"FleQ is described as an **atypical NtrC-family enhancer-binding protein (EBP)** that functions within the **σ54/RpoN transcription paradigm**, with a tripartite architecture: an **N-terminal REC-like (receiver-like) domain**, a **central AAA+ ATPase domain** (containing the σ54 interaction functionality), and a **C-terminal helix–turn–helix (HTH) DNA-binding domain**."

"A key noncanonical feature is that FleQ’s receiver-like region **lacks the canonical conserved phospho-acceptor Asp** typical of many NtrC-like response regulators, implying FleQ is not regulated by a cognate sensor kinase in the standard phosphorylation-dependent manner."

"A genome-wide ChIP-seq analysis in KT2440 identified FleQ as a **global regulator**. Peak calling initially found **279 peaks** in KT2440; applying a **≥5-fold enrichment** threshold retained **103 peaks**, of which **69.31%** were intergenic and **98%** were upstream of ORFs, leading to assignment of **~160 genes** as likely directly regulated in KT2440."

"A 2024 authoritative review synthesizes structural and biochemical evidence (primarily from *P. aeruginosa* but presented as conserved across *Pseudomonas*) that **c-di-GMP binds the AAA+ ATPase domain of FleQ** and allosterically **inhibits ATPase activity**, enabling FleQ to switch from flagellar activation to matrix gene activation/repression at a single promoter without dissociation."

"FleQ is a **cytoplasmic DNA-binding transcriptional regulator** acting at chromosomal promoter regions (supported by its HTH DNA-binding domain and direct promoter binding in EMSA and promoter-associated ChIP peaks)."

"Primary function (KT2440, evidence-weighted):** FleQ (Q88ET0) is best annotated as a **global transcriptional regulator** and **master activator of the σ54-dependent flagellar cascade**, while also functioning as a **c-di-GMP–responsive switch** that directly regulates biofilm determinants including **LapA adhesin (lapA)** and **cellulose-associated genes (bcs operon)**."