cysG Resolved · high auto-curated
H37Rv Rv2847c · MTBC0 mtbc0_003026 ·
405 aa · 3175320–3176537 (-) ·
RefSeq NP_215025.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase |
|---|---|
| MTBC0 PGAP re-annotation | uroporphyrinogen-III C-methyltransferase |
| Revised (this work) | Uroporphyrinogen-III C-methyltransferase. Pfam: NAD_binding_7 (PF13241.13), TP_methylase (PF00590.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6X5I7
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | uroporphyrinogen-III C-methyltransferase |
| EC (curated) |
EC 2.1.1.107
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | cysG |
| eggNOG description | uroporphyrin-III c-methyltransferase |
| Orthologous group | COG0007 |
| EC number |
EC 1.3.1.76, EC 2.1.1.107, EC 4.99.1.4
|
| KEGG orthology |
K02302, K02303
|
| 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 | 0.085 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 2 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_7 | PF13241.13 | 1.7e-24 | 10–114 | Putative NAD(P)-binding |
TP_methylase | PF00590.26 | 1.4e-48 | 162–372 | Tetrapyrrole (Corrin/Porphyrin) Methylases |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hemD (uroporphyrin-III C-methyltransferase), high confidence from genomic context alone (score 989 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0511 hemD |
uroporphyrin-III C-methyltransferase | 995 | 989 ctx | neighborhood:544 coexpression:690 database:900 textmining:625 |
Rv0510 hemC |
porphobilinogen deaminase | 994 | 980 ctx | fusion:899 cooccurence:733 textmining:761 |
Rv0260c |
transcriptional regulator | 985 | 970 ctx | neighborhood:544 database:900 textmining:535 |
Rv2066 cobIJ |
bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase | 991 | 969 ctx | neighborhood:544 database:900 textmining:745 |
Rv0259c hyp |
hypothetical protein | 976 | 965 ctx | fusion:466 coexpression:908 |
Rv1286 cysC |
adenylyl-sulfate kinase | 990 | 963 ctx | neighborhood:544 coexpression:908 textmining:745 |
Rv2393 che1 |
ferrochelatase | 955 | 935 | coexpression:909 |
Rv2678c hemE |
uroporphyrinogen decarboxylase | 957 | 920 | database:900 textmining:487 |
Rv2391 sirA |
sulfite reductase | 967 | 919 ctx | cooccurence:549 coexpression:799 textmining:618 |
Rv2392 cysH |
phosphoadenosine phosphosulfate reductase | 932 | 899 ctx | cooccurence:408 coexpression:808 |
Rv1285 cysD |
sulfate adenylyltransferase subunit 2 | 906 | 861 | coexpression:808 |
Rv2846c efpA |
MFS-type transporter EfpA | 854 | 854 ctx | neighborhood:853 |
Rv2848c cobB |
cobyrinic acid A,C-diamide synthase | 921 | 850 ctx | neighborhood:721 cooccurence:477 textmining:499 |
Rv2064 cobG |
precorrin-3B synthase | 882 | 825 | coexpression:799 |
Rv2849c cobO |
cob(I)alamin adenosyltransferase | 886 | 795 ctx | neighborhood:721 textmining: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
- Legacy H37Rv annotation: multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase
- MTBC0 PGAP product: uroporphyrinogen-III C-methyltransferase
- Pfam (hmmscan --cut_ga): NAD_binding_7 PF13241.13 (E=2e-24), TP_methylase PF00590.26 (E=1e-48)
- (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_215025.2)
- Domains: Pfam-A via hmmscan --cut_ga — NAD_binding_7 (PF13241.13), TP_methylase (PF00590.26)
- 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 I6X5I7 (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 —
105 functional partner(s); context anchor
hemD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003026|Rv2847c|cysG MTENPYLVGLRLAGKKVVVVGGGTVAQRRLPLLIASGADVHVIAPSVTPAVEAMDQITLSVRDYRDGDLDGAWYAIAATDDARVNVAVVAEAERRRIFCVRADIAVEGTAVTPASFSYAGLSVGVLAGGEHRRSAAIRSAIREALQQGVITAQSSDVLSGGVALVGGGPGDPELITVRGRRLLAQADVVVADRLAPPELLAELPPHVEVIDAAKIPYGRAMAQDAINAVLIERARSGNFVVRLKGGDPFVFARGYEEVLACAHAGIPVTVVPGVTSAIAVPAMAGVPVTHRAMTHEFVVVSGHLAPGHPESLVNWDALAALTGTIVLLMAVERIELFVDVLLKGGRTADTPVLVVQHGTTAAQQTLRATLADTPEKVRAAGIRPPAIIVIGAVVGLSGVRGLNNS