purC Resolved · high auto-curated

H37Rv Rv0780 · MTBC0 mtbc0_000829 · 297 aa · 877767–878660 (+) · RefSeq NP_215294.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)phosphoribosylaminoimidazole-succinocarboxamide synthase
MTBC0 PGAP re-annotationphosphoribosylaminoimidazolesuccinocarboxamide synthase
Revised (this work)Phosphoribosylaminoimidazolesuccinocarboxamide synthase. Pfam: SAICAR_synt (PF01259.25).

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

Curated reference (UniProt)

UniProt P9WHN1 SwissProt · reviewed · Evidence at protein level
UniProt namePhosphoribosylaminoimidazole-succinocarboxamide synthase
EC (curated) EC 6.3.2.6

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namepurC
eggNOG descriptionBelongs to the SAICAR synthetase family
Orthologous groupCOG0152
EC number EC 6.3.2.6, EC 6.3.4.13
KEGG orthology K01923, K01945
KEGG pathways map00230, map01100, map01110, map01130
KEGG modules M00048
Gene Ontology (68) GO:0003674, GO:0003824, GO:0004639, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0006139, GO:0006163, GO:0006164, GO:0006188, GO:0006189 +56 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 1.34 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 4 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
SAICAR_syntPF01259.25 2.3e-7511–260 SAICAR synthetase

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

Closest characterised functional partner: purD (phosphoribosylamine--glycine ligase), high confidence from genomic context alone (score 994 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0772 purD phosphoribosylamine--glycine ligase 998 994 ctx fusion:898 coexpression:857 textmining:732
Rv0777 purB adenylosuccinate lyase PurB 997 992 coexpression:857 database:900 textmining:738
Rv3275c purE 5-(carboxyamino)imidazole ribonucleotide mutase 992 991 coexpression:858 database:900
Rv0956 purN phosphoribosylglycinamide formyltransferase PurN 957 932 coexpression:861 textmining:407
Rv0957 purH bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase 982 925 coexpression:859 experimental:420 textmining:772
Rv0803 purL phosphoribosylformylglycinamidine synthase 2 921 897 coexpression:858
Rv0809 purM phosphoribosylformylglycinamidine cyclo-ligase PurM 936 892 coexpression:857 textmining:431
Rv0808 purF amidophosphoribosyltransferase 916 891 coexpression:857
Rv0788 purQ phosphoribosylformylglycinamidine synthase 911 884 coexpression:858
Rv0787A purS hyp hypothetical protein 910 883 coexpression:857
Rv3276c purK 5-(carboxyamino)imidazole ribonucleotide synthase 952 869 coexpression:858 textmining:656
Rv0782 ptrBb Rv0782, (MTCY369.26), len: 552 aa. Probable ptrBb,second part of protease II, equivalent to C-terminus of NP_302455.1|NC_002677 protease II 805 804 ctx neighborhood:800
Rv0781 ptrBa Rv0781, (MTCY369.25), len: 236 aa. Probable ptrBa,first part of protease II, equivalent to N-terminus of NP_302455.1|NC_002677 protease II f 802 802 ctx neighborhood:800
Rv0357c purA adenylosuccinate synthetase 831 738 coexpression:661
Rv1832 gcvB glycine dehydrogenase 756 725 coexpression:700

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: phosphoribosylaminoimidazole-succinocarboxamide synthase
  • MTBC0 PGAP product: phosphoribosylaminoimidazolesuccinocarboxamide synthase
  • Pfam (hmmscan --cut_ga): SAICAR_synt PF01259.25 (E=2e-75)
  • (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_215294.1)
  • Domains: Pfam-A via hmmscan --cut_ga — SAICAR_synt (PF01259.25)
  • 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 COG0152
  • Curated reference: UniProt P9WHN1 (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 — 59 functional partner(s); context anchor purD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000829|Rv0780|purC
MRPALSDYQHVASGKVREIYRVDDEHLLLVASDRISAYDYVLDSTIPDKGRVLTAMSAFFFGLVDAPNHLAGPPDDPRIPDEVLGRALVVRRLEMLPVECVARGYLTGSGLLDYQATGKVCGIALPPGLVEASRFATPLFTPATKAALGDHDENISFDRVVEMVGALRANQLRDRTLQTYVQAADHALTRGIIIADTKFEFGIDRHGNLLLADEIFTPDSSRYWPADDYRAGVVQTSFDKQFVRSWLTGSESGWDRGSDRPPPPLPEHIVEATRARYINAYERISELKFDDWIGPGA