manA Resolved · high auto-curated
H37Rv Rv3255c · MTBC0 mtbc0_003463 ·
408 aa · 3657184–3658410 (-) ·
RefSeq NP_217772.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | mannose-6-phosphate isomerase |
|---|---|
| MTBC0 PGAP re-annotation | mannose-6-phosphate isomerase%2C class I |
| Revised (this work) | Mannose-6-phosphate isomerase%2C class I. Pfam: PMI_typeI_cat (PF20511.5). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O05898
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | mannose-6-phosphate isomerase |
| EC (curated) |
EC 5.3.1.8
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
G Carbohydrate transport and metabolism
|
|---|---|
| Preferred name | manA |
| eggNOG description | mannose-6-phosphate isomerase |
| Orthologous group | COG1482 |
| EC number |
EC 5.3.1.8
|
| KEGG orthology |
K01809
|
| KEGG pathways |
map00051, map00520, map01100, map01110, map01130
|
| KEGG modules |
M00114
|
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 | 0.243 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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 |
|---|---|---|---|---|
PMI_typeI_cat | PF20511.5 | 5.5e-25 | 4–150 | Phosphomannose isomerase type I, catalytic domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pmmA (phosphomannomutase PmmA), high confidence from genomic context alone (score 990 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3257c pmmA |
phosphomannomutase PmmA | 994 | 990 ctx | neighborhood:882 database:900 textmining:417 |
Rv3256c hyp |
hypothetical protein | 989 | 945 ctx | neighborhood:881 coexpression:553 textmining:809 |
Rv0946c pgi |
glucose-6-phosphate isomerase | 944 | 927 | database:900 |
Rv2029c pfkB |
6-phosphofructokinase PfkB | 917 | 906 | database:900 |
Rv3308 pmmB |
phosphomannomutase PmmB | 982 | 905 | database:900 textmining:822 |
Rv3436c glmS |
glucosamine--fructose-6-phosphate aminotransferase | 957 | 904 | database:900 textmining:574 |
Rv3010c pfkA |
6-phosphofructokinase | 916 | 903 | database:900 |
Rv1099c glpX |
fructose 1,6-bisphosphatase | 904 | 901 | database:900 |
Rv3258c hyp |
hypothetical protein | 641 | 624 ctx | neighborhood:618 |
Rv3259 hyp |
hypothetical protein | 554 | 554 ctx | neighborhood:552 |
Rv1438 tpi |
triosephosphate isomerase | 571 | 496 | |
Rv2783c gpsI |
bifunctional guanosine pentaphosphate synthetase/polyribonucleotide nucleotidyltransferase | 472 | 473 ctx | fusion:465 |
Rv3335c yhjD |
integral membrane protein | 420 | 420 | |
Rv2852c mqo |
malate:quinone oxidoreductase | 448 | 278 | |
Rv0620 galK |
galactokinase | 423 | 269 |
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: mannose-6-phosphate isomerase
- MTBC0 PGAP product: mannose-6-phosphate isomerase%2C class I
- Pfam (hmmscan --cut_ga): PMI_typeI_cat PF20511.5 (E=6e-25)
- (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_217772.1)
- Domains: Pfam-A via hmmscan --cut_ga — PMI_typeI_cat (PF20511.5)
- 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
COG1482 - Curated reference: UniProt O05898 (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 —
22 functional partner(s); context anchor
pmmA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003463|Rv3255c|manA MELLRGALRTYAWGSRTAIAEFTGRPVPAAHPEAELWFGAHPGDPAWLQTPHGQTSLLEALVADPEGQLGSASRARFGDVLPFLVKVLAADEPLSLQAHPSAEQAVEGYLREERMGIPVSSPVRNYRDTSHKPELLVALQPFEALAGFREAARTTELLRALAVSDLDPFIDLLSEGSDADGLRALFTTWITAPQPDIDVLVPAVLDGAIQYVSSGATEFGAEAKTVLELGERYPGDAGVLAALLLNRISLAPGEAIFLPAGNLHAYVRGFGVEVMANSDNVLRGGLTPKHVDVPELLRVLDFAPTPKARLRPPIRREGLGLVFETPTDEFAATLLVLDGDHLGHEVDASSGHDGPQILLCTEGSATVHGKCGSLTLQRGTAAWVAADDGPIRLTAGQPAKLFRATVGL