manB Resolved · high auto-curated
H37Rv Rv3264c · MTBC0 - ·
359 aa · 3644898–3645977 (-) ·
RefSeq YP_177951.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | D-alpha-D-mannose-1-phosphate guanylyltransferase ManB |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | D-alpha-D-mannose-1-phosphate guanylyltransferase ManB. Pfam: NTP_transferase (PF00483.30), NTP_transf_3 (PF12804.14), GMPPB_C (PF25087.2). |
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 |
L7N6A5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Mannose-1-phosphate guanylyltransferase |
| EC (curated) |
EC 2.7.7.13
|
| Curated function | Catalyzes the formation of GDP-mannose from D-mannose-1-phosphate and GTP. Plays an important role in the synthesis of different glycoconjugates which are responsible for cell wall structure, virulence and immunomodulatory activity of M.tuberculosis. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
J Translation, ribosomal structure and biogenesisM Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | manC |
| eggNOG description | Nucleotidyl transferase |
| Orthologous group | COG1208 |
| EC number |
EC 2.7.7.13
|
| KEGG orthology |
K00966
|
| KEGG pathways |
map00051, map00520, map01100, map01110
|
| KEGG modules |
M00114, M00361, M00362
|
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 | 0.072 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 1 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 |
|---|---|---|---|---|
NTP_transferase | PF00483.30 | 1.5e-47 | 8–236 | Nucleotidyl transferase |
NTP_transf_3 | PF12804.14 | 1.3e-10 | 8–134 | MobA-like NTP transferase domain |
GMPPB_C | PF25087.2 | 1.1e-13 | 251–334 | GMPPB C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rmlD (dTDP-4-dehydrorhamnose reductase), high confidence from genomic context alone (score 935 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3257c pmmA |
phosphomannomutase PmmA | 967 | 951 | coexpression:435 database:900 |
Rv3308 pmmB |
phosphomannomutase PmmB | 964 | 941 | coexpression:414 database:900 textmining:419 |
Rv3266c rmlD |
dTDP-4-dehydrorhamnose reductase | 958 | 935 ctx | neighborhood:879 coexpression:481 |
Rv1511 gmdA |
GDP-D-mannose dehydratase GmdA | 914 | 906 | database:900 |
Rv3265c wbbL1 |
N-acetylglucosaminyl-diphospho-decaprenol L-rhamnosyltransferase | 895 | 891 ctx | neighborhood:881 |
Rv3267 lcp1 hyp |
hypothetical protein | 847 | 847 ctx | neighborhood:783 |
Rv3465 rmlC |
dTDP-4-dehydrorhamnose 3,5-epimerase | 846 | 800 | coexpression:783 |
Rv0334 rmlA |
glucose-1-phosphate thymidylyltransferase | 785 | 753 | coexpression:733 |
Rv0114 gmhB |
D-glycero-alpha-D-manno-heptose-1,7-bisphosphate 7-phosphatase | 714 | 671 ctx | fusion:571 |
Rv3634c galE1 |
UDP-glucose 4-epimerase | 683 | 665 | coexpression:429 |
Rv1937 |
oxygenase | 739 | 643 | coexpression:454 |
Rv0112 gca |
GDP-mannose 4,6-dehydratase | 634 | 613 | coexpression:414 |
Rv2448c valS |
valine--tRNA ligase | 603 | 604 ctx | cooccurence:580 |
Rv3784 |
dTDP-glucose 4,6-dehydratase | 640 | 594 | coexpression:469 |
Rv2580c hisS |
histidine--tRNA ligase | 624 | 573 ctx | cooccurence:454 |
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): D-alpha-D-mannose-1-phosphate guanylyltransferase ManB
- Pfam (hmmscan --cut_ga): NTP_transferase PF00483.30 (E=2e-47), NTP_transf_3 PF12804.14 (E=1e-10), GMPPB_C PF25087.2 (E=1e-13)
- (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_177951.1)
- Domains: Pfam-A via hmmscan --cut_ga — NTP_transferase (PF00483.30), NTP_transf_3 (PF12804.14), GMPPB_C (PF25087.2)
- 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
COG1208 - Curated reference: UniProt L7N6A5 (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 —
78 functional partner(s); context anchor
rmlD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3264c|manB MATHQVDAVVLVGGKGTRLRPLTLSAPKPMLPTAGLPFLTHLLSRIAAAGIEHVILGTSYKPAVFEAEFGDGSALGLQIEYVTEEHPLGTGGGIANVAGKLRNDTAMVFNGDVLSGADLAQLLDFHRSNRADVTLQLVRVGDPRAFGCVPTDEEDRVVAFLEKTEDPPTDQINAGCYVFERNVIDRIPQGREVSVEREVFPALLADGDCKIYGYVDASYWRDMGTPEDFVRGSADLVRGIAPSPALRGHRGEQLVHDGAAVSPGALLIGGTVVGRGAEIGPGTRLDGAVIFDGVRVEAGCVIERSIIGFGARIGPRALIRDGVIGDGADIGARCELLSGARVWPGVFLPDGGIRYSSDV