UniProt:O14543 SOCS3

chain
  • chain:1-225
checksum 08581DC411EFFF19
comment
  • 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).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 (PubMed:10421843). Binds specific activated tyrosine residues of the leptin, EPO, IL12, GSCF and gp130 receptors (PubMed:12027890, PubMed:14559241). Interaction with CSNK1E stabilizes SOCS3 protein (PubMed:15070676). Component of the probable ECS(SOCS3) E3 ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and SOCS3 (PubMed:15601820). Interacts with CUL5, RNF7, ELOB and ELOC (PubMed:15601820). Interacts with CUL2 (PubMed:15601820). Interacts with FGFR3 (PubMed:16410555). Interacts with INSR (By similarity). Interacts with BCL10; this interaction may interfere with BCL10-binding with PELI2 (By similarity). Interacts with NOD2 (via CARD domain); the interaction promotes NOD2 degradation (PubMed:23019338).INTERACTION 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.PTM Phosphorylated on tyrosine residues after stimulation by the cytokines, IL-2, EPO or IGF1.DISEASE There is some evidence that SOCS3 may be a susceptibility gene for atopic dermatitis linked to 17q25. SOCS3 messenger RNA is significantly more highly expressed in skin from patients with atopic dermatitis than in skin from healthy controls. Furthermore, a genetic association between atopic dermatitis and a haplotype in the SOCS3 gene has been found in two independent groups of patients.
crossReference
databaseName UniProt
dbId 64814
description
  • recommendedName: fullName evidence="15"Suppressor of cytokine signaling 3 shortName: SOCS-3 alternativeName: Cytokine-inducible SH2 protein 3 shortName: CIS-3 alternativeName: STAT-induced STAT inhibitor 3 shortName: SSI-3
displayName UniProt:O14543 SOCS3
geneName
  • SOCS3
  • CIS3
  • SSI3
identifier O14543
isSequenceChanged false
keyword
  • Growth regulation
  • Pharmaceutical
  • Phosphoprotein
  • Proteomics identification
  • Reference proteome
  • SH2 domain
  • Signal transduction inhibitor
  • Ubl conjugation pathway
modified [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType Protein
name
  • SOCS3
otherIdentifier
  • 11719217_a_at
  • 11719218_at
  • 16849400
  • 206359_3p_at
  • 206359_PM_at
  • 206359_at
  • 206360_PM_s_at
  • 206360_s_at
  • 227697_3p_at
  • 227697_PM_at
  • 227697_at
  • 3772287
  • 3772288
  • 3772289
  • 3772290
  • 3772291
  • 3772292
  • 3772293
  • 3772294
  • 3772296
  • 3772297
  • 40968_at
  • 42363_r_at
  • 49140_at
  • 8018864
  • 9021
  • A_23_P207058
  • A_23_P351069
  • GE53118
  • GO:0001784
  • GO:0003723
  • GO:0004860
  • GO:0005126
  • GO:0005515
  • GO:0005829
  • GO:0007165
  • GO:0007259
  • GO:0009898
  • GO:0009968
  • GO:0016567
  • GO:0019221
  • GO:0030154
  • GO:0030292
  • GO:0035198
  • GO:0035556
  • GO:0043066
  • GO:0045597
  • GO:0046426
  • GO:0046627
  • GO:0048856
  • GO:0050728
  • GO:0060670
  • GO:0060674
  • GO:0070102
  • GO:0072540
  • GO:0097398
  • GO:0098772
  • GO:1990830
  • HMNXSV003036284
  • Hs.296176.0.S2_3p_s_at
  • Hs.311405.0.A1_3p_at
  • Hs.311405.0.A1_3p_s_at
  • Hs.311405.0.A1_3p_x_at
  • ILMN_1781001
  • ILMN_2156250
  • PH_hs_0025550
  • TC17001917.hg
  • g4507234_3p_a_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • SOCS3_HUMAN
  • O14509
sequenceLength 225
species [Species:48887] Homo sapiens
stId uniprot:O14543
url http://purl.uniprot.org/uniprot/O14543
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