hemE Resolved · high auto-curated
H37Rv Rv2678c · MTBC0 mtbc0_002852 ·
357 aa · 3016302–3017375 (-) ·
RefSeq NP_217194.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | uroporphyrinogen decarboxylase |
|---|---|
| MTBC0 PGAP re-annotation | uroporphyrinogen decarboxylase |
| Revised (this work) | Uroporphyrinogen decarboxylase. Pfam: URO-D (PF01208.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WFE1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uroporphyrinogen decarboxylase |
| EC (curated) |
EC 4.1.1.37
|
| Curated function | Catalyzes the decarboxylation of four acetate groups of uroporphyrinogen-III to yield coproporphyrinogen-III. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | hemE |
| eggNOG description | Catalyzes the decarboxylation of four acetate groups of uroporphyrinogen-III to yield coproporphyrinogen-III |
| Orthologous group | COG0407 |
| EC number |
EC 4.1.1.37
|
| KEGG orthology |
K01599
|
| KEGG pathways |
map00860, map01100, map01110
|
| KEGG modules |
M00121
|
| Gene Ontology (43) |
GO:0003674, GO:0003824, GO:0004853, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006725, GO:0006778, GO:0006779, GO:0006783 +31 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 | 0.242 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 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 |
|---|---|---|---|---|
URO-D | PF01208.24 | 9.7e-121 | 8–356 | Uroporphyrinogen decarboxylase (URO-D) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hemY (protoporphyrinogen oxidase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2677c hemY |
protoporphyrinogen oxidase | 999 | 1000 ctx | neighborhood:881 cooccurence:756 coexpression:916 database:900 textmining:535 |
Rv0510 hemC |
porphobilinogen deaminase | 981 | 974 ctx | fusion:776 cooccurence:553 coexpression:668 |
Rv1485 hemZ |
ferrochelatase | 989 | 952 ctx | cooccurence:764 coexpression:773 textmining:788 |
Rv0511 hemD |
uroporphyrin-III C-methyltransferase | 956 | 928 | database:900 textmining:418 |
Rv2676c hemQ hyp |
hypothetical protein | 927 | 924 ctx | neighborhood:881 |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 957 | 920 | database:900 textmining:487 |
Rv0260c |
transcriptional regulator | 945 | 912 | database:900 textmining:412 |
Rv2675c hyp |
hypothetical protein | 828 | 820 ctx | neighborhood:773 |
Rv2679 echA15 |
enoyl-CoA hydratase EchA15 | 792 | 793 ctx | neighborhood:788 |
Rv0512 hemB |
delta-aminolevulinic acid dehydratase | 860 | 772 ctx | cooccurence:535 textmining:416 |
Rv2680 hyp |
hypothetical protein | 698 | 698 ctx | neighborhood:694 |
Rv2681 hyp |
hypothetical protein | 697 | 697 ctx | neighborhood:694 |
Rv0524 hemL |
glutamate-1-semialdehyde 2,1-aminomutase | 886 | 624 ctx | cooccurence:421 textmining:709 |
Rv0509 hemA |
glutamyl-tRNA reductase | 853 | 617 ctx | cooccurence:446 textmining:633 |
Rv2388c hemN |
oxygen-independent coproporphyrinogen III oxidase | 661 | 558 | database:500 |
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: uroporphyrinogen decarboxylase
- MTBC0 PGAP product: uroporphyrinogen decarboxylase
- Pfam (hmmscan --cut_ga): URO-D PF01208.24 (E=1e-120)
- (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_217194.1)
- Domains: Pfam-A via hmmscan --cut_ga — URO-D (PF01208.24)
- 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
COG0407 - Curated reference: UniProt P9WFE1 (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 —
47 functional partner(s); context anchor
hemY - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002852|Rv2678c|hemE MSTRRDLPQSPYLAAVTGRKPSRVPVWFMRQAGRSLPEYRALRERYSMLAACFEPDVACEITLQPIRRYDVDAAILFSDIVVPLRAAGVDLDIVADVGPVIADPVRTAADVAAMKPLDPQAIQPVLVAASLLVAELGDVPLIGFAGAPFTLASYLVEGGPSRHHAHVKAMMLAEPASWHALMAKLTDLTIAFLVGQIDAGVDAIQVFDSWAGALSPIDYRQYVLPHSARVFAALGEHGVPMTHFGVGTAELLGAMSEAVTAGERPGRGAVVGVDWRTPLTDAAARVVPGTALQGNLDPAVVLAGWPAVERAARAVVDDGRRAVDAGAAGHIFNLGHGVLPESDPAVLADLVSLVHSL