Fig. 1

Reported FZD4 proteins with disease-causing missense proteins. a Protein domain structural models for FZ-CRD proteins. HUGO gene symbols proteins are shown next to the protein structure and the NCBI accession number is shown next to each protein model. Available PDB codes are in bold at the far right. [PDZ: PDZ binding motif, KTXXXW: lysine-threonine-X-X-X-tryptophan, TM: transmembrane, FZ-CRD: frizzled cysteine- rich domain, TK: tyrosine kinase domain, Ig: immunoglobulin domain, Ser/Thr: Serine-threonine/tyrosine-protein kinase, KD: kinase domain, Trypsin: trypsin-like protease domain, SPCR: scavenger receptor cysteine-rich domain, and L: low density lipoprotein receptor repeats. b Multiple sequence alignment of FZD4, MuSK and ROR2 FZ-CRDs. Conserved cysteines are shown in red color. FZ-CRD show homology with a conserved pattern of “CnCnCX8CX6CnCX3CX6,7CnCnC” (Pei and Grishin 2012) C: conserved cysteine; n: a variable number of residues, Xn: n residues, and Xn1, n2: n1 to n2 residues in α-helices forming a common Frizzled fold across four α-helices connected by disulfide bridges shown and labelled in red as: “C1–C5, C2–C4, C3–C8, C6–C10, and C7–C9” . For FZD4, one inserted region is shown as the number of inserted residues underlined in bold. Different residues exist between conserved C7 and C8. For FZDs the number is six and RTKs have seven residues