purK Resolved · high auto-curated

H37Rv Rv3276c · MTBC0 mtbc0_003484 · 429 aa · 3680778–3682067 (-) · RefSeq NP_217793.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)5-(carboxyamino)imidazole ribonucleotide synthase
MTBC0 PGAP re-annotation5-(carboxyamino)imidazole ribonucleotide synthase
Revised (this work)5-(carboxyamino)imidazole ribonucleotide synthase. Pfam: RS_preATP-grasp-like (PF22660.3), CPSase_L_D2 (PF02786.23), ATP-grasp (PF02222.28), PurK_C (PF17769.8).

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

Curated reference (UniProt)

UniProt P9WHL9 SwissProt · reviewed · Evidence at protein level
UniProt nameN5-carboxyaminoimidazole ribonucleotide synthase
EC (curated) EC 6.3.4.18
Curated functionCatalyzes the ATP-dependent conversion of 5-aminoimidazole ribonucleotide (AIR) and HCO(3)(-) to N5-carboxyaminoimidazole ribonucleotide (N5-CAIR).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namepurK
eggNOG descriptionCatalyzes the ATP-dependent conversion of 5- aminoimidazole ribonucleotide (AIR) and HCO(3)(-) to N5- carboxyaminoimidazole ribonucleotide (N5-CAIR)
Orthologous groupCOG0026
EC number EC 6.3.4.18
KEGG orthology K01589
KEGG pathways map00230, map01100, map01110, map01130
KEGG modules M00048
Gene Ontology (11) GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0044424, GO:0044444, GO:0044464, GO:0071944

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 0.089 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 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
RS_preATP-grasp-likePF22660.3 8.2e-2120–115 Ribonucleotide synthetase preATP-grasp domain
CPSase_L_D2PF02786.23 1.4e-07116–279 Carbamoyl-phosphate synthase L chain, ATP binding domain
ATP-graspPF02222.28 1.2e-61123–302 ATP-grasp domain
PurK_CPF17769.8 8.0e-16324–384 Phosphoribosylaminoimidazole carboxylase C-terminal domain

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

Closest characterised functional partner: purE (5-(carboxyamino)imidazole ribonucleotide mutase), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3275c purE 5-(carboxyamino)imidazole ribonucleotide mutase 999 1000 ctx neighborhood:881 fusion:900 cooccurence:738 coexpression:891 database:900 textmining:954
Rv0809 purM phosphoribosylformylglycinamidine cyclo-ligase PurM 995 992 ctx cooccurence:420 coexpression:857 database:900 textmining:449
Rv0788 purQ phosphoribosylformylglycinamidine synthase 946 929 ctx cooccurence:479 coexpression:858
Rv0803 purL phosphoribosylformylglycinamidine synthase 2 959 928 ctx cooccurence:473 coexpression:859 textmining:462
Rv0772 purD phosphoribosylamine--glycine ligase 953 924 ctx cooccurence:452 coexpression:856 textmining:416
Rv0957 purH bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase 991 915 coexpression:859 textmining:904
Rv0808 purF amidophosphoribosyltransferase 992 901 coexpression:857 textmining:928
Rv0956 purN phosphoribosylglycinamide formyltransferase PurN 942 900 coexpression:859 textmining:455
Rv0787A purS hyp hypothetical protein 911 879 coexpression:840
Rv0777 purB adenylosuccinate lyase PurB 978 870 coexpression:859 textmining:845
Rv0780 purC phosphoribosylaminoimidazole-succinocarboxamide synthase 952 869 coexpression:858 textmining:656
Rv3274c fadE25 acyl-CoA dehydrogenase 855 855 ctx neighborhood:849
Rv0423c thiC phosphomethylpyrimidine synthase 801 802 database:800
Rv0389 purT phosphoribosylglycinamide formyltransferase PurT 786 761 coexpression:642
Rv0357c purA adenylosuccinate synthetase 743 665 coexpression:653

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: 5-(carboxyamino)imidazole ribonucleotide synthase
  • MTBC0 PGAP product: 5-(carboxyamino)imidazole ribonucleotide synthase
  • Pfam (hmmscan --cut_ga): RS_preATP-grasp-like PF22660.3 (E=8e-21), CPSase_L_D2 PF02786.23 (E=1e-07), ATP-grasp PF02222.28 (E=1e-61), PurK_C PF17769.8 (E=8e-16)
  • (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_217793.1)
  • Domains: Pfam-A via hmmscan --cut_ga — RS_preATP-grasp-like (PF22660.3), CPSase_L_D2 (PF02786.23), ATP-grasp (PF02222.28), PurK_C (PF17769.8)
  • 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 COG0026
  • Curated reference: UniProt P9WHL9 (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 — 47 functional partner(s); context anchor purE
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003484|Rv3276c|purK
MMAVASSRTPAVTSFIAPLVAMVGGGQLARMTHQAAIALGQNLRVLVTSADDPAAQVTPNVVIGSHTDLAALRRVAAGADVLTFDHEHVPNELLEKLVADGVNVAPSPQALVHAQDKLVMRQRLAAAGVAVPRYAGIKDPDEIDVFAARVDAPIVVKAVRGGYDGRGVRMARDVADARDFARECLADGVAVLVEERVDLRRELSALVARSPFGQGAAWPVVQTVQRDGTCVLVIAPAPALPDDLATAAQRLALQLADELGVVGVLAVELFETTDGALLVNELAMRPHNSGHWTIDGARTSQFEQHLRAVLDYPLGDSDAVVPVTVMANVLGAAQPPAMSVDERLHHLFARMPDARVHLYGKAERPGRKVGHINFLGSDVAQLCERAELAAHWLSHGRWTDGWDPHRASDDAVGVPPACGGRSDEEERRL