prsA Resolved · high auto-curated

H37Rv Rv1017c · MTBC0 mtbc0_001092 · 326 aa · 1142838–1143818 (-) · RefSeq NP_215533.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribose-phosphate pyrophosphokinase
MTBC0 PGAP re-annotationribose-phosphate diphosphokinase
Revised (this work)Ribose-phosphate diphosphokinase. Pfam: Pribosyltran_N (PF13793.13), Pribosyltran (PF00156.34), Pribosyl_synth (PF14572.13).

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

Curated reference (UniProt)

UniProt P9WKE3 SwissProt · reviewed · Evidence at protein level
UniProt nameRibose-phosphate pyrophosphokinase
EC (curated) EC 2.7.6.1
Curated functionInvolved in the biosynthesis of the central metabolite phospho-alpha-D-ribosyl-1-pyrophosphate (PRPP) and of the decaprenylphosphoryl-arabinose (DPA), an essential precursor for the mycobacterial cell wall biosynthesis. Catalyzes the transfer of pyrophosphoryl group from ATP to 1-hydroxyl of ribose-5-phosphate (Rib-5-P) to yield phosphoribosyl diphosphate (PRPP) and AMP. It can also use GTP, CTP and UTP as diphosphoryl donors.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred nameprs
eggNOG descriptionInvolved in the biosynthesis of the central metabolite phospho-alpha-D-ribosyl-1-pyrophosphate (PRPP) via the transfer of pyrophosphoryl group from ATP to 1-hydroxyl of ribose-5-phosphate (Rib-5-P)
Orthologous groupCOG0462
EC number EC 2.7.6.1
KEGG orthology K00948
KEGG pathways map00030, map00230, map01100, map01110, map01120, map01130, map01200, map01230
KEGG modules M00005
Gene Ontology (39) GO:0000287, GO:0003674, GO:0003824, GO:0004749, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006015, GO:0006793, GO:0006796 +27 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 0.25 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 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)

PfamAccessioni-EvalueResiduesDescription
Pribosyltran_NPF13793.13 3.9e-4912–128 N-terminal domain of ribose phosphate pyrophosphokinase
PribosyltranPF00156.34 2.9e-17161–263 Phosphoribosyl transferase domain
Pribosyl_synthPF14572.13 1.8e-20216–322 Phosphoribosyl synthetase-associated domain

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

Closest characterised functional partner: glmU (bifunctional UDP-N-acetylglucosamine pyrophosphorylase/glucosamine-1-phosphate N-acetyltransferase), high confidence from genomic context alone (score 960 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2496c bkdB 3-methyl-2-oxobutanoate dehydrogenase subunit beta 989 987 coexpression:407 experimental:869 database:844
Rv1248c kgd multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase 987 980 experimental:831 database:844 textmining:429
Rv1018c glmU bifunctional UDP-N-acetylglucosamine pyrophosphorylase/glucosamine-1-phosphate N-acetyltransferase 969 960 ctx neighborhood:778 cooccurence:442 coexpression:700
Rv1449c tkt transketolase 964 944 coexpression:463 database:900
Rv2436 rbsK ribokinase RbsK 934 925 database:900
Rv0808 purF amidophosphoribosyltransferase 959 918 database:900 textmining:519
Rv2465c rpiB ribose-5-phosphate isomerase B 928 906 database:900
Rv3068c pgmA phosphoglucomutase PgmA 910 901 database:900
Rv1015c rplY 50S ribosomal protein L25/general stress protein Ctc 873 852 ctx neighborhood:503 coexpression:714
Rv1826 gcvH glycine cleavage system protein H 855 849 database:844
Rv1016c lpqT lipoprotein LpqT 833 834 ctx neighborhood:832
Rv2215 dlaT pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase 845 831 experimental:434 database:623
Rv2121c hisG ATP phosphoribosyltransferase 863 827 database:800
Rv2495c bkdC branched-chain keto acid dehydrogenase E2 component 839 825 experimental:434 database:623
Rv1734c hyp hypothetical protein 838 824 experimental:434 database:623

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: ribose-phosphate pyrophosphokinase
  • MTBC0 PGAP product: ribose-phosphate diphosphokinase
  • Pfam (hmmscan --cut_ga): Pribosyltran_N PF13793.13 (E=4e-49), Pribosyltran PF00156.34 (E=3e-17), Pribosyl_synth PF14572.13 (E=2e-20)
  • (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_215533.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Pribosyltran_N (PF13793.13), Pribosyltran (PF00156.34), Pribosyl_synth (PF14572.13)
  • 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 COG0462
  • Curated reference: UniProt P9WKE3 (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 — 204 functional partner(s); context anchor glmU
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001092|Rv1017c|prsA
MSHDWTDNRKNLMLFAGRAHPELAEQVAKELDVHVTSQDAREFANGEIFVRFHESVRGCDAFVLQSCPAPVNRWLMEQLIMIDALKRGSAKRITAVMPFYPYARQDKKHRGREPISARLIADLLKTAGADRIVTVDLHTDQIQGFFDGPVDHMRGQNLLTGYIRDNYPDGNMVVVSPDSGRVRIAEKWADALGGVPLAFIHKTRDPRVPNQVVSNRVVGDVAGRTCVLIDDMIDTGGTIAGAVALLHNDGAGDVIIAATHGVLSDPAAQRLASCGAREVIVTNTLPIGEDKRFPQLTVLSIAPLLASTIRAVFENGSVTGLFDGDA