Rv2613c Resolved · high auto-curated

H37Rv Rv2613c · MTBC0 mtbc0_002781 · 195 aa · 2964162–2964749 (-) · RefSeq NP_217129.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)AP-4-A phosphorylase
MTBC0 PGAP re-annotationATP adenylyltransferase
Revised (this work)ATP adenylyltransferase. Pfam: DcpS_C (PF11969.14), HIT (PF01230.30).

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

Curated reference (UniProt)

UniProt P9WMK9 SwissProt · reviewed · Evidence at protein level
UniProt nameAP-4-A phosphorylase
EC (curated) EC 2.7.7.53
Curated functionCatabolizes diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) into ADP and ATP. It does not catalyze the reverse phosphorolysis reaction. The optimum substrates are dinucleoside polyphosphates containing four or five phosphate residues.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
G Carbohydrate transport and metabolism
eggNOG descriptionCOG0537 Diadenosine tetraphosphate (Ap4A) hydrolase and other HIT family hydrolases
Orthologous groupCOG0537
EC number EC 2.7.7.53
KEGG orthology K19710
KEGG pathways map00230
Gene Ontology (64) GO:0003674, GO:0003824, GO:0003877, GO:0004551, GO:0005575, GO:0005623, GO:0005886, GO:0006139, GO:0006725, GO:0006753, GO:0006793, GO:0006796 +52 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 0.339 · purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 1 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
DcpS_CPF11969.14 1.6e-0668–157 Scavenger mRNA decapping enzyme C-term binding
HITPF01230.30 5.1e-1670–159 HIT domain

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

Closest characterised functional partner: pgsA1 (CDP-diacylglycerol--inositol 3-phosphatidyltransferase), high confidence from genomic context alone (score 922 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2612c pgsA1 CDP-diacylglycerol--inositol 3-phosphatidyltransferase 964 922 ctx neighborhood:882 textmining:565
Rv2611c phosphatidylinositol mannoside acyltransferase 964 906 ctx neighborhood:882 textmining:638
Rv2610c pimA alpha-(1-2)-phosphatidylinositol mannosyltransferase 945 905 ctx neighborhood:879 textmining:456
Rv1286 cysC adenylyl-sulfate kinase 903 904 database:900
Rv1285 cysD sulfate adenylyltransferase subunit 2 902 903 database:900
Rv2614c thrS threonine--tRNA ligase 955 900 ctx neighborhood:881 textmining:569
Rv2609c membrane protein 934 831 ctx neighborhood:798 textmining:631
Rv1390 rpoZ DNA-directed RNA polymerase subunit omega 711 711 database:585
Rv0668 rpoC DNA-directed RNA polymerase subunit beta' 658 646 database:592
Rv3457c rpoA DNA-directed RNA polymerase subunit alpha 611 612 database:595
Rv3211 rhlE ATP-dependent RNA helicase RhlE 617 610 database:538
Rv1253 deaD ATP-dependent RNA helicase DeaD 611 604 database:538
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 610 604 database:586
Rv0861c ercc3 DNA helicase Ercc3 574 575 database:543
Rv2605c tesB2 acyl-CoA thioesterase II 572 572 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: AP-4-A phosphorylase
  • MTBC0 PGAP product: ATP adenylyltransferase
  • Pfam (hmmscan --cut_ga): DcpS_C PF11969.14 (E=2e-06), HIT PF01230.30 (E=5e-16)
  • (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_217129.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DcpS_C (PF11969.14), HIT (PF01230.30)
  • 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 COG0537
  • Curated reference: UniProt P9WMK9 (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 pgsA1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002781|Rv2613c|
MSDEDRTDRATEDHTIFDRGVGQRDQLQRLWTPYRMNYLAEAPVKRDPNSSASPAQPFTEIPQLSDEEGLVVARGKLVYAVLNLYPYNPGHLMVVPYRRVSELEDLTDLESAELMAFTQKAIRVIKNVSRPHGFNVGLNLGTSAGGSLAEHLHVHVVPRWGGDANFITIIGGSKVIPQLLRDTRRLLATEWARQP