SOCS3 (suppressor of cytokine signaling 3)

Gene

• Entrez ID: 9021
• Gene name: Suppressor of cytokine signaling 3
• Gene symbol: SOCS3
• Synonyms: ATOD4, CIS3, Cish3, SOCS-3, SSI-3, SSI3
• Chromosome: 17
• Chromosome location: 17q25.3
• Summary: 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. 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. [provided by RefSeq, Jul 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005062	hsa-miR-203a-3p	Immunohistochemistry, In situ hybridization, Microarray, Western blot	17622355
MIRT005062	hsa-miR-203a-3p	Luciferase reporter assay, qRT-PCR, Western blot	22207897
MIRT005062	hsa-miR-203a-3p	ELISA, qRT-PCR	23775225
MIRT007129	hsa-miR-30c-5p	qRT-PCR	23418453
MIRT007129	hsa-miR-30c-5p	PAR-CLIP	23592263
MIRT007129	hsa-miR-30c-5p	ELISA, Luciferase reporter assay, qRT-PCR, Western blot	26707189
MIRT054389	hsa-let-7f-5p	Luciferase reporter assay	22894925
MIRT438094	hsa-miR-19a-3p	HITS-CLIP	22473208
MIRT438094	hsa-miR-19a-3p	Luciferase reporter assay	23894411
MIRT438546	hsa-miR-221-3p	Luciferase reporter assay, Western blot	25019494
MIRT438883	hsa-miR-155-5p	qRT-PCR	23428672
MIRT467398	hsa-miR-1304-5p	PAR-CLIP	23592263
MIRT467399	hsa-miR-6765-5p	PAR-CLIP	23592263
MIRT467400	hsa-miR-4477a	PAR-CLIP	23592263
MIRT467401	hsa-miR-4765	PAR-CLIP	23592263
MIRT467402	hsa-miR-508-3p	PAR-CLIP	23592263
MIRT467403	hsa-miR-759	PAR-CLIP	23592263
MIRT467404	hsa-miR-126-5p	PAR-CLIP	23592263
MIRT467405	hsa-miR-8062	PAR-CLIP	23592263
MIRT467406	hsa-miR-5586-3p	PAR-CLIP	23592263
MIRT467407	hsa-miR-4797-5p	PAR-CLIP	23592263
MIRT467408	hsa-miR-30e-5p	PAR-CLIP	23592263
MIRT467409	hsa-miR-30d-5p	PAR-CLIP	23592263
MIRT467410	hsa-miR-30a-5p	PAR-CLIP	23592263
MIRT467411	hsa-miR-30b-5p	PAR-CLIP	23592263
MIRT534113	hsa-miR-335-3p	PAR-CLIP	22012620
MIRT534114	hsa-miR-4795-3p	PAR-CLIP	22012620
MIRT534115	hsa-miR-4473	PAR-CLIP	22012620
MIRT534116	hsa-miR-512-3p	PAR-CLIP	22012620
MIRT534117	hsa-miR-4724-5p	PAR-CLIP	22012620
MIRT534118	hsa-miR-520f-3p	PAR-CLIP	22012620
MIRT534119	hsa-miR-302c-3p	PAR-CLIP	22012620
MIRT534120	hsa-miR-340-5p	PAR-CLIP	22012620
MIRT726475	hsa-miR-19b-3p	HITS-CLIP	22473208
MIRT733214	hsa-miR-15b-5p	qRT-PCR, Western blot	25888955
MIRT733215	hsa-miR-16-5p	qRT-PCR, Western blot	25888955
MIRT733441	hsa-miR-455-5p	qRT-PCR	28260062

Transcription factors

Transcription factor	Regulation	Reference
CEBPA	Activation	19332118
NFKB1	Unknown	23335796
RELA	Unknown	23335796
SP3	Unknown	10570957
STAT1	Unknown	19115200
STAT3	Activation	11788008;15184887;19332118;20357037;22179221
STAT3	Unknown	23335796
STAT4	Repression	14559241

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001784	Function	Phosphotyrosine residue binding	IEA
GO:0004860	Function	Protein kinase inhibitor activity	TAS	9266833
GO:0005515	Function	Protein binding	IPI	19027008, 24728074, 25203322, 25416956, 32296183
GO:0005829	Component	Cytosol	TAS
GO:0005942	Component	Phosphatidylinositol 3-kinase complex	IBA	21873635
GO:0006469	Process	Negative regulation of protein kinase activity	IEA
GO:0007259	Process	Receptor signaling pathway via JAK-STAT	IEA
GO:0016567	Process	Protein ubiquitination	IEA
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0040008	Process	Regulation of growth	IEA
GO:0042531	Process	Positive regulation of tyrosine phosphorylation of STAT protein	TAS
GO:0042532	Process	Negative regulation of tyrosine phosphorylation of STAT protein	IMP	25019494
GO:0043066	Process	Negative regulation of apoptotic process	IEA
GO:0043551	Process	Regulation of phosphatidylinositol 3-kinase activity	IEA
GO:0043687	Process	Post-translational protein modification	TAS
GO:0045597	Process	Positive regulation of cell differentiation	IEA
GO:0046426	Process	Negative regulation of receptor signaling pathway via JAK-STAT	IMP	25019494
GO:0046627	Process	Negative regulation of insulin receptor signaling pathway	IEA
GO:0046854	Process	Phosphatidylinositol phosphorylation	IBA	21873635
GO:0046935	Function	1-phosphatidylinositol-3-kinase regulator activity	IBA	21873635
GO:0050728	Process	Negative regulation of inflammatory response	IEA
GO:0060334	Process	Regulation of interferon-gamma-mediated signaling pathway	TAS
GO:0060670	Process	Branching involved in labyrinthine layer morphogenesis	IEA
GO:0060674	Process	Placenta blood vessel development	IEA
GO:0060707	Process	Trophoblast giant cell differentiation	IEA
GO:0070102	Process	Interleukin-6-mediated signaling pathway	TAS
GO:1990830	Process	Cellular response to leukemia inhibitory factor	IEA

Other IDs

• MIM: 604176
• HGNC: 19391
• e!Ensembl: ENSG00000184557

Protein

• UniProt ID: O14543
• Protein name: Suppressor of cytokine signaling 3 (SOCS-3) (Cytokine-inducible SH2 protein 3) (CIS-3) (STAT-induced STAT inhibitor 3) (SSI-3)
• Protein 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 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 (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 (PubMed:15601820).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00017	SH2	46 → 127	SH2 domain	Domain

• Sequence:

  MVTHSKFPAAGMSRPLDTSLRLKTFSSKSEYQLVVNAVRKLQESGFYWSAVTGGEANLLL
  SAEPAGTFLIRDSSDQRHFFTLSVKTQSGTKNLRIQCEGGSFSLQSDPRSTQPVPRFDCV
  LKLVHHYMPPPGAPSFPSPPTEPSSEVPEQPSAQPLPGSPPRRAYYIYSGGEKIPLVLSR
  PLSSNVATLQHLCRKTVNGHLDSYEKVTQLPGPIREFLDQYDAPL

• Sequence length: 225