Rv2825c Still unknown · low

H37Rv Rv2825c · MTBC0 - · 215 aa · 3132892–3133539 (-) · RefSeq NP_217341.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Conserved hypothetical; function unknown. Structure-based hint rejected: structural ASCH hit contradicts the DUF1802 Pfam assignment; function unknown.

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 P71627 TrEMBL · unreviewed · Predicted
UniProt nameDUF1802 family protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionDomain of unknown function (DUF1802)
Orthologous groupCOG4293

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 1.879 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 5 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
DUF1802PF08819.18 1.3e-5538–208 Domain of unknown function (DUF1802)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 91.7 (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
5guq-assembly4_D 1.00 0.54 1.2e-03 sig 5guq-assembly4_D Crystal structure of ASCH from Zymomonas mobilis
5y7d-assembly1_A-2 1.00 0.55 1.6e-03 sig 5y7d-assembly1_A-2 Crystal structure of human Endothelial-overexpressed LPS associated factor 1
5y6c-assembly2_B 1.00 0.49 4.8e-04 sig 5y6c-assembly2_B Crystal structure of ZmASCH S128A mutant protein from Zymomonas mobilis
5y6b-assembly4_D 1.00 0.50 8.8e-04 sig 5y6b-assembly4_D Crystal structure of ZmASCH Y47F mutant protein from Zymomonas mobilis
6kit-assembly1_A 0.99 0.52 4.2e-03 sig 6kit-assembly1_A Structure of mouse CXorf40A, Selenomethionine derivative
1jhd-assembly1_A-2 0.04 0.34 2.6e+00 1jhd-assembly1_A-2 Crystal Structure of Bacterial ATP Sulfurylase from the Riftia pachyptila Symbiont
7ohq-assembly1_X 0.02 0.19 2.3e+00 7ohq-assembly1_X Nog1-TAP associated immature ribosomal particle population C from S. cerevisiae
6ft6-assembly1_X 0.01 0.21 6.7e+00 6ft6-assembly1_X Structure of the Nop53 pre-60S particle bound to the exosome nuclear cofactors

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

Closest characterised functional partner: Rv3779 (transmembrane protein), medium confidence from genomic context alone (score 640 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2828c hyp hypothetical protein 852 852 coexpression:804
Rv3779 transmembrane protein 640 640 ctx cooccurence:640
Rv0048c membrane protein 533 533 ctx cooccurence:533
Rv0517 acyltransferase 513 513 ctx cooccurence:513
Rv0875c hyp hypothetical protein 500 501 ctx cooccurence:485
Rv2827c hyp hypothetical protein 493 492 ctx neighborhood:480
Rv2826c hyp hypothetical protein 487 487 ctx neighborhood:480
Rv2824c cas6 CRISPR-associated endoribonuclease Cas6 463 464 ctx neighborhood:458
Rv2816c cas2 CRISPR-associated endoribonuclease Cas2 464 463
Rv2823c cas10 CRISPR-associated protein Cas10/Csm1 460 461 ctx neighborhood:458
Rv2819c csm5 CRISPR type III-associated RAMP protein Csm5 460 460 ctx neighborhood:457
Rv2822c csm2 CRISPR type III-associated protein Csm2 459 460 ctx neighborhood:458
Rv2820c csm4 CRISPR type III-associated RAMP protein Csm4 459 459 ctx neighborhood:457
Rv2821c csm3 CRISPR type III-associated RAMP protein Csm3 459 459 ctx neighborhood:457
Rv1845c blaR sensor-transducer protein BlaR 422 423 coexpression:423

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

  • Structural Foldseek hit not propagated -- structural ASCH hit contradicts the DUF1802 Pfam assignment; function unknown
  • Reviewed against literature (extended structural cross-check, 2026-06-02)

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_217341.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF1802 (PF08819.18)
  • 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 COG4293
  • Curated reference: UniProt P71627 (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 91.7, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 16 functional partner(s); context anchor Rv3779
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2825c|
MKLPGAKRLGDDRRPLGTLRCWRHSDIGPARGIVVTPALKEWSAAVHALLDGRQTVLLRKGGIGEKRFEVAAHEFLLFPTVAHSHAERVRPEHRDLLGPAAADSTDECVLLRAAAKVVAALPVNRPEGLDAIEDLHIWTAESVRADRLDFRPKHKLAVLVVSAIPLAEPVRLARRPEYGGCTSWVQLPVTPTLAAPVHDEAALAEVAARVREAVG