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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

SOCS3 Gene

protein-coding GIFtS: 68
GCID: GC17M076352

suppressor of cytokine signaling 3

Explore 88 diseases affiliated with
SOCS3 via

MalaCards

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Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Suppressor Of Cytokine Signaling 3¹ ²		Cytokine-Inducible SH2 Protein 3² ³
CIS3¹ ² ³ ⁵		CIS-3² ³
SOCS-3¹ ² ³		STAT-Induced STAT Inhibitor 3² ³
SSI-3¹ ² ³		ATOD4²
SSI3² ³ ⁵		Cytokine-Induced SH2 Protein 3²
Cish3¹ ²

External Ids:	HGNC: 19391¹	Entrez Gene: 9021²	Ensembl: ENSG00000184557⁷	OMIM: 604176⁵	UniProtKB: O14543³

Export aliases for SOCS3 gene to outside databases

Previous GC identifers: GC17M079741 GC17M076815 GC17M076951 GC17M076949 GC17M073864 GC17M071775

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for SOCS3:

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)

UniProtKB/Swiss-Prot: SOCS3_HUMAN, O14543

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)

Gene Wiki entry for SOCS3

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000017.10 NC_018928.1 NT_010783.15

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the SOCS3 gene promoter:
STAT5B GATA-3 Pax-5 NRSF form 1 AP-4 NRSF form 2 PPAR-gamma1 c-Rel c-Myb PPAR-gamma2
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): SOCS3 promoter sequence

Search SABiosciences Chromatin IP Primers for SOCS3

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat SOCS3

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17q25.3 Ensembl cytogenetic band: 17q25.3 HGNC cytogenetic band: 17q25.3

SOCS3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SOCS3 gene location

GeneLoc information about chromosome 17 GeneLoc Exon Structure

GeneLoc location for GC17M076352: view genomic region (about GC identifiers)

Start:	76,352,859 bp from pter	End:	76,356,158 bp from pter
Size:	3,300 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: SOCS3_HUMAN, O14543 (See protein sequence)

Recommended Name: Suppressor of cytokine signaling 3

Size: 225 amino acids; 24770 Da

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. Interacts with FGFR3. Interacts with INSR (By similarity). Interacts with

BCL10; this interaction may interfere with BCL10-binding with PELI2 (By similarity)

Secondary accessions: O14509

Explore the universe of human proteins at neXtProt for SOCS3: NX_O14543

Post-translational modifications:

Phosphorylated on tyrosine residues after stimulation by the cytokines, IL-2, EPO or IGF1¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_O14543

SOCS3 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_003946.3

ENSEMBL proteins:

ENSP00000330341 ENSP00000464727

Reactome Protein details: O14543
Human Recombinant Protein Products for SOCS3:

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	Novus Biologicals SOCS3 Protein Novus Biologicals SOCS3 Lysates
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for SOCS3

Gene Ontology (GO): 2 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005737	cytoplasm	--	--
GO:0005829	cytosol	TAS	--

SOCS3 for ontologies About GeneDecksing

SOCS3 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of SOCS3
	R&D Systems Antibodies for SOCS3 (SOCS-3)
	Cell Signaling Technology (CST) Antibodies for SOCS3
	OriGene Antibodies (see all 12): SOCS3 OriGene Custom Antibody Services for SOCS3
	GenScript Custom Superior Antibodies Services for SOCS3
	Novus Biologicals SOCS3 Antibodies
	Abcam antibodies for SOCS3
	Uscn Antibodies for SOCS3
	ThermoFisher Antibody for SOCS3

Assay Products for SOCS3:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for SOCS3
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for SOCS3

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

SOCS3 for domains About GeneDecksing

2 InterPro domains/families:

IPR001496 SOCS_C

IPR000980 SH2

Graphical View of Domain Structure for InterPro Entry O14543

ProtoNet protein and cluster: O14543

2 Blocks protein families:

IPB000980 SH2 domain signature

IPB001496 SOCS protein

UniProtKB/Swiss-Prot: SOCS3_HUMAN, O14543

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)

Similarity: Contains 1 SH2 domain

Similarity: Contains 1 SOCS box domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: SOCS3_HUMAN, O14543

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)

Gene Ontology (GO): 2 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004860	protein kinase inhibitor activity	TAS	9266833
GO:0005515	protein binding	--	--

SOCS3 for ontologies About GeneDecksing

Phenotypes:
2 GenomeRNAi human phenotypes for SOCS3:

Decreased viability with pacli

Wnt reporter downregulated

15/16 MGI mutant phenotypes (inferred from 6 alleles) (MGI details for Socs3) (see all 16):

adipose tissue	behavior/neurological	cardiovascular system	cellular	digestive/alimentary
embryogenesis	growth/size	hematopoietic system	homeostasis/metabolism	immune system
integument	liver/biliary system	mortality/aging	normal	respiratory system

SOCS3 for phenotypes About GeneDecksing

Animal Models:
Mouse knock-outs for SOCS3: Socs3^tm1Jni Socs3^tm2.1Wsa

inGenious Targeting Laboratory - Customizable classic, inducible, and humanized mouse model solutions for SOCS3

miRNA Products:		miRTarBase miRNAs that target SOCS3: hsa-mir-203 (MIRT005062)

		OriGene 3'-UTR Clone: SOCS3 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat SOCS3
		8/46 QIAGEN miScript miRNA Assays for microRNAs that regulate SOCS3 (see all 46):
		hsa-miR-520f hsa-miR-30d hsa-miR-759 hsa-miR-218 hsa-miR-508-3p hsa-miR-1304 hsa-miR-30a hsa-miR-383

		SwitchGear 3'UTR luciferase reporter plasmid: SOCS3 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for SOCS3 (see all 6) OriGene siRNA: SOCS3
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat SOCS3
		Sirion Biotech Custom design and validation of potent shRNA sequences against SOCS3

Gene Editing Products:			DNA2.0 Custom Protein Engineering Service for SOCS3
			Sirion Biotech Customized adenovirus for overexpression of SOCS3 Sirion Biotech Customized adenovirus for potent knockdown of SOCS3

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for SOCS3 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for SOCS3 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: SOCS3 (NM_003955)
		Sino Biological Human cDNA Clone for SOCS3
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for SOCS3
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat SOCS3

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for SOCS3
		Search LifeMap BioReagents cell lines for SOCS3
		Sirion Biotech Customized stable knockdown cell line services for SOCS3 Sirion Biotech Customized inducible knockdown cell line services for SOCS3 Sirion Biotech Customized stable overexpressing cell line services for SOCS3 Sirion Biotech Customized inducible overexpressing cell line services for SOCS3

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SOCS3

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/45 super-pathways (see all 45) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Development_CNTF receptor signaling

Development_CNTF receptor signaling	1.00	Development_Leptin signaling via JAK/STAT and MAPK cascades	0.25
Development CNTF receptor signaling	1.00	Development Leptin signaling via JAK/STAT and MAPK cascades	0.25
Immune response_IL-6 signaling pathway	0.30	Insulin signaling pathway	0.17
Immune response IL-6 signaling pathway	0.30

Development_PDGF signaling via STATs and NF-kB

Immune response_IL-23 signaling pathway	0.44	Immune response IL-10 signaling pathway	0.28
Immune response IL-23 signaling pathway	0.41	IL23-mediated signaling events	0.15
Immune response_IL-10 signaling pathway	0.28

Development_Prolactin receptor signaling

	Development_Prolactin receptor signaling	1.00			Prolactin Signaling Pathway	0.39
	Development Prolactin receptor signaling	1.00			Leptin signaling pathway	0.32

Immune response_IL-2 activation and signaling pathway

	Immune response IL-2 activation and signaling pathway	1.00			Immune response_IL-3 activation and signaling pathway	0.41
	Immune response_IL-2 activation and signaling pathway	1.00			Immune response IL-3 activation and signaling pathway	0.41

Antigen processing: Ubiquitination & Proteasome degradation

	Antigen processing: Ubiquitination & Proteasome degradation	1.00			Polyubiquitination of substrate	0.75
	Class I MHC mediated antigen processing & presentation	0.83			Ubiquitin mediated proteolysis	0.36

Pathway sources
See GeneCards unified pathways
Show all pathways

5/14 EMD Millipore Pathways for SOCS3 (see all 14)

	Immune response IL-23 signaling pathway
	Development Leptin signaling via JAK/STAT and MAPK cascades
	Immune response IL-9 signaling pathway
	Development EPO-induced Jak-STAT pathway
	Immune response IL-3 activation and signaling pathway

5/10 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for SOCS3 (see all 10)

	IL-9 Pathway
	STAT3 Pathway
	IL-10 Pathway
	IL-4 Pathway
	JAK-STAT Pathway

2 Cell Signaling Technology (CST) Pathways for SOCS3

	Tyrosine Kinases / Adaptors
	Jak/Stat Pathway

5/14 GeneGo (Thomson Reuters) Pathways for SOCS3 (see all 14)

	Immune response IL-6 signaling pathway
	Development Leptin signaling via JAK/STAT and MAPK cascades
	Development CNTF receptor signaling
	Immune response Oncostatin M signaling via JAK-Stat in human cells
	Immune response IL-9 signaling pathway

5/20 BioSystems Pathways for SOCS3 (see all 20)

	Type II interferon signaling (IFNG)
	Oncostatin M Signaling Pathway
	Adipogenesis
	EGFR1 Signaling Pathway
	Insulin Signaling

5/14 Reactome Pathways for SOCS3 (see all 14)

	Regulation of IFNA signaling
	Interferon alpha/beta signaling
	Interferon gamma signaling
	Cytokine Signaling in Immune system
	Polyubiquitination of substrate

5/8 Kegg Pathways (Kegg details for SOCS3) (see all 8):

	Ubiquitin mediated proteolysis
	Osteoclast differentiation
	Jak-STAT signaling pathway
	Insulin signaling pathway
	Adipocytokine signaling pathway

UniProtKB/Swiss-Prot: SOCS3_HUMAN, O14543

Pathway: Protein modification; protein ubiquitination

SOCS3 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for SOCS3

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/128 Interacting proteins for SOCS3 (O14543^{2, 3} ENSP00000330341⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 128)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
MAP1S	Q66K74²^,³, ENSP00000325313⁴	MINT-6796936 MINT-6796894 MINT-6796909 MINT-6796957 MINT-6796979 MINT-6796875 I2D: score=2 STRING: ENSP00000325313
MAPK11	Q15759²^,³, ENSP00000333685⁴	MINT-8260548 I2D: score=2 STRING: ENSP00000333685
PIN1	Q13526²^,³	MINT-63063 I2D: score=5
MAPK6	Q16659²^,³	MINT-8262022 I2D: score=2
PDPK1	O15530²^,³	MINT-8265621 I2D: score=2

About this table

Gene Ontology (GO): 5/39 biological process terms (GO ID links to tree view) (see all 39): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001666	response to hypoxia	--	--
GO:0001932	regulation of protein phosphorylation	--	--
GO:0006469	negative regulation of protein kinase activity	TAS	9266833
GO:0007165	signal transduction	--	--
GO:0007243	intracellular protein kinase cascade	--	--

SOCS3 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

SOCS3 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for SOCS3
UniProtKB/Swiss-Prot: SOCS3_HUMAN, O14543

Pharmaceutical: Could be used as a possible therapeutic agent for treating rheumatoid arthritis

10/26 Novoseek chemical compound relationships for SOCS3 gene (see all 26) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
gp 130	75.9	39	10829066 (6), 12403768 (4), 18986700 (3), 12593670 (3) (see all 16)
tyrosine	60.2	94	10373548 (5), 12783885 (4), 10585430 (3), 10421843 (3) (see all 49)
ifn-alpha	52.1	8	15618960 (2), 18616672 (1), 11340296 (1)
5-aza-2'deoxycytidine	51.1	12	18507841 (2), 17376806 (1), 16007195 (1), 19929568 (1) (see all 7)
ribavirin	33.7	1	19624774 (1)
glucose	11.1	18	19435854 (3), 20067961 (2), 17194639 (2), 15331532 (2) (see all 10)
con a	8.25	1	16474852 (1)
phosphatidylinositol	6.93	1	12396724 (1)
acth	4.04	6	10098488 (2), 11268394 (1), 12639901 (1), 15249728 (1)
cocaine	2.54	2	18638026 (1), 19726709 (1)

Search CenterWatch for drugs/clinical trials and news about SOCS3

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, Sirion Biotech, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for SOCS3 gene:

NM_003955.3

Unigene Cluster for SOCS3:

Suppressor of cytokine signaling 3

Hs.527973 [show with all ESTs]

Unigene Representative Sequence: NM_003955

2 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000330871(uc002jvl.2) ENST00000587578

miRNA Products:		OriGene 3'-UTR Clone: SOCS3 Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat SOCS3
		8/46 QIAGEN miScript miRNA Assays for microRNAs that regulate SOCS3 (see all 46):
		hsa-miR-520f hsa-miR-30d hsa-miR-759 hsa-miR-218 hsa-miR-508-3p hsa-miR-1304 hsa-miR-30a hsa-miR-383

		SwitchGear 3'UTR luciferase reporter plasmid: SOCS3 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for SOCS3 (see all 6) OriGene siRNA: SOCS3
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		Sirion Biotech Custom design and validation of potent shRNA sequences against SOCS3

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		GenScript: all cDNA clones in your preferred vector: SOCS3 (NM_003955)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for SOCS3
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat SOCS3

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for SOCS3 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat SOCS3
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat SOCS3
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat SOCS3

Additional cDNA sequence:

AB004904.1 AB006967.1 AF159854.1 AK309756.1 AK314212.1 BC060858.1 BT019544.1 CR536497.1

CR541694.1

4 DOTS entries:

DT.412699 DT.92419300 DT.100791006 DT.91746741

24/124 AceView cDNA sequences (see all 124):

BM922355 AI761922 AI968957 CA447987 AI924575 CA866699 BG057691 AW055348

AI830013 CD366103 AW664221 AB006967 NM_003955 CA423840 BQ016286 BQ004289

AI678436 BG236059 CR541694 BG752935 BQ003407 BQ018132 CB267550 CR536497

GeneLoc Exon Structure

2 Alternative Splicing Database (ASD) splice patterns (SP) for SOCS3 About this scheme

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

ECgene alternative splicing isoforms for SOCS3

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

SOCS3 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: CCTCCCAGCT

About this image

SOCS3 expression in embryonic tissues and stem cells
Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

2 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Ovary

Antral Follicle

Mature Granulosa Cells

Ovary

Lung

Lung Bud

Lung

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 2 LifeMap Cells

Name

Category

Secondary follicles (Primary Cell)

Ovary, Reproductive System

Definitive endoderm-like cells (A scalable, suspensi...)

See SOCS3 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for SOCS3

SOURCE GeneReport for Unigene cluster: Hs.527973

UniProtKB/Swiss-Prot: SOCS3_HUMAN, O14543

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

SABiosciences Expression via Pathway-Focused PCR Arrays including SOCS3 (see all 14):

Nephrotoxicity in human mouse rat

Prostate Cancer in human mouse rat

Liver Cancer in human mouse rat

JAK / STAT Signaling Pathway in human mouse rat

Ubiquitin Ligases in human mouse rat

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals.

Orthologs for SOCS3 gene from 5/14 species (see all 14) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	SOCS3¹	suppressor of cytokine signaling 3	84.69(n) 89.47(a)		395299 NM_204600.1 NP_989931.1
lizard (Anolis carolinensis)	Reptilia	SOCS3⁶ --	--	85(a) 38(a)	1 ↔ 1 possible ortholog	2(102114598-102115233) GL343329.1(604631-605137)
African clawed frog (Xenopus laevis)	Amphibia	socs3-prov²	suppressor of cytokine signaling 3	73.43(n)		BC054214.1
zebrafish (Danio rerio)	Actinopterygii	wufj09e12²	wufj09e12	78.33(n)		335409 BC049326.1
honey bee (Apis mellifera)	Insecta	--	--	31(a)	1 → many	Group8.34(5736-6146)

ENSEMBL Gene Tree for SOCS3 (if available)
TreeFam Gene Tree for SOCS3 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for SOCS3 gene

SOCS4² SOCS5² SOCS7² SOCS6² SOCS1² CISH² SOCS2²

1 SIMAP similar gene for SOCS3 using alignment to 3 protein entries: SOCS3_HUMAN (see all proteins):

SOCS2

SOCS3 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
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SNP ID	Valid	Clinical significance	Chr 17 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs111033850^1,2	C	other	76356213(-)	`AGGAAC/TCGGGG`	1	--	us2k¹		0	--	--	--	--
rs187289832^1,2		--	76352376(+)	`AGGGGA/GTGGGG`	1	--	ds500¹		0	--	--	--	--
rs192175547^1,2		--	76352418(+)	`CACCCC/TTCCCC`	1	--	ds500¹		0	--	--	--	--
rs77344606^1,2	F	--	76352424(+)	`TCCCCC/ACACTT`	1	--	ds500¹		1		WA	118
rs143286673^1,2		--	76352475(+)	`GGACCC/TCATGT`	1	--	ds500¹		0	--	--	--	--
rs183843486^1,2		--	76352483(+)	`TGTCTC/GGGCTT`	1	--	ds500¹		0	--	--	--	--
rs76848919^1,2	C,F	--	76352554(+)	`GCTTTG/CACCAC`	1	--	ds500¹		3		NA	124
rs188282321^1,2		--	76352575(+)	`GCTCCC/TTGCAA`	1	--	ds500¹		0	--	--	--	--
rs147887475^1,2		--	76352812(+)	`GGCACA/GGGGCG`	1	--	ds500¹		0	--	--	--	--
rs141500264^1,2		--	76352919(+)	`GAATAC/TAAATA`	1	--	ut3¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for SOCS3 (76352859 - 76356158 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 1 variation for SOCS3
1 CNV: 5033
Human Gene Mutation Database (HGMD): SOCS3

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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SOCS3 for disorders About GeneDecksing

OMIM gene information: 604176 OMIM disorders: --

UniProtKB/Swiss-Prot: SOCS3_HUMAN, O14543

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

20/88 diseases for SOCS3 (see all 88): About MalaCards

vogt-koyanagi-harada disease polycythemia vera dengue hemorrhagic fever pre-eclampsia

anaplastic large cell lymphoma type 2 diabetes mellitus hemorrhagic fever inflammatory bowel disease

polycythemia herpes simplex diabetes mellitus insulin resistance

muscle hypertrophy hepatitis c anorexia nervosa systemic lupus erythematosus

intrahepatic cholestasis allergic conjunctivitis lupus erythematosus primary polycythemia

2 diseases from the University of Copenhagen DISEASES database for SOCS3:

Cancer Diabetes mellitus

10/53 Novoseek disease relationships for SOCS3 gene (see all 53) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
insulin resistance	49.9	21	18171427 (2), 12475383 (2), 15169905 (2), 17327450 (2) (see all 12)
leukemia	43	12	9811457 (2), 20372794 (1), 11714737 (1), 16616006 (1) (see all 10)
polycythemia vera	42.6	6	18815196 (2), 16781479 (1), 17325857 (1)
inflammation	40.5	23	20067961 (3), 20005910 (2), 15947106 (1), 17198696 (1) (see all 19)
obesity	39.5	17	16299039 (3), 17445271 (2), 19083014 (2), 16402267 (1) (see all 10)
insulin sensitivity	39	7	16402267 (2), 16920065 (2), 15249995 (1), 15072573 (1) (see all 5)
hepatitis c chronic	36.6	8	19624774 (2), 17881539 (1), 16299039 (1), 17668875 (1) (see all 5)
necrosis	34.3	17	16352613 (2), 15491991 (1), 18656467 (1), 20067961 (1) (see all 15)
asthma allergic	29.4	1	16476192 (1)
tumors	27.3	57	15385932 (4), 17376806 (3), 19996282 (3), 19738059 (2) (see all 33)

Genetic Association Database (GAD): SOCS3
Human Genome Epidemiology (HuGE) Navigator: SOCS3 (25 documents)

Export disorders for SOCS3 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for SOCS3 gene, integrated from 9 sources (see all 554):
(articles sorted by number of sources associating them with SOCS3)

Utopia: connect your pdf to the dynamic
world of online information

Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3. (PubMed id 9266833)^{1, 2, 3, 9} Minamoto S.... Kishimoto T. (1997)
Cloning and characterization of novel CIS family genes. (PubMed id 9344848)^{1, 2, 3} Masuhara M.... Yoshimura A. (1997)
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. (PubMed id 10421843)^{1, 2, 9} Sasaki A.... Yoshimura A. (1999)
A new high affinity binding site for suppressor of cytokine signaling-3 on the erythropoietin receptor. (PubMed id 12027890)^{1, 2, 9} Hoertner M.... Haan S. (2002)
Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor. (PubMed id 11071852)^{1, 2, 9} Dey B.R.... Nissley P. (2000)
Suppressors of cytokine signaling (SOCS) 1 and SOCS3 interact with and modulate fibroblast growth factor receptor signaling. (PubMed id 16410555)^{1, 2, 9} Ben-Zvi T....Monsonego-Ornan E. (2006)
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. (PubMed id 14559241)^{1, 2, 9} Yamamoto K.... Miura O. (2003)
Mutation analysis of suppressor of cytokine signalling 3, a candidate gene in Type 1 diabetes and insulin sensitivity. (PubMed id 15249995)^{1, 4, 9} Gylvin T....Pociot F. (2004)
Elevated expression and genetic association links the SOCS3 gene to atopic dermatitis. (PubMed id 16685656)^{1, 2} Ekelund E.... Bradley M. (2006)
Involvement of casein kinase Iepsilon in cytokine-induced granulocytic differentiation. (PubMed id 15070676)^{1, 2} Okamura A....Matsui T. (2004)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 9021	HGNC: 19391	AceView: SOCS3	Ensembl:ENSG00000184557	euGenes: HUgn9021
ECgene: SOCS3	Kegg: 9021	H-InvDB: SOCS3

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for SOCS3	Pharmacogenomics, SNPs, Pathways

Intellectual Property for SOCS3 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for SOCS3 gene:
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GeneCards and IP:
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suppressor of cytokine signaling 3

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SOCS3 Gene

suppressor of cytokine signaling 3

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