Secreted frizzled-related protein 4 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''SFRP4''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
Secreted
frizzled
Frizzled is a family of atypical G protein-coupled receptor, G protein-coupled receptors that serve as receptors in the Wnt signaling pathway and other signaling pathways. When activated, Frizzled leads to activation of Dishevelled in the cytosol ...
-related protein 4 (SFRP4) is a member of the SFRP family that contains a
cysteine
Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...
-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of
Wnt signaling
In cellular biology, the Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt, pronounced "wint", is a portmanteau created from the ...
. The expression of SFRP4 in
ventricular myocardium
Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall o ...
correlates with
apoptosis
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
related gene expression.
Biallelic, recessive variants in the ''SFRP4'' gene result in the genetic disorder of bone, Pyle disease, that is characterized by a failure of long bone remodeling with increased fragility. The association between SFRP4 deficiency and Pyle disease has highlighted the importance of SFRP4 in the formation of the bone cortex, and of the importance of bone cortex for the mechanical stability of long bone elements.
SFRP4 is a hub gene in a
Type 2 Diabetes
Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent ...
-associated gene coexpression module in human
islets
An islet ( ) is generally a small island. Definitions vary, and are not precise, but some suggest that an islet is a very small, often unnamed, island with little or no vegetation to support human habitation. It may be made of rock, sand and ...
, and reduces glucose-induced insulin secretion through decreased
β-cell exocytosis
Exocytosis is a term for the active transport process that transports large molecules from cell to the extracellular area. Hormones, proteins and neurotransmitters are examples of large molecules that can be transported out of the cell. Exocytosis ...
. Expression and release of SFRP4 from islets is enhanced by
interleukin-1β
Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the ''IL1B'' gene."Catabolin" ...
. SFRP4 is elevated in serum several years before clinical diagnosis of Type 2 Diabetes. Individuals who have above-average levels of SFRP4 in the blood are five times more likely to develop diabetes in the next few years than those with below-average levels.
SFRP4 concentration seems to correlate with obesity and systemic insulin resistance
[Hörbelt T., Knebel B., Fahlbusch P., Barbosa D., de Wiza D.H., Van de Velde F., Van Nieuwenhove Y., Lapauw B., Thoresen G.H., Al-Hasani H. The adipokine sFRP4 induces insulin resistance and lipogenesis in the liver. Biochim. Biophys. Acta. Mol. Basis Dis. 2019;1865:2671–2684. doi: 10.1016/j.bbadis.2019.07.008]
References
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