Rv2680 Still unknown · low auto-curated

H37Rv Rv2680 · MTBC0 mtbc0_002854 · 210 aa · 3018520–3019152 (+) · RefSeq NP_217196.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF3000 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF3000. Function unknown. Foldseek best (non-significant) hit: 8any-assembly1_f Human mitochondrial ribosome in complex with LRPPRC, (prob 0.44, TM 0.39).

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

Curated reference (UniProt)

UniProt O86317 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF3000)
Orthologous group2AIF4

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, 1 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)

PfamAccessioni-EvalueResiduesDescription
DUF3000PF11452.14 4.0e-7223–202 Protein of unknown function (DUF3000)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 88.0 (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
8any-assembly1_f 0.44 0.39 6.8e-02 8any-assembly1_f Human mitochondrial ribosome in complex with LRPPRC, SLIRP, A-site, P-site, E-site tRNAs and mRNA
5aj4-assembly1_AJ 0.38 0.39 1.4e-01 5aj4-assembly1_AJ Structure of the 55S mammalian mitoribosome.
6bok-assembly1_RA 0.28 0.33 1.1e-01 6bok-assembly1_RA E. coli release factor 1 (containing deletion 302-304) bound to the 70S ribosome
3fzb-assembly1_H 0.25 0.40 2.0e-01 3fzb-assembly1_H Crystal structure of the tail terminator protein from phage lambda (gpU-WT)
7nqh-assembly1_AJ 0.21 0.39 4.3e-01 7nqh-assembly1_AJ 55S mammalian mitochondrial ribosome with mtRF1a and P-site tRNAMet
6vmi-assembly1_f 0.21 0.41 4.8e-01 6vmi-assembly1_f Structure of the human mitochondrial ribosome-EF-G1 complex (ClassIII)
9d94-assembly1_If 0.16 0.41 5.8e-01 9d94-assembly1_If Mycobacteriophage Bxb1 portal and connector assembly - Composite map and model
8pk0-assembly1_f 0.16 0.41 6.1e-01 8pk0-assembly1_f human mitoribosomal large subunit assembly intermediate 1 with GTPBP10-GTPBP7

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

Closest characterised functional partner: echA15 (enoyl-CoA hydratase EchA15), high confidence from genomic context alone (score 753 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2681 hyp hypothetical protein 974 975 ctx neighborhood:882 coexpression:744
Rv2676c hemQ hyp hypothetical protein 822 822 ctx neighborhood:694 cooccurence:434
Rv2679 echA15 enoyl-CoA hydratase EchA15 753 753 ctx neighborhood:747
Rv2413c hyp hypothetical protein 738 739 ctx cooccurence:738
Rv2256c hyp hypothetical protein 743 733 ctx cooccurence:728
Rv2050 rbpA RNA polymerase-binding protein RbpA 733 733 ctx cooccurence:733
Rv2219 transmembrane protein 711 712 ctx cooccurence:710
Rv2677c hemY protoporphyrinogen oxidase 703 703 ctx neighborhood:694
Rv2678c hemE uroporphyrinogen decarboxylase 698 698 ctx neighborhood:694
Rv2699c hyp hypothetical protein 680 680 ctx cooccurence:680
Rv2708c hyp hypothetical protein 670 671 ctx cooccurence:669
Rv2169c transmembrane protein 670 670 ctx cooccurence:670
Rv1830 HTH-type transcriptional regulator 642 643 ctx cooccurence:634
Rv2146c transmembrane protein 641 641 ctx cooccurence:637
Rv1087A Rv1087A, len: 106 aa (fragment). Conserved hypothetical protein, highly similar to C-terminus of near ORF O53434|YA86_MYCTU|Rv1086|MT1118|MT 637 637 ctx cooccurence:637

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: DUF3000 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF3000 PF11452.14 (E=4e-72)
  • Foldseek best: 8any-assembly1_f Human mitochondrial ribosome in complex with LRPPRC, SLIRP, A-s (prob 0.44, E=7e-02, TM=0.39)
  • (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_217196.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF3000 (PF11452.14)
  • 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 2AIF4
  • Curated reference: UniProt O86317 (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 88.0, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 53 functional partner(s); context anchor echA15
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002854|Rv2680|
MTSAGDDAERSDEEERRLTSAEPALFREAVAAMNAVTVRPEIELGPIRPPQRLAPYSYALGAEIKHPELDVIPERSEGDAFGRLIMLYDPDGSDAWDGTIRLVAYVQADLDSSEAVDPLLPEVAWSWLVDALTARTDQVRALGGTVTATTSVRYGDISGPPRAHQLELRASWTATTPDLGAHVQAFCDVLEHAAGLPPAGVTDLGSRSRA