Rv3108 Still unknown · low auto-curated

H37Rv Rv3108 · MTBC0 - · 146 aa · 3477060–3477500 (+) · RefSeq NP_217624.1

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: 6qc3-assembly1_B5 Ovine respiratory supercomplex I+III2 open class 1 (prob 0.02, TM 0.19).

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 O05785 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.

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

pN/pS 1.009 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 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 53.2 (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
6qc3-assembly1_B5 0.02 0.19 5.6e+00 6qc3-assembly1_B5 Ovine respiratory supercomplex I+III2 open class 1

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

Closest characterised functional partner: agpS (alkyldihydroxyacetonephosphate synthase), medium confidence from genomic context alone (score 547 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3107c agpS alkyldihydroxyacetonephosphate synthase 547 547 ctx neighborhood:545
Rv3109 moaA1 cyclic pyranopterin monophosphate synthase 742 489 ctx neighborhood:476 textmining:517
Rv3110 moaB1 pterin-4-alpha-carbinolamine dehydratase 445 403
Rv3111 moaC1 cyclic pyranopterin monophosphate synthase accessory protein 693 399 textmining:511
Rv3112 moaD1 molybdenum cofactor biosynthesis protein MoaD 690 381 textmining:520
Rv0218 transmembrane protein 621 50 textmining:618
Rv3611 Rv3611, (MTCY07H7B.11c), len: 217 aa. Hypothetical unknown arg-, pro-rich protein. Possible ORF containing several direct repeats. 632 47 textmining:630
Rv3124 moaR1 transcriptional regulator MoaR 435 45 textmining:433
Rv1529 fadD24 fatty-acid--CoA ligase FadD24 440 44 textmining:439
Rv2089c pepE dipeptidase PepE 440 44 textmining:439
Rv0147 aldehyde dehydrogenase 435 42 textmining:435
Rv2900c fdhF formate dehydrogenase subunit alpha FdhF 625 41 textmining:625
Rv1066 hyp hypothetical protein 566 41 textmining:566
Rv1084 hyp hypothetical protein 514 41 textmining:514
Rv3201c adnB ATP-dependent DNA helicase 439 41 textmining:439

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: 6qc3-assembly1_B5 Ovine respiratory supercomplex I+III2 open class 1 (prob 0.02, E=6e+00, TM=0.19)
  • (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_217624.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Curated reference: UniProt O05785 (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 53.2, low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 15 functional partner(s); context anchor agpS
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3108|
MTPNAASTGDSAKNTITGCCLITARALVARTRSISLPGMPFRMPADYHNASSDEPTNRHPWPAPARCCRHEWRTMRRTNACDRRRFGLSLTIHEDACRIISVVPVVLEVRRAEPAHPATPYPEPLARCSRSPGLNESSHMSGRIPP