hemB Resolved · high auto-curated
H37Rv Rv0512 · MTBC0 mtbc0_000540 ·
329 aa · 608059–609048 (+) ·
RefSeq NP_215026.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | delta-aminolevulinic acid dehydratase |
|---|---|
| MTBC0 PGAP re-annotation | porphobilinogen synthase |
| Revised (this work) | Porphobilinogen synthase. Pfam: ALAD (PF00490.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMP5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Delta-aminolevulinic acid dehydratase |
| EC (curated) |
EC 4.2.1.24
|
| Curated function | Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | hemB |
| eggNOG description | Belongs to the ALAD family |
| Orthologous group | COG0113 |
| EC number |
EC 4.2.1.24
|
| KEGG orthology |
K01698
|
| KEGG pathways |
map00860, map01100, map01110, map01120
|
| KEGG modules |
M00121
|
| Gene Ontology (52) |
GO:0003674, GO:0003824, GO:0004655, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006725, GO:0006778 +40 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 | 0.415 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 6 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 |
|---|---|---|---|---|
ALAD | PF00490.28 | 2.1e-131 | 9–327 | Delta-aminolevulinic acid dehydratase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hemC (porphobilinogen deaminase), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0510 hemC |
porphobilinogen deaminase | 999 | 999 ctx | neighborhood:750 cooccurence:774 coexpression:764 database:900 textmining:644 |
Rv0524 hemL |
glutamate-1-semialdehyde 2,1-aminomutase | 997 | 992 ctx | cooccurence:772 coexpression:622 database:900 textmining:689 |
Rv0511 hemD |
uroporphyrin-III C-methyltransferase | 997 | 991 ctx | neighborhood:781 cooccurence:680 coexpression:868 textmining:765 |
Rv0514 |
transmembrane protein | 977 | 977 ctx | neighborhood:869 coexpression:833 |
Rv0509 hemA |
glutamyl-tRNA reductase | 984 | 953 ctx | neighborhood:748 cooccurence:763 textmining:693 |
Rv0513 |
transmembrane protein | 903 | 903 ctx | neighborhood:869 |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 873 | 792 ctx | cooccurence:724 textmining:416 |
Rv2678c hemE |
uroporphyrinogen decarboxylase | 860 | 772 ctx | cooccurence:535 textmining:416 |
Rv0508 hyp |
hypothetical protein | 712 | 712 ctx | neighborhood:708 |
Rv0260c |
transcriptional regulator | 737 | 603 | coexpression:526 |
Rv2071c cobM |
precorrin-4 C(11)-methyltransferase | 622 | 569 ctx | cooccurence:532 |
Rv0526 |
thioredoxin | 561 | 546 | coexpression:435 |
Rv0515 hyp |
hypothetical protein | 525 | 525 ctx | neighborhood:518 |
Rv2677c hemY |
protoporphyrinogen oxidase | 690 | 496 | textmining:411 |
Rv3307 deoD |
purine nucleoside phosphorylase | 454 | 455 |
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: delta-aminolevulinic acid dehydratase
- MTBC0 PGAP product: porphobilinogen synthase
- Pfam (hmmscan --cut_ga): ALAD PF00490.28 (E=2e-131)
- (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_215026.1)
- Domains: Pfam-A via hmmscan --cut_ga — ALAD (PF00490.28)
- 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
COG0113 - Curated reference: UniProt P9WMP5 (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 —
44 functional partner(s); context anchor
hemC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000540|Rv0512|hemB MSMSSYPRQRPRRLRSTVAMRRLVAQTSLEPRHLVLPMFVADGIDEPRPITSMPGVVQHTRDSLRRAAAAAVAAGVGGLMLFGVPRDQDKDGVGSAGIDPDGILNVALRDLAKDLGEATVLMADTCLDEFTDHGHCGVLDDRGRVDNDATVARYVELAVAQAESGAHVVGPSGMMDGQVAAIRDGLDAAGYIDVVILAYAAKFASAFYGPFREAVSSSLSGDRRTYQQEPGNAAEALREIELDLDEGADIVMVKPAMGYLDVVAAAADVSPVPVAAYQVSGEYAMIRAAAANNWIDERAAVLESLTGIRRAGADIVLTYWAVDAAGWLT