Rv0100 Resolved · high

H37Rv Rv0100 · MTBC0 mtbc0_000109 · 78 aa · 109946–110182 (+) · RefSeq NP_214614.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationacyl 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 nameAcyl carrier protein Rv0100
Curated functionAcyl-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 descriptionPhosphopantetheine attachment site
Orthologous group2B15P

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)

PfamAccessioni-EvalueResiduesDescription
PP-bindingPF00550.32 3.4e-103–68 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.

PartnerProductScoreNo text-miningChannels (≥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.

#IndexActivationInterpretation
113041 1.03 Phosphopantetheine carrier–ANL interface activation
27052 0.97 ACP/PCP PPant-serine hotspot
31454 0.87 NRPS/PKS and ANL modules
413936 0.85 Phosphopantetheinylation site helix
5332 0.78 ACP/PCP pre-PPant serine loop
612204 0.78 Small-residue-rich microloops and repeats
712446 0.62 Glycine-rich Ppant and ATP loops
8314 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