Functional domains of KLF1 and variants reported in the literature. The KLF1 protein (362 amino acids) contains two N-terminal transactivation domains (TAD1 and TAD2) which are required for it to work as a transcriptional activator. The 3 zinc fingers (ZF1, ZF2, and ZF3) located at the C terminus form the DNA-binding domain, which enables KLF1 to bind to specific sites in the genome, typically CACCC boxes and related GC-rich elements. Residues conserved in all human KLF factors are indicated. The cysteine and histidine residues involved in zinc coordination are highlighted in blue; residues contacting DNA are highlighted in yellow. The arrows point to residues making base-specific contacts thus recognizing KLF1-binding sites in the genome. Variants are color-coded: class 1, green; class 2, blue; class 3, red; class 4, black. See supplemental Table 1 for details and references.