dgt Resolved · high auto-curated

H37Rv Rv2344c · MTBC0 mtbc0_002496 · 431 aa · 2647207–2648502 (-) · RefSeq NP_216860.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)deoxyguanosine triphosphate triphosphohydrolase
MTBC0 PGAP re-annotationdeoxyguanosinetriphosphate triphosphohydrolase
Revised (this work)Deoxyguanosinetriphosphate triphosphohydrolase. Pfam: HD (PF01966.29), HD_assoc (PF13286.12).

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

Curated reference (UniProt)

UniProt P9WNY7 SwissProt · reviewed · Evidence at protein level
UniProt nameDeoxyguanosinetriphosphate triphosphohydrolase-like protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namedgt
eggNOG descriptiondGTPase family. Type 2 subfamily
Orthologous groupCOG0232
EC number EC 3.1.5.1
KEGG orthology K01129
KEGG pathways map00230
Gene Ontology (78) GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006139, GO:0006163, GO:0006195, GO:0006203, GO:0006725, GO:0006753, GO:0006793 +66 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 0.285 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 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
HDPF01966.29 3.5e-1472–220 HD domain
HD_assocPF13286.12 8.3e-16330–416 Phosphohydrolase-associated domain

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

Closest characterised functional partner: dnaG (DNA primase), high confidence from genomic context alone (score 899 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2445c ndkA nucleoside diphosphate kinase 904 905 database:900
Rv3307 deoD purine nucleoside phosphorylase 904 904 database:900
Rv1617 pykA pyruvate kinase 901 901 database:900
Rv2343c dnaG DNA primase 938 899 ctx neighborhood:881 textmining:411
Rv2345 transmembrane protein 787 787 ctx neighborhood:785
Rv3859c gltB glutamate synthase large subunit 544 545 ctx neighborhood:544
Rv1307 atpH ATP synthase subunit b/delta 440 441
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 430 430
Rv1003 rsmI rRNA small subunit methyltransferase I 426 426 coexpression:416
Rv2230c GTP cyclohydrolase 417 417
Rv1658 argG argininosuccinate synthase 406 407
Rv0429c def polypeptide deformylase 593 342 textmining:408
Rv2362c recO DNA repair protein RecO 684 285 textmining:576
Rv2364c era GTPase Era 487 153 textmining:419
Rv3708c asd aspartate-semialdehyde dehydrogenase 563 133 textmining:518

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: deoxyguanosine triphosphate triphosphohydrolase
  • MTBC0 PGAP product: deoxyguanosinetriphosphate triphosphohydrolase
  • Pfam (hmmscan --cut_ga): HD PF01966.29 (E=4e-14), HD_assoc PF13286.12 (E=8e-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_216860.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HD (PF01966.29), HD_assoc (PF13286.12)
  • 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 COG0232
  • Curated reference: UniProt P9WNY7 (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 — 22 functional partner(s); context anchor dnaG
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002496|Rv2344c|dgt
MSASEHDPYDDFDRQRRVAEAPKTAGLPGTEGQYRSDFARDRARVLHSAALRRLADKTQVVGPREGDTPRTRLTHSLEVAQIGRGMAIGLGCDLDLVELAGLAHDIGHPPYGHNGERALDEVAASHGGFEGNAQNFRILTSLEPKVVDAQGLSAGLNLTRASLDAVTKYPWMRGDGLGSQRRKFGFYDDDRESAVWVRQGAPPERACLEAQVMDWADDVAYSVHDVEDGVVSERIDLRVLAAEEDAAALARLGEREFSRVSADELMAAARRLSRLPVVAAVGKYDATLSASVALKRLTSELVGRFASAAIATTRAAAGPGPLVRFRADLQVPDLVRAEVAVLKILALQFIMSDPRHLETQARQRERIHRVAHRLYSGAPQTLDPVYAAAFNTAADDAARLRVVVDQIASYTEGRLERIDADQLGVSRNALD