycE | 530 | 530 ctx | neighborhood:530 |
Rv3594 hyp |
hypothetical protein | 493 | 493 ctx | neighborhood:493 |
Rv0959 hyp |
hypothetical protein | 415 | 416 ctx | cooccurence:414 |
Rv3590c PE_PGRS58 |
PE-PGRS family protein PE_PGRS58 | 413 | 413 ctx | neighborhood:413 |
Rv0206c mmpL3 |
transmembrane transport protein MmpL3 | 626 | 200 | textmining:552 |
Rv0265c |
iron ABC transporter substrate-binding lipoprotein | 708 | 190 | textmining:655 |
Rv2388c hemN |
oxygen-independent coproporphyrinogen III oxidase | 663 | 112 | textmining:637 |
Rv0202c mmpL11 |
transmembrane transport protein MmpL11 | 683 | 78 | textmining:670 |
Rv2711 ideR |
iron-dependent repressor and activator IdeR | 479 | 73 | textmining:461 |
Rv1348 irtA |
iron ABC transporter ATP-binding protein/permease IrtA | 462 | 73 | textmining:444 |
Rv0451c mmpS4 |
membrane protein MmpS4 | 516 | 51 | textmining:511 |
Rv3533c PPE62 |
PPE family protein PPE62 | 543 | 47 | textmining:541 |
Rv0203 hyp |
hypothetical protein | 870 | 45 | textmining:870 |
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: heme-degrading monooxygenase
- MTBC0 PGAP product: mycobilin-forming heme oxygenase MhuD
- Pfam (hmmscan --cut_ga): ABM PF03992.23 (E=5e-20)
- (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_218109.1)
- Domains: Pfam-A via hmmscan --cut_ga — ABM (PF03992.23)
- 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
COG2329 - Curated reference: UniProt P9WKH3 (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 —
18 functional partner(s); context anchor
lpqF - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003811|Rv3592|mhuD MPVVKINAIEVPAGAGPELEKRFAHRAHAVENSPGFLGFQLLRPVKGEERYFVVTHWESDEAFQAWANGPAIAAHAGHRANPVATGASLLEFEVVLDVGGTGKTA