purA Resolved · high auto-curated
H37Rv Rv0357c · MTBC0 mtbc0_000377 ·
432 aa · 438833–440131 (-) ·
RefSeq NP_214871.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | adenylosuccinate synthetase |
|---|---|
| MTBC0 PGAP re-annotation | adenylosuccinate synthase |
| Revised (this work) | Adenylosuccinate synthase. Pfam: Adenylsucc_synt (PF00709.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHN3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Adenylosuccinate synthetase |
| EC (curated) |
EC 6.3.4.4
|
| Curated function | Plays an important role in the de novo pathway of purine nucleotide biosynthesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | purA |
| eggNOG description | Plays an important role in the de novo pathway of purine nucleotide biosynthesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP |
| Orthologous group | COG0104 |
| EC number |
EC 6.3.4.4
|
| KEGG orthology |
K01939
|
| KEGG pathways |
map00230, map00250, map01100
|
| KEGG modules |
M00049
|
| Gene Ontology (69) |
GO:0003674, GO:0003824, GO:0004019, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0006139, GO:0006163, GO:0006164, GO:0006167, GO:0006725 +57 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 | 0.108 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 13 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Adenylsucc_synt | PF00709.28 | 3.7e-180 | 5–422 | Adenylosuccinate synthetase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: guaA (GMP synthase), high confidence from genomic context alone (score 908 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0777 purB |
adenylosuccinate lyase PurB | 998 | 989 | coexpression:834 database:900 textmining:861 |
Rv3411c guaB2 |
inosine-5'-monophosphate dehydrogenase | 993 | 974 | coexpression:645 database:900 textmining:753 |
Rv1843c guaB1 |
inosine-5'-monophosphate dehydrogenase | 981 | 973 | coexpression:645 database:900 |
Rv0957 purH |
bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase | 988 | 972 | coexpression:671 database:900 textmining:618 |
Rv3410c guaB3 |
oxidoreductase | 977 | 971 | coexpression:646 database:900 |
Rv0356c hyp |
hypothetical protein | 944 | 945 ctx | neighborhood:801 coexpression:733 |
Rv1380 pyrB |
aspartate carbamoyltransferase | 943 | 926 | database:900 |
Rv1658 argG |
argininosuccinate synthase | 940 | 922 | database:900 |
Rv3624c hpt |
hypoxanthine-guanine phosphoribosyltransferase | 990 | 921 | database:900 textmining:882 |
Rv2201 asnB |
asparagine synthetase | 930 | 909 | database:900 |
Rv3396c guaA |
GMP synthase | 961 | 908 ctx | cooccurence:606 coexpression:650 textmining:602 |
Rv1595 nadB |
L-aspartate oxidase | 913 | 901 | database:900 |
Rv1538c ansA |
L-aparaginase | 900 | 901 | database:900 |
Rv3709c ask |
aspartokinase | 858 | 854 | database:800 |
Rv3601c panD |
aspartate 1-decarboxylase | 810 | 811 | database:800 |
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: adenylosuccinate synthetase
- MTBC0 PGAP product: adenylosuccinate synthase
- Pfam (hmmscan --cut_ga): Adenylsucc_synt PF00709.28 (E=4e-180)
- (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_214871.1)
- Domains: Pfam-A via hmmscan --cut_ga — Adenylsucc_synt (PF00709.28)
- 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
COG0104 - Curated reference: UniProt P9WHN3 (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 —
136 functional partner(s); context anchor
guaA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000377|Rv0357c|purA MPAIVLIGAQWGDEGKGKATDLLGGRVQWVVRYQGGNNAGHTVVLPTGENFALHLIPSGVLTPGVTNVIGNGVVIDPGVLLNELRGLQDRGVDTAKLLISADAHLLMPYHIAIDKVTERYMGSKKIGTTGRGIGPCYQDKIARIGIRVADVLDPEQLTHKVEAACEFKNQVLVKIYNRKALDPAQVVDALLEQAEGFKHRIADTRLLLNAALEAGETVLLEGSQGTLLDVDHGTYPYVTSSNPTAGGAAVGSGIGPTRIGTVLGILKAYTTRVGSGPFPTELFDEHGEYLSKTGREFGVTTGRRRRCGWFDAVIARYAARVNGITDYFLTKLDVLSSLESVPVCVGYEIDGRRTRDMPMTQRDLCRAKPVYEELPGWWEDISGAREFDDLPAKARDYVLRLEQLAGAPVSCIGVGPGREQTIVRRDVLQDRP