MTBC Gene Atlas

Rv3909 Still unknown · low auto-curated

H37Rv Rv3909 · MTBC0 mtbc0_004143 · 802 aa · 4418444–4420852 (+) · RefSeq NP_218426.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF6049. Function unknown.

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

Curated reference (UniProt)

UniProt O05436 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2DUHC

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 0.878 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 8 synonymous, 18 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
DUF6049PF19516.5 1.9e-1212–420 Family of unknown function (DUF6049)

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

Closest characterised functional partner: murJ (peptidoglycan biosynthesis protein), high confidence from genomic context alone (score 934 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3910 murJ peptidoglycan biosynthesis protein 953 934 ctx neighborhood:881 cooccurence:446
Rv3908 mutT4 mutator protein MutT 939 888 ctx neighborhood:881 textmining:478
Rv3911 sigM ECF RNA polymerase sigma factor SigM 827 828 ctx neighborhood:724
Rv3912 rsmA anti-sigma-M factor RsmA 821 821 ctx neighborhood:815
Rv3906c hyp hypothetical protein 811 804 ctx neighborhood:669
Rv3835 hyp hypothetical protein 776 776 ctx cooccurence:774
Rv2164c hyp hypothetical protein 771 772 ctx cooccurence:769
Rv2843 hyp hypothetical protein 770 770 ctx cooccurence:767
Rv3658c transmembrane protein 769 769 ctx cooccurence:768
Rv1024 membrane protein 768 768 ctx cooccurence:765
Rv1111c hyp hypothetical protein 760 761 ctx cooccurence:757
Rv0538 membrane protein 760 760 ctx cooccurence:744
Rv2709 transmembrane protein 751 751 ctx cooccurence:751
Rv2739c transferase 750 751 ctx cooccurence:747
Rv0007 membrane protein 743 744 ctx cooccurence:740

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: hypothetical protein
  • Pfam (hmmscan --cut_ga): DUF6049 PF19516.5 (E=2e-12)
  • (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_218426.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF6049 (PF19516.5)
  • 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 2DUHC
  • Curated reference: UniProt O05436 (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 — 117 functional partner(s); context anchor murJ
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004143|Rv3909|
MTALQLRWAALARVTSAIGVVAGLGMALTVPSAAPHALAGEPSPTPFVQVRIDQVTPDVVTTSSEPHVTVSGTVTNTGDRPVRDVMVRLEHAAAVTSSTALRTSLDGGTDQYQPAADFLTVAPELDRGQEAGFTLSAPLRSLTRPSLAVNQPGIYPVLVNVNGTPDYGAPARLDNARFLLPVVGVPPDQATDFGSAVAPETTAPVWITMLWPLADRPRLAPGAPGGTVPVRLVDDDLANSLANGGRLDILLSAAEFATNREVDPDGAVGRALCLAIDPDLLITVNAMTGGYVVSDSPDGAAQLPGTPTHPGTGQAAASSWLDRLRTLVHRTCVTPLPFAQADLDALQRVNDPRLSAIATISPADIVDRILDVSSTRGATVLPDGPLTGRAINLLSTHGSTVAVAAADFSPEEQQGSSQIGSALLPATAPRRLSPRVVAAPFDPAVGAALAAAGTNPTVPTYLDPSLFVRIAHESITARRQDALGAMLWRSLEPNAAPRTQILVPPASWSLASDDAQVILTALATAIRSGLAVPRPLPAVIADAAARTEPPEPPGAYSAARGRFNDDITTQIGGQVARLWKLTSALTIDDRTGLTGVQYTAPLREDMLRALSQSLPPDTRNGLAQQRLAVVGKTIDDLFGAVTIVNPGGSYTLATEHSPLPLALHNGLAVPIRVRLQVDAPPGMTVADVGQIELPPGYLPLRVPIEVNFTQRVAVDVSLRTPDGVALGEPVRLSVHSNAYGKVLFAITLSAAAVLVTLAGRRLWHRFRGQPDRADLDRPDLPTGKHAPQRRAVASRDDEKHRV