Rv0260c Resolved · high auto-curated
H37Rv Rv0260c · MTBC0 mtbc0_000276 ·
381 aa · 311896–313041 (-) ·
RefSeq NP_214774.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transcriptional regulator |
|---|---|
| MTBC0 PGAP re-annotation | uroporphyrinogen-III synthase |
| Revised (this work) | Uroporphyrinogen-III synthase. Pfam: HEM4 (PF02602.21), Trans_reg_C (PF00486.35). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P95217
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible transcriptional regulatory protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolismK Transcription
|
|---|---|
| Preferred name | hemD |
| eggNOG description | Uroporphyrinogen-III synthase |
| Orthologous group | COG1587 |
| EC number |
EC 4.2.1.75
|
| KEGG orthology |
K01719
|
| 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 | 0.432 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 7 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.25% of strains (368) · clonal |
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 |
|---|---|---|---|---|
HEM4 | PF02602.21 | 2.8e-28 | 24–268 | Uroporphyrinogen-III synthase HemD |
Trans_reg_C | PF00486.35 | 7.4e-12 | 306–372 | Transcriptional regulatory protein, C terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cysG (multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase), high confidence from genomic context alone (score 970 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0510 hemC |
porphobilinogen deaminase | 981 | 972 | coexpression:684 database:900 |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 985 | 970 ctx | neighborhood:544 database:900 textmining:535 |
Rv0259c hyp |
hypothetical protein | 969 | 966 ctx | neighborhood:882 cooccurence:630 |
Rv0511 hemD |
uroporphyrin-III C-methyltransferase | 952 | 933 | database:900 |
Rv2678c hemE |
uroporphyrinogen decarboxylase | 945 | 912 | database:900 textmining:412 |
Rv0261c narK3 |
nitrate/nitrite transporter | 913 | 894 ctx | neighborhood:585 cooccurence:631 |
Rv0267 narU |
nitrite extrusion protein NarU | 795 | 764 ctx | cooccurence:574 |
Rv0258c hyp |
hypothetical protein | 771 | 761 ctx | neighborhood:760 |
Rv1371 |
membrane protein | 769 | 761 | coexpression:734 |
Rv0253 nirD |
nitrite reductase small subunit NirD | 765 | 755 ctx | cooccurence:629 |
Rv0252 nirB |
nitrite reductase large subunit NirB | 802 | 731 ctx | cooccurence:636 |
Rv2329c narK1 |
nitrate/nitrite transporter | 726 | 656 ctx | cooccurence:608 |
Rv0512 hemB |
delta-aminolevulinic acid dehydratase | 737 | 603 | coexpression:526 |
Rv2692 ceoC |
TRK system potassium uptake protein CeoC | 592 | 583 | coexpression:452 |
Rv2691 ceoB |
TRK system potassium uptake protein CeoB | 570 | 570 | coexpression:452 |
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: transcriptional regulator
- MTBC0 PGAP product: uroporphyrinogen-III synthase
- Pfam (hmmscan --cut_ga): HEM4 PF02602.21 (E=3e-28), Trans_reg_C PF00486.35 (E=7e-12)
- (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_214774.1)
- Domains: Pfam-A via hmmscan --cut_ga — HEM4 (PF02602.21), Trans_reg_C (PF00486.35)
- 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
COG1587 - Curated reference: UniProt P95217 (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 —
43 functional partner(s); context anchor
cysG - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000276|Rv0260c| MAQAHSAPLTGYRIAVTSARRAEELCALLRRQGAEVCSAPAIKMIALPDDDELQNNTEALIADPPDILVAHTGIGFRGWLAAAEGWGLANELLESLSSARIISRGPKATGALRAAGLREEWSPDSESSHEVLEYLLESGVSRTRIAVQLHGAADSWDPFPEFLGGLRFAGAQVVPIRVYRWKPAPLGGVFDHLVTGIARRQFDAVTFTSAPAAAAVLERSRELDIEDQLLAALRTDVHAMCVGPVTSRPLIRKGVPTSAPERMRLGALARHIAEELPLLGSCTFKAAGHVIEIRGTSVLVDDSVKPLSPSGMAILRALVHRPGGVVSRGDLLRVLPGDGSDTHAVDTAVLRLRTALGDKNIVATVVKRGYRLAVDSRHDDV