SOCS3

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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
Identifiers
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
Orthologs
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:
76.35 – 76.36 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]

Function[edit]

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 this gene is induced by various cytokines, including IL6, IL10, and interferon (IFN)-gamma. The protein encoded by this gene can bind to JAK2 kinase, and inhibit the activity of JAK2 kinase. For signaling of IL-6, Epo, GCSF and Leptin, binding of SOCS3 to the respective cytokine receptor has been found to be cruicial for the inhibitory function of SOCS3.

Function[edit]

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]

Interactions[edit]

SOCS3 has been shown to interact with:

Regulation[edit]

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

See also[edit]

References[edit]

  1. ^ Minamoto S, Ikegame K, Ueno K, Narazaki M, Naka T, Yamamoto H et al. (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 et al. (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. PMID 12027890. 
  7. ^ a b Lehmann U, Schmitz J, Weissenbach M, Sobota RM, Hortner M, Friederichs K et al. (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 et al. (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. 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 et al. (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 et al. (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]