Rv3268 Family assigned · low
H37Rv Rv3268 · MTBC0 - ·
229 aa · 3649420–3650109 (+) ·
RefSeq NP_217785.3
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | TIGR03089-family protein, uncharacterised. NOTE: the acetyl-CoA-synthetase fold is shared, but the genuine Mtb acetyl-CoA synthetase is Rv3667 (acsA), a different gene. |
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P96873
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | TIGR03089 family protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| eggNOG description | COG0365 Acyl-coenzyme A synthetases AMP-(fatty) acid ligases |
| Orthologous group | COG0318 |
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 | 0.758 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 5 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.40% of strains (585) · 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 96.4 (very high). A confident model makes the fold comparison meaningful.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
2p2q-assembly1_A |
1.00 | 0.82 | 6.1e-11 sig | 2p2q-assembly1_A Acetyl-CoA Synthetase, R584E mutation |
8biq-assembly1_C |
1.00 | 0.79 | 3.9e-11 sig | 8biq-assembly1_C Crystal structure of acyl-COA synthetase from Metallosphaera sedula in complex with acetyl-AMP |
2p2f-assembly1_A |
1.00 | 0.82 | 6.5e-11 sig | 2p2f-assembly1_A Acetyl-CoA Synthetase, wild-type with acetate, AMP, and CoA bound |
8rwj-assembly1_D |
1.00 | 0.84 | 1.5e-10 sig | 8rwj-assembly1_D cryoEM structure of Acs1 filament determined by FilamentID |
2p2m-assembly1_A |
1.00 | 0.82 | 2.0e-10 sig | 2p2m-assembly1_A Acetyl-CoA Synthetase, R194A mutation |
2p2m-assembly2_B |
1.00 | 0.83 | 2.2e-10 sig | 2p2m-assembly2_B Acetyl-CoA Synthetase, R194A mutation |
2p20-assembly2_B |
1.00 | 0.83 | 2.4e-10 sig | 2p20-assembly2_B Acetyl-CoA Synthetase, R584A mutation |
2p2j-assembly2_B |
1.00 | 0.82 | 3.1e-10 sig | 2p2j-assembly2_B Acetyl-CoA Synthetase, K609A mutation |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3267 lcp1 hyp |
hypothetical protein | 951 | 951 ctx | neighborhood:825 coexpression:734 |
Rv1312 hyp |
hypothetical protein | 697 | 697 ctx | cooccurence:697 |
Rv0719 rplF |
50S ribosomal protein L6 | 697 | 697 | experimental:402 database:510 |
Rv1527c pks5 |
polyketide synthase | 709 | 684 | |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 707 | 682 | |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 706 | 681 | |
Rv2048c pks12 |
polyketide synthase | 706 | 681 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 705 | 680 | |
Rv3800c pks13 |
polyketide synthase | 673 | 641 | |
Rv2946c pks1 |
polyketide synthase | 665 | 633 | |
Rv3807c |
decaprenylphosphoryl-5-phosphoribose phosphatase | 612 | 610 | database:500 |
Rv3839 hyp |
hypothetical protein | 609 | 609 ctx | cooccurence:609 |
Rv1661 pks7 |
polyketide synthase | 630 | 608 | |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 629 | 608 | |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 629 | 608 |
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
- PGAP: hypothetical; Pfam family TIGR03089
- Foldseek fold = acetyl-CoA synthetase, but that enzyme is Rv3667 (paralogue-of-fold trap)
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_217785.3)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
COG0318 - Curated reference: UniProt P96873 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 96.4, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 91 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3268| MLRADPVGPRITYYDDATGERIELSAVTLANWAAKTGNLLRDELAAGPASRVAILLPAHWQTAAVLFGVWWIGAQAILDDSPADVALCTADRLAEADAVVNSAAVAGEVAVLSLDPFGRPATGLPVGVTDYATAVRVHGDQIVPEHNPGPVLAGRSVEQILRDCAASAAARGLTAADRVLSTASWAGPDELVDGLLAILAAGASLVQVANPDPAMLQRRIATEKVTRVL