argC Resolved · high auto-curated

H37Rv Rv1652 · MTBC0 mtbc0_001761 · 352 aa · 1877618–1878676 (+) · RefSeq NP_216168.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)N-acetyl-gamma-glutamyl-phoshate reductase
MTBC0 PGAP re-annotationN-acetyl-gamma-glutamyl-phosphate reductase
Revised (this work)N-acetyl-gamma-glutamyl-phosphate reductase. Pfam: Semialdhyde_dh (PF01118.31), Semialdhyde_dhC_1 (PF22698.2), Semialdhyde_dhC (PF02774.24).

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

Curated reference (UniProt)

UniProt P9WPZ9 SwissProt · reviewed · Evidence at protein level
UniProt nameN-acetyl-gamma-glutamyl-phosphate reductase
EC (curated) EC 1.2.1.38
Curated functionCatalyzes the NADPH-dependent reduction of N-acetyl-5-glutamyl phosphate to yield N-acetyl-L-glutamate 5-semialdehyde.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred nameargC
eggNOG descriptionCatalyzes the NADPH-dependent reduction of N-acetyl-5- glutamyl phosphate to yield N-acetyl-L-glutamate 5-semialdehyde
Orthologous groupCOG0002
EC number EC 1.2.1.38
KEGG orthology K00145
KEGG pathways map00220, map01100, map01110, map01130, map01210, map01230
KEGG modules M00028, M00845
Gene Ontology (15) GO:0000166, GO:0003674, GO:0005488, GO:0008150, GO:0036094, GO:0040007, GO:0043167, GO:0043168, GO:0048037, GO:0050661, GO:0050662, GO:0070401 +3 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 0.127 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 15 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)

PfamAccessioni-EvalueResiduesDescription
Semialdhyde_dhPF01118.31 1.6e-1811–140 Semialdehyde dehydrogenase, NAD binding domain
Semialdhyde_dhC_1PF22698.2 6.9e-51158–320 Semialdehyde dehydrogenase, dimerisation domain
Semialdhyde_dhCPF02774.24 2.7e-29167–323 Semialdehyde dehydrogenase, dimerisation domain

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

Closest characterised functional partner: argD (acetylornithine aminotransferase), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1655 argD acetylornithine aminotransferase 999 1000 ctx neighborhood:881 cooccurence:669 coexpression:937 database:900 textmining:925
Rv1654 argB acetylglutamate kinase 999 1000 ctx neighborhood:882 fusion:611 cooccurence:764 coexpression:973 database:900 textmining:923
Rv1653 argJ bifunctional glutamate N-acetyltransferase/amino-acid acetyltransferase 999 999 ctx neighborhood:881 cooccurence:736 coexpression:984 textmining:876
Rv1656 argF ornithine carbamoyltransferase 999 995 ctx neighborhood:835 coexpression:961 textmining:895
Rv1657 argR arginine repressor 997 986 ctx neighborhood:881 coexpression:888 textmining:811
Rv1658 argG argininosuccinate synthase 995 984 ctx neighborhood:812 coexpression:901 textmining:759
Rv1659 argH argininosuccinate lyase 996 977 ctx neighborhood:783 coexpression:868 textmining:844
Rv1213 glgC glucose-1-phosphate adenylyltransferase 833 783 coexpression:765
Rv2321c rocD2 Rv2321c, (MTCY3G12.13), len: 181 aa. Probable rocD2,ornithine aminotransferase, highly similar to C-terminal region of other ornithine amino 834 767 coexpression:678
Rv2322c rocD1 Rv2322c, (MTCY3G12.12), len: 221 aa. Probable rocD1,ornithine aminotransferase, highly similar to N-terminal region of other ornithine amino 812 736 coexpression:678
Rv1384 carB carbamoyl-phosphate synthase large subunit 820 642 coexpression:612 textmining:519
Rv1202 dapE succinyl-diaminopimelate desuccinylase DapE 656 620
Rv3859c gltB glutamate synthase large subunit 712 604 ctx neighborhood:544
Rv1647 adenylate cyclase 546 547 ctx neighborhood:544
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 546 547 ctx neighborhood:544

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: N-acetyl-gamma-glutamyl-phoshate reductase
  • MTBC0 PGAP product: N-acetyl-gamma-glutamyl-phosphate reductase
  • Pfam (hmmscan --cut_ga): Semialdhyde_dh PF01118.31 (E=2e-18), Semialdhyde_dhC_1 PF22698.2 (E=7e-51), Semialdhyde_dhC PF02774.24 (E=3e-29)
  • (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_216168.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Semialdhyde_dh (PF01118.31), Semialdhyde_dhC_1 (PF22698.2), Semialdhyde_dhC (PF02774.24)
  • 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 COG0002
  • Curated reference: UniProt P9WPZ9 (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 — 41 functional partner(s); context anchor argD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001761|Rv1652|argC
MQNRQVANATKVAVAGASGYAGGEILRLLLGHPAYADGRLRIGALTAATSAGSTLGEHHPHLTPLAHRVVEPTEAAVLGGHDAVFLALPHGHSAVLAQQLSPETLIIDCGADFRLTDAAVWERFYGSSHAGSWPYGLPELPGARDQLRGTRRIAVPGCYPTAALLALFPALAADLIEPAVTVVAVSGTSGAGRAATTDLLGAEVIGSARAYNIAGVHRHTPEIAQGLRAVTDRDVSVSFTPVLIPASRGILATCTARTRSPLSQLRAAYEKAYHAEPFIYLMPEGQLPRTGAVIGSNAAHIAVAVDEDAQTFVAIAAIDNLVKGTAGAAVQSMNLALGWPETDGLSVVGVAP