hemD Resolved · high auto-curated
H37Rv Rv0511 · MTBC0 - ·
565 aa · 602819–604516 (+) ·
RefSeq YP_177733.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | uroporphyrin-III C-methyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Uroporphyrin-III C-methyltransferase. Pfam: TP_methylase (PF00590.26), HEM4 (PF02602.21). |
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 |
Q6MX34
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable uroporphyrin-III C-methyltransferase HemD |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | hemD |
| eggNOG description | Uroporphyrinogen-III synthase |
| Orthologous group | COG0007 |
| EC number |
EC 2.1.1.107, EC 4.2.1.75
|
| KEGG orthology |
K01719, K13542
|
| KEGG pathways |
map00860, map01100, map01110, map01120
|
| 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 | 0.75 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 8 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 |
|---|---|---|---|---|
TP_methylase | PF00590.26 | 2.4e-38 | 11–246 | Tetrapyrrole (Corrin/Porphyrin) Methylases |
HEM4 | PF02602.21 | 7.0e-64 | 309–539 | Uroporphyrinogen-III synthase HemD |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hemC (porphobilinogen deaminase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0510 hemC |
porphobilinogen deaminase | 999 | 1000 ctx | neighborhood:833 fusion:598 cooccurence:724 coexpression:935 database:900 textmining:771 |
Rv0512 hemB |
delta-aminolevulinic acid dehydratase | 997 | 991 ctx | neighborhood:781 cooccurence:680 coexpression:868 textmining:765 |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 995 | 989 ctx | neighborhood:544 coexpression:690 database:900 textmining:625 |
Rv0509 hemA |
glutamyl-tRNA reductase | 992 | 979 ctx | neighborhood:829 cooccurence:736 coexpression:563 textmining:669 |
Rv2066 cobIJ |
bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase | 987 | 964 ctx | neighborhood:544 database:900 textmining:660 |
Rv0514 |
transmembrane protein | 953 | 954 ctx | neighborhood:773 coexpression:805 |
Rv0513 |
transmembrane protein | 952 | 953 ctx | neighborhood:773 coexpression:801 |
Rv0260c |
transcriptional regulator | 952 | 933 | database:900 |
Rv2678c hemE |
uroporphyrinogen decarboxylase | 956 | 928 | database:900 textmining:418 |
Rv0529 ccsA |
cytochrome C-type biogenesis protein CcsA | 876 | 876 | coexpression:822 |
Rv1286 cysC |
adenylyl-sulfate kinase | 946 | 831 ctx | neighborhood:544 coexpression:645 textmining:694 |
Rv0528 |
transmembrane protein | 815 | 816 | coexpression:733 |
Rv0508 hyp |
hypothetical protein | 790 | 777 ctx | neighborhood:773 |
Rv1324 |
thioredoxin | 773 | 773 | coexpression:761 |
Rv2391 sirA |
sulfite reductase | 865 | 762 | coexpression:642 textmining:456 |
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): uroporphyrin-III C-methyltransferase
- Pfam (hmmscan --cut_ga): TP_methylase PF00590.26 (E=2e-38), HEM4 PF02602.21 (E=7e-64)
- (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_177733.1)
- Domains: Pfam-A via hmmscan --cut_ga — TP_methylase (PF00590.26), HEM4 (PF02602.21)
- 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
COG0007 - Curated reference: UniProt Q6MX34 (TrEMBL, unreviewed; 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 —
107 functional partner(s); context anchor
hemC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0511|hemD MTRGRKPRPGRIVFVGSGPGDPGLLTTRAAAVLANAALVFTDPDVPEPVVALIGTDLPPVSGPAPAEPVAGNGDAAGGGSAQEHGRAASAVVSGGPDIRPALGDPADVAKTLTAEARSGVDVVRLVAGDPLTVDAVISEVNAVARTHLHIEIVPGLAASSAVPTYAGLPLGSSHTVADVRIDPENTDWDALAAAPGPLILQATASHLAESARSLIDHQLAESTPCVVTAHGTTCQQRSVETTLQGLTDPAVLGATDPACSANGRDSQAGPLIVTIGKTVTSRAKLNWWESRALYGWTVLVPRTKDQAGEMSERLTSYGALPVEVPTIAVEPPRSPAQMERAVKGLVDGRFQWIVFTSTNAVRAVWEKFGEFGLDARAFSGVKIACVGESTADRVRAFGISPELVPSGEQSSLGLLDDFPPYDSVFDPVNRVLLPRADIATETLAEGLRERGWEIEDVTAYRTVRAAPPPATTREMIKTGGFDAVCFTSSSTVRNLVGIAGKPHARTIIACIGPKTAETAAEFGLRVDVQPDTAAIGPLVDALAEHAARLRAEGALPPPRKKSRRR