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Aliases for SOCS3 Gene

Aliases for SOCS3 Gene

  • Suppressor Of Cytokine Signaling 3 2 3 5
  • Cytokine-Inducible SH2 Protein 3 3 4
  • STAT-Induced STAT Inhibitor 3 3 4
  • SOCS-3 3 4
  • SSI-3 3 4
  • CIS3 3 4
  • SSI3 3 4
  • ATOD4 3
  • Cish3 3
  • 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 Cytokine Signaling in Immune system and IL-2 Signaling Pathway. Gene Ontology (GO) annotations related to this gene include protein kinase inhibitor activity. An important paralog of this gene is CISH.

UniProtKB/Swiss-Prot 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

Additional gene information for SOCS3 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SOCS3 Gene

Genomics for SOCS3 Gene

GeneHancer (GH) Regulatory Elements for SOCS3 Gene

Promoters and enhancers for SOCS3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH17I078349 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 575 +4.2 4214 11.9 HDGF PKNOX1 FOXA2 SMAD1 ZFP64 ARID4B SIN3A ZNF2 ZBTB7B IRF4 SOCS3 GC17M078357 USP36 PGS1 ENGASE LOC101928674 CYTH1 BIRC5 TMC6 TMC8
GH17I078368 Promoter/Enhancer 2.9 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 27 -17.8 -17803 18.9 MLX DMAP1 IRF4 YY1 SLC30A9 ZNF213 E2F8 ZNF143 SP3 NFYC PGS1 SOCS3 TNRC6C LOC101928674 DNAH17 CYTH1 USP36 GC17M078378 GC17M078384 RN7SL236P
GH17I078313 Promoter/Enhancer 2.1 FANTOM5 Ensembl ENCODE dbSUPER 35.8 +43.8 43845 5.3 HDGF PKNOX1 FOXA2 SMAD1 ARNT ARID4B SIN3A ZNF2 ZBTB7B ZNF213 LOC105371912 SOCS3 USP36 PGS1 ENSG00000200063 CYTH1 GC17M078340
GH17I078336 Promoter/Enhancer 2.2 FANTOM5 Ensembl ENCODE dbSUPER 30.8 +19.0 18954 9 PKNOX1 SIN3A IRF4 ZNF121 FOS ATF7 RUNX3 JUNB REST SREBF1 SOCS3 USP36 PGS1 ENSG00000200063 RNU6-638P CYTH1 GC17M078340 LOC105371912
GH17I078645 Enhancer 1.6 FANTOM5 Ensembl ENCODE dbSUPER 32.5 -286.1 -286098 2.4 ATF1 KLF17 KLF5 IRF4 RAD21 ATF7 BCLAF1 IKZF2 RUNX3 CREM SOCS3 PGS1 CYTH1 ENGASE USP36 GC17P078652 GC17P078635
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around SOCS3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SOCS3 gene promoter:

Genomic Locations for SOCS3 Gene

Genomic Locations for SOCS3 Gene
chr17:78,356,777-78,360,079
(GRCh38/hg38)
Size:
3,303 bases
Orientation:
Minus strand
chr17:76,352,859-76,356,158
(GRCh37/hg19)

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

ENSEMBL proteins:
REFSEQ proteins:

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

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
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

Clone Products

  • Addgene plasmids 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
nucleus 3
plasma membrane 2
extracellular 2
mitochondrion 2
peroxisome 2
cytoskeleton 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for SOCS3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IEA --
GO:0005737 cytoplasm IBA --
GO:0005829 cytosol TAS --
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

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

UniProtKB/Swiss-Prot O14543-SOCS3_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for SOCS3 Gene

Inactivates:

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

(14) Drugs for SOCS3 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(12) 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

Unigene Clusters for SOCS3 Gene

Suppressor of cytokine signaling 3:
Representative Sequences:

Clone Products

  • Addgene plasmids 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
ECgene alternative splicing isoforms for
SOCS3

Expression for SOCS3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP 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, PaxDb, and MOPED for SOCS3 Gene



Protein tissue co-expression partners for SOCS3 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of SOCS3 Gene:

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(4.5)
  • Nervous system(3.6)
  • Liver(3.1)
  • Blood(2.8)
  • Intestine(2.8)
  • Lung(2.8)
  • Lymph node(2.6)
  • Bone marrow(2.5)
  • Spleen(2.5)
  • Heart(2.3)
  • Kidney(2.2)
  • Pancreas(2.2)
  • Adrenal gland(2.1)
  • Gall bladder(2.1)
  • Eye(2)
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 33 34
  • 100 (n)
dog
(Canis familiaris)
Mammalia SOCS3 33 34
  • 94.67 (n)
cow
(Bos Taurus)
Mammalia SOCS3 33 34
  • 92.3 (n)
mouse
(Mus musculus)
Mammalia Socs3 33 16 34
  • 90.81 (n)
rat
(Rattus norvegicus)
Mammalia Socs3 33
  • 89.93 (n)
oppossum
(Monodelphis domestica)
Mammalia SOCS3 34
  • 89 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SOCS3 34
  • 86 (a)
OneToOne
chicken
(Gallus gallus)
Aves SOCS3 33 34
  • 84.69 (n)
lizard
(Anolis carolinensis)
Reptilia SOCS3 34
  • 89 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia socs3 33
  • 68.51 (n)
African clawed frog
(Xenopus laevis)
Amphibia socs3-prov 33
zebrafish
(Danio rerio)
Actinopterygii socs3b 34 33
  • 67.8 (n)
OneToMany
socs3a 34
  • 61 (a)
OneToMany
wufj09e12 33
Species where no ortholog for SOCS3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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 squirt (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)

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 from dbSNP and Humsavar for SOCS3 Gene

SNP ID Clin Chr 17 pos Variation AA Info Type
rs1000211656 -- 78,356,749(-) G/A/T downstream_transcript_variant
rs1000470773 -- 78,357,861(-) C/G 3_prime_UTR_variant
rs1000542531 -- 78,357,664(-) G/A 3_prime_UTR_variant
rs1000668995 -- 78,357,625(-) C/T 3_prime_UTR_variant
rs1001357088 -- 78,357,213(-) G/A 3_prime_UTR_variant

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

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

Disorder Aliases PubMed IDs
dermatitis, atopic, 4
  • atod4
overnutrition
infectious anterior uveitis
  • infectious secondary iridocyclitis
articulation disorder
  • articulation impairment
polycythemia vera
  • pv
- 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
genes like me logo Genes that share disorders with SOCS3: view

No data available for Genatlas for SOCS3 Gene

Publications for SOCS3 Gene

  1. 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 22 44 58
  2. 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 22 44 58
  3. A new high affinity binding site for suppressor of cytokine signaling-3 on the erythropoietin receptor. (PMID: 12027890) Hörtner M … Haan S (European journal of biochemistry 2002) 3 4 22 58
  4. Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor. (PMID: 11071852) Dey BR … Nissley P (Biochemical and biophysical research communications 2000) 3 4 22 58
  5. 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. (PMID: 10421843) Sasaki A … Yoshimura A (Genes to cells : devoted to molecular & cellular mechanisms 1999) 3 4 22 58

Products for SOCS3 Gene

  • Addgene plasmids for SOCS3

Sources for SOCS3 Gene

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