argG Resolved · high auto-curated

H37Rv Rv1658 · MTBC0 mtbc0_001767 · 398 aa · 1883405–1884601 (+) · RefSeq NP_216174.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)argininosuccinate synthase
MTBC0 PGAP re-annotationargininosuccinate synthase
Revised (this work)Argininosuccinate synthase. Pfam: Arginosuc_synth (PF00764.26), Arginosuc_syn_C (PF20979.3).

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

Curated reference (UniProt)

UniProt P9WPW7 SwissProt · reviewed · Evidence at protein level
UniProt nameArgininosuccinate synthase
EC (curated) EC 6.3.4.5

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred nameargG
eggNOG descriptionBelongs to the argininosuccinate synthase family. Type 1 subfamily
Orthologous groupCOG0137
EC number EC 6.3.4.5
KEGG orthology K01940
KEGG pathways map00220, map00250, map01100, map01110, map01130, map01230, map05418
KEGG modules M00029, M00844, M00845
Gene Ontology (54) GO:0000050, GO:0000053, GO:0003674, GO:0003824, GO:0004055, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006082 +42 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 0.126 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 16 synonymous, 6 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
Arginosuc_synthPF00764.26 2.0e-754–165 Arginosuccinate synthase N-terminal HUP domain
Arginosuc_syn_CPF20979.3 4.0e-101174–391 Arginosuccinate synthase C-terminal domain

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

Closest characterised functional partner: argH (argininosuccinate lyase), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1659 argH argininosuccinate lyase 999 1000 ctx neighborhood:785 cooccurence:768 coexpression:972 database:900 textmining:804
Rv1656 argF ornithine carbamoyltransferase 999 1000 ctx neighborhood:879 coexpression:976 database:900 textmining:951
Rv1654 argB acetylglutamate kinase 999 996 ctx neighborhood:857 coexpression:973 textmining:821
Rv1655 argD acetylornithine aminotransferase 997 995 ctx neighborhood:879 coexpression:932 textmining:462
Rv1653 argJ bifunctional glutamate N-acetyltransferase/amino-acid acetyltransferase 995 991 ctx neighborhood:812 coexpression:946 textmining:551
Rv1657 argR arginine repressor 997 988 ctx neighborhood:879 coexpression:908 textmining:799
Rv1384 carB carbamoyl-phosphate synthase large subunit 995 988 ctx fusion:720 coexpression:794 database:800 textmining:651
Rv1652 argC N-acetyl-gamma-glutamyl-phoshate reductase 995 984 ctx neighborhood:812 coexpression:901 textmining:759
Rv0357c purA adenylosuccinate synthetase 940 922 database:900
Rv2201 asnB asparagine synthetase 925 915 database:900
Rv1538c ansA L-aparaginase 924 907 database:900
Rv1380 pyrB aspartate carbamoyltransferase 912 907 database:900
Rv1001 arcA arginine deiminase 914 901 database:900
Rv1595 nadB L-aspartate oxidase 913 901 database:900
Rv1383 carA carbamoyl-phosphate synthase small subunit 919 895 coexpression:456 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 synthase
  • MTBC0 PGAP product: argininosuccinate synthase
  • Pfam (hmmscan --cut_ga): Arginosuc_synth PF00764.26 (E=2e-75), Arginosuc_syn_C PF20979.3 (E=4e-101)
  • (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_216174.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Arginosuc_synth (PF00764.26), Arginosuc_syn_C (PF20979.3)
  • 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 COG0137
  • Curated reference: UniProt P9WPW7 (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 — 72 functional partner(s); context anchor argH
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001767|Rv1658|argG
MSERVILAYSGGLDTSVAISWIGKETGREVVAVAIDLGQGGEHMDVIRQRALDCGAVEAVVVDARDEFAEGYCLPTVLNNALYMDRYPLVSAISRPLIVKHLVAAAREHGGGIVAHGCTGKGNDQVRFEVGFASLAPDLEVLAPVRDYAWTREKAIAFAEENAIPINVTKRSPFSIDQNVWGRAVETGFLEHLWNAPTKDIYAYTEDPTINWGVPDEVIVGFERGVPVSVDGKPVSMLAAIEELNRRAGAQGVGRLDVVEDRLVGIKSREIYEAPGAMVLITAHTELEHVTLERELGRFKRQTDQRWAELVYDGLWYSPLKAALEAFVAKTQEHVSGEVRLVLHGGHIAVNGRRSAESLYDFNLATYDEGDSFDQSAARGFVYVHGLSSKLAARRDLR