Rv1691 Family assigned · low

H37Rv Rv1691 · MTBC0 mtbc0_001799 · 250 aa · 1927964–1928716 (+) · RefSeq NP_216207.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)TPR-repeat fold (PDB 2PL2); putative protein-protein-interaction scaffold.

Curated reference (UniProt)

UniProt O33193 TrEMBL · unreviewed · Evidence at protein level
UniProt nameTetratrico peptide repeat group 5 domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionTetratricopeptide repeat
Orthologous groupCOG0457

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 0.224 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 3 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.85% of strains (1237) · clonal

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 96.1 (very high). 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
2pl2-assembly1_B 1.00 0.74 5.2e-03 sig 2pl2-assembly1_B Crystal structure of TTC0263: a thermophilic TPR protein in Thermus thermophilus HB27
5g05-assembly1_K 1.00 0.63 2.2e-03 sig 5g05-assembly1_K Cryo-EM structure of combined apo phosphorylated APC
5a31-assembly1_Y 1.00 0.67 5.4e-03 sig 5a31-assembly1_Y Structure of the human APC-Cdh1-Hsl1-UbcH10 complex.
4ui9-assembly1_K 1.00 0.61 5.7e-03 sig 4ui9-assembly1_K Atomic structure of the human Anaphase-Promoting Complex
2ho1-assembly1_A 1.00 0.59 8.5e-03 sig 2ho1-assembly1_A Functional Characterization of Pseudomonas Aeruginosa pilF
8j8p-assembly1_C 1.00 0.58 1.2e-02 8j8p-assembly1_C Structure of the four-component Paf1 complex from Saccharomyces eubayanus
5m72-assembly1_A 1.00 0.54 5.4e-03 sig 5m72-assembly1_A Structure of the human SRP68-72 protein-binding domain complex
8qoy-assembly1_A 1.00 0.55 1.4e-02 8qoy-assembly1_A Capsular polysaccharide synthesis multienzyme of Actinobacillus Pleuropneumoniae serotype 3

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

Closest characterised functional partner: Rv1692 (phosphatase), high confidence from genomic context alone (score 976 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1692 phosphatase 996 976 ctx neighborhood:882 fusion:795 textmining:876
Rv2299c htpG chaperone protein HtpG 933 926 experimental:786 database:631
Rv2555c alaS alanine--tRNA ligase 925 920 experimental:775 database:644
Rv1695 ppnK inorganic polyphosphate/ATP-NAD kinase 986 900 ctx neighborhood:882 textmining:870
Rv1694 tlyA 16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA 946 886 ctx neighborhood:882 textmining:548
Rv1693 hyp hypothetical protein 984 883 ctx neighborhood:882 textmining:870
Rv3457c rpoA DNA-directed RNA polymerase subunit alpha 878 871 experimental:668 database:607
Rv1696 recN DNA repair protein RecN 981 869 ctx neighborhood:867 textmining:866
Rv1390 rpoZ DNA-directed RNA polymerase subunit omega 867 867 experimental:515 database:594
Rv0696 mftF mycofactocin biosynthesis glycosyltransferase MftF 823 805 experimental:788
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 811 791 experimental:476 database:592
Rv0492c GMC-type oxidoreductase 799 791 experimental:411 database:583
Rv2919c glnB nitrogen regulatory protein P-II 805 787 experimental:787
Rv0312 hyp hypothetical protein 784 772 experimental:455 database:567
Rv0350 dnaK chaperone protein DnaK 781 769 experimental:455 database:567

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: hypothetical protein
  • Foldseek best: 2pl2-assembly1_B Crystal structure of TTC0263: a thermophilic TPR protein in The (prob 1.00, E=5e-03, TM=0.74)
  • (structure-only promotion reviewed by hand, 2026-06-01)

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_216207.1)
  • 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 COG0457
  • Curated reference: UniProt O33193 (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 96.1, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 133 functional partner(s); context anchor Rv1692
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001799|Rv1691|
MVDDRQGRRGGRRPRSAAADNRPAFRDGPAIPPGIHARQLAPEIRRELSTLDRATADAVACHLVAAGELIDDDPEAALRHARAARVRASRIAAVREAVGIAAYRCGDWAQALAELRAARRMGSKSPLLALIADCERGLGRPQRAIELARGSEAVELSGDAADELRIVAAGARADLGQLEQALTVLSTPQLDPGRTGSTAARLFYAYAEILLALGRGDEALQWFLRSAAADIDGVTDAEDRVDELGAREQK