Rv3604c Still unknown · low auto-curated

H37Rv Rv3604c · MTBC0 mtbc0_003822 · 397 aa · 4070007–4071200 (-) · RefSeq NP_218121.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationDUF6779 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF6779. 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 O06278 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable conserved transmembrane protein rich in alanine and arginine and proline

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2F5G1

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 2.25 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 12 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
DUF6779PF20570.4 1.9e-2845–150 Domain of unknown function (DUF6779)

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

Closest characterised functional partner: Rv0955 (integral membrane protein), high confidence from genomic context alone (score 776 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3605c hyp hypothetical protein 780 780 ctx neighborhood:734
Rv0955 integral membrane protein 776 776 ctx cooccurence:773
Rv3912 rsmA anti-sigma-M factor RsmA 769 770 ctx cooccurence:769
Rv1159 pimE polyprenol-phosphate-mannose-dependent alpha-(1-2)-phosphatidylinositol pentamannoside mannosyltransferase 769 769 ctx cooccurence:754
Rv0804 hyp hypothetical protein 747 747 ctx cooccurence:746
Rv0256c PPE2 PPE family protein PPE2 745 745 ctx cooccurence:744
Rv3602c panC pantothenate synthetase 741 741 ctx neighborhood:740
Rv3600c coaX type III pantothenate kinase 741 741 ctx neighborhood:740
Rv3603c hyp hypothetical protein 740 740 ctx neighborhood:740
Rv3601c panD aspartate 1-decarboxylase 740 740 ctx neighborhood:740
Rv3607c folB dihydroneopterin aldolase 738 738 ctx neighborhood:734
Rv3606c folK 2-amino-4-hydroxy-6-hydroxymethyldihydropteridinepyrophosphokinase 737 737 ctx neighborhood:734
Rv2378c mbtG L-lysine N6-monooxygenase 737 737 ctx cooccurence:737
Rv3608c folP1 dihydropteroate synthase 736 737 ctx neighborhood:734
Rv3609c folE GTP cyclohydrolase I 735 736 ctx neighborhood:734

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: transmembrane protein
  • MTBC0 PGAP product: DUF6779 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF6779 PF20570.4 (E=2e-28)
  • (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_218121.2)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF6779 (PF20570.4)
  • 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 2F5G1
  • Curated reference: UniProt O06278 (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 — 112 functional partner(s); context anchor Rv0955
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003822|Rv3604c|
MTVLSRGARVRRGGRRPGWVLLTALLVLAIGASSALVFTDRVELLKLAVLLALWAAVAGAFVSVLYRRQSDVDQARVRDLKLVYDLQLDREISARREYELTLESQLRRELASELRAPAADEVAALRAELAALRTSLEILFDADLEHRPALGTVEKEARAARALDGESPPADWVSSDRVMAVRGGDGASRTDEASIIDVPEVGVPPVSGGPRHYEAPPPPQPEPLFEPRHRPPPLPPQQERPVWQPVTSHGQWLPAETPGSQWASVEPETTPAAPPPGRRRRARHASPADQAYNPPAYVELAAQYGESGRRSRHSAEHRDHDIGGSGAGTGERPPSPPMAPPPPAEPTRRHRTADTPPDDSGGLHARDPLTGGQSVADLMARLQVESTGGGRRRRRGE