Rv3644c Family assigned · medium auto-curated

H37Rv Rv3644c · MTBC0 mtbc0_003861 · 401 aa · 4105221–4106426 (-) · RefSeq NP_218161.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)DNA polymerase
MTBC0 PGAP re-annotationDNA polymerase III subunit delta'
Revised (this work)DNA polymerase III subunit delta'. Pfam: DNA_pol3_delta2 (PF13177.13), AAA (PF00004.36), DNApol3-delta_C (PF09115.16).

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

Curated reference (UniProt)

UniProt O06363 TrEMBL · unreviewed · Evidence at protein level
UniProt nameDNA polymerase III subunit delta'
EC (curated) EC 2.7.7.7

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred nameholB
eggNOG descriptionDNA polymerase III
Orthologous groupCOG0470
EC number EC 2.7.7.7
KEGG orthology K02341
KEGG pathways map00230, map00240, map01100, map03030, map03430, map03440
KEGG modules M00260
Gene Ontology (34) GO:0005575, GO:0005622, GO:0005623, GO:0006139, GO:0006259, GO:0006260, GO:0006261, GO:0006725, GO:0006807, GO:0008150, GO:0008152, GO:0009058 +22 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 0.192 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 8 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_delta2PF13177.13 5.2e-3637–179 DNA polymerase III, delta subunit
AAAPF00004.36 3.4e-0444–178 ATPase family associated with various cellular activities (AAA)
DNApol3-delta_CPF09115.16 7.1e-05325–380 DNA polymerase III, delta subunit, C terminal

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

Closest characterised functional partner: dnaN (DNA polymerase III subunit beta), high confidence from genomic context alone (score 987 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2413c hyp hypothetical protein 995 995 ctx cooccurence:690 experimental:829 database:900
Rv0002 dnaN DNA polymerase III subunit beta 988 987 ctx cooccurence:454 experimental:773 database:900
Rv1547 dnaE1 DNA polymerase III subunit alpha 983 982 experimental:773 database:900
Rv2191 hyp hypothetical protein 971 961 experimental:474 database:900
Rv3711c dnaQ DNA polymerase III subunit epsilon 951 947 experimental:474 database:900
Rv3721c dnaZX DNA polymerase III subunit gamma/tau 924 925 database:900
Rv0054 ssb single-strand DNA-binding protein 843 829 experimental:773
Rv2478c hyp hypothetical protein 823 806 experimental:773
Rv3370c dnaE2 error-prone DNA polymerase 805 787 experimental:773
Rv2116 lppK lipoprotein LppK 799 780 experimental:773
Rv2977c thiL thiamine-monophosphate kinase 733 734 coexpression:733
Rv3195 hyp hypothetical protein 623 623 ctx cooccurence:622
Rv2343c dnaG DNA primase 661 616 ctx cooccurence:595
Rv2362c recO DNA repair protein RecO 649 602 ctx cooccurence:424
Rv1830 HTH-type transcriptional regulator 584 585

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: DNA polymerase
  • MTBC0 PGAP product: DNA polymerase III subunit delta'
  • Pfam (hmmscan --cut_ga): DNA_pol3_delta2 PF13177.13 (E=5e-36), AAA PF00004.36 (E=3e-04), DNApol3-delta_C PF09115.16 (E=7e-05)
  • (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_218161.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DNA_pol3_delta2 (PF13177.13), AAA (PF00004.36), DNApol3-delta_C (PF09115.16)
  • 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 COG0470
  • Curated reference: UniProt O06363 (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 — 47 functional partner(s); context anchor dnaN
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003861|Rv3644c|
MSGVFTRLVGQQAVEAELLATAKAARRDSAHSAGGGGTMTHAWLLTGPPGSGRSVAALCFAAALQCTSGGEPGCGRCRACTTTLAGTHADVRRVIPEGLSIGVDEMRAIVQIAARRPTTGHWQIVVIEDADRLTEGAANALLKVVEEPPPSTVFLLCAPSVDPEDIAVTLRSRCRHVALVTPSTHAIAQVLSDGDGLDPDTANWAASVSGGHVGRARRLATDPQARQRRERALGLARDAATPSRAYAAAEELVAGAEAEALALTAQRIEAETEELRTALGAGGTGKGTGAALRGATGAMKDLERRQKSRQTRASRDALDRALIDLATYFRDALLVAAHAGGVRANHPDMADRVAALAAHAPPERLLRCIEAVLACREALAVNVKPKFAVDAMVATIGQELR