Rv2609c Family assigned · medium auto-curated

H37Rv Rv2609c · MTBC0 mtbc0_002777 · 351 aa · 2960363–2961418 (-) · RefSeq NP_217125.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane protein
MTBC0 PGAP re-annotationNUDIX domain-containing protein
Revised (this work)NUDIX domain-containing protein. Pfam: NUDIX (PF00293.35).

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

Curated reference (UniProt)

UniProt I6YDV4 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable conserved membrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
eggNOG descriptionpfam nudix
Orthologous groupCOG0494

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 0.375 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 2 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
NUDIXPF00293.35 7.4e-20177–316 NUDIX domain

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

Closest characterised functional partner: pimA (alpha-(1-2)-phosphatidylinositol mannosyltransferase), high confidence from genomic context alone (score 968 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2610c pimA alpha-(1-2)-phosphatidylinositol mannosyltransferase 982 968 ctx neighborhood:781 cooccurence:506 coexpression:732 textmining:479
Rv3433c nnr bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase 941 933 experimental:787 database:643
Rv2611c phosphatidylinositol mannoside acyltransferase 951 893 ctx neighborhood:798 cooccurence:490 textmining:566
Rv2613c AP-4-A phosphorylase 934 831 ctx neighborhood:798 textmining:631
Rv2614c thrS threonine--tRNA ligase 877 819 ctx neighborhood:798
Rv2612c pgsA1 CDP-diacylglycerol--inositol 3-phosphatidyltransferase 884 814 ctx neighborhood:798 textmining:402
Rv3211 rhlE ATP-dependent RNA helicase RhlE 783 770 experimental:403 database:615
Rv1253 deaD ATP-dependent RNA helicase DeaD 782 769 experimental:403 database:615
Rv2524c fas fatty acid synthase 715 705 database:406
Rv2418c octT hyp hypothetical protein 703 704 ctx cooccurence:680
Rv0556 transmembrane protein 656 656 ctx cooccurence:651
Rv1340 rphA ribonuclease PH 683 652 database:636
Rv1109c hyp hypothetical protein 650 650 ctx cooccurence:649
Rv3415c hyp hypothetical protein 649 649 ctx cooccurence:648
Rv3196 hyp hypothetical protein 648 648 ctx cooccurence:625

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: membrane protein
  • MTBC0 PGAP product: NUDIX domain-containing protein
  • Pfam (hmmscan --cut_ga): NUDIX PF00293.35 (E=7e-20)
  • (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_217125.1)
  • Domains: Pfam-A via hmmscan --cut_ga — NUDIX (PF00293.35)
  • 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 COG0494
  • Curated reference: UniProt I6YDV4 (TrEMBL, unreviewed; 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 — 152 functional partner(s); context anchor pimA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002777|Rv2609c|
MTWLVLAGAVLLVVLVAFGAWGYQTANRLNRLNVRYDLSWQSLDSALARRAVVARAVAIDAYGGAPQGSRLAALADAAEGAPRHARENAENELSAALAMVNPASLPAALIAELADAEARVLLARRFHNDAVRDTLALGERRLVRLLRLGGTAVLPTYFEIVERPHALVHGDQGASGRRTSARVVLLDDSGAVLLLCGSDPANPAFRDGAAPKWWFTVGGQVRPGERLAQAAARELAEETGLRVAPADMIGPIWRRDEVFEFNGSLIDSEEFYLVHRTRRFEPAVQGRTELERRYIRDARWCDANDIAQLVAAGERVYPLQLGELLPAANRLVDVALDNGAARDAGVPQPIR