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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''SOCS3''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. This gene encodes a member of the STAT-induced

STAT STAT, Stat. , or stat may refer to: * Stat (system call), a Unix system call that returns file attributes of an inode * ''Stat'' (TV series), an American sitcom that aired in 1991 * Stat (website), a health-oriented news website * STAT protein, a ...

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 * SOCS1 * SOCS2 * SOCS3 * SOCS4 * SOCS5 * SOCS6 * SOCS7 Suppressor of cytokine signaling 7 is a pro ...

), 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'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...

chicken The chicken (''Gallus gallus domesticus'') is a domesticated junglefowl species, with attributes of wild species such as the grey and the Ceylon junglefowl that are originally from Southeastern Asia. Rooster or cock is a term for an adult m ...

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 even more loosely to inclu ...

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 ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

signaling in

adipose tissue Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular e ...

and the

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

, but not in

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

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

insulin resistance Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood gluco ...

. SOCS3 contributes to both

leptin resistance Leptin (from Greek λεπτός ''leptos'', "thin" or "light" or "small") is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate energy balance by inhibiting hunger, which in turn dimini ...

and

as a result of increased

ceramide Ceramides are a family of waxy lipid molecules. A ceramide is composed of N-acetylsphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make up ...

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

resistance in

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...

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

hematopoiesis Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...

, 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 Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: *

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

, *

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 all cytokine receptors. It forms one subunit of the type I cytokine receptor within the IL-6 receptor famil ...

, *

Insulin-like growth factor 1 receptor The insulin-like growth factor 1 (IGF-1) receptor is a protein found on the surface of human cells. It is a transmembrane receptor that is activated by a hormone called insulin-like growth factor 1 ( IGF-1) and by a related hormone called IGF-2. ...

, *

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-CSF re ...

, *

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 huma ...

, and *

RAS p21 protein activator 1 RAS p21 protein activator 1 or RasGAP (Ras GTPase activating protein), also known as RASA1, is a 120- kDa cytosolic human protein that provides two principal activities: * Inactivation of Ras from its active GTP-bound form to its inactive GDP-bo ...

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