Rv0535 Resolved · high auto-curated

H37Rv Rv0535 · MTBC0 - · 264 aa · 626457–627251 (+) · RefSeq NP_215049.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)5'-methylthioadenosine phosphorylase
MTBC0 PGAP re-annotation
Revised (this work)5'-methylthioadenosine phosphorylase. Pfam: PNP_UDP_1 (PF01048.27).

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

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 O06401 SwissProt · reviewed · Evidence at protein level
UniProt nameS-methyl-5'-thioadenosine phosphorylase
EC (curated) EC 2.4.2.28
Curated functionCatalyzes the reversible phosphorylation of S-methyl-5'-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. Involved in the breakdown of MTA, a major by-product of polyamine biosynthesis. Responsible for the first step in the methionine salvage pathway after MTA has been generated from S-adenosylmethionine. Prefers MTA, with 2% activity on adenosine, 0.8% activity on S-adenosyl-L-homocysteine and no activity on other tested nucleosides.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namemtnP
eggNOG descriptionCatalyzes the reversible phosphorylation of S-methyl-5'- thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. Involved in the breakdown of MTA, a major by-product of polyamine biosynthesis. Responsible for the first step in the methionine salvage pathway after MTA has been generated from S- adenosylmethionine. Has broad substrate specificity with 6- aminopurine nucleosides as preferred substrates
Orthologous groupCOG0005
EC number EC 2.4.2.28
KEGG orthology K00772
KEGG pathways map00270, map01100
KEGG modules M00034

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 0.115 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 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
PNP_UDP_1PF01048.27 2.4e-359–239 Phosphorylase superfamily

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

Closest characterised functional partner: galE3 (UDP-glucose 4-epimerase GalE), high confidence from genomic context alone (score 934 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0536 galE3 UDP-glucose 4-epimerase GalE 991 934 ctx neighborhood:882 cooccurence:441 textmining:875
Rv0091 mtn 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase 992 903 database:900 textmining:929
Rv2601 speE spermidine synthase 986 901 database:900 textmining:870
Rv2584c apt adenine phosphoribosyltransferase 913 900 ctx fusion:766 database:408
Rv0534c menA 1,4-dihydroxy-2-naphthoate octaprenyltransferase 792 792 ctx neighborhood:791
Rv0533c fabH 3-oxoacyl-ACP synthase III 558 558 ctx neighborhood:558
Rv0539 dolichyl-phosphate sugar synthase 936 533 ctx cooccurence:416 textmining:870
Rv0435c ATPase 463 463
Rv0512 hemB delta-aminolevulinic acid dehydratase 454 455
Rv3396c guaA GMP synthase 588 437
Rv0489 gpm1 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase 431 432 database:400
Rv0540 hyp hypothetical protein 920 410 textmining:870
Rv0478 deoC 2-deoxyribose-5-phosphate aldolase 441 405
Rv3308 pmmB phosphomannomutase PmmB 428 387
Rv3441c mrsA phosphoglucosamine mutase 411 387

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): 5'-methylthioadenosine phosphorylase
  • Pfam (hmmscan --cut_ga): PNP_UDP_1 PF01048.27 (E=2e-35)
  • (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_215049.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PNP_UDP_1 (PF01048.27)
  • 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 COG0005
  • Curated reference: UniProt O06401 (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 — 24 functional partner(s); context anchor galE3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0535|
MHNNGRMLGVIGGSGFYTFFGSDTRTVNSDTPYGQPSAPITIGTIGVHDVAFLPRHGAHHQYSAHAVPYRANMWALRALGVRRVFGPCAVGSLDPELEPGAVVVPDQLVDRTSGRADTYFDFGGVHAAFADPYCPTLRAAVTGLPGVVDGGTMVVIQGPRFSTRAESQWFAAAGCNLVNMTGYPEAVLARELELCYAAIALVTDVDAGVAAGDGVKAADVFAAFGENIELLKRLVRAAIDRVADERTCTHCQHHAGVPLPFELP