Rv3404c Resolved · high auto-curated

H37Rv Rv3404c · MTBC0 mtbc0_003618 · 234 aa · 3849319–3850023 (-) · RefSeq NP_217921.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationdTDP-4-amino-4%2C6-dideoxyglucose formyltransferase
Revised (this work)DTDP-4-amino-4%2C6-dideoxyglucose formyltransferase. Pfam: Formyl_trans_N (PF00551.25), N_formyltrans_C (PF18216.7).

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

Curated reference (UniProt)

UniProt P9WKZ3 SwissProt · reviewed · Evidence at protein level
UniProt namedTDP-4-amino-4,6-dideoxyglucose formyltransferase
EC (curated) EC 2.1.2.-
Curated functionSugar N-formyltransferase that catalyzes the conversion of dTDP-4-amino-4,6-dideoxyglucose into dTDP-4-formamido-4,6-dideoxyglucose using N(10)-formyltetrahydrofolate as the carbon source. Plays a role in virulence. Has no activity on dTDP-3-amino-3,6-dideoxyglucose, dTDP-3-amino-3,6-dideoxygalactose, UDP-4-amino-4-deoxyarabinose, and GDP-4-amino-4,6-dideoxymannose.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category J Translation, ribosomal structure and biogenesis
eggNOG descriptionFormyl transferase
Orthologous groupCOG0223
Gene Ontology (61) GO:0003674, GO:0003824, GO:0004479, GO:0005488, GO:0005515, GO:0006139, GO:0006396, GO:0006399, GO:0006400, GO:0006412, GO:0006413, GO:0006464 +49 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 0.463 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 3 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
Formyl_trans_NPF00551.25 3.0e-1556–150 Formyl transferase
N_formyltrans_CPF18216.7 6.5e-15177–226 N-formyltransferase dimerization C-terminal domain

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

Closest characterised functional partner: Rv3405c (HTH-type transcriptional regulator), medium confidence from genomic context alone (score 642 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1407 fmu 16S rRNA m5C967 methyltransferase 980 970 coexpression:966
Rv3403c hyp hypothetical protein 798 799 ctx neighborhood:746
Rv0018c pstP phosphoserine/threonine phosphatase PstP 748 749 coexpression:703
Rv2533c nusB N utilization substance protein B 710 683 coexpression:650
Rv3402c hyp hypothetical protein 676 657
Rv1402 priA primosomal protein N' 655 655 coexpression:613
Rv3405c HTH-type transcriptional regulator 642 642 ctx neighborhood:640
Rv3012c gatC glutamyl-tRNA(GLN) amidotransferase subunit C 572 556
Rv0429c def polypeptide deformylase 582 527 coexpression:413
Rv3356c folD bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase 549 489 coexpression:460
Rv3025c iscS cysteine desulfurase 460 460
Rv0236c aftD alpha-(1->3)-arabinofuranosyltransferase 494 452 coexpression:421
Rv1901 cinA competence damage-inducible protein CinA 447 447 coexpression:404
Rv2879c rlmN Conserved hypothetical protein; Specifically methylates position 2 of adenine 2503 in 23S rRNA and position 2 of adenine 37 in tRNAs; Belong 446 447 coexpression:428
Rv2880c Rv2880c, (MTCY274.11c), len: 275 aa. Conserved hypothetical protein, highly similar in N-terminus to others e.g. O86754|SC6A9.22c hypothetic 445 445 coexpression:426

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: dTDP-4-amino-4%2C6-dideoxyglucose formyltransferase
  • Pfam (hmmscan --cut_ga): Formyl_trans_N PF00551.25 (E=3e-15), N_formyltrans_C PF18216.7 (E=6e-15)
  • (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_217921.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Formyl_trans_N (PF00551.25), N_formyltrans_C (PF18216.7)
  • 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 COG0223
  • Curated reference: UniProt P9WKZ3 (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 — 38 functional partner(s); context anchor Rv3405c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003618|Rv3404c|
MTILILTDNVHAHALAVDLQARHGDMDVYQSPIGQLPGVPRCDVAERVAEIVERYDLVLSFHCKQRFPAALIDGVRCVNVHPGFNPYNRGWFPQVFSIIDGQKVGVTIHEIDDQLDHGPIIAQRECAIESWDSSGSVYARLMDIERELVLEHFDAIRDGSYTAKSPATEGNLNLKKDFEQLRRLDLNERGTFGHFLNRLRALTHDDFRNAWFVDASGRKVFVRVVLEPEKPAEA