Rv0612 Still unknown · low auto-curated

H37Rv Rv0612 · MTBC0 mtbc0_000644 · 201 aa · 709876–710481 (+) · RefSeq NP_215126.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 6lja-assembly1_A Crystal Structure of exoHep from Bacteroides intestin (prob 0.23, TM 0.31).

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

Curated reference (UniProt)

UniProt I6X9E8 TrEMBL · unreviewed · Predicted
UniProt nameUncharacterized protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group29FX3

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 3 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 83.1 (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
6lja-assembly1_A 0.23 0.31 7.8e-01 6lja-assembly1_A Crystal Structure of exoHep from Bacteroides intestinalis DSM 17393 complexed with disaccharide product
6ljl-assembly1_A 0.14 0.31 1.9e+00 6ljl-assembly1_A Crystal Structure of exoHep-Y390A/H555A complexed with a tetrasaccharide substrate
6qnx-assembly1_A 0.09 0.37 6.5e+00 6qnx-assembly1_A Structure of the SA2/SCC1/CTCF complex
5yvi-assembly1_A 0.08 0.19 1.8e+00 5yvi-assembly1_A Crystal structure of Karyopherin beta2 in complex with FUS(456-526)
6e10-assembly1_A 0.07 0.23 3.3e+00 6e10-assembly1_A PTEX Core Complex in the Engaged (Extended) State
8j2y-assembly1_A 0.06 0.28 5.6e+00 8j2y-assembly1_A Acidimicrobiaceae bacterium photocobilins protein, dark state
7ml2-assembly1_1 0.06 0.35 8.0e+00 7ml2-assembly1_1 RNA polymerase II pre-initiation complex (PIC3)
5imu-assembly1_A 0.05 0.35 8.0e+00 5imu-assembly1_A A fragment of conserved hypothetical protein Rv3899c (residues 184-410) from Mycobacterium tuberculosis

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv0611c hyp hypothetical protein 582 582 ctx neighborhood:579
Rv0610c hyp hypothetical protein 470 470 ctx neighborhood:467

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

  • Legacy H37Rv annotation: hypothetical protein
  • MTBC0 PGAP product: hypothetical protein
  • Foldseek best: 6lja-assembly1_A Crystal Structure of exoHep from Bacteroides intestinalis DSM 1 (prob 0.23, E=8e-01, TM=0.31)
  • (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_215126.1)
  • 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 29FX3
  • Curated reference: UniProt I6X9E8 (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 83.1, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 2 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000644|Rv0612|
MLGPIRQPRLTVRPGRLPGMIAGVAAKRMNREQFFRAASGLDEDRLRKALWNLYWRGTANMRERIEAELASAGRARPARKIKPPADPDIVGWEVDEFVSLARSGAYLGGDRRVSPRERSRWRFTFKRLAAEAQDALRAEDAEPAASALEQLIDLAREADGYDYFRSDDPVAAAGFVVSDVAAAGHPHFREFAAEIGAAIPP