Rv1357c Resolved · high auto-curated

H37Rv Rv1357c · MTBC0 mtbc0_001457 · 307 aa · 1535995–1536918 (-) · RefSeq NP_215873.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationcyclic diguanylate phosphodiesterase
Revised (this work)Cyclic diguanylate phosphodiesterase. Pfam: EAL (PF00563.26).

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

Curated reference (UniProt)

UniProt P9WM07 SwissProt · reviewed · Predicted
UniProt nameUncharacterized protein Rv1357c

UniProt still lists this protein as Uncharacterized protein Rv1357c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category T Signal transduction mechanisms
eggNOG descriptionEAL domain
Orthologous groupCOG2200
Gene Ontology (57) GO:0003674, GO:0003824, GO:0006139, GO:0006725, GO:0006753, GO:0006793, GO:0006796, GO:0006807, GO:0008081, GO:0008150, GO:0008152, GO:0009056 +45 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 0.643 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 6 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
EALPF00563.26 3.0e-6661–298 EAL domain

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv1354c hyp hypothetical protein 948 903 coexpression:858 textmining:487
Rv1356c hyp hypothetical protein 864 864 coexpression:860
Rv1358 transcriptional regulator 871 863 coexpression:804
Rv1364c sigma factor regulatory protein 868 862 coexpression:843
Rv1355c moeY molybdopterin biosynthesis protein MoeY 848 848 coexpression:848
Rv0894 transcriptional regulator 731 731 coexpression:731
Rv0895 diacyglycerol O-acyltransferase 554 555 coexpression:553
Rv1359 transcriptional regulator 534 534 coexpression:404
Rv1353c HTH-type transcriptional regulator 450 449 coexpression:449
Rv3287c rsbW anti-sigma factor RsbW 416 417 coexpression:410
Rv1173 fbiC FO synthase 416 417 coexpression:417
Rv3657c membrane protein 411 412 coexpression:409
Rv0990c hyp hypothetical protein 411 412 coexpression:403
Rv3658c transmembrane protein 408 408 coexpression:405

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: cyclic diguanylate phosphodiesterase
  • Pfam (hmmscan --cut_ga): EAL PF00563.26 (E=3e-66)
  • (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_215873.1)
  • Domains: Pfam-A via hmmscan --cut_ga — EAL (PF00563.26)
  • 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 COG2200
  • Curated reference: UniProt P9WM07 (SwissProt, reviewed; 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 — 14 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001457|Rv1357c|
MDRCCQRATAFACALRPTKLIDYEEMFRGAMQARAMVANPDQWADSDRDQVNTRHYLSTSMRVALDRGEFFLVYQPIIRLADNRIIGAEALLRWEHPTLGTLLPGRFIDRAENNGLMVPLTAFVLEQACRHVRSWRDHSTDPQPFVSVNVSASTICDPGFLVLVEGVLGETGLPAHALQLELAEDARLSRDEKAVTRLQELSALGVGIAIDDFGIGFSSLAYLPRLPVDVVKLGGKFIECLDGDIQARLANEQITRAMIDLGDKLGITVTAKLVETPSQAARLRAFGCKAAQGWHFAKALPVDFFRE