Rv0540 Family assigned · low

H37Rv Rv0540 · MTBC0 mtbc0_000569 · 220 aa · 635923–636585 (+) · RefSeq NP_215054.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF2064 domain-containing protein
Revised (this work)DUF2064; fold of a putative nucleotide-diphospho-sugar transferase (PDB 3CGX); putative sugar/nucleotidyl transferase.

Curated reference (UniProt)

UniProt O06406 TrEMBL · unreviewed · Evidence at protein level
UniProt nameGlycosyltransferase involved in cell wall biogenesis

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionUncharacterized protein conserved in bacteria (DUF2064)
Orthologous groupCOG3222
KEGG orthology K09931

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 0.19 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 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)

PfamAccessioni-EvalueResiduesDescription
DUF2064PF09837.16 4.1e-2944–165 Uncharacterized protein conserved in bacteria (DUF2064)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 97.8 (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
3cgx-assembly1_A 1.00 0.83 2.1e-15 sig 3cgx-assembly1_A Crystal structure of putative nucleotide-diphospho-sugar transferase (YP_389115.1) from Desulfovibrio desulfuricans G20 at 1.90 A resolution
6bwg-assembly1_A 1.00 0.74 1.6e-09 sig 6bwg-assembly1_A Crystal structure of native Rv2983 from Mycobacterium tuberculosis
7p97-assembly2_BBB 1.00 0.71 5.6e-10 sig 7p97-assembly2_BBB Structure of 3-phospho-D-glycerate guanylyltransferase with product 3-GPPG bound
2i5e-assembly1_B 1.00 0.77 3.8e-08 sig 2i5e-assembly1_B Crystal Structure of a Protein of Unknown Function MM2497 from Methanosarcina mazei Go1, Probable Nucleotidyltransferase
6bwh-assembly3_C 1.00 0.76 2.0e-08 sig 6bwh-assembly3_C Crystal structure of Mycoibacterium tuberculosis Rv2983 in complex with PEP
6bwg-assembly2_B 1.00 0.73 3.8e-08 sig 6bwg-assembly2_B Crystal structure of native Rv2983 from Mycobacterium tuberculosis
2wee-assembly2_B 1.00 0.63 1.2e-06 sig 2wee-assembly2_B Crystal structure of Rv0371c from Mycobacterium tuberculosis H37Rv
2wee-assembly1_A 1.00 0.64 1.6e-06 sig 2wee-assembly1_A Crystal structure of Rv0371c from Mycobacterium tuberculosis H37Rv

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

Closest characterised functional partner: Rv0539 (dolichyl-phosphate sugar synthase), high confidence from genomic context alone (score 985 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0539 dolichyl-phosphate sugar synthase 997 985 ctx neighborhood:882 fusion:499 cooccurence:766 textmining:870
Rv0218 transmembrane protein 885 886 ctx neighborhood:521 cooccurence:771
Rv0536 galE3 UDP-glucose 4-epimerase GalE 975 817 ctx cooccurence:770 textmining:870
Rv0541c integral membrane protein 974 811 ctx cooccurence:771 textmining:870
Rv0538 membrane protein 806 806 ctx neighborhood:804
Rv0219 transmembrane protein 684 684 ctx cooccurence:637
Rv2963 integral membrane protein 453 453 ctx cooccurence:453
Rv0535 pnp 5'-methylthioadenosine phosphorylase 920 410 textmining:870
Rv2855 mtr mycothione reductase 735 81 textmining:724
Rv2051c ppm1 polyprenol-monophosphomannose synthase 663 78 textmining:650
Rv3631 transferase 874 77 textmining:870
Rv0091 mtn 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase 808 47 textmining:807

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

  • MTBC0 PGAP product: DUF2064 domain-containing protein
  • Pfam: DUF2064 PF09837.16
  • Foldseek best: 3cgx-assembly1_A Crystal structure of putative nucleotide-diphospho-sugar transf (prob 1.00, E=2e-15, TM=0.83)
  • (structure-only promotion reviewed by hand, 2026-06-01)

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_215054.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF2064 (PF09837.16)
  • 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 COG3222
  • Curated reference: UniProt O06406 (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 97.8, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 12 functional partner(s); context anchor Rv0539
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000569|Rv0540|
MSCLPVSVLVVAKAPEPGRVKTRLAAAIGDKVAADIAAAALLDTLDAVAAAPVTARAVALTGDLDSAADSAEIRRRLKSFTVFRQRGDAFADRLANAHVDAADGYPVLQIGMDTPQVTAELLADCARLLLQIPAVLGLAFDGGWWVLGIRTPTAAECLRAVPMSQPDTGELTLKALRDNGIDVTLVQRLGDFDIVDDIALVRDCCAPGSRFAQATRAAGL