hemY Resolved · high auto-curated
H37Rv Rv2677c · MTBC0 - ·
452 aa · 2992634–2993992 (-) ·
RefSeq YP_177675.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | protoporphyrinogen oxidase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Protoporphyrinogen oxidase. Pfam: NAD_binding_8 (PF13450.13), Amino_oxidase (PF01593.31). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WMP1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Coproporphyrinogen III oxidase |
| EC (curated) |
EC 1.3.3.15
|
| Curated function | Involved in coproporphyrin-dependent heme b biosynthesis. Catalyzes the oxidation of coproporphyrinogen III to coproporphyrin III. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | hemG |
| eggNOG description | Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX |
| Orthologous group | COG1232 |
| EC number |
EC 1.3.3.15, EC 1.3.3.4
|
| KEGG orthology |
K00231
|
| KEGG pathways |
map00860, map01100, map01110
|
| KEGG modules |
M00121
|
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 | 0.577 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 3 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 |
|---|---|---|---|---|
NAD_binding_8 | PF13450.13 | 5.4e-13 | 8–76 | NAD(P)-binding Rossmann-like domain |
Amino_oxidase | PF01593.31 | 1.6e-31 | 13–443 | Flavin containing amine oxidoreductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hemE (uroporphyrinogen decarboxylase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2678c hemE |
uroporphyrinogen decarboxylase | 999 | 1000 ctx | neighborhood:881 cooccurence:756 coexpression:916 database:900 textmining:535 |
Rv1485 hemZ |
ferrochelatase | 997 | 993 ctx | cooccurence:749 coexpression:712 database:900 textmining:582 |
Rv2850c |
magnesium chelatase | 992 | 943 | coexpression:436 database:900 textmining:875 |
Rv2676c hemQ hyp |
hypothetical protein | 931 | 921 ctx | neighborhood:881 |
Rv0958 |
magnesium chelatase | 909 | 907 | database:900 |
Rv2679 echA15 |
enoyl-CoA hydratase EchA15 | 790 | 791 ctx | neighborhood:788 |
Rv3242c hyp |
hypothetical protein | 787 | 788 | coexpression:776 |
Rv2675c hyp |
hypothetical protein | 786 | 786 ctx | neighborhood:776 |
Rv2680 hyp |
hypothetical protein | 703 | 703 ctx | neighborhood:694 |
Rv2681 hyp |
hypothetical protein | 698 | 698 ctx | neighborhood:694 |
Rv0509 hemA |
glutamyl-tRNA reductase | 737 | 576 ctx | cooccurence:449 textmining:405 |
Rv0510 hemC |
porphobilinogen deaminase | 735 | 534 | textmining:457 |
Rv2393 che1 |
ferrochelatase | 559 | 509 | database:500 |
Rv0512 hemB |
delta-aminolevulinic acid dehydratase | 690 | 496 | textmining:411 |
Rv0526 |
thioredoxin | 662 | 471 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): protoporphyrinogen oxidase
- Pfam (hmmscan --cut_ga): NAD_binding_8 PF13450.13 (E=5e-13), Amino_oxidase PF01593.31 (E=2e-31)
- (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 YP_177675.1)
- Domains: Pfam-A via hmmscan --cut_ga — NAD_binding_8 (PF13450.13), Amino_oxidase (PF01593.31)
- 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
COG1232 - Curated reference: UniProt P9WMP1 (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 —
40 functional partner(s); context anchor
hemE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2677c|hemY MTPRSYCVVGGGISGLTSAYRLRQAVGDDATITLFEPADRLGGVLRTEHIGGQPMDLGAEAFVLRRPEMPALLAELGLSDRQLASTGARPLIYSQQRLHPLPPQTVVGIPSSAGSMAGLVDDATLARIDAEAARPFTWQVGSDPAVADLVADRFGDQVVARSVDPLLSGVYAGSAATIGLRAAAPSVAAALDRGATSVTDAVRQALPPGSGGPVFGALDGGYQVLLDGLVRRSRVHWVRARVVQLERGWVLRDETGGRWQADAVILAVPAPRLARLVDGIAPRTHAAARQIVSASSAVVALAVPGGTAFPHCSGVLVAGDESPHAKAITLSSRKWGQRGDVALLRLSFGRFGDEPALTASDDQLLAWAADDLVTVFGVAVDPVDVRVRRWIEAMPQYGPGHADVVAELRAGLPPTLAVAGSYLDGIGVPACVGAAGRAVTSVIEALDAQVAR