gca Resolved · high auto-curated
H37Rv Rv0112 · MTBC0 mtbc0_000122 ·
318 aa · 136454–137410 (+) ·
RefSeq NP_214626.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | GDP-mannose 4,6-dehydratase |
|---|---|
| MTBC0 PGAP re-annotation | GDP-mannose 4%2C6-dehydratase |
| Revised (this work) | GDP-mannose 4%2C6-dehydratase. Pfam: RmlD_sub_bind (PF04321.24), Epimerase (PF01370.28), GDP_Man_Dehyd (PF16363.12). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53634
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible GDP-mannose 4,6-dehydratase Gca |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
G Carbohydrate transport and metabolismM Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | gca |
| eggNOG description | GDP-mannose 4,6 dehydratase |
| Orthologous group | COG0451 |
| EC number |
EC 1.1.1.281
|
| KEGG orthology |
K15856
|
| KEGG pathways |
map00051, map00520
|
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 | 0.721 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 6 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.15% of strains (222) · 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 |
|---|---|---|---|---|
RmlD_sub_bind | PF04321.24 | 2.4e-10 | 1–157 | RmlD substrate binding domain |
Epimerase | PF01370.28 | 9.0e-49 | 4–238 | NAD dependent epimerase/dehydratase family |
GDP_Man_Dehyd | PF16363.12 | 5.3e-59 | 5–304 | GDP-mannose 4,6 dehydratase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gmhA (phosphoheptose isomerase), high confidence from genomic context alone (score 952 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1511 gmdA |
GDP-D-mannose dehydratase GmdA | 956 | 955 | database:900 |
Rv0113 gmhA |
phosphoheptose isomerase | 954 | 952 ctx | neighborhood:579 coexpression:863 |
Rv0114 gmhB |
D-glycero-alpha-D-manno-heptose-1,7-bisphosphate 7-phosphatase | 937 | 934 ctx | neighborhood:509 coexpression:829 |
Rv0115 hddA |
D-alpha-D-heptose-7-phosphate kinase HddA | 934 | 931 ctx | neighborhood:509 coexpression:827 |
Rv1512 epiA |
nucleotide-sugar epimerase EpiA | 911 | 912 | database:900 |
Rv0705 rpsS |
30S ribosomal protein S19 | 817 | 818 | experimental:463 database:574 |
Rv0700 rpsJ |
30S ribosomal protein S10 | 815 | 812 | experimental:463 database:557 |
Rv0682 rpsL |
30S ribosomal protein S12 | 860 | 807 | experimental:463 database:573 |
Rv3459c rpsK |
30S ribosomal protein S11 | 805 | 798 | experimental:463 database:558 |
Rv0710 rpsQ |
30S ribosomal protein S17 | 804 | 798 | experimental:463 database:578 |
Rv0707 rpsC |
30S ribosomal protein S3 | 804 | 797 | experimental:463 database:578 |
Rv0721 rpsE |
30S ribosomal protein S5 | 797 | 790 | experimental:463 database:575 |
Rv2056c rpsN2 |
30S ribosomal protein S14 | 789 | 790 | experimental:436 database:548 |
Rv0717 rpsN1 |
30S ribosomal protein S14 | 788 | 789 | experimental:436 database:548 |
Rv0718 rpsH |
30S ribosomal protein S8 | 795 | 788 | experimental:463 database:578 |
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: GDP-mannose 4,6-dehydratase
- MTBC0 PGAP product: GDP-mannose 4%2C6-dehydratase
- Pfam (hmmscan --cut_ga): RmlD_sub_bind PF04321.24 (E=2e-10), Epimerase PF01370.28 (E=9e-49), GDP_Man_Dehyd PF16363.12 (E=5e-59)
- (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_214626.1)
- Domains: Pfam-A via hmmscan --cut_ga — RmlD_sub_bind (PF04321.24), Epimerase (PF01370.28), GDP_Man_Dehyd (PF16363.12)
- 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
COG0451 - Curated reference: UniProt O53634 (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 —
90 functional partner(s); context anchor
gmhA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000122|Rv0112|gca MKVWITGAGGMMGSHLAEMLLAAGHDVYATYCRPTIDPSDLQFNGAEVDITDWCSVYDSIATFRPDAVFHLAAQSYPAVSWARPVETLTTNMVGTAIVFEALRRVRPHAKIIVAGSSAEYGFVDPSEVPINERRELRPLHPYGVSKAATDMLAYQYHKSYGMHTVVARIFNCTGPRKVGDALSDFVRRCTWLEHHPEQSAIRVGNLKTKRTIVDVRDLNRALMLMLDKGEAGADYNVGGSIAYEMGDVLKQVIAACKRDDIVPEVDPALLRPTDEKIIYGDCSKLAAITGWQQEICLTQTIADMFDYWRSKSESALMV