argF Resolved · high auto-curated

H37Rv Rv1656 · MTBC0 mtbc0_001765 · 307 aa · 1881964–1882887 (+) · RefSeq NP_216172.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ornithine carbamoyltransferase
MTBC0 PGAP re-annotationornithine carbamoyltransferase
Revised (this work)Ornithine carbamoyltransferase. Pfam: OTCace_N (PF02729.27), OTCace (PF00185.31).

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

Curated reference (UniProt)

UniProt P9WIT9 SwissProt · reviewed · Evidence at protein level
UniProt nameOrnithine carbamoyltransferase
EC (curated) EC 2.1.3.3
Curated functionReversibly catalyzes the transfer of the carbamoyl group from carbamoyl phosphate (CP) to the N(epsilon) atom of ornithine (ORN) to produce L-citrulline, which is a substrate for argininosuccinate synthetase, the enzyme involved in the final step in arginine biosynthesis.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred nameargF
eggNOG descriptionReversibly catalyzes the transfer of the carbamoyl group from carbamoyl phosphate (CP) to the N(epsilon) atom of ornithine (ORN) to produce L-citrulline
Orthologous groupCOG0078
EC number EC 2.1.3.3
KEGG orthology K00611
KEGG pathways map00220, map01100, map01110, map01130, map01230
KEGG modules M00029, M00844
Gene Ontology (49) GO:0000050, GO:0003674, GO:0003824, GO:0004585, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0006082, GO:0006520, GO:0006525, GO:0006526 +37 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 0.471 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 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
OTCace_NPF02729.27 7.4e-483–141 Aspartate/ornithine carbamoyltransferase, carbamoyl-P binding domain
OTCacePF00185.31 1.6e-55148–303 Aspartate/ornithine carbamoyltransferase, Asp/Orn binding domain

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).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1658 argG argininosuccinate synthase 999 1000 ctx neighborhood:879 coexpression:976 database:900 textmining:951
Rv1653 argJ bifunctional glutamate N-acetyltransferase/amino-acid acetyltransferase 999 1000 ctx neighborhood:881 cooccurence:489 coexpression:942 database:900 textmining:781
Rv1654 argB acetylglutamate kinase 999 998 ctx neighborhood:881 coexpression:976 textmining:929
Rv1655 argD acetylornithine aminotransferase 999 997 ctx neighborhood:882 coexpression:948 textmining:868
Rv1652 argC N-acetyl-gamma-glutamyl-phoshate reductase 999 995 ctx neighborhood:835 coexpression:961 textmining:895
Rv1659 argH argininosuccinate lyase 997 994 ctx neighborhood:783 coexpression:968 textmining:603
Rv1657 argR arginine repressor 997 987 ctx neighborhood:882 coexpression:892 textmining:804
Rv1001 arcA arginine deiminase 987 983 coexpression:767 database:900
Rv1384 carB carbamoyl-phosphate synthase large subunit 992 979 ctx fusion:818 coexpression:431 database:800 textmining:657
Rv1383 carA carbamoyl-phosphate synthase small subunit 957 951 ctx fusion:550 coexpression:453 database:800
Rv1380 pyrB aspartate carbamoyltransferase 861 840 database:800
Rv2321c rocD2 Rv2321c, (MTCY3G12.13), len: 181 aa. Probable rocD2,ornithine aminotransferase, highly similar to C-terminal region of other ornithine amino 802 736 coexpression:645
Rv2322c rocD1 Rv2322c, (MTCY3G12.12), len: 221 aa. Probable rocD1,ornithine aminotransferase, highly similar to N-terminal region of other ornithine amino 792 723 coexpression:646
Rv1661 pks7 polyketide synthase 669 641 ctx neighborhood:588
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 772 550 ctx neighborhood:544 textmining:515

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: ornithine carbamoyltransferase
  • MTBC0 PGAP product: ornithine carbamoyltransferase
  • Pfam (hmmscan --cut_ga): OTCace_N PF02729.27 (E=7e-48), OTCace PF00185.31 (E=2e-55)
  • (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_216172.1)
  • Domains: Pfam-A via hmmscan --cut_ga — OTCace_N (PF02729.27), OTCace (PF00185.31)
  • 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 COG0078
  • Curated reference: UniProt P9WIT9 (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 — 38 functional partner(s); context anchor argG
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001765|Rv1656|argF
MIRHFLRDDDLSPAEQAEVLELAAELKKDPVSRRPLQGPRGVAVIFDKNSTRTRFSFELGIAQLGGHAVVVDSGSTQLGRDETLQDTAKVLSRYVDAIVWRTFGQERLDAMASVATVPVINALSDEFHPCQVLADLQTIAERKGALRGLRLSYFGDGANNMAHSLLLGGVTAGIHVTVAAPEGFLPDPSVRAAAERRAQDTGASVTVTADAHAAAAGADVLVTDTWTSMGQENDGLDRVKPFRPFQLNSRLLALADSDAIVLHCLPAHRGDEITDAVMDGPASAVWDEAENRLHAQKALLVWLLERS