Rv3394c Family assigned · medium auto-curated

H37Rv Rv3394c · MTBC0 mtbc0_003606 · 527 aa · 3834881–3836464 (-) · RefSeq NP_217911.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDNA polymerase Y family protein
Revised (this work)DNA polymerase Y family protein. Pfam: IMS (PF00817.26).

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

Curated reference (UniProt)

UniProt O50419 TrEMBL · unreviewed · Predicted
UniProt nameUmuC domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred namedinB_2
eggNOG descriptionDNA polymerase
Orthologous groupCOG0389
KEGG orthology K14161

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 0.777 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 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
IMSPF00817.26 3.8e-1125–148 impB/mucB/samB family

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

Closest characterised functional partner: dnaE2 (error-prone DNA polymerase), high confidence from genomic context alone (score 889 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3395c hyp hypothetical protein 999 998 ctx neighborhood:882 cooccurence:772 coexpression:936 textmining:661
Rv3370c dnaE2 error-prone DNA polymerase 917 889 ctx cooccurence:773 coexpression:450
Rv0002 dnaN DNA polymerase III subunit beta 861 853 experimental:627 database:612
Rv2116 lppK lipoprotein LppK 861 852 experimental:627 database:612
Rv2737c recA recombinase A 826 808 experimental:439 database:523
Rv1629 polA DNA polymerase I 770 678 database:553
Rv2101 helZ helicase HelZ 687 667 database:452
Rv1278 hyp hypothetical protein 668 635 database:548
Rv2090 5'-3' exonuclease 656 635 database:553
Rv0938 ligD multifunctional non-homologous end joining DNA repair protein/ATP dependent DNA ligase LigD 678 632 database:521
Rv3395A membrane protein 610 611 ctx neighborhood:609
Rv3731 ligC DNA ligase C 632 610 database:521
Rv1329c dinG ATP-dependent helicase DinG 645 607 database:577
Rv2720 lexA repressor LexA 629 589 experimental:463
Rv3646c topA DNA topoisomerase I 645 587 database:548

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 Y family protein
  • Pfam (hmmscan --cut_ga): IMS PF00817.26 (E=4e-11)
  • (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_217911.1)
  • Domains: Pfam-A via hmmscan --cut_ga — IMS (PF00817.26)
  • 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 COG0389
  • Curated reference: UniProt O50419 (TrEMBL, unreviewed; Predicted)
  • 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 — 63 functional partner(s); context anchor dnaE2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003606|Rv3394c|
MMASARVLAIWCMDWPAVAAAAAAGLSATAPVAVTLANRVIACSATARAAGVRRGLRRREAAARCPQLFIATADADRDARLFEGVIAAVDDLVPRAELLRPGLLVLPVRGPARFFGSEQMAAERLIDAVAAAGAECQVGIADRLSTAVFAARAGRIVEPGGDARFLSLLSIRQLATEPSLSGPGRDDLTDLLWRMGIRTIGQFAALSRTDVASRFGADAVAAHRFARGEPERAPCGREPPPDLAAELACDPPIDRVDAAAFAGRSLAAELHRALMAAGVGCTRLAIHAVTANGEERSRVWRCAEPLTEDATADRVRWQLDGWLNNRNARDRPTAAVTLLRLQAVETVSASEGLQLPLWGGLGEQDRLRARRALVRVQGLLGPEAVRVPVLSGGHGPAERITLTVLGLVAPEPVPQADPGQPWPGRLPDPSPAVLFDDPVDLLDAQGNPIRVTSRGMFSADPARLRVRGRDDRLRWWAGPWPDDERWWDPDRASGRTARAQVLLDGDPGTALLLCYRQRRWYLEGSYE