Rv3678A Family assigned · low auto-curated · to review

H37Rv Rv3678A · MTBC0 - · 53 aa · 4118530–4118691 (-) · RefSeq YP_178004.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)No Pfam domain above threshold; Foldseek indicates a fold similar to 8i0t-assembly1_C The cryo-EM structure of human Bact-III complex (prob 1.00, TM 0.82). Structure-based, putative.

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).

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 I6X824 TrEMBL · unreviewed · Evidence at protein level
UniProt nameDUF4177 domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionDomain of unknown function (DUF4177)
Orthologous group2E3JZ

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, 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)

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 73.0 (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
8i0t-assembly1_C 1.00 0.82 2.1e-01 8i0t-assembly1_C The cryo-EM structure of human Bact-III complex
8i0w-assembly1_C 1.00 0.82 2.1e-01 8i0w-assembly1_C The cryo-EM structure of human C complex
6ahd-assembly1_C 1.00 0.81 2.5e-01 6ahd-assembly1_C The Cryo-EM Structure of Human Pre-catalytic Spliceosome (B complex) at 3.8 angstrom resolution
3jb9-assembly1_B 1.00 0.79 3.2e-01 3jb9-assembly1_B Cryo-EM structure of the yeast spliceosome at 3.6 angstrom resolution
6icz-assembly1_C 0.99 0.81 3.6e-01 6icz-assembly1_C Cryo-EM structure of a human post-catalytic spliceosome (P complex) at 3.0 angstrom
5a9x-assembly1_A 0.99 0.77 3.4e-01 5a9x-assembly1_A Structure of GDP bound BipA
8h6e-assembly1_5C 0.99 0.81 4.3e-01 8h6e-assembly1_5C Cryo-EM structure of human exon-defined spliceosome in the late pre-B state.
4zck-assembly1_A 0.99 0.80 5.1e-01 4zck-assembly1_A Crystal Structure of C-terminal Fragment of Escherichia coli BipA/TypA

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

Closest characterised functional partner: Rv3677c (beta lactamase), high confidence from genomic context alone (score 869 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3678c hyp hypothetical protein 875 875 ctx neighborhood:867
Rv3677c beta lactamase 869 869 ctx neighborhood:867
Rv3679 anion transporter ATPase 785 785 ctx neighborhood:783
Rv3680 anion transporter ATPase 785 785 ctx neighborhood:783
Rv1211 hyp hypothetical protein 773 773 ctx cooccurence:770
Rv3597c lsr2 iron-regulated H-NS-like protein 484 484 ctx cooccurence:481

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: 8i0t-assembly1_C The cryo-EM structure of human Bact-III complex (prob 1.00, E=2e-01, TM=0.82)
  • (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 YP_178004.1)
  • 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 2E3JZ
  • Curated reference: UniProt I6X824 (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 73.0, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 6 functional partner(s); context anchor Rv3677c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3678A|
MTQPTAWEYATVPLLTHATKQILDQWGADGWELVAVLPGPTGEQHVAYLKRPK