argH Resolved · high auto-curated
H37Rv Rv1659 · MTBC0 mtbc0_001768 ·
470 aa · 1884681–1886093 (+) ·
RefSeq NP_216175.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | argininosuccinate lyase |
|---|---|
| MTBC0 PGAP re-annotation | argininosuccinate lyase |
| Revised (this work) | Argininosuccinate lyase. Pfam: Lyase_1 (PF00206.26), ASL_C2 (PF14698.12). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WPY7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Argininosuccinate lyase |
| EC (curated) |
EC 4.3.2.1
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | argH |
| eggNOG description | argininosuccinate lyase |
| Orthologous group | COG0165 |
| EC number |
EC 4.3.2.1
|
| KEGG orthology |
K01755
|
| KEGG pathways |
map00220, map00250, map01100, map01110, map01130, map01230
|
| KEGG modules |
M00029, M00844, M00845
|
| Gene Ontology (45) |
GO:0003674, GO:0003824, GO:0004056, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0006082, GO:0006520, GO:0006525, GO:0006526 +33 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 | 0.311 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 5 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 |
|---|---|---|---|---|
Lyase_1 | PF00206.26 | 4.0e-59 | 17–306 | Lyase |
ASL_C2 | PF14698.12 | 1.7e-25 | 369–436 | Argininosuccinate lyase C-terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: argG (argininosuccinate synthase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1658 argG |
argininosuccinate synthase | 999 | 1000 ctx | neighborhood:785 cooccurence:768 coexpression:972 database:900 textmining:804 |
Rv1656 argF |
ornithine carbamoyltransferase | 997 | 994 ctx | neighborhood:783 coexpression:968 textmining:603 |
Rv1654 argB |
acetylglutamate kinase | 997 | 988 ctx | neighborhood:783 coexpression:929 textmining:767 |
Rv1655 argD |
acetylornithine aminotransferase | 995 | 988 ctx | neighborhood:783 coexpression:915 textmining:661 |
Rv1653 argJ |
bifunctional glutamate N-acetyltransferase/amino-acid acetyltransferase | 994 | 983 ctx | neighborhood:783 coexpression:894 textmining:679 |
Rv1657 argR |
arginine repressor | 994 | 981 ctx | neighborhood:783 coexpression:915 textmining:735 |
Rv1652 argC |
N-acetyl-gamma-glutamyl-phoshate reductase | 996 | 977 ctx | neighborhood:783 coexpression:868 textmining:844 |
Rv0777 purB |
adenylosuccinate lyase PurB | 956 | 916 | database:900 textmining:510 |
Rv1001 arcA |
arginine deiminase | 919 | 901 | database:900 |
Rv1240 mdh |
malate dehydrogenase | 860 | 851 | database:800 |
Rv1098c fum |
fumarate hydratase | 846 | 814 | database:800 |
Rv2852c mqo |
malate:quinone oxidoreductase | 829 | 812 | database:800 |
Rv1131 prpC |
methylcitrate synthase PrpC | 824 | 808 | database:800 |
Rv0896 gltA2 |
citrate synthase 1 | 824 | 807 | database:800 |
Rv0889c citA |
citrate synthase 2 | 824 | 807 | 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: argininosuccinate lyase
- MTBC0 PGAP product: argininosuccinate lyase
- Pfam (hmmscan --cut_ga): Lyase_1 PF00206.26 (E=4e-59), ASL_C2 PF14698.12 (E=2e-25)
- (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_216175.1)
- Domains: Pfam-A via hmmscan --cut_ga — Lyase_1 (PF00206.26), ASL_C2 (PF14698.12)
- 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
COG0165 - Curated reference: UniProt P9WPY7 (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 —
87 functional partner(s); context anchor
argG - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001768|Rv1659|argH MSTNEGSLWGGRFAGGPSDALAALSKSTHFDWVLAPYDLTASRAHTMVLFRAGLLTEEQRDGLLAGLDSLAQDVADGSFGPLVTDEDVHAALERGLIDRVGPDLGGRLRAGRSRNDQVAALFRMWLRDAVRRVATGVLDVVGALAEQAAAHPSAIMPGKTHLQSAQPILLAHHLLAHAHPLLRDLDRIVDFDKRAAVSPYGSGALAGSSLGLDPDAIAADLGFSAAADNSVDATAARDFAAEAAFVFAMIAVDLSRLAEDIIVWSSTEFGYVTLHDSWSTGSSIMPQKKNPDIAELARGKSGRLIGNLAGLLATLKAQPLAYNRDLQEDKEPVFDSVAQLELLLPAMAGLVASLTFNVQRMAELAPAGYTLATDLAEWLVRQGVPFRSAHEAAGAAVRAAEQRGVGLQELTDDELAAISPELTPQVREVLTIEGSVSARDCRGGTAPGRVAEQLNAIGEAAERLRRQLVR