Rv0360c Still unknown · low auto-curated

H37Rv Rv0360c · MTBC0 - · 145 aa · 438302–438739 (-) · RefSeq NP_214874.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF3151. Function unknown. Foldseek best (non-significant) hit: 8ump-assembly1_A T33-ml35 - Designed Tetrahedral Protein Cage Using Ma (prob 1.00, TM 0.56).

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 O06310 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF3151)
Orthologous group2DMMI

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 0.356 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 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)

PfamAccessioni-EvalueResiduesDescription
DUF3151PF11349.14 6.0e-5917–140 Protein of unknown function (DUF3151)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 88.8 (confident). 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.

TargetProbTME-valueDescription
8ump-assembly1_A 1.00 0.56 3.3e-02 8ump-assembly1_A T33-ml35 - Designed Tetrahedral Protein Cage Using Machine Learning Algorithms
4gcn-assembly2_B 0.99 0.58 1.1e-01 4gcn-assembly2_B N-terminal domain of stress-induced protein-1 (STI-1) from C.elegans
6gxz-assembly1_A 0.97 0.60 4.4e-01 6gxz-assembly1_A Crystal structure of the human RPAP3(TPR2)-PIH1D1(CS) complex
1na3-assembly1_A 0.97 0.67 5.2e-01 1na3-assembly1_A Design of Stable alpha-Helical Arrays from an Idealized TPR Motif
6gxz-assembly2_C 0.97 0.60 4.9e-01 6gxz-assembly2_C Crystal structure of the human RPAP3(TPR2)-PIH1D1(CS) complex
8fwd-assembly1_C 0.96 0.56 3.8e-01 8fwd-assembly1_C Fast and versatile sequence- independent protein docking for nanomaterials design using RPXDock
3fwv-assembly2_B 0.94 0.57 4.0e-01 3fwv-assembly2_B Crystal Structure of a Redesigned TPR Protein, T-MOD(VMY), in Complex with MEEVF Peptide
2e2e-assembly1_B 0.92 0.54 2.8e-01 2e2e-assembly1_B TPR domain of NrfG mediates the complex formation between heme lyase and formate-dependent nitrite reductase in Escherichia Coli O157:H7

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

Closest characterised functional partner: mca (mycothiol S-conjugate amidase), high confidence from genomic context alone (score 741 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1082 mca mycothiol S-conjugate amidase 741 741 ctx cooccurence:741
Rv2466c hyp hypothetical protein 747 738 ctx cooccurence:738
Rv0361 membrane protein 726 726 ctx neighborhood:726
Rv0819 mshD mycothiol acetyltransferase 696 696 ctx cooccurence:693
Rv2199c ctaF cytochrome c oxidase polypeptide 4 657 657 ctx cooccurence:657
Rv2260 hyp hypothetical protein 649 650 ctx cooccurence:648
Rv2194 qcrC ubiquinol-cytochrome C reductase cytochrome subunit C 612 612 ctx cooccurence:610
Rv1170 mshB 1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase 601 601 ctx cooccurence:601
Rv2196 qcrB ubiquinol-cytochrome C reductase cytochrome subunit B 583 583 ctx cooccurence:582
Rv0528 transmembrane protein 564 564 ctx cooccurence:562
Rv1457c antibiotic ABC transporter permease 536 518 ctx cooccurence:518
Rv0498 hyp hypothetical protein 516 516 ctx cooccurence:516
Rv0801 hyp hypothetical protein 515 515 ctx cooccurence:512
Rv2917 hyp hypothetical protein 510 511 ctx cooccurence:478
Rv2286c hyp hypothetical protein 495 496 ctx cooccurence:490

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
  • Pfam (hmmscan --cut_ga): DUF3151 PF11349.14 (E=6e-59)
  • Foldseek best: 8ump-assembly1_A T33-ml35 - Designed Tetrahedral Protein Cage Using Machine Lear (prob 1.00, E=3e-02, TM=0.56)
  • (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_214874.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF3151 (PF11349.14)
  • 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 2DMMI
  • Curated reference: UniProt O06310 (TrEMBL, unreviewed; 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 88.8, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 33 functional partner(s); context anchor mca
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0360c|
MTKRTITPMTSMGDLLGPEPILLPGDSDAEAELLANESPSIVAAAHPSASVAWAVLAEGALADDKTVTAYAYARTGYHRGLDQLRRHGWKGFGPVPYSHQPNRGFLRCVAALARAAAAIGETDEYGRCLDLLDDCDPAARPALGL