ureC Family assigned · medium auto-curated

H37Rv Rv1850 · MTBC0 mtbc0_001963 · 577 aa · 2115999–2117732 (+) · RefSeq NP_216366.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)urease subunit alpha
MTBC0 PGAP re-annotationurease subunit alpha
Revised (this work)Urease subunit alpha. Pfam: Urease_alpha (PF00449.27), Amidohydro_1 (PF01979.27).

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

Curated reference (UniProt)

UniProt P9WFF1 SwissProt · reviewed · Evidence at protein level
UniProt nameUrease subunit alpha
EC (curated) EC 3.5.1.5

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred nameureC
eggNOG descriptionBelongs to the metallo-dependent hydrolases superfamily. Urease alpha subunit family
Orthologous groupCOG0804
EC number EC 3.5.1.5
KEGG orthology K01428
KEGG pathways map00220, map00230, map00791, map01100, map01120, map05120
Gene Ontology (2) GO:0008150, GO:0040007

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 0.392 · purifying
Polymorphic sites (≥ 0.1% of strains) 8 synonymous, 9 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
Urease_alphaPF00449.27 3.7e-513–126 Urease alpha-subunit, N-terminal domain
Amidohydro_1PF01979.27 1.1e-70132–459 Amidohydrolase family

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

Closest characterised functional partner: ureB (urease subunit beta), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1849 ureB urease subunit beta 999 1000 ctx neighborhood:882 fusion:706 cooccurence:774 coexpression:883 experimental:928 database:900 textmining:707
Rv1848 ureA urease subunit gamma 999 1000 ctx neighborhood:882 fusion:900 cooccurence:774 coexpression:860 experimental:928 database:900
Rv1852 ureG urease accessory protein UreG 997 991 ctx neighborhood:874 cooccurence:774 coexpression:722 textmining:692
Rv1851 ureF urease accessory protein UreF 996 991 ctx neighborhood:882 coexpression:887 textmining:625
Rv1853 ureD urease accessory protein UreD 961 925 ctx neighborhood:874 coexpression:431 textmining:513
Rv1847 esterase 804 805 ctx neighborhood:804
Rv3151 nuoG NADH-quinone oxidoreductase subunit G 612 65 textmining:603
Rv0198c zmp1 zinc metalloprotease 450 57 textmining:441
Rv1392 metK S-adenosylmethionine synthetase 640 55 textmining:635
Rv2605c tesB2 acyl-CoA thioesterase II 661 47 textmining:659
Rv1326c glgB 1,4-alpha-glucan branching protein 531 47 textmining:528
Rv1886c fbpB diacylglycerol acyltransferase/mycolyltransferase Ag85B 531 47 textmining:529
Rv3859c gltB glutamate synthase large subunit 518 46 textmining:516
Rv2604c snoP glutamine amidotransferase SnoP 517 46 textmining:515
Rv1980c mpt64 immunogenic protein Mpt64 425 46 textmining:422

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: urease subunit alpha
  • MTBC0 PGAP product: urease subunit alpha
  • Pfam (hmmscan --cut_ga): Urease_alpha PF00449.27 (E=4e-51), Amidohydro_1 PF01979.27 (E=1e-70)
  • (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_216366.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Urease_alpha (PF00449.27), Amidohydro_1 (PF01979.27)
  • 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 COG0804
  • Curated reference: UniProt P9WFF1 (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 — 20 functional partner(s); context anchor ureB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001963|Rv1850|ureC
MARLSRERYAQLYGPTTGDRIRLADTNLLVEVTEDRCGGPGLAGDEAVFGGGKVLRESMGQGRASRADGAPDTVITGAVIIDYWGIIKADIGIRDGRIVGIGKAGNPDIMTGVHRDLVVGPSTEIISGNRRIVTAGTVDCHVHLICPQIIVEALAAGTTTIIGGGTGPAEGTKATTVTPGEWHLARMLESLDGWPVNFALLGKGNTVNPDALWEQLRGGASGFKLHEDWGSTPAAIDTCLAVADVAGVQVALHSDTLNETGFVEDTIGAIAGRSIHAYHTEGAGGGHAPDIITVAAQPNVLPSSTNPTRPHTVNTLDEHLDMLMVCHHLNPRIPEDLAFAESRIRPSTIAAEDVLHDMGAISMIGSDSQAMGRVGEVVLRTWQTAHVMKARRGALEGDPSGSQAADNNRVRRYIAKYTICPAIAHGMDHLIGSVEVGKLADLVLWEPAFFGVRPHVVLKGGAIAWAAMGDANASIPTPQPVLPRPMFGAAAATAAATSVHFVAPQSIDARLADRLAVNRGLAPVADVRAVGKTDLPLNDALPSIEVDPDTFTVRIDGQVWQPQPAAELPMTQRYFLF