SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including IL6ST/gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity and regulates IL6 signaling. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

1. Downregulation of miR-340 inhibited GC cell proliferation, arrested cell cycle, and facilitated apoptosis through upregulating SOCS3 expression to suppress JAK-STAT3 signaling pathway. PMID: 29658372
2. Low SOCS3 expression is associated with higher grade breast cancer. PMID: 30453988
3. Low SOCS3 expression is associated with invasion and lymph node metastasis in gastric cancer. PMID: 29970682
4. Results show the CAT haplotype in SOCS3 was associated with metabolic syndrome (MetS) in Mexican Mestizos, and type 2 diabetes in Mexican Amerindians. PMID: 30176313
5. SOCS3 overexpression decreased JAK-STAT3 signaling pathway activity, declined Bcl-2 expression, inhibited cell proliferation, elevated cell apoptosis, and enhanced Adriamycin sensitivity in T24 cells PMID: 28742207
6. SOCS3 DNA methylation is associated with body weight and moderates the effect of cumulative stress on obesity. PMID: 27826092
7. polymorphisms associated with risk of head and neck squamous cancer PMID: 27977878
8. SOCS3 was targeted by miR30a- 5p in allergic rhinitis PMID: 29471302
9. Cellular viability was significantly decreased, whereas IL6 and TNFalpha levels were significantly increased, following High Glucose stimulation of A549 cells. In addition, the protein levels of SOCS3, pJAK2 and pSTAT3 were significantly increased in High Glucosetreated cells. PMID: 28713982
10. this study shows that Nrf2 activation induces lipocyte phenotype in hepatic stellate cells via enhancing SOCS3-dependent feedback inhibition on JAK2/STAT3 cascade PMID: 28601022
11. Our study showed that the expressions of HER2, STAT3, and SOCS3 are associated with the progression of ovarian cancer (OC), and higher expressions of HER2 and STAT3 and lower expression of SOCS3 predict poor prognosis of OC. PMID: 28448787
12. Authors found that SOCS3 and SOCS1 expression was reduced in vivo, in tumor lesions of BCC and SCC, as compared to other skin inflammatory conditions such as psoriasis, despite the high number of IL-22-secreting TILs. PMID: 28445952
13. the presence of SOCS3 methylation is a marker to predict treatment response and prognosis in HCC patients receiving TACE therapy. PMID: 28404963
14. anti-miR-203 suppresses breast cancer cell proliferation in vitro by targeting SOCS3 [review] PMID: 27517632
15. miR-2909 could play a vital role in prostate carcinogenesis through modulation of ISGylation system and TGFbeta signalling via STAT1/SOCS3. PMID: 28622443
16. Data show that miR-222-3p targeted SOCS3 genes and down-regulation of SOCS3 correlated with an increased expression of STAT3 activation. PMID: 27172798
17. increased SOCS3 in combined IL-33 heterozygotes and minor allele homozygotes may be relevant for hay fever development PMID: 27171815
18. In summary, this study has shown that LIF is implicated in the HG-mediated inhibition of osteoblast differentiation, via promoting STAT3/SOCS3 signaling. This study may provide insights into the signal pathway of HG-induced bone loss or delayed injured joint healing. PMID: 28064096
19. Data suggest that SOCS3 is an important signaling protein in CLL, and Hsp90 inhibitors represent an approach to target transcriptional repression in B cell lymphoproliferative disorders. PMID: 27107422
20. 6-Hydroxy-3-O-methyl-kaempferol 6-O-glucopyranoside potentiated the inhibitory effect of IFN-alpha on hepatocellular carcinoma cell proliferation through activation of the JAK/STAT signaling pathway by inhibiting SOCS3 expression. PMID: 29031523
21. SOCS3 was down-regulated in CML cell lines and most of BMNCs from CML patients, and the expression level of SOCS3 was associated with the inhibition of cell proliferation and drug resistance of CML cells. PMID: 27516205
22. SOCS3 is involved in suppression of Helicobacter pylori induced STAT3 phosphorylation by docosahexaenoic acid pretreatment. PMID: 27079734
23. The increased miR-203 expression is associated with the reduced anti-inflammatory mediator SOCS-3 expression and the increased endothelial adhesion molecule expression in maternal vessel endothelium in preeclampsia. PMID: 27753461
24. Our results show, for the first time, that SOCS-3 regulates leptin-induced responses in cartilage PMID: 27716333
25. In M1-activated human monocyte-derived macrophages, SOCS3 silencing decreased expression of proinflammatory markers and increased M2 macrophage markers. SOCS3 knockdown radically affects the temporal dynamics of M1 macrophages' particle engulfment through increased PI3K and Ras-related C3 botulinum toxin substrate 1 (Rac1) activity. SOCS3 drives macrophage inflammatory responses and modulates key phagocytosis signaling. PMID: 27106674
26. The results of this study demonstrated that HBx of hepatitis B virus impairs interferon signaling via increased expression of SOCS3 and PP2A. PMID: 27459003
27. Overexpression of SOCS3 inhibited proliferation, migration, invasion and tumorigenic ability of colorectal cancer cells while increased cell apoptosis. Reduced expression of SOCS3 promoted the growth and metastasis of colorectal cancer. PMID: 28603075
28. SOCS3, which is a critical negative regulator of cytokine response to tuberculosis infection and its nearby lncRNA XLOC_012582, were highly expressed in active tuberculosis B cells. PMID: 28125665
29. Data show that the suppressor of cytokine signaling-3 (SOCS3) promoter hypermethylation was associated with relatively low mRNA expression in tumor tissues. PMID: 28179578
30. Data show that ELOVL7, SOCS3, ACSL4 and CLU were upregulated while PRKAR1A and ABCG1 were downregulated in the phlegm-dampness group. PMID: 27928700
31. There are pronounced changes in the expression of SOCS3 only in Non-allergic Asthma. PMID: 28378729
32. epigenetic signatures at AQP3 and SOCS3 engage in low-grade inflammation across different tissues, possible via JAK/STAT mediated pathways PMID: 27824951
33. SHP2, SOCS3 and PIAS3 levels are reduced in medulloblastomas in vivo and in vitro, of which PIAS3 downregulation is more reversely correlated with STAT3 activation. In resveratrol-suppressed medulloblastoma cells with STAT3 downregulation and decreased incidence of STAT3 nuclear translocation, PIAS3 is upregulated, the SHP2 level remains unchanged and SOCS3 is downregulated. PMID: 28035977
34. SOCS3 methylation status was associated with multiple metabolic syndrome traits, including central obesity, fat depots, insulin responsiveness, and plasma lipids. PMID: 27564309
35. reduced type I interferon production in obesity is caused by SOCS3 overexpression as well as tolerance induced by leptin PMID: 27704310
36. Data suggest that single nucleotide polymorphisms (SNPs) in suppressor of cytokine signaling 3 (SOCS3) may play a role in the pathogenesis of metabolic syndrome (MS). PMID: 27611604
37. that siRNA-mediated SOCS3 knock-down in human osteoarthritic chondrocytes increased production of IL-1beta-induced prostaglandin E2 PMID: 28296552
38. SOCS3 promoter was methylated in H2228 cells as well as in three cases of seven EML4-ALK-positive lung cancer tissues. PMID: 27666544
39. Data suggest that microRNA miR19a3p plays an important role in beta cell function, and that the miR-19a-3p/suppressor of cytokine signaling 3 (SOCS3) axis may become a potential therapeutic target for diabetes. PMID: 27666763
40. Significantly higher levels of suppressor of cytokine signalling proteins SOCS3 and SOCS4 in non-healing chronic wounds compared to the healing/healed chronic wounds were observed at the transcript level. PMID: 27635428
41. The rs115785973 could be regulated by miR-4308 which caused an up-regulation ofsuppressor of cytokine signaling 3 in patients with GA and AA genotype. PMID: 27160093
42. SOCS3 along with STAT3 participates in regulatory mechanisms in ccRCC. PMID: 26797799
43. None of the clinicopathological parameters were associated with the expressions of FIH-1 and SOCS3 at mRNA level. PMID: 26749281
44. Micronome revealed miR-19a/b as key regulator of SOCS3 during cancer related inflammation of oral squamous cell carcinoma. PMID: 27581787
45. IGFBP2 and SOCS3 were up-regulated in Kashin-Beck disease chondrocytes and decreased with increasing selenium concentrations. IGFBP2 expressed highest in the middle zone of KBD cartilage, SOCS3 expressed higher in the middle and deep zone. IGFBP2 and SOCS3 may be the biomarkers for KBD diagnosis and evaluating the effect of selenium supplement. PMID: 27099071
46. Results show that IFN-alpha antagonizes STAT3 and SOCS3 signaling triggered by hepatitis C virus (HCV )and that STAT3 regulation correlates inversely with SOCS3 induction by IFN-alpha, which may be important in better understanding the complex interplay between IFN-alpha and signal molecules during HCV infection. PMID: 26945996
47. data show that HBV-induced mitochondrial ROS production represses SOCS3 expression through Snail-mediated epigenetic silencing, leading to the sustained activation of IL-6/STAT3 pathway and ultimately contributing to hepatocarcinogenesis. PMID: 26794444
48. demonstrate an epigenetic mechanism of SOCS3 up-regulation in steroid resistant children with the nephrotic syndrome. The assessment of methylation/unmethylation of SOCS3 promoter might be an early marker for steroid responsiveness in NS patients PMID: 26828667
49. Treatment of isolinderalactone increased the protein level of SCOS3, decreased phosphorylation of the STAT3 and suppressed expression of the down-stream genes of the X-linked inhibitor of apoptosis protein PMID: 26707189
50. Dysregulation of SOCS3 functions can cause a variety of diseases, including allergy, autoimmune diseases, inflammation and cancer. (Review) PMID: 26429311

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Widely expressed with high expression in heart, placenta, skeletal muscle, peripheral blood leukocytes, fetal and adult lung, and fetal liver and kidney. Lower levels in thymus.

HGNC: 19391

OMIM: 604176

KEGG: hsa:9021

STRING: 9606.ENSP00000330341

UniGene: Hs.527973