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Suppressor of cytokine signaling 3
Protein SOCS3 PDB 2bbu.png
PDB rendering based on 2bbu.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols SOCS3 ; ATOD4; CIS3; Cish3; SOCS-3; SSI-3; SSI3
External IDs OMIM604176 MGI1201791 HomoloGene2941 GeneCards: SOCS3 Gene
RNA expression pattern
PBB GE SOCS3 206359 at tn.png
PBB GE SOCS3 206360 s at tn.png
More reference expression data
Species Human Mouse
Entrez 9021 12702
Ensembl ENSG00000184557 ENSMUSG00000053113
UniProt O14543 O35718
RefSeq (mRNA) NM_003955 NM_007707
RefSeq (protein) NP_003946 NP_031733
Location (UCSC) Chr 17:
78.36 – 78.36 Mb
Chr 11:
117.97 – 117.97 Mb
PubMed search [1] [2]

Suppressor of cytokine signaling 3 (SOCS3 or SOCS-3) is a protein that in humans is encoded by the SOCS3 gene.[1][2] This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling.


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.

SOCS3 contributes to both leptin resistance and insulin resistance as a result of increased ceramide synthesis.[3]

Studies of the mouse counterpart of this gene suggested the roles of this gene in the negative regulation of fetal liver hematopoiesis, and placental development.[4]

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


SOCS3 has been shown to interact with:


There is some evidence that the expression of SOCS3 is regulated by the microRNA miR-203.[11][12]

See also[edit]


  1. ^ Minamoto S, Ikegame K, Ueno K, Narazaki M, Naka T, Yamamoto H, Matsumoto T, Saito H, Hosoe S, Kishimoto T (September 1997). "Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3". Biochem Biophys Res Commun 237 (1): 79–83. doi:10.1006/bbrc.1997.7080. PMID 9266833. 
  2. ^ a b Masuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, Wakioka T, Tanimura S, Sasaki A, Misawa H, Yokouchi M, Ohtsubo M, Yoshimura A (November 1997). "Cloning and characterization of novel CIS family genes". Biochem Biophys Res Commun 239 (2): 439–46. doi:10.1006/bbrc.1997.7484. PMID 9344848. 
  3. ^ Yang G, Badeanlou L, Bielawski J, Roberts AJ, Hannun YA, Samad F (2009). "Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome". American Journal of Physiology 297 (1): E211–E224. doi:10.1152/ajpendo.91014.2008. PMC 2711669. PMID 19435851. 
  4. ^ "Entrez Gene: SOCS3 suppressor of cytokine signaling 3". 
  5. ^ a b Sasaki A, Yasukawa H, Shouda T, Kitamura T, Dikic I, Yoshimura A (September 2000). "CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2". J. Biol. Chem. 275 (38): 29338–47. doi:10.1074/jbc.M003456200. PMID 10882725. 
  6. ^ Hörtner M, Nielsch U, Mayr LM, Heinrich PC, Haan S (May 2002). "A new high affinity binding site for suppressor of cytokine signaling-3 on the erythropoietin receptor". Eur. J. Biochem. 269 (10): 2516–26. doi:10.1046/j.1432-1033.2002.02916.x. PMID 12027890. 
  7. ^ a b Lehmann U, Schmitz J, Weissenbach M, Sobota RM, Hortner M, Friederichs K, Behrmann I, Tsiaris W, Sasaki A, Schneider-Mergener J, Yoshimura A, Neel BG, Heinrich PC, Schaper F (January 2003). "SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130". J. Biol. Chem. 278 (1): 661–71. doi:10.1074/jbc.M210552200. PMID 12403768. 
  8. ^ Dey BR, Furlanetto RW, Nissley P (November 2000). "Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor". Biochem. Biophys. Res. Commun. 278 (1): 38–43. doi:10.1006/bbrc.2000.3762. PMID 11071852. 
  9. ^ Sasaki A, Yasukawa H, Suzuki A, Kamizono S, Syoda T, Kinjyo I, Sasaki M, Johnston JA, Yoshimura A (June 1999). "Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain". Genes Cells 4 (6): 339–51. doi:10.1046/j.1365-2443.1999.00263.x. PMID 10421843. 
  10. ^ Cacalano NA, Sanden D, Johnston JA (May 2001). "Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras". Nat. Cell Biol. 3 (5): 460–5. doi:10.1038/35074525. PMID 11331873. 
  11. ^ Lena AM, Shalom-Feuerstein R, Rivetti di Val Cervo P, Aberdam D, Knight RA, Melino G, Candi E (2008). "miR-203 represses 'stemness' by repressing DeltaNp63.". Cell Death Differ 15 (7): 1187–95. doi:10.1038/cdd.2008.69. PMID 18483491. 
  12. ^ Wei T, Orfanidis K, Xu N, Janson P, Ståhle M, Pivarcsi A, Sonkoly E (2010). "The expression of microRNA-203 during human skin morphogenesis.". Exp Dermatol 19 (9): 854–6. doi:10.1111/j.1600-0625.2010.01118.x. PMID 20698882. 

Further reading[edit]