Rv3566A Still unknown · low auto-curated

H37Rv Rv3566A · MTBC0 - · 88 aa · 4008167–4008433 (-) · RefSeq YP_177990.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 8xt2-assembly1_Lg Cryo-EM structure of the human 55S mitoribosome with (prob 0.01, TM 0.22).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

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 I6YGI1 TrEMBL · unreviewed · Predicted
UniProt nameArylamine N-acetyltransferase

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS n/a
Polymorphic sites (≥ 0.1% of strains) 0 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)

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 35.3 (very low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.

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.

TargetProbTME-valueDescription
8xt2-assembly1_Lg 0.01 0.22 8.7e+00 8xt2-assembly1_Lg Cryo-EM structure of the human 55S mitoribosome with 10uM Tigecycline
8any-assembly1_1 0.01 0.22 9.2e+00 8any-assembly1_1 Human mitochondrial ribosome in complex with LRPPRC, SLIRP, A-site, P-site, E-site tRNAs and mRNA

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: nat (arylamine N-acetyltransferase), high confidence from genomic context alone (score 939 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3566c nat arylamine N-acetyltransferase 938 939 ctx neighborhood:781 coexpression:731
Rv3567c hsaB flavin-dependent monooxygenase reductase subunit HsaB 826 826 ctx neighborhood:412 coexpression:716
Rv3568c hsaC extradiol dioxygenase 475 475
Rv3569c hsaD 4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase 414 414
Rv0590A Mce-family related protein; Rv0590A, len: 84 aa. Probable continuation of mce2B|Rv0590. Can find no frameshift to account for this. Possible 619 55 textmining:614
Rv1146 mmpL13b transmembrane transport protein 549 47 textmining:547
Rv0590 mce2B Mce-family protein Mce2B; Rv0590, (MTCY19H5.32c), len: 275 aa. Mce2B; belongs to 24-membered Mycobacterium tuberculosis Mce protein family ( 441 47 textmining:438
Rv1145 mmpL13a transmembrane transport protein 440 47 textmining:437
Rv1089A celA2a Rv1089A, len: 34 aa. Probable celA2a, first part of cellulase (endoglucanase), similar to N-terminus of others. This region is a possible MT 657 46 textmining:656
Rv3233c Rv3233c, (MTCY20B11.08c), len: 196 aa. Possible triacylglycerol synthase (See Daniel et al., 2004), similar to C-terminus of Q9RIU8|SCM11.13 546 46 textmining:544
Rv3234c tgs3 diacyglycerol O-acyltransferase 512 44 textmining:511
Rv0304c PPE5 PPE family protein PPE5 440 44 textmining:439
Rv1090 celA2b Rv1090, (MTV017.43), len: 151 aa. Probable celA2b,second part of cellulase (endoglucanase), similar to C-terminus of others e.g. O08468 cell 653 41 textmining:653
Rv0305c PPE6 PPE family protein PPE6 548 41 textmining:548

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
  • Foldseek best: 8xt2-assembly1_Lg Cryo-EM structure of the human 55S mitoribosome with 10uM Tige (prob 0.01, E=9e+00, TM=0.22)
  • (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 YP_177990.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Curated reference: UniProt I6YGI1 (TrEMBL, unreviewed; Predicted)
  • 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 35.3, very low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 14 functional partner(s); context anchor nat
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3566A|
MSGADPPTRRAFGQMARAATGWVSVSGQFAVAADTCRCEGTLFAVDPETHVANHNRCDIVGRLRDERPNTLRSVRRGDEVRMATWHWI