Size: 8487 bases. The SFRP2 gene is located on the long arm of Chromosome 4, and consists of 3 coding exons, with exon 2 being significantly smaller than the other two. No known splice variants.

mRNA size 2005 bp, ORF size 888 bp.

SFRP2 contains several domains which potentially govern protein-protein interactions.
- Beginning at the N-terminus there is a 24 aa hydrophobic signal domain, which presumably governs the targeting of SFRP2 to the secretory pathway.
- The CRD/FZ (cysteine-rich/Frizzled) domain allows SFRP proteins to antagonise Wnt/Frizzled binding at the plasma membrane either by sequestration of the Wnt ligand or dominant-negative binding to complimentary regions within the Frizzled protein.
- The C345C/Netrin domain is an accessory binding domain for SFRP2-Wnt interaction.
- The PDZ ligand domain is a short sequence which is recognised by PDZ proteins such as Dishevelled (Dvl), and other proteins which interact with the cytoplasmic portion of Frizzled (Schulte and Bryja, 2007). Notably, a recent study (Zhang et al., 2009) has used synthetic PDZ ligands to interfere with Dvl/FZD cytoplasmic interaction, and thus antagonise canonical Wnt signalling. Additionally, another group subsequently showed that the NSAID Sulindac inhibits canonical Wnt signaling by blocking the PDZ domain of Dvl (Lee et al., 2009). These data suggest that the presence of a PDZ ligand in SFRP2 may indicate a previously-unexplored role for SFRP2 as a cytoplasmic antagonist of Wnt signalling.
- A phosphoproteomic study has revealed phosphorylation of SFRP2 at serine-289 in response to growth factor stimulation (Olsen et al., 2006). Bioinformatic analysis suggests that this site is a motif for recognition and phosphorylation by PKA. Additionally, bioinformatic analysis of the SFRP2 sequence suggests a site for phosphorylation by GSK3β (itself an inhibitor of β-catenin) at either serine-34 or serine-38. Although the potential significance of phosphorylation at this site is unclear, it may overlap with the Nec 1/Nec 2 cleavage site and prevent removal of the N-terminal signal domain. Typically, Nec 1/2 is responsible for the cleavage of pro-proteins into their active form, and perhaps phosphorylation in this region is a mechanism by which GSK3β may regulate SFRP2 activity.

Widely expressed.

Nucleus, cytoplasm and secreted.

SFRP2 is a member of the secreted Frizzled-related protein (SFRP) family of soluble extracellular Wnt antagonists, which act in conjunction with the Dickkopf (DKK) class of Wnt antagonists. SFRP2 is thought to act primarily by binding directly to and sequestering Wnt ligands, but may also act by direct binding to the Wnt-receptor complex. Binding occurs primarily via the cysteine-rich domain, which bears a high degree of homology to similar domains in the Frizzled (Fzd) receptor. SFRP activity may conversely promote Wnt pathway signalling in some contexts, as a consequence of SFRP proteins interacting with each other and titrating each others activity, or by SFRP binding and stabilising Wnt-Fzd complexes.

SFRP2 has a high degree of homology to both other SFRP family members, as well as Fzd receptors via the cysteine-rich domain.