Rv3898c Still unknown · low auto-curated

H37Rv Rv3898c · MTBC0 mtbc0_004131 · 110 aa · 4407907–4408236 (-) · RefSeq NP_218415.1

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: 5sva-assembly1_T Mediator-RNA Polymerase II Pre-Initiation Complex (prob 0.38, TM 0.59).

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

Curated reference (UniProt)

UniProt O05447 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 group2BK8T

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 1.429 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 missense, 1 nonsense, 1 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.31% of strains (447) · 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 49.4 (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
5sva-assembly1_T 0.38 0.59 1.9e+00 5sva-assembly1_T Mediator-RNA Polymerase II Pre-Initiation Complex
4jq5-assembly2_H 0.16 0.43 1.9e+00 4jq5-assembly2_H Crystal structure of the human Nup49CCS2+3* coiled-coil segment
4jq5-assembly1_B 0.14 0.43 2.6e+00 4jq5-assembly1_B Crystal structure of the human Nup49CCS2+3* coiled-coil segment
4jq5-assembly3_K 0.14 0.42 2.4e+00 4jq5-assembly3_K Crystal structure of the human Nup49CCS2+3* coiled-coil segment
4jq5-assembly3_L 0.11 0.43 3.4e+00 4jq5-assembly3_L Crystal structure of the human Nup49CCS2+3* coiled-coil segment
2osz-assembly2_D 0.11 0.41 3.4e+00 2osz-assembly2_D Structure of Nup58/45 suggests flexible nuclear pore diameter by intermolecular sliding
8bqs-assembly1_De 0.08 0.41 4.2e+00 8bqs-assembly1_De Cryo-EM structure of the I-II-III2-IV2 respiratory supercomplex from Tetrahymena thermophila
1vp7-assembly1_A 0.07 0.42 5.4e+00 1vp7-assembly1_A Crystal structure of Exodeoxyribonuclease VII small subunit (NP_881400.1) from Bordetella pertussis at 2.40 A resolution

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

Closest characterised functional partner: eccC2 (ESX-2 type VII secretion system protein EccC), medium confidence from genomic context alone (score 480 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3897c hyp hypothetical protein 803 803 ctx neighborhood:757
Rv1617 pykA pyruvate kinase 508 509 coexpression:509
Rv3900c hyp hypothetical protein 503 503 ctx neighborhood:498
Rv3899c hyp hypothetical protein 486 486 ctx neighborhood:484
Rv3894c eccC2 ESX-2 type VII secretion system protein EccC 480 480 ctx neighborhood:466
Rv3895c eccB2 ESX-2 secretion system protein EccB 488 473 ctx neighborhood:471
Rv3896c hyp hypothetical protein 466 466 ctx neighborhood:463

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: 5sva-assembly1_T Mediator-RNA Polymerase II Pre-Initiation Complex (prob 0.38, E=2e+00, TM=0.59)
  • (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_218415.1)
  • 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 2BK8T
  • Curated reference: UniProt O05447 (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 49.4, very low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 7 functional partner(s); context anchor eccC2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004131|Rv3898c|
MTGDQNPAPGPAPGVPIKVTPEILLQVLTTPPASGPAPFPAVPVDLPAPADIANGALFAAGNSGVPGDVESSGLEDLDRRAHAADAVQKFSANEADAAQQFQGVGAQAEA