hemC Resolved · high auto-curated
H37Rv Rv0510 · MTBC0 mtbc0_000538 ·
309 aa · 605314–606243 (+) ·
RefSeq NP_215024.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | porphobilinogen deaminase |
|---|---|
| MTBC0 PGAP re-annotation | hydroxymethylbilane synthase |
| Revised (this work) | Hydroxymethylbilane synthase. Pfam: Porphobil_deam (PF01379.26), Porphobil_deamC (PF03900.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMP3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Porphobilinogen deaminase |
| EC (curated) |
EC 2.5.1.61
|
| Curated function | Tetrapolymerization of the monopyrrole PBG into the hydroxymethylbilane pre-uroporphyrinogen in several discrete steps. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | hemC |
| eggNOG description | Tetrapolymerization of the monopyrrole PBG into the hydroxymethylbilane pre-uroporphyrinogen in several discrete steps |
| Orthologous group | COG0181 |
| EC number |
EC 2.5.1.61
|
| KEGG orthology |
K01749
|
| KEGG pathways |
map00860, map01100, map01110, map01120
|
| KEGG modules |
M00121
|
| Gene Ontology (44) |
GO:0003674, GO:0003824, GO:0004418, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006725, GO:0006778, GO:0006779, GO:0006783 +32 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 | 0.192 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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 |
|---|---|---|---|---|
Porphobil_deam | PF01379.26 | 2.9e-69 | 2–204 | Porphobilinogen deaminase, dipyromethane cofactor binding domain |
Porphobil_deamC | PF03900.21 | 5.3e-18 | 219–296 | Porphobilinogen deaminase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hemD (uroporphyrin-III C-methyltransferase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0511 hemD |
uroporphyrin-III C-methyltransferase | 999 | 1000 ctx | neighborhood:833 fusion:598 cooccurence:724 coexpression:935 database:900 textmining:771 |
Rv0512 hemB |
delta-aminolevulinic acid dehydratase | 999 | 999 ctx | neighborhood:750 cooccurence:774 coexpression:764 database:900 textmining:644 |
Rv0509 hemA |
glutamyl-tRNA reductase | 999 | 998 ctx | neighborhood:876 fusion:742 cooccurence:768 coexpression:720 textmining:856 |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 994 | 980 ctx | fusion:899 cooccurence:733 textmining:761 |
Rv2678c hemE |
uroporphyrinogen decarboxylase | 981 | 974 ctx | fusion:776 cooccurence:553 coexpression:668 |
Rv0260c |
transcriptional regulator | 981 | 972 | coexpression:684 database:900 |
Rv0513 |
transmembrane protein | 928 | 928 ctx | neighborhood:744 coexpression:732 |
Rv0524 hemL |
glutamate-1-semialdehyde 2,1-aminomutase | 955 | 915 ctx | cooccurence:769 coexpression:564 textmining:502 |
Rv0514 |
transmembrane protein | 811 | 812 ctx | neighborhood:744 |
Rv0508 hyp |
hypothetical protein | 809 | 809 ctx | neighborhood:808 |
Rv2071c cobM |
precorrin-4 C(11)-methyltransferase | 749 | 714 ctx | fusion:414 cooccurence:492 |
Rv1107c xseB |
exodeoxyribonuclease VII small subunit | 678 | 678 | coexpression:678 |
Rv1445c devB |
6-phosphogluconolactonase | 659 | 628 ctx | fusion:620 |
Rv0507 mmpL2 |
transmembrane transport protein MmpL2 | 620 | 620 ctx | neighborhood:618 |
Rv0506 mmpS2 |
membrane protein MmpS2 | 618 | 619 ctx | neighborhood:619 |
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: porphobilinogen deaminase
- MTBC0 PGAP product: hydroxymethylbilane synthase
- Pfam (hmmscan --cut_ga): Porphobil_deam PF01379.26 (E=3e-69), Porphobil_deamC PF03900.21 (E=5e-18)
- (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_215024.1)
- Domains: Pfam-A via hmmscan --cut_ga — Porphobil_deam (PF01379.26), Porphobil_deamC (PF03900.21)
- 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
COG0181 - Curated reference: UniProt P9WMP3 (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 —
50 functional partner(s); context anchor
hemD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000538|Rv0510|hemC MIRIGTRGSLLATTQAATVRDALIAGGHSAELVTISTEGDRSMAPIASLGVGVFTTALREAMEAGLVDAAVHSYKDLPTAADPRFTVAAIPPRNDPRDAVVARDGLTLGELPVGSLVGTSSPRRAAQLRALGLGLEIRPLRGNLDTRLNKVSSGDLDAIVVARAGLARLGRLDDVTETLEPVQMLPAPAQGALAVECRAGDSRLVAVLAELDDADTRAAVTAERALLADLEAGCSAPVGAIAEVVESIDEDGRVFEELSLRGCVAALDGSDVIRASGIGSCGRARELGLSVAAELFELGARELMWGVRH