grcC1 Resolved · high auto-curated
H37Rv Rv0562 · MTBC0 mtbc0_000591 ·
335 aa · 656322–657329 (+) ·
RefSeq NP_215076.1
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 |
O06428
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Nonaprenyl diphosphate synthase |
| EC (curated) |
EC 2.5.1.10, EC 2.5.1.29, EC 2.5.1.85
|
| Curated function | Catalyzes the sequential condensations of isopentenyl pyrophosphate (IPP) with geranyl diphosphate (GPP) to yield (2E,6E)-farnesyl diphosphate (E,E-FPP), with E,E-FPP to yield geranylgeranyl diphosphate (GGPP) and with GGPP to yield nonaprenyl diphosphate. May also have weak activity with dimethylallyl diphosphate (DMAPP). |
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 | 0.18 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 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 |
|---|---|---|---|---|
polyprenyl_synt | PF00348.23 | 6.0e-65 | 43–286 | Polyprenyl synthetase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: menJ (oxidoreductase), high confidence from genomic context alone (score 736 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3398c idsA1 |
multifunctional dimethylallyltransferase/geranyltranstransferase/farnesyltranstransferase | 948 | 925 | database:900 |
Rv3383c idsB |
polyprenyl synthetase IdsB | 941 | 925 | database:900 |
Rv2173 idsA2 |
geranylgeranyl pyrophosphate synthetase IdsA | 946 | 924 | database:900 |
Rv0989c grcC2 |
polyprenyl-diphosphate synthase GrcC | 906 | 903 | database:900 |
Rv3397c phyA |
phytoene synthase | 903 | 864 | database:800 |
Rv0561c menJ |
oxidoreductase | 751 | 736 ctx | neighborhood:620 |
Rv1086 |
(2Z,6E)-farnesyl diphosphate synthase | 904 | 722 ctx | cooccurence:695 textmining:672 |
Rv2361c uppS |
decaprenyl diphosphate synthase | 936 | 673 ctx | cooccurence:643 textmining:814 |
Rv0563 htpX |
protease HtpX | 646 | 632 ctx | neighborhood:581 |
Rv2445c ndkA |
nucleoside diphosphate kinase | 577 | 555 | coexpression:415 |
Rv0560c |
benzoquinone methyltransferase | 556 | 540 ctx | neighborhood:529 |
Rv2752c rnj |
ribonuclease J | 533 | 534 | coexpression:518 |
Rv0721 rpsE |
30S ribosomal protein S5 | 528 | 528 | coexpression:417 |
Rv0559c hyp |
hypothetical protein | 520 | 520 ctx | neighborhood:520 |
Rv1023 eno |
enolase | 524 | 507 |
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=6e-65)
- (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_215076.1)
- 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 O06428 (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 —
43 functional partner(s); context anchor
menJ - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000591|Rv0562|grcC1 MRTPATVVAGVDLGDAVFAAAVRAGVARVEQLMDTELRQADEVMSDSLLHLFNAGGKRFRPLFTVLSAQIGPQPDAAAVTVAGAVIEMIHLATLYHDDVMDEAQVRRGAPSANAQWGNNVAILAGDYLLATASRLVARLGPEAVRIIADTFAQLVTGQMRETRGTSENVDSIEQYLKVVQEKTGSLIGAAGRLGGMFSGATDEQVERLSRLGGVVGTAFQIADDIIDIDSESDESGKLPGTDVREGVHTLPMLYALRESGPDCARLRALLNGPVDDDAEVREALTLLRASPGMARAKDVLAQYAAQARHELALLPDVPGRRALAALVDYTVSRHG