Suppressor of cytokine signaling 3 (SOCS3 or SOCS-3) 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 ''SOCS3''

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 ...

. This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (

SOCS SOCS (suppressor of cytokine signaling proteins) refers to a family of genes involved in inhibiting the JAK-STAT signaling pathway. Genes * CISH (gene), CISH * SOCS1 * SOCS2 * SOCS3 * SOCS4 * SOCS5 * SOCS6 * SOCS7 Structure All SOCS have certai ...

), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. SOCS3 is a conserved gene, found in across the animal kingdom, including ''

Drosophila ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...

'',

chicken The chicken (''Gallus gallus domesticus'') is a domesticated subspecies of the red junglefowl (''Gallus gallus''), originally native to Southeast Asia. It was first domesticated around 8,000 years ago and is now one of the most common and w ...

s, and

crocodile Crocodiles (family (biology), family Crocodylidae) or true crocodiles are large, semiaquatic reptiles that live throughout the tropics in Africa, Asia, the Americas and Australia. The term "crocodile" is sometimes used more loosely to include ...

Function

The expression of SOCS3 gene is induced by various cytokines, including IL6, IL10, and interferon (IFN)-gamma. For signaling of IL-6, Epo, GCSF and Leptin, binding of SOCS3 to the respective cytokine receptor has been found to be crucial for the inhibitory function of SOCS3. Overexpression of SOCS3 inhibits

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

signaling in

adipose tissue Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...

and the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

, but not in

muscle Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...

. But deletion of SOCS3 in the skeletal muscle of mice protects against obesity-related

insulin resistance Insulin resistance (IR) is a pathological response in which cells in insulin-sensitive tissues in the body fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia. Insulin is a horm ...

. SOCS3 contributes to both leptin resistance and insulin resistance as a result of increased

ceramide Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid joined by an amide bond. Ceramides are found in high concentrations within the cell membrane of Eukaryote, eukaryotic cells, since they are co ...

synthesis. For that reason, studies have shown that removal of the SOCS gene prevents against insulin resistance in

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

Studies of the mouse counterpart of this gene suggested the roles of this gene in the negative regulation of fetal liver

hematopoiesis Haematopoiesis (; ; also hematopoiesis in American English, sometimes h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten ...

, and placental development. The SOCS3 protein can bind to JAK2 kinase, and inhibits the activity of JAK2 kinase.

Interactions

SOCS3 has been shown to interact with: *

Erythropoietin receptor The erythropoietin receptor (EpoR) is a protein that in humans is encoded by the ''EPOR'' gene. EpoR is a 52 kDa peptide with a single carbohydrate chain resulting in an approximately 56–57 kDa protein found on the surface of EPO res ...

, *

Glycoprotein 130 Glycoprotein 130 (also known as gp130, IL6ST, IL6R-beta or CD130) is a transmembrane protein which is the founding member of the class of tall cytokine receptors. It forms one subunit of the type I cytokine receptor within the IL-6 receptor ...

, * Insulin-like growth factor 1 receptor, *

Janus kinase 2 Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CS ...

, *

PTPN11 Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), Src homology region 2 domain-containing phosphatase-2 (SHP-2), or protein-tyrosine phosphatase 2C (PTP-2C) is an enzyme that in hu ...

, and * RAS p21 protein activator 1.

Regulation

There is some evidence that the expression of SOCS3 is regulated by the microRNA miR-203, miR-409-3p and miR-1896.

Function

Interactions

Regulation

See also

References

Further reading