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 kin... See more...

Aliases for SOCS3 Gene

Aliases for SOCS3 Gene

  • Suppressor Of Cytokine Signaling 3 2 3 4 5
  • SOCS-3 2 3 4
  • SSI-3 2 3 4
  • CIS3 2 3 4
  • Cytokine-Inducible SH2 Protein 3 3 4
  • STAT-Induced STAT Inhibitor 3 3 4
  • Cish3 2 3
  • SSI3 3 4
  • ATOD4 3
  • SOCS3 5
  • CIS-3 4

External Ids for SOCS3 Gene

Previous GeneCards Identifiers for SOCS3 Gene

  • GC17M079741
  • GC17M076815
  • GC17M076951
  • GC17M076949
  • GC17M073864
  • GC17M076352
  • GC17M071775

Summaries for SOCS3 Gene

Entrez Gene Summary for SOCS3 Gene

  • 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]

GeneCards Summary for SOCS3 Gene

SOCS3 (Suppressor Of Cytokine Signaling 3) is a Protein Coding gene. Diseases associated with SOCS3 include Dermatitis, Atopic, 4 and Overnutrition. Among its related pathways are Interleukin-11 Signaling Pathway and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include protein kinase inhibitor activity. An important paralog of this gene is CISH.

UniProtKB/Swiss-Prot Summary for SOCS3 Gene

  • 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).

Gene Wiki entry for SOCS3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SOCS3 Gene

Genomics for SOCS3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SOCS3 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SOCS3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SOCS3

Top Transcription factor binding sites by QIAGEN in the SOCS3 gene promoter:
  • AP-4
  • c-Myb
  • c-Rel
  • GATA-3
  • NRSF form 1
  • NRSF form 2
  • Pax-5
  • PPAR-gamma1
  • PPAR-gamma2
  • STAT5B

Genomic Locations for SOCS3 Gene

Genomic Locations for SOCS3 Gene
chr17:78,356,778-78,360,925
(GRCh38/hg38)
Size:
4,148 bases
Orientation:
Minus strand
chr17:76,352,859-76,356,158
(GRCh37/hg19)
Size:
3,300 bases
Orientation:
Minus strand

Genomic View for SOCS3 Gene

Genes around SOCS3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SOCS3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SOCS3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SOCS3 Gene

Proteins for SOCS3 Gene

  • Protein details for SOCS3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O14543-SOCS3_HUMAN
    Recommended name:
    Suppressor of cytokine signaling 3
    Protein Accession:
    O14543
    Secondary Accessions:
    • O14509

    Protein attributes for SOCS3 Gene

    Size:
    225 amino acids
    Molecular mass:
    24770 Da
    Quaternary structure:
    • 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).

neXtProt entry for SOCS3 Gene

Post-translational modifications for SOCS3 Gene

  • Phosphorylated on tyrosine residues after stimulation by the cytokines, IL-2, EPO or IGF1.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SOCS3 Gene

Antibody Products

  • Abcam antibodies for SOCS3

No data available for DME Specific Peptides for SOCS3 Gene

Domains & Families for SOCS3 Gene

Gene Families for SOCS3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for SOCS3 Gene

InterPro:
Blocks:
  • SH2 domain signature
  • SOCS protein, C-terminal
ProtoNet:

Suggested Antigen Peptide Sequences for SOCS3 Gene

GenScript: Design optimal peptide antigens:
  • cDNA, FLJ94944, highly similar to Homo sapiens suppressor of cytokine signaling 3 (SOCS3), mRNA (Q6FI39_HUMAN)
  • STAT-induced STAT inhibitor 3 (SOCS3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O14543

UniProtKB/Swiss-Prot:

SOCS3_HUMAN :
  • 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 ESS and SH2 domains are required for JAK phosphotyrosine binding. Further interaction with the KIR domain is necessary for signal and kinase inhibition.
  • The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.
genes like me logo Genes that share domains with SOCS3: view

Function for SOCS3 Gene

Molecular function for SOCS3 Gene

UniProtKB/Swiss-Prot 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).

Phenotypes From GWAS Catalog for SOCS3 Gene

Gene Ontology (GO) - Molecular Function for SOCS3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001784 phosphotyrosine residue binding IEA --
GO:0004860 protein kinase inhibitor activity TAS 9266833
GO:0005515 protein binding IPI 19027008
GO:0046935 1-phosphatidylinositol-3-kinase regulator activity IBA 21873635
genes like me logo Genes that share ontologies with SOCS3: view
genes like me logo Genes that share phenotypes with SOCS3: view

Animal Models for SOCS3 Gene

MGI Knock Outs for SOCS3:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SOCS3

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SOCS3 Gene

Localization for SOCS3 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SOCS3 gene
Compartment Confidence
cytosol 5
plasma membrane 3
extracellular 3
mitochondrion 3
nucleus 3
cytoskeleton 2
peroxisome 2
endoplasmic reticulum 2
endosome 2
lysosome 2
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SOCS3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0005942 phosphatidylinositol 3-kinase complex IBA 21873635
genes like me logo Genes that share ontologies with SOCS3: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for SOCS3 Gene

Pathways & Interactions for SOCS3 Gene

PathCards logo

SuperPathways for SOCS3 Gene

genes like me logo Genes that share pathways with SOCS3: view

Pathways by source for SOCS3 Gene

14 GeneGo (Thomson Reuters) pathways for SOCS3 Gene
  • Development CNTF receptor signaling
  • Development EPO-induced Jak-STAT pathway
  • Development Prolactin receptor signaling
  • Development_Leptin signaling via JAK/STAT and MAPK cascades
  • Development_Thrombopoetin signaling via JAK-STAT pathway
10 Qiagen pathways for SOCS3 Gene
  • Growth Hormone Signaling
  • IL-10 Pathway
  • IL-22 Pathway
  • IL-4 Pathway
  • IL-6 Pathway
2 Cell Signaling Technology pathways for SOCS3 Gene
1 GeneTex pathway for SOCS3 Gene

UniProtKB/Swiss-Prot O14543-SOCS3_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for SOCS3 Gene

Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for SOCS3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001932 regulation of protein phosphorylation IEA --
GO:0006469 negative regulation of protein kinase activity IEA --
GO:0007259 JAK-STAT cascade IEA --
GO:0009968 negative regulation of signal transduction IEA --
GO:0016567 protein ubiquitination IEA --
genes like me logo Genes that share ontologies with SOCS3: view

Drugs & Compounds for SOCS3 Gene

(13) Drugs for SOCS3 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(13) Additional Compounds for SOCS3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with SOCS3: view

Transcripts for SOCS3 Gene

mRNA/cDNA for SOCS3 Gene

3 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SOCS3

Alternative Splicing Database (ASD) splice patterns (SP) for SOCS3 Gene

ExUns: 1a · 1b ^ 2a · 2b · 2c
SP1: - -
SP2:

Relevant External Links for SOCS3 Gene

GeneLoc Exon Structure for
SOCS3

Expression for SOCS3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SOCS3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SOCS3 Gene

This gene is overexpressed in Adipose - Visceral (Omentum) (x8.2), Fallopian Tube (x6.3), and Whole Blood (x4.1).

Protein differential expression in normal tissues from HIPED for SOCS3 Gene

This gene is overexpressed in Adipocyte (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for SOCS3 Gene



Protein tissue co-expression partners for SOCS3 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SOCS3

SOURCE GeneReport for Unigene cluster for SOCS3 Gene:

Hs.527973

mRNA Expression by UniProt/SwissProt for SOCS3 Gene:

O14543-SOCS3_HUMAN
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.

Evidence on tissue expression from TISSUES for SOCS3 Gene

  • Muscle(4.6)
  • Nervous system(3.9)
  • Liver(3.5)
  • Intestine(3.3)
  • Blood(3.3)
  • Lymph node(3.3)
  • Bone marrow(3.2)
  • Spleen(3.2)
  • Lung(3.1)
  • Heart(3)
  • Kidney(2.9)
  • Pancreas(2.9)
  • Adrenal gland(2.7)
  • Skin(2.7)
  • Eye(2.7)
  • Gall bladder(2.6)
  • Thyroid gland(2.5)
  • Stomach(2.4)
  • Bone(2.1)
genes like me logo Genes that share expression patterns with SOCS3: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for SOCS3 Gene

Orthologs for SOCS3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for SOCS3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SOCS3 30 31
  • 100 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia SOCS3 30 31
  • 94.67 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SOCS3 30 31
  • 92.3 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Socs3 30 17 31
  • 90.81 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Socs3 30
  • 89.93 (n)
Oppossum
(Monodelphis domestica)
Mammalia SOCS3 31
  • 89 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia SOCS3 31
  • 86 (a)
OneToOne
Chicken
(Gallus gallus)
Aves SOCS3 30 31
  • 84.69 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia SOCS3 31
  • 89 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia socs3 30
  • 68.51 (n)
African clawed frog
(Xenopus laevis)
Amphibia socs3-prov 30
Zebrafish
(Danio rerio)
Actinopterygii socs3b 30 31
  • 67.8 (n)
OneToMany
socs3a 31
  • 61 (a)
OneToMany
wufj09e12 30
Species where no ortholog for SOCS3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for SOCS3 Gene

ENSEMBL:
Gene Tree for SOCS3 (if available)
TreeFam:
Gene Tree for SOCS3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SOCS3: view image

Paralogs for SOCS3 Gene

Paralogs for SOCS3 Gene

genes like me logo Genes that share paralogs with SOCS3: view

Variants for SOCS3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SOCS3 Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
rs1061489 - p.His125Tyr

Additional dbSNP identifiers (rs#s) for SOCS3 Gene

Structural Variations from Database of Genomic Variants (DGV) for SOCS3 Gene

Variant ID Type Subtype PubMed ID
nsv1112715 CNV deletion 24896259
nsv833555 CNV loss 17160897

Variation tolerance for SOCS3 Gene

Residual Variation Intolerance Score: 42.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.59; 12.76% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SOCS3 Gene

Human Gene Mutation Database (HGMD)
SOCS3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SOCS3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SOCS3 Gene

Disorders for SOCS3 Gene

MalaCards: The human disease database

(39) MalaCards diseases for SOCS3 Gene - From: OMIM, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
dermatitis, atopic, 4
  • atod4
overnutrition
primary polycythemia
  • polycythemia vera
hepatitis c
  • chronic hepatitis c
dermatitis
  • eczema
- elite association - COSMIC cancer census association via MalaCards
Search SOCS3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SOCS3_HUMAN
  • Note=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. {ECO:0000269 PubMed:16685656}.

Additional Disease Information for SOCS3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with SOCS3: view

No data available for Genatlas for SOCS3 Gene

Publications for SOCS3 Gene

  1. Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3. (PMID: 9266833) Minamoto S … Kishimoto T (Biochemical and biophysical research communications 1997) 2 3 4 23
  2. Polymorphisms near SOCS3 are associated with obesity and glucose homeostasis traits in Hispanic Americans from the Insulin Resistance Atherosclerosis Family Study. (PMID: 19083014) Talbert ME … Bowden DW (Human genetics 2009) 3 23 41
  3. Analysis of sequence variations in the suppressor of cytokine signaling (SOCS)-3 gene in extremely obese children and adolescents. (PMID: 17445271) Hölter K … Hinney A (BMC medical genetics 2007) 3 23 41
  4. Suppressors of cytokine signaling (SOCS) 1 and SOCS3 interact with and modulate fibroblast growth factor receptor signaling. (PMID: 16410555) Ben-Zvi T … Monsonego-Ornan E (Journal of cell science 2006) 3 4 23
  5. Common polymorphisms in SOCS3 are not associated with body weight, insulin sensitivity or lipid profile in normal female twins. (PMID: 16402267) Jamshidi Y … O'Dell SD (Diabetologia 2006) 3 23 41

Products for SOCS3 Gene

  • Addgene plasmids for SOCS3

Sources for SOCS3 Gene