CV_2726 (UniProt Q7NUH2) is a 147-residue MarR-family winged helix-turn-helix transcription factor from Chromobacterium violaceum ATCC 12472. The HTH marR-type domain (PROSITE PS50995) covers the whole protein. Like other MarR proteins, it is expected to act as a cytoplasmic homodimer that binds operator DNA in or near target promoters and regulates their transcription. In most characterized MarR proteins, a small-molecule ligand or an oxidant lowers this DNA-binding affinity. PANTHER places it in subfamily PTHR33164:SF43. That subfamily is broad: CV_2726 shares only 20-29% identity with its characterized members, which include M. tuberculosis Rv2887 (a salicylate-responsive repressor of a methyltransferase gene) and staphylococcal TcaR (a regulator of the ica operon and of teicoplanin susceptibility). No experimental data exist for CV_2726, so its operator, regulon, effector ligand and regulatory sign are unknown.
Summary: UniRule transfer, based on the MarR-type winged-HTH domain that covers the whole 147-residue protein (PS50995, residues 1-147). DNA binding is correct. However, MarR-family proteins bind particular operator sequences rather than DNA in general, and GO:0003700 (also annotated here) is defined as selective binding to a specific DNA sequence.
Reason: The term is correct but general. The MarR winged-HTH architecture supports sequence-specific operator binding, which is the DNA-binding mode implied by the accepted GO:0003700 transcription factor activity. Refine the term to sequence-specific DNA binding (GO:0043565). The actual operator sequence is unknown.
Summary: InterPro2GO mapping from IPR000835 (HTH_MarR-typ) and IPR039422 (MarR/SlyA-like). Every characterized member of PTHR33164:SF43 (Rv2887, TcaR) and the family archetype, E. coli MarR, is a DNA-binding transcriptional regulator. CV_2726 has the complete MarR domain. This molecular function is conserved across the family and is the right level of specificity for an uncharacterized member.
Reason: The core, family-conserved activity. A full-length MarR-type winged-HTH domain and membership of PTHR33164 support it. Whether it acts as a repressor or an activator is not established, so the generic term is as precise as the evidence allows.
Supporting Evidence:
file:genes/CHRVO/Q7NUH2/Q7NUH2-uniprot.txt
DR InterPro; IPR039422; MarR/SlyA-like.
file:genes/CHRVO/Q7NUH2/Q7NUH2-uniprot.txt
DR PANTHER; PTHR33164; TRANSCRIPTIONAL REGULATOR, MARR FAMILY; 1.
Summary: UniRule transfer. A MarR-family regulator controls transcription but does none of the work of transcription itself (RNA polymerase does). The accurate process term, regulation of DNA-templated transcription (GO:0006355), is already annotated.
Reason: The process is transcription itself, carried out by RNA polymerase. The regulator's role is captured by GO:0006355, which this gene already carries.
GO:0006355 regulation of DNA-templated transcription
IEA GO_REF:0000120
ACCEPT
Summary: Combined automated annotation. It agrees with the PAINT IBD for GO:0006355 at PTN002109389, the PTHR33164 node seeded by experimentally characterized MarR-family members across Proteobacteria and Firmicutes. CV_2726 descends from this node and shows no sign of divergence. Its domain is intact and covers the full length of the protein.
Reason: This is the core biological process of a MarR-family transcription factor and is supported by phylogenetic placement. Positive or negative regulation cannot be asserted because the regulatory sign of CV_2726 is unknown.
Summary: TreeGrafter transfer of the PAINT IBD for GO:0006950 at PTN002109389. The seeds are E. coli MarR (P27245) and B. subtilis O34777. The curator judged a stress-response role to be ancestral to the family. CV_2726 shows no sign of divergence from it. Its closest characterized SF43 relative, Rv2887, responds to salicylate-type phenolic compounds. Still, no stress, signal or regulon has been identified for CV_2726, and the term is very broad.
Reason: Kept to respect the PAINT node placement, since no target-specific evidence argues against it. It is non-core because the specific stress, if any, is unknown, and members of SF43 respond to quite different signals (salicylate, antibiotics, aromatic substrates).
No published knockouts or biochemical assays specific to CV_2726/Q7NUH2
Core Functions
MarR-family winged-HTH transcription factor that is expected to bind operator DNA as a homodimer and regulate transcription of target genes. Its operator, regulon, effector ligand and regulatory sign are unknown.
Q: What operator does CV_2726 bind, and which genes does it control? The neighbouring genes (an alcohol dehydrogenase, an acyl-CoA dehydrogenase and hydrolase, MarC) do not clearly point to a regulon.
Q: Does a phenolic or aromatic ligand, as with Rv2887 and salicylate, release CV_2726 from DNA, or is it oxidant-sensitive? Its sequence has two cysteines (C77 and C94); whether either aligns with the redox-sensing cysteine of OhrR-type regulators has not been tested.
Suggested Experiments
Experiment: EMSA or DNase I footprinting of purified CV_2726 on intergenic regions near CV_2726/CV_2727/CV_2728, followed by RNA-seq of a CV_2726 deletion mutant to define its regulon. Then screen phenolic compounds and oxidants for release from DNA.
External Prediction Reviews
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
ProtNLM2 made no predictions (GO or subcellular location) for CV_2726, a MarR-family winged helix-turn-helix transcription factor; the model returned only the protein name "HTH marR-type domain-containing protein". This is an assessed absence. The gene review supports DNA-binding transcription factor activity and sequence-specific DNA binding from the full-length MarR domain, but the protein has no experimental characterization, so there is no predicted term to score.