rmlA Resolved · high auto-curated
H37Rv Rv0334 · MTBC0 mtbc0_000354 ·
288 aa · 401981–402847 (+) ·
RefSeq NP_214848.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | glucose-1-phosphate thymidylyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | glucose-1-phosphate thymidylyltransferase RfbA |
| Revised (this work) | Glucose-1-phosphate thymidylyltransferase RfbA. Pfam: NTP_transferase (PF00483.30), NTP_transf_3 (PF12804.14). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WH13
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Glucose-1-phosphate thymidylyltransferase |
| EC (curated) |
EC 2.7.7.24
|
| Curated function | Catalyzes the conversion of glucose-1-phosphate and dTTP to dTDP-glucose and pyrophosphate. Involved in the biosynthesis of the dTDP-L-rhamnose which is a component of the critical linker, D-N-acetylglucosamine-L-rhamnose disaccharide, which connects the galactan region of arabinogalactan to peptidoglycan via a phosphodiester linkage. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | rmlA |
| eggNOG description | Catalyzes the formation of dTDP-glucose, from dTTP and glucose 1-phosphate, as well as its pyrophosphorolysis |
| Orthologous group | COG1209 |
| EC number |
EC 2.7.7.24
|
| KEGG orthology |
K00973
|
| KEGG pathways |
map00521, map00523, map00525, map01130
|
| KEGG modules |
M00793
|
| Gene Ontology (82) |
GO:0000271, GO:0000287, GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0005975, GO:0005976, GO:0005996 +70 more
|
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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 0 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 | 4.7e-74 | 3–236 | Nucleotidyl transferase |
NTP_transf_3 | PF12804.14 | 3.9e-09 | 3–122 | MobA-like NTP transferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rmlB (dTDP-glucose 4,6-dehydratase), high confidence from genomic context alone (score 995 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3464 rmlB |
dTDP-glucose 4,6-dehydratase | 999 | 995 ctx | cooccurence:772 coexpression:734 database:900 textmining:965 |
Rv3465 rmlC |
dTDP-4-dehydrorhamnose 3,5-epimerase | 999 | 992 ctx | fusion:715 cooccurence:763 coexpression:858 textmining:963 |
Rv3784 |
dTDP-glucose 4,6-dehydratase | 991 | 985 ctx | cooccurence:435 coexpression:733 database:900 textmining:415 |
Rv3266c rmlD |
dTDP-4-dehydrorhamnose reductase | 998 | 969 ctx | cooccurence:763 coexpression:853 textmining:963 |
Rv0322 udgA |
UDP-glucose 6-dehydrogenase UdgA | 958 | 932 ctx | neighborhood:544 coexpression:857 textmining:417 |
Rv0993 galU |
UTP--glucose-1-phosphate uridylyltransferase | 927 | 915 | database:900 |
Rv3068c pgmA |
phosphoglucomutase PgmA | 914 | 906 | database:900 |
Rv1510 hyp |
hypothetical protein | 901 | 886 | coexpression:858 |
Rv3809c glf |
UDP-galactopyranose mutase | 910 | 870 | coexpression:859 |
Rv0333 hyp |
hypothetical protein | 840 | 840 ctx | neighborhood:838 |
Rv0332 hyp |
hypothetical protein | 818 | 811 ctx | neighborhood:805 |
Rv3264c manB |
D-alpha-D-mannose-1-phosphate guanylyltransferase ManB | 785 | 753 | coexpression:733 |
Rv3630 |
integral membrane protein | 773 | 745 | coexpression:730 |
Rv3265c wbbL1 |
N-acetylglucosaminyl-diphospho-decaprenol L-rhamnosyltransferase | 893 | 665 ctx | cooccurence:525 textmining:696 |
Rv3468c |
dTDP-glucose 4,6-dehydratase | 664 | 645 | database:500 |
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: glucose-1-phosphate thymidylyltransferase
- MTBC0 PGAP product: glucose-1-phosphate thymidylyltransferase RfbA
- Pfam (hmmscan --cut_ga): NTP_transferase PF00483.30 (E=5e-74), NTP_transf_3 PF12804.14 (E=4e-09)
- (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_214848.1)
- Domains: Pfam-A via hmmscan --cut_ga — NTP_transferase (PF00483.30), NTP_transf_3 (PF12804.14)
- 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
COG1209 - Curated reference: UniProt P9WH13 (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 —
51 functional partner(s); context anchor
rmlB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000354|Rv0334|rmlA MRGIILAGGSGTRLYPITMGISKQLLPVYDKPMIYYPLTTLMMAGIRDIQLITTPHDAPGFHRLLGDGAHLGVNISYATQDQPDGLAQAFVIGANHIGADSVALVLGDNIFYGPGLGTSLKRFQSISGGAIFAYWVANPSAYGVVEFGAEGMALSLEEKPVTPKSNYAVPGLYFYDNDVIEIARGLKKSARGEYEITEVNQVYLNQGRLAVEVLARGTAWLDTGTFDSLLDAADFVRTLERRQGLKVSIPEEVAWRMGWIDDEQLVQRARALVKSGYGNYLLELLERN