cobC Resolved · high auto-curated
H37Rv Rv2231c · MTBC0 - ·
364 aa · 2504605–2505699 (-) ·
RefSeq NP_216747.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | aminotransferase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Aminotransferase. Pfam: Aminotran_1_2 (PF00155.28). |
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 |
P9WQ89
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Histidinol-phosphate aminotransferase Rv2231c |
| EC (curated) |
EC 2.6.1.9
|
| Curated function | Aminotransferase that catalyzes the conversion of histidinol phosphate and 2-oxoglutarate into L-glutamate and imidazole acetol phosphate. Might play a significant role in mediating histidine biosynthesis during infection. Facilitates mycobacterial survival and virulence in macrophages. Rv2231c is recognized by host TLR4 receptor at the macrophage cell surface to regulate downstream signaling cascades. Inhibits macrophage activation and production of pro-inflammatory cytokines to dampen innate defense. Can inhibit macrophage apoptosis. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | cobC |
| eggNOG description | Aminotransferase |
| Orthologous group | COG0079 |
| EC number |
EC 2.6.1.9, EC 4.1.1.81
|
| KEGG orthology |
K00817, K04720
|
| KEGG pathways |
map00340, map00350, map00360, map00400, map00401, map00860, map00960, map01100, map01110, map01130, map01230
|
| KEGG modules |
M00026
|
| Gene Ontology (2) |
GO:0008150, GO:0040007
|
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 | 0.755 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 4 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.11% of strains (162) · 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 |
|---|---|---|---|---|
Aminotran_1_2 | PF00155.28 | 2.6e-26 | 41–332 | Aminotransferase class I and II |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2230c (GTP cyclohydrolase), high confidence from genomic context alone (score 976 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1601 hisB |
imidazole glycerol-phosphate dehydratase | 979 | 977 | coexpression:693 database:900 |
Rv2230c |
GTP cyclohydrolase | 996 | 976 ctx | neighborhood:882 coexpression:805 textmining:870 |
Rv3754 tyrA |
prephenate dehydrogenase TyrA | 968 | 965 | coexpression:649 database:900 |
Rv2848c cobB |
cobyrinic acid A,C-diamide synthase | 963 | 960 ctx | fusion:900 cooccurence:427 |
Rv0255c cobQ1 |
cobyric acid synthase | 952 | 944 ctx | fusion:899 |
Rv1600 hisC1 |
histidinol-phosphate aminotransferase | 916 | 916 | database:900 |
Rv3772 hisC2 |
histidinol-phosphate aminotransferase | 910 | 910 | database:900 |
Rv3838c pheA |
prephenate dehydratase | 916 | 908 | database:900 |
Rv3137 hisN |
histidinol-phosphatase | 908 | 903 | database:900 |
Rv1908c katG |
catalase-peroxidase | 905 | 900 | database:900 |
Rv2228c |
multifunctional RNASE H/alpha-ribazole phosphatase/acid phosphatase | 959 | 890 ctx | neighborhood:882 textmining:646 |
Rv2229c hyp |
hypothetical protein | 984 | 888 ctx | neighborhood:882 textmining:870 |
Rv3215 entC |
isochorismate synthase | 810 | 804 | database:800 |
Rv2949c |
chorismate pyruvate-lyase | 800 | 800 | database:800 |
Rv1602 hisH |
imidazole glycerol phosphate synthase subunit HisH | 813 | 793 | coexpression:694 |
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): aminotransferase
- Pfam (hmmscan --cut_ga): Aminotran_1_2 PF00155.28 (E=3e-26)
- (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_216747.1)
- Domains: Pfam-A via hmmscan --cut_ga — Aminotran_1_2 (PF00155.28)
- 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
COG0079 - Curated reference: UniProt P9WQ89 (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 —
60 functional partner(s); context anchor
Rv2230c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2231c|cobC MLWILGPHTGPLLFDAVASLDTSPLAAARYHGDQDVAPGVLDFAVNVRHDRPPEWLVRQLAALLPELARYPSTDDVHRAQDAVAERHGRTRDEVLPLVGAAEGFALLHNLSPVRAAIVVPAFTEPAIALSAAGITAHHVVLKPPFVLDTAHVPDDADLVVVGNPTNPTSVLHLREQLLELRRPGRILVVDEAFADWVPGEPQSLADDSLPDVLVLRSLTKTWSLAGLRVGYALGSPDVLARLTVQRAHWPLGTLQLTAIAACCAPRAVAAAAADAVRLTALRAEMVAGLRSVGAEVVDGAAPFVLFNIADADGLRNYLQSKGIAVRRGDTFVGLDARYLRAAVRPEWPVLVAAIAEWAKRGGRR