secreted frizzled-related protein 1; FRP-1; sFRP-1; secreted apoptosis-related protein 2; SARP-2 (SFRP1, FRP, FRP1, SARP2)
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Function
- soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts
- role in regulating cell growth & differentiation in specific cell types
- SFRP1 decreases intracellular beta-catenin levels (putative)
- has antiproliferative effects on vascular cells, in vitro & in vivo, & can induce, in vivo, an angiogenic response
- in vascular cell cycle, delays the G1 phase & entry into the S phase (putative)
- in kidney development, inhibits tubule formation & bud growth in metanephros
- inhibits WNT1/WNT4-mediated TCF-dependent transcription
- interacts with WNT1, WNT2 & FRZD6
- interacts with WNT4 & WNT8 (putative)
Structure
- the FZ domain is involved in binding with Wnt ligands
- belongs to the secreted frizzled-related protein (sFRP) family
- contains 1 FZ (frizzled) domain
- contains 1 NTR domain
Compartment
- secreted
- cell membrane or extracellular matrix-associated
- released by heparin-binding
Expression
- widely expressed
- absent from lung, liver & peripheral blood leukocytes
- highest levels in heart & fetal kidney
- also expressed in testis, ovary, fetal brain & lung, leiomyomal cells, myometrial cells & vascular smooth muscle cells
- expressed in foreskin fibroblasts & in keratinocytes
- down-regulated in colorectal cacrcinoma & breast cancer
- up-regulated in uterine leiomyomas under high estrogenic conditions
- expression, in leiomyomal cells, also increased both under hypoxic & serum deprivation conditions
Pharmacology
- may have therapeutic use in cardiac surgery