SOCS2 (suppressor of cytokine signaling 2)

	Diagram representing the structure of SOCS proteins. At least eight proteins belonging to the SOCS family of proteins are shown (upper panel). They are characterized by the presence of an SH2 central domain and the SOCS box domain at the C-terminus. A small domain called kinase inhibitory region (KIR), only found in SOCS1 and SOCS3, is shown as a small box at the N-terminal region. SOCS proteins can interact with phosphotyrosine phosphorylated proteins through their SH2 domain and with Elongin BC through their SOCS box domain. Other proteins containing a SOCS box domain but lacking a SH2 domain are also shown (lower panel). Adapted from Elliot and Johnston (Elliott and Johnston, 2004) with modifications.
Description	Reference sequence for SOCS2 protein: NP_001257399.1. SOCS2 contains 198 amino acid residues with a molecular weight of 22172 Da. SOCS2 belongs to the SOCS box family. SOCS2 contains a C terminal SOCS box (residue 151-197) for ElonginB,C/Cullin5/Rbx2 interaction. The unstructured N-terminal region (residue 1-47) and the SH2 domain (residue 48-156) is implicated in substrate interaction. The SH2 domain is known to interact with conserved phosphotyrosine residues on target proteins imparting substrate specificity to SOCS box proteins.
Expression	SOCS mRNA and protein levels are constitutively low in unstimulated cells, but their expression is rapidly induced upon cytokine stimulation, thereby creating a negative feedback loop. Although constitutively expressed SOCS2 mRNA has been detected in several tissues and cell types, its expression is, in general, induced by stimulation with different cytokines and hormones (Rico-Bautista et al., 2006). SOCS2 promoter analysis indicates the presence of AhR and STAT5 binding sites that confer responsiveness to dioxin (Boverhof et al., 2004) and GH (Vidal et al., 2006), respectively.
Localisation	Intracellular, cytoplasm. SOCS2 can be located in the nuclear compartment when overexpressed in cell cultures.
Function	The function of SOCS proteins rely, on one hand, in their ability to bind tyrosine phosphorylated proteins through their SH2 domains and, on the other hand, to bind Elongins B/C through their SOCS box domains which in turn engages with the Cullin5/Rbx2 complex to assemble an E3 ubiquitin ligase. SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction (Rico-Bautista et al., 2006). Being a substrate recognition module for Cullin5/Rbx2 E3 ligase complex, SOCS2 is involved in regulating protein turnover by targeting proteins for proteasome-mediated degradation. SOCS2 binds and promote the ubiquitination of the Growth Hormone receptor (GHR) controlling GHR content in different tissues (Metcalf et al., 2000; Vesterlund et al., 2011). Through the negative regulation of GHR signaling, SOCS2 exerts multiple actions in growth and metabolisms (Greenhalgh et al., 2005; Zadjali et al., 2012). SOCS2 is also a critical regulator of inflammatory responses and immune cell differentiation (Machado et al., 2006; Hu et al., 2009a). Recently, SOCS2 is being implicated in the progression of multiple human cancers (Schultheis et al., 2002; Harris et al., 2006; Newton et al., 2010; Iglesias-Gato et al., 2014).
Homology	HomoloGene (NCBI) Genes identified as putative homologs: NP_003868.1 SOCS2, H.sapiens; XP_001139989.1 SOCS2, P.troglodytes; XP_002798772.1 SOCS2, M.mulatta; XP_005629280.1 SOCS2, C.lupus; NP_803489.1 SOCS2, B.taurus; NP_001162126.1 Socs2, M.musculus; NP_478115.1 Socs2, R.norvegicus; NP_989871.1 SOCS2, G.gallus; NP_001120898.1 socs2, X.tropicalis; NP_001108022.1 socs2, D.rerio

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