[1]
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NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT TYR-125.
TISSUE=T-cell lymphoma;
DOI=10.1006/bbrc.1997.7080; PubMed=9266833 [NCBI, ExPASy, EBI, Israel, Japan]
Minamoto S.,
Ikegame K.,
Ueno K.,
Narazaki M.,
Naka T.,
Yamamoto H.,
Matsumoto T.,
Saito H.,
Hosoe S.,
Kishimoto T.;
"Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3.";
Biochem. Biophys. Res. Commun. 237:79-83(1997).
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[2]
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NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1006/bbrc.1997.7484; PubMed=9344848 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Cloning and characterization of novel CIS family genes.";
Biochem. Biophys. Res. Commun. 239:439-446(1997).
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[3]
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NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Skeletal muscle;
DOI=10.1006/bbrc.2000.3762; PubMed=11071852 [NCBI, ExPASy, EBI, Israel, Japan]
Dey B.R.,
Furlanetto R.W.,
Nissley P.;
"Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor.";
Biochem. Biophys. Res. Commun. 278:38-43(2000).
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[4]
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NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Placenta;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
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[5]
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INTERACTION WITH JAK2, AND MUTAGENESIS OF LEU-22; PHE-25; GLU-30; TYR-31; VAL-34; LEU-41; GLY-45 AND ARG-71.
DOI=10.1046/j.1365-2443.1999.00263.x; PubMed=10421843 [NCBI, ExPASy, EBI, Israel, Japan]
Sasaki A.,
Yasukawa H.,
Suzuki A.,
Kamizono S.,
Syoda T.,
Kinjyo I.,
Sasaki M.,
Johnston J.A.,
Yoshimura A.;
"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 4:339-351(1999).
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[6]
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INTERACTION WITH EPOR, AND MUTAGENESIS OF GLY-53; LEU-58; LEU-93 AND ARG-94.
DOI=10.1046/j.1432-1033.2002.02916.x; PubMed=12027890 [NCBI, ExPASy, EBI, Israel, Japan]
Hoertner M.,
Nielsch U.,
Mayr L.M.,
Heinrich P.C.,
Haan S.;
"A new high affinity binding site for suppressor of cytokine signaling-3 on the erythropoietin receptor.";
Eur. J. Biochem. 269:2516-2526(2002).
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[7]
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INTERACTION WITH IL12RB2, AND MUTAGENESIS OF ARG-71.
DOI=10.1016/j.bbrc.2003.09.140; PubMed=14559241 [NCBI, ExPASy, EBI, Israel, Japan]
Yamamoto K.,
Yamaguchi M.,
Miyasaka N.,
Miura O.;
"SOCS-3 inhibits IL-12-induced STAT4 activation by binding through its SH2 domain to the STAT4 docking site in the IL-12 receptor beta2 subunit.";
Biochem. Biophys. Res. Commun. 310:1188-1193(2003).
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[8]
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INTERACTION WITH CSNK1E, AND PROTEIN STABILIZATION.
DOI=10.1182/blood-2003-08-2768; PubMed=15070676 [NCBI, ExPASy, EBI, Israel, Japan]
Okamura A.,
Iwata N.,
Nagata A.,
Tamekane A.,
Shimoyama M.,
Gomyo H.,
Yakushijin K.,
Urahama N.,
Hamaguchi M.,
Fukui C.,
Chihara K.,
Ito M.,
Matsui T.;
"Involvement of casein kinase Iepsilon in cytokine-induced granulocytic differentiation.";
Blood 103:2997-3004(2004).
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[9]
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FUNCTION IN AN E3 UBIQUITIN-PROTEIN LIGASE COMPLEX, AND INTERACTION WITH CUL5; RNF7; TCEB1 AND TCEB2.
DOI=10.1101/gad.1252404; PubMed=15601820 [NCBI, ExPASy, EBI, Israel, Japan]
Kamura T.,
Maenaka K.,
Kotoshiba S.,
Matsumoto M.,
Kohda D.,
Conaway R.C.,
Conaway J.W.,
Nakayama K.I.;
"VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases.";
Genes Dev. 18:3055-3065(2004).
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[10]
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POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO ATOD4.
DOI=10.1086/504272; PubMed=16685656 [NCBI, ExPASy, EBI, Israel, Japan]
Ekelund E.,
Saeaef A.,
Tengvall-Linder M.,
Melen E.,
Link J.,
Barker J.,
Reynolds N.J.,
Meggitt S.J.,
Kere J.,
Wahlgren C.-F.,
Pershagen G.,
Wickman M.,
Nordenskjoeld M.,
Kockum I.,
Bradley M.;
"Elevated expression and genetic association links the SOCS3 gene to atopic dermatitis.";
Am. J. Hum. Genet. 78:1060-1065(2006).
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- FUNCTION: 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 gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. Regulates IL-6 signaling in vivo (By similarity). 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. Seems to recognize IL6ST (By similarity).
- PATHWAY: Protein modification; protein ubiquitination.
- SUBUNIT: Interacts with multiple activated proteins of the tyrosine kinase signaling pathway including IGF1 receptor, insulin receptor and JAK2. Binding to JAK2 is mediated through the KIR and SH2 domains to a phosphorylated tyrosine residue within the JAK2 JH1 domain. Binds specific activated tyrosine residues of the leptin, EPO, IL12, GSCF and gp130 receptors. Interaction with CSNK1E stabilizes SOCS3 protein. Component of the probable ECS(SOCS3) E3 ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and SOCS3. Interacts with CUL5, RNF7, TCEB1 and TCEB2. Interacts with CUL2.
- TISSUE SPECIFICITY: 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.
- DOMAIN: The ESS and SH2 domains are required for JAK phosphotyrosine binding. Further interaction with the KIR domain is necessary for signal and kinase inhibition.
- DOMAIN: The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes (By similarity).
- PTM: Phosphorylated on tyrosine residues after stimulation by the cytokines, IL-2, EPO or IGF1.
- DISEASE: Genetic variation in the promoter region of SOCS3 may be associated with susceptibility to atopic dermatitis 4 (ATOD4) [MIM:605805]. Atopic dermatitis [MIM:603165], also known as eczema commonly begins in infancy or early childhook and is characterized by ichy and inflamed skin.
- PHARMACEUTICAL: SOCS3 could be used as a possible therapeutic agent for treating rheumatoid arthritis.
- SIMILARITY: Contains 1 SH2 domain.
- SIMILARITY: Contains 1 SOCS box domain.
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