grcC2 Resolved · high auto-curated
H37Rv Rv0989c · MTBC0 mtbc0_001060 ·
325 aa · 1113741–1114718 (-) ·
RefSeq NP_215504.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | polyprenyl-diphosphate synthase GrcC |
|---|---|
| MTBC0 PGAP re-annotation | polyprenyl-diphosphate synthase GrcC |
| Revised (this work) | Polyprenyl-diphosphate synthase GrcC. Pfam: polyprenyl_synt (PF00348.23). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O05572
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Dimethylallyltranstransferase |
| EC (curated) |
EC 2.5.1.1
|
| Curated function | Catalyzes the addition of isopentenyl diphosphate (IPP) onto dimethylallyl diphosphate (DMAPP) to form geranyl pyrophosphate (GPP). Is probably involved in the biosynthesis of decaprenyl diphosphate, which is required for mycobacterial cell wall synthesis. Could be required for host endothelial-cell invasion and/or intracellular survival. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | hepT |
| eggNOG description | Belongs to the FPP GGPP synthase family |
| Orthologous group | COG0142 |
| EC number |
EC 2.5.1.30
|
| KEGG orthology |
K00805
|
| KEGG pathways |
map00900, map01110
|
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 | 5.534 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 16 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.24% of strains (355) · 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 |
|---|---|---|---|---|
polyprenyl_synt | PF00348.23 | 1.6e-42 | 36–274 | Polyprenyl synthetase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1086 ((2Z,6E)-farnesyl diphosphate synthase), medium confidence from genomic context alone (score 628 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3383c idsB |
polyprenyl synthetase IdsB | 944 | 928 | database:900 |
Rv3398c idsA1 |
multifunctional dimethylallyltransferase/geranyltranstransferase/farnesyltranstransferase | 948 | 926 | database:900 |
Rv2173 idsA2 |
geranylgeranyl pyrophosphate synthetase IdsA | 943 | 918 | database:900 |
Rv0562 grcC1 |
polyprenyl-diphosphate synthase GrcC | 906 | 903 | database:900 |
Rv3397c phyA |
phytoene synthase | 903 | 863 | database:800 |
Rv1086 |
(2Z,6E)-farnesyl diphosphate synthase | 749 | 628 ctx | cooccurence:596 |
Rv0990c hyp |
hypothetical protein | 632 | 618 ctx | neighborhood:616 |
Rv2752c rnj |
ribonuclease J | 526 | 527 | coexpression:511 |
Rv0721 rpsE |
30S ribosomal protein S5 | 516 | 516 | coexpression:411 |
Rv0510 hemC |
porphobilinogen deaminase | 530 | 503 | coexpression:403 |
Rv2445c ndkA |
nucleoside diphosphate kinase | 517 | 493 | coexpression:409 |
Rv2361c uppS |
decaprenyl diphosphate synthase | 761 | 491 ctx | cooccurence:448 textmining:549 |
Rv1023 eno |
enolase | 487 | 469 | |
Rv0558 menH |
demethylmenaquinone methyltransferase | 487 | 469 ctx | cooccurence:417 |
Rv0991c hyp |
hypothetical protein | 467 | 467 ctx | neighborhood:465 |
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: polyprenyl-diphosphate synthase GrcC
- MTBC0 PGAP product: polyprenyl-diphosphate synthase GrcC
- Pfam (hmmscan --cut_ga): polyprenyl_synt PF00348.23 (E=2e-42)
- (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_215504.1)
- Domains: Pfam-A via hmmscan --cut_ga — polyprenyl_synt (PF00348.23)
- 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
COG0142 - Curated reference: UniProt O05572 (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 —
35 functional partner(s); context anchor
Rv1086 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001060|Rv0989c|grcC2 MIPAVSLGDPQFTANVHDGIARITELINSELSQADEVMRDTVAHLVDAGGTPFRPLFTVLAAQLGSDPDGWEVTVAGAAIELMHLGTLCHDRVVDESDMSRKTPSDNTRWTNNFAILAGDYRFATASQLASRLDPEAFAVVAEAFAELITGQMRATRGPASHIDTIEHYLRVVHEKTGSLIAASGQLGAALSGAAEEQIRRVARLGRMIGAAFEISRDIIAISGDSATLSGADLGQAVHTLPMLYALREQTPDTSRLRELLAGPIHDDHVAEALTLLRCSPGIGKAKNVVAAYAAQAREELPYLPDRQPRRALATLIDHAVSACD