Rv2413c Family assigned · medium auto-curated

H37Rv Rv2413c · MTBC0 mtbc0_002569 · 316 aa · 2734619–2735569 (-) · RefSeq NP_216929.3

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDNA polymerase III subunit delta
Revised (this work)DNA polymerase III subunit delta. Pfam: DNA_pol3_delta_C (PF21694.3).

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

Curated reference (UniProt)

UniProt P71730 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable DNA polymerase III subunit delta
EC (curated) EC 2.7.7.7
Curated functionDNA polymerase III is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. Pol III also exhibits 3'-5' exonuclease activity. The delta subunit interacts with the gamma/tau subunit to load the beta sliding clamp (dnaN) onto the DNA (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred nameholA
eggNOG descriptionDNA polymerase III, delta
Orthologous groupCOG1466
EC number EC 2.7.7.7
KEGG orthology K02340
KEGG pathways map00230, map00240, map01100, map03030, map03430, map03440
KEGG modules M00260

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 1.487 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 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
DNA_pol3_delta_CPF21694.3 2.7e-08193–304 DNA polymerase III delta subunit, C-terminal domain

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

Closest characterised functional partner: Rv3644c (DNA polymerase), high confidence from genomic context alone (score 995 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3644c DNA polymerase 995 995 ctx cooccurence:690 experimental:829 database:900
Rv0002 dnaN DNA polymerase III subunit beta 989 988 experimental:829 database:900
Rv3721c dnaZX DNA polymerase III subunit gamma/tau 987 986 experimental:829 database:900
Rv1547 dnaE1 DNA polymerase III subunit alpha 988 985 experimental:829 database:900
Rv2191 hyp hypothetical protein 966 944 experimental:442 database:900 textmining:413
Rv3711c dnaQ DNA polymerase III subunit epsilon 948 942 experimental:442 database:900
Rv2414c hyp hypothetical protein 888 880 ctx neighborhood:839
Rv3370c dnaE2 error-prone DNA polymerase 895 857 experimental:829
Rv2116 lppK lipoprotein LppK 851 832 experimental:829
Rv2415c hyp hypothetical protein 836 830 ctx neighborhood:829
Rv2050 rbpA RNA polymerase-binding protein RbpA 769 769 ctx cooccurence:769
Rv2708c hyp hypothetical protein 760 761 ctx cooccurence:759
Rv2680 hyp hypothetical protein 738 739 ctx cooccurence:738
Rv2146c transmembrane protein 742 726 ctx cooccurence:719
Rv2219 transmembrane protein 725 726 ctx cooccurence:725

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: hypothetical protein
  • MTBC0 PGAP product: DNA polymerase III subunit delta
  • Pfam (hmmscan --cut_ga): DNA_pol3_delta_C PF21694.3 (E=3e-08)
  • (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_216929.3)
  • Domains: Pfam-A via hmmscan --cut_ga — DNA_pol3_delta_C (PF21694.3)
  • 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 COG1466
  • Curated reference: UniProt P71730 (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 — 82 functional partner(s); context anchor Rv3644c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002569|Rv2413c|
MHLVLGDEELLVERAVADVLRSARQRAGTADVPVSRMRAGDVGAYELAELLSPSLFAEERIVVLGAAAEAGKDAAAVIESAAADLPAGTVLVVVHSGGGRAKSLANQLRSMGAQVHPCARITKVSERADFIRSEFASLRVKVDDETVTALLDAVGSDVRELASACSQLVADTGGAVDAAAVRRYHSGKAEVRGFDIADKAVAGDVAGAAEALRWAMMRGEPLVVLADALAEAVHTIGRVGPQSGDPYRLAAQLGMPPWRVQKAQKQARRWSRDTVATAMRLVAELNANVKGAVADADYALESAVRQVAELVADRGR