Fig. 1

Structural features of CD133. a Membrane topology. The human CD133 protein comprises three extracellular domains (EC1–3), an N-terminal domain (EC1) and two larger loops (EC2 and EC3) bearing nine glycosylation sites. N-glycan structures vary with the subcellular localization of CD133 and the state of cell differentiation, which may influence its interaction with protein partners. The intracellular domains (IC1–3) consist of two small cytoplasmic loops (IC1–2) and the C-terminal domain (IC3). ECs and ICs are separated by five transmembrane domains (1–5, pink cylinders). CD133 carries a cluster of cysteine residues located at the boundary of the first transmembrane segment and the IC1 domain (dotted green line). These residues may be subject to palmitoylation. Two potential ganglioside-binding sites are located in the EC1 and EC2 domains (orange and yellow cylinders). Two major tyrosine (Y) residues, 828 and 852, in IC3 can be phosphorylated and regulate the activity of several signaling pathways. Lysine (K) 138 interacts with HDAC6 and Arl13b. The outer and inner leaflets of the plasma membrane are shown with membrane cholesterol (red), highlighting the association of CD133 with cholesterol-dependent membrane microdomains. Amino acid numbering is based on the human splice variant CD133.s2; the approximate number of amino acid residues in a given domain, which may vary from one splice variant to another, is indicated in parentheses. b Genomic organization of mammalian CD133. Vertical lines indicate exon boundaries, the dashed line the presence of an alternative splice acceptor site, while transmembrane domains are highlighted in pink. Major facultative exons within ORF are indicated in brackets. The exons are numbered as the initial start codon is located in exon 2. c PROM1 promoters. Six distinct promoters were identified (blue boxes) in human PROM1 gene with various facultative exons (A-E5, black boxes) that are part of exon 1. The P1-P3 promoters show high proportion of CpG islands. The major transcription factors impacting positively or negatively on PROM1 gene expression are indicated in green and red, respectively. Figures are not to scale. Illustration in a is adapted from Ref [3] and incorporates data from Refs [94, 161, 209, 219], while those in panels b and c are adapted from Refs [95] and [111], respectively