Rv1540 Resolved · high auto-curated

H37Rv Rv1540 · MTBC0 mtbc0_001647 · 308 aa · 1752654–1753580 (+) · RefSeq NP_216056.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)	RNA pseudouridine synthase
MTBC0 PGAP re-annotation	RNA pseudouridine synthase
Revised (this work)	RNA pseudouridine synthase. Pfam: PseudoU_synth_2 (PF00849.28).

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

Curated reference (UniProt)

UniProt	`P9WHQ3` SwissProt · reviewed · Evidence at protein level
UniProt name	Uncharacterized RNA pseudouridine synthase Rv1540
EC (curated)	`EC 5.4.99.-`

UniProt still lists this protein as Uncharacterized RNA pseudouridine synthase Rv1540; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category	`J` Translation, ribosomal structure and biogenesis
Preferred name	rluD
eggNOG description	Responsible for synthesis of pseudouridine from uracil
Orthologous group	`COG0564`
EC number	`EC 5.4.99.23`
KEGG orthology	`K06180`
Gene Ontology (44)	`GO:0000154`, `GO:0000455`, `GO:0001522`, `GO:0003674`, `GO:0003824`, `GO:0005575`, `GO:0005622`, `GO:0005623`, `GO:0005737`, `GO:0005829`, `GO:0006139`, `GO:0006364` +32 more

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, 3 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)

Pfam	Accession	i-Evalue	Residues	Description
`PseudoU_synth_2`	PF00849.28	5.7e-26	90–243	RNA pseudouridylate synthase

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

Closest characterised functional partner: lspA (lipoprotein signal peptidase), high confidence from genomic context alone (score 910 excluding text-mining).

Partner	Product	Score	No text-mining	Channels (≥400)
`Rv1539` lspA	lipoprotein signal peptidase	909	910 ctx	neighborhood:881
`Rv0701` rplC	50S ribosomal protein L3	862	856	experimental:804
`Rv0723` rplO	50S ribosomal protein L15	856	856	experimental:806
`Rv3443c` rplM	50S ribosomal protein L13	852	852	experimental:806
`Rv2442c` rplU	50S ribosomal protein L21	850	850	experimental:813
`Rv3456c` rplQ	50S ribosomal protein L17	847	847	experimental:813
`Rv0715` rplX	50S ribosomal protein L24	838	839	experimental:803
`Rv2420c` rsfS hyp	hypothetical protein	843	828	experimental:815
`Rv0640` rplK	50S ribosomal protein L11	827	819	experimental:809
`Rv0714` rplN	50S ribosomal protein L14	815	811	experimental:803
`Rv1538c` ansA	L-aparaginase	789	790 ctx	neighborhood:788
`Rv2440c` obg	GTPase Obg	801	780 ctx	cooccurence:594 experimental:442
`Rv0702` rplD	50S ribosomal protein L4	705	692 ctx	cooccurence:430 experimental:456
`Rv1643` rplT	50S ribosomal protein L20	702	685 ctx	cooccurence:464
`Rv2373c` dnaJ2	chaperone protein DnaJ	678	679	experimental:660

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: RNA pseudouridine synthase
MTBC0 PGAP product: RNA pseudouridine synthase
Pfam (hmmscan --cut_ga): PseudoU_synth_2 PF00849.28 (E=6e-26)
(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_216056.1)
Domains: Pfam-A via hmmscan --cut_ga — PseudoU_synth_2 (PF00849.28)
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 COG0564
Curated reference: UniProt P9WHQ3 (SwissProt, reviewed; 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)
Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 100 functional partner(s); context anchor lspA
Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001647|Rv1540|
MADRSMPVPDGLAGMRVDTGLARLLGLSRTAAAALAEEGAVELNGVPAGKSDRLVSGALLQVRLPEAPAPLQNTPIDIEGMTILYSDDDIVAVDKPAAVAAHASVGWTGPTVLGGLAAAGYRITTSGVHERQGIVHRLDVGTSGVMVVAISERAYTVLKRAFKYRTVDKRYHALVQGHPDPSSGTIDAPIGRHRGHEWKFAITKNGRHSLTHYDTLEAFVAASLLDVHLETGRTHQIRVHFAALHHPCCGDLVYGADPKLAKRLGLDRQWLHARSLAFAHPADGRRVEIVSPYPADLQHALKILRGEG