Rv1319c Resolved · high auto-curated

H37Rv Rv1319c · MTBC0 - · 535 aa · 1480894–1482501 (-) · RefSeq NP_215835.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)adenylate cyclase
MTBC0 PGAP re-annotation
Revised (this work)Adenylate cyclase. Pfam: HAMP (PF00672.31), Guanylate_cyc (PF00211.26).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WQ31 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv1319c

UniProt still lists this protein as Uncharacterized protein Rv1319c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category T Signal transduction mechanisms
eggNOG descriptionThought to play a role in regulation of cellular metabolism by catalysing the synthesis of a second messenger, camp catalytic activity ATP 3',5'-cyclic AMP pyrophosphate
Orthologous groupCOG2114
EC number EC 4.6.1.1
KEGG orthology K01768
KEGG pathways map00230, map02025, map04113, map04213
KEGG modules M00695
Gene Ontology (57) GO:0003674, GO:0003824, GO:0004016, GO:0005575, GO:0005576, GO:0006139, GO:0006163, GO:0006164, GO:0006171, GO:0006725, GO:0006753, GO:0006793 +45 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 0.416 · purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 8 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.20% of strains (292) · clonal

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
HAMPPF00672.31 7.8e-09276–327 HAMP domain
Guanylate_cycPF00211.26 1.8e-13361–524 Adenylate and Guanylate cyclase catalytic domain

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

Closest characterised functional partner: Rv1320c (adenylate cyclase), high confidence from genomic context alone (score 764 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1617 pykA pyruvate kinase 905 902 database:900
Rv2445c ndkA nucleoside diphosphate kinase 905 902 database:900
Rv0805 cpdA 3',5'-cyclic adenosine monophosphate phosphodiesterase CpdA 922 900 database:900
Rv2583c relA bifunctional (p)ppGpp synthase/hydrolase RelA 900 900 database:900
Rv3109 moaA1 cyclic pyranopterin monophosphate synthase 806 807 database:800
Rv0869c moaA2 molybdenum cofactor biosynthesis protein MoaA 806 807 database:800
Rv1415 ribA2 bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase 802 803 database:800
Rv1940 ribA1 riboflavin biosynthesis protein RibA 802 803 database:800
Rv3609c folE GTP cyclohydrolase I 800 800 database:800
Rv1320c adenylate cyclase 774 764 ctx neighborhood:760
Rv2212 adenylyl cyclase 687 667 ctx cooccurence:667
Rv1647 adenylate cyclase 678 660 ctx cooccurence:660
Rv1318c adenylate cyclase 657 655 ctx neighborhood:650
Rv1321 nucS endonuclease NucS 565 565 ctx neighborhood:565
Rv1636 TB15.3 iron-regulated universal stress protein 544 541 ctx cooccurence:541

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): adenylate cyclase
  • Pfam (hmmscan --cut_ga): HAMP PF00672.31 (E=8e-09), Guanylate_cyc PF00211.26 (E=2e-13)
  • (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_215835.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HAMP (PF00672.31), Guanylate_cyc (PF00211.26)
  • 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 COG2114
  • Curated reference: UniProt P9WQ31 (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 Rv1320c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1319c|
MPAKKTMAQRLGQALETMTRQCGQLPETPAYGSWLLGRVSESPSRRWVRIKRIVTVYIMTANLTGIVVALLVVTFAFPVPSIYTDAPWWVTFGVAPAYATLALAIGTYWITTRIVRASIRWAIEERAPSQADGRNTLLLPFRVAAVHLILWDIGGALLATLYGLANRVFVTIILFSVTICGVLVATNCYLFTEFALRPVAAKALEAGRPPRRFAPGIMGRTMTVWSLGSGVPVTGIATTALYVLLVHNLTETQLASAVLILSITTLIFGFLVMWILAWLTAAPVRVVRAALKRVEQGDLRGDLVVFDGTELGELQRGFNAMVNGLRERERVRDLFGRHVGREVAAAAERERPQLGGEDRHAAVVFVDIVGSTQLVDNQPAAHVVKLLNRFFAIVVNEVDRHHGLINKFAGDAALAIFGAPNRLDRPEDAALAAARAIADRLANEMPEVQAGIGVAAGQIVAGNVGAKQRFEYTVVGKPVNQAARLCELAKSHPARLLASSDTLHAASETERAHWSLGETVTLRGHEQPTRLAVPT