Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
| MTBC0 PGAP re-annotation | acyl carrier protein |
| Revised (this work) | Acyl carrier protein (ACP). Pfam PP-binding (PF00550) is the phosphopantetheine-attachment site: the protein carries acyl intermediates as a 4'-phosphopantetheine thioester for fatty-acid / polyketide biosynthesis. A standalone ACP, likely partnering a biosynthetic cluster in this genomic region. |
Curated reference (UniProt)
| UniProt |
P9WM65
SwissProt · reviewed
· Evidence at protein level
|
| UniProt name | Acyl carrier protein Rv0100 |
| Curated function | Acyl-carrier protein (ACP) involved in the biosynthesis of a unique class of isonitrile lipopeptides (INLPs) that seem to function as virulence factors in M.tuberculosis and to play a role in metal acquisition. Is the dedicated ACP for the loading of activated acyl groups catalyzed by FadD10. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
| eggNOG description | Phosphopantetheine attachment site |
| Orthologous group | 2B15P |
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 |
0.176 · strong purifying
|
| Polymorphic sites (≥ 0.1% of strains) |
2 synonymous, 1 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 |
PP-binding | PF00550.32 |
3.4e-10 | 3–68 |
Phosphopantetheine attachment site |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
nrp (peptide synthetase Nrp),
high confidence from genomic context alone
(score 983 excluding text-mining).
This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
Rv0101 nrp |
peptide synthetase Nrp |
996 |
983 ctx |
neighborhood:882 coexpression:860 textmining:803 |
Rv0099 fadD10 |
fatty-acid--CoA ligase FadD10 |
996 |
983 ctx |
neighborhood:882 coexpression:860 textmining:803 |
Rv0097 |
oxidoreductase |
993 |
969 ctx |
neighborhood:785 coexpression:860 textmining:809 |
Rv0098 fcoT |
fatty acyl CoA thioesterase FcoT |
995 |
964 ctx |
neighborhood:776 coexpression:848 textmining:870 |
Rv0096 PPE1 |
PPE family protein PPE1 |
971 |
942 ctx |
neighborhood:719 coexpression:802 textmining:536 |
Rv0095c hyp |
hypothetical protein |
563 |
525 ctx |
neighborhood:521 |
Rv0102 |
integral membrane protein |
555 |
461 ctx |
neighborhood:461 |
Rv0103c ctpB |
cation-transporter P-type ATPase B |
433 |
93 |
textmining:401 |
Rv3506 fadD17 |
long-chain-fatty-acid--CoA ligase FadD17 |
433 |
45 |
textmining:431 |
Rv0109 PE_PGRS1 |
PE-PGRS family protein PE_PGRS1 |
514 |
41 |
textmining:514 |
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
- MTBC0 PGAP product: 'acyl carrier protein'
- Pfam: PP-binding PF00550 (E=3.4e-10) -- 4'-phosphopantetheine attachment site
ESM Atlas signal (exploratory)
Ancestral protein hash 6ec6fa858ba4743f77f4180a37ea0e27 ·
10 ESM-space neighbours (max similarity 0.947).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
| 1 | 13041 |
1.03 |
Phosphopantetheine carrier–ANL interface activation |
| 2 | 7052 |
0.97 |
ACP/PCP PPant-serine hotspot |
| 3 | 1454 |
0.87 |
NRPS/PKS and ANL modules |
| 4 | 13936 |
0.85 |
Phosphopantetheinylation site helix |
| 5 | 332 |
0.78 |
ACP/PCP pre-PPant serine loop |
| 6 | 12204 |
0.78 |
Small-residue-rich microloops and repeats |
| 7 | 12446 |
0.62 |
Glycine-rich Ppant and ATP loops |
| 8 | 314 |
0.59 |
Amphipathic interdomain docking linkers |
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_214614.1)
- Domains: Pfam-A via hmmscan --cut_ga — PP-binding (PF00550.32)
- 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
2B15P
- Curated reference: UniProt
P9WM65
(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 —
10 functional partner(s); context anchor
nrp
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000109|Rv0100|
MRDRILAAVCDVLYIDEADLIDGDETDLRDLGLDSVRFVLLMKQLGVNRQSELPSRLAANPSIAGWLRELEAVCTEFG
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