glnD Resolved · high auto-curated

H37Rv Rv2918c · MTBC0 mtbc0_003100 · 808 aa · 3249083–3251509 (-) · RefSeq NP_217434.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)bifunctional uridylyltransferase/uridylyl-removing enzyme
MTBC0 PGAP re-annotation[protein-PII] uridylyltransferase
Revised (this work)[protein-PII] uridylyltransferase. Pfam: GlnD_UR_UTase (PF08335.17), HD (PF01966.29).

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

Curated reference (UniProt)

UniProt P9WN29 SwissProt · reviewed · Evidence at protein level
UniProt nameBifunctional uridylyltransferase/uridylyl-removing enzyme
EC (curated) EC 2.7.7.59, EC 3.1.4.-
Curated functionModifies, by uridylylation and deuridylylation, the PII regulatory protein (GlnB), in response to the nitrogen status of the cell that GlnD senses through the glutamine level. Under low glutamine levels, catalyzes the conversion of the PII protein and UTP to PII-UMP and PPi, while under higher glutamine levels, GlnD hydrolyzes PII-UMP to PII and UMP (deuridylylation). Thus, controls uridylylation state and activity of the PII protein, and plays an important role in the regulation of nitrogen assimilation and metabolism (Probable).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
Preferred nameglnD
eggNOG descriptionModifies, by uridylylation and deuridylylation, the PII regulatory proteins (GlnB and homologs), in response to the nitrogen status of the cell that GlnD senses through the glutamine level. Under low glutamine levels, catalyzes the conversion of the PII proteins and UTP to PII-UMP and PPi, while under higher glutamine levels, GlnD hydrolyzes PII-UMP to PII and UMP (deuridylylation). Thus, controls uridylylation state and activity of the PII proteins, and plays an important role in the regulation of nitrogen
Orthologous groupCOG2844
EC number EC 2.7.7.59
KEGG orthology K00990
KEGG pathways map02020
Gene Ontology (17) GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0008773, GO:0016020, GO:0016740, GO:0016772, GO:0016779, GO:0030312 +5 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 1.472 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 12 missense, 0 nonsense, 4 frameshift
Disruption 4 distinct premature-stop/frameshift site(s); most common in 0.77% of strains (1125) · convergent

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
GlnD_UR_UTasePF08335.17 2.0e-10171–276 GlnD PII-uridylyltransferase
HDPF01966.29 1.3e-11431–523 HD domain

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

Closest characterised functional partner: glnB (nitrogen regulatory protein P-II), high confidence from genomic context alone (score 996 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2919c glnB nitrogen regulatory protein P-II 999 996 ctx neighborhood:805 cooccurence:617 experimental:468 database:900 textmining:955
Rv2920c amt ammonium transporter integral membrane protein 937 842 ctx neighborhood:805 textmining:621
Rv2848c cobB cobyrinic acid A,C-diamide synthase 733 733 coexpression:733
Rv2921c ftsY signal recognition particle receptor FtsY 607 607 ctx neighborhood:605
Rv3859c gltB glutamate synthase large subunit 874 550 ctx neighborhood:544 textmining:733
Rv2923c hyp hypothetical protein 521 521 ctx neighborhood:417
Rv0876c transmembrane protein 487 487 ctx cooccurence:484
Rv3687c rsfB anti-anti-sigma factor RsfB 426 427 ctx cooccurence:423
Rv2922c smc chromosome partition protein Smc 421 419 ctx neighborhood:419
Rv2922A acyP acylphosphatase 419 418 ctx neighborhood:416
Rv2221c glnE [glutamate--ammonia-ligase 893 298 textmining:855
Rv2220 glnA1 glutamine synthetase 918 231 textmining:898
Rv0260c transcriptional regulator 445 223
Rv2890c rpsB 30S ribosomal protein S2 547 114 textmining:511
Rv3396c guaA GMP synthase 449 112 textmining:405

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: bifunctional uridylyltransferase/uridylyl-removing enzyme
  • MTBC0 PGAP product: [protein-PII] uridylyltransferase
  • Pfam (hmmscan --cut_ga): GlnD_UR_UTase PF08335.17 (E=2e-10), HD PF01966.29 (E=1e-11)
  • (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_217434.1)
  • Domains: Pfam-A via hmmscan --cut_ga — GlnD_UR_UTase (PF08335.17), HD (PF01966.29)
  • 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 COG2844
  • Curated reference: UniProt P9WN29 (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 — 24 functional partner(s); context anchor glnB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003100|Rv2918c|glnD
MEAESPCAASDLAVARRELLSGNHRELDPVGLRQTWLDLHESWLIDKADEIGIADASGFAIVGVGGLGRRELLPYSDLDVLLLHDGKPADILRPVADRLWYPLWDANIRLDHSVRTVSEALTIANSDLMAALGMLEARHIAGDQQLSFALIDGVRRQWRNGIRSRMGELVEMTYARWRRCGRIAQRAEPDLKLGRGGLRDVQLLDALALAQLIDRHGIGHTDLPAGSLDGAYRTLLDVRTELHRVSGRGRDHLLAQFADEISAALGFGDRFDLARTLSSAGRTIGYHAEAGLRTAANALPRRGISALVRRPKRRPLDEGVVEYAGEIVLARDAEPEHDPGLVLRVAAASADTGLPIGAATLSRLAASVPDLPTPWPQEALDDLLVVLSAGPTTVATIEALDRTGLWGRLLPEWEPIRDLPPRDVAHKWTVDRHVVETAVHAAPLATRVARPDLLALGALLHDIGKGRGTDHSVLGAELVIPVCTRLGLSPPDVRTLSKLVRHHLLLPITATRRDLNDPKTIEAVSEALGGDPQLLEVLHALSEADSKATGPGVWSDWKASLVDDLVRRCRMVMAGESLPQAEPTAPHYLSLAADHGVHVEISPRDGERIDAVIVAPDERGLVSKAAAVLALNSLRVHSASVNVHQGVAITEFVVSPLFGSPPAAELVRQQFVGALNGDVDVLGMLQKRDSDAASLVSARAGDVQAGVPVTRTAAPPRILWLDTAAPAKLILEVRAMDRAGLLALLAGALEGAGAGIVWAKVNTFGSTAADVFCVTVPAELDARAAVEQHLLEVLGASVDVVVDEPVGD