hddA Resolved · high auto-curated
H37Rv Rv0115 · MTBC0 mtbc0_000125 ·
355 aa · 138678–139839 (+) ·
RefSeq NP_214629.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | D-alpha-D-heptose-7-phosphate kinase HddA |
|---|---|
| MTBC0 PGAP re-annotation | D-alpha-D-heptose-7-phosphate kinase HddA |
| Revised (this work) | D-alpha-D-heptose-7-phosphate kinase HddA. Pfam: GHMP_kinases_N (PF00288.33), GHMP_kinases_C (PF08544.19). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53637
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | D-glycero-alpha-D-manno-heptose 7-phosphate kinase |
| EC (curated) |
EC 2.7.1.168
|
| Curated function | Catalyzes the phosphorylation of D-glycero-alpha-D-manno-heptose 7-phosphate at the C-1 position to form D-glycero-alpha-D-manno-heptose 1,7-bisphosphate (By similarity). Exhibits ATPase activity in vitro. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | hddA |
| eggNOG description | GHMP kinases C terminal |
| Orthologous group | COG2605 |
| EC number |
EC 2.7.1.168
|
| KEGG orthology |
K07031
|
| KEGG pathways |
map00540
|
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) pseudogene candidate
| pN/pS | 0.445 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 5 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 29.73% of strains (43164) · 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 |
|---|---|---|---|---|
GHMP_kinases_N | PF00288.33 | 6.4e-16 | 83–169 | GHMP kinases N terminal domain |
GHMP_kinases_C | PF08544.19 | 9.7e-09 | 244–323 | GHMP kinases C terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gmhB (D-glycero-alpha-D-manno-heptose-1,7-bisphosphate 7-phosphatase), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0114 gmhB |
D-glycero-alpha-D-manno-heptose-1,7-bisphosphate 7-phosphatase | 999 | 999 ctx | neighborhood:802 cooccurence:699 coexpression:860 database:900 |
Rv0113 gmhA |
phosphoheptose isomerase | 998 | 999 ctx | neighborhood:710 cooccurence:736 coexpression:811 database:900 |
Rv0112 gca |
GDP-mannose 4,6-dehydratase | 934 | 931 ctx | neighborhood:509 coexpression:827 |
Rv3465 rmlC |
dTDP-4-dehydrorhamnose 3,5-epimerase | 596 | 581 | coexpression:546 |
Rv3264c manB |
D-alpha-D-mannose-1-phosphate guanylyltransferase ManB | 567 | 496 | |
Rv0322 udgA |
UDP-glucose 6-dehydrogenase UdgA | 499 | 475 | coexpression:432 |
Rv2047c hyp |
hypothetical protein | 460 | 434 | |
Rv0139 |
oxidoreductase | 460 | 434 | |
Rv0501 galE2 |
UDP-glucose 4-epimerase GalE | 450 | 423 | |
Rv1010 ksgA |
rRNA small subunit methyltransferase A | 423 | 423 | coexpression:414 |
Rv1988 erm(37) |
23S rRNA (adenine(2058)-N(6))-methyltransferase Erm(37) | 410 | 410 | coexpression:401 |
Rv1106c |
3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase | 435 | 408 | |
Rv2768c PPE43 |
PPE family protein PPE43 | 659 | 54 | textmining:655 |
Rv0116c ldtA |
L,D-transpeptidase LdtA | 440 | 50 | textmining:435 |
Rv3778c |
aminotransferase | 632 | 47 | textmining:630 |
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: D-alpha-D-heptose-7-phosphate kinase HddA
- MTBC0 PGAP product: D-alpha-D-heptose-7-phosphate kinase HddA
- Pfam (hmmscan --cut_ga): GHMP_kinases_N PF00288.33 (E=6e-16), GHMP_kinases_C PF08544.19 (E=1e-08)
- (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_214629.1)
- Domains: Pfam-A via hmmscan --cut_ga — GHMP_kinases_N (PF00288.33), GHMP_kinases_C (PF08544.19)
- 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
COG2605 - Curated reference: UniProt O53637 (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 —
19 functional partner(s); context anchor
gmhB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000125|Rv0115|hddA MAILRGRAPLRLGLGGGGTDVEPYSSQFGGRILSVTIDKYAYAFAERGTGDEIAFRSPDRDRAGQASIDDLASLEEDFPLHVAVYRRVIAEFNGGTPFPLQLATQVDAPPGSGLGSSSALVVAMLLTTCALIGSSPGPYELARLAWEIERVDLGMAGGWQDHYAAAFGGFNFMESRPNGEVVVNPLRIRREVIAELEASLLLYFGGVSRLSSEVIADQQRNVVERDADALAATHSICAEALEMKDLLVVGDIPGFADSLLRGWQAKKRTSTRISNPAIEHAYQVAQSSGMVAGKVSGAGGGGFLMMIVDPRRRIEVARSLERECGGSVAPCLFTKGGAVTWHIPESTAPRKAWSC