Reviewed, UniProtKB/Swiss-Prot O88583 (SOCS3_RAT)

Names and origin

Protein names

Recommended name:
    Suppressor of cytokine signaling 3
      Short name=SOCS-3
Alternative name(s):
    Cytokine-inducible SH2 protein 3

Gene names

Name:	Socs3
Synonyms:	Cish3

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	225 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

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. 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.
Pathway	Protein modification; protein ubiquitination.
Subunit 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. Binds specific activated tyrosine residues of the leptin, EPO, IL12, GSCF and gp130 receptors. Interaction with CSNK1E stabilize 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 By similarity.
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 By similarity.
Post-translational modification	Phosphorylated on tyrosine residues after stimulation by the cytokines, IL-2, EPO or IGF1 By similarity.
Sequence similarities	Contains 1 SH2 domain. Contains 1 SOCS box domain.

Ontologies

Keywords
Biological process	Growth regulation Ubl conjugation pathway
Domain	SH2 domain
Molecular function	Signal transduction inhibitor
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	JAK-STAT cascade Inferred from direct assay. Source: RGD aging Inferred from expression pattern. Source: RGD modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW organ regeneration Inferred from expression pattern. Source: RGD regulation of cell growth Traceable author statement. Source: RGD response to cytokine stimulus Inferred from expression pattern. Source: RGD response to drug Inferred from expression pattern. Source: RGD response to estradiol stimulus Inferred from expression pattern. Source: RGD response to food Inferred from expression pattern. Source: RGD response to gamma radiation Inferred from expression pattern. Source: RGD response to heat Inferred from expression pattern. Source: RGD response to hypoxia Inferred from expression pattern. Source: RGD response to insulin stimulus Inferred from expression pattern. Source: RGD response to lipopolysaccharide Inferred from expression pattern. Source: RGD response to organic cyclic substance Inferred from expression pattern. Source: RGD response to progesterone stimulus Inferred from expression pattern. Source: RGD
Cellular component	cytoplasm Inferred from direct assay. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 225	225	Suppressor of cytokine signaling 3		PRO_0000181245
Regions
	Domain	46 – 142	97	SH2
	Domain	177 – 224	48	SOCS box
	Region	22 – 33	12	Kinase inhibitory region (KIR)
	Region	34 – 45	12	Extended SH2 subdomain (ESS)
Experimental info
	Sequence conflict	75	1	D → G in CAB56083. Ref.2
	Sequence conflict	85	1	E → K in CAB56083. Ref.2
	Sequence conflict	145	1	F → S in CAB56083. Ref.2
	Sequence conflict	164	1	A → G in CAB56083. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O88583-1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: BC95FF2074125D8F	FASTA	225	24,808
	10 20 30 40 50 60 MVTHSKFPAA GMSRPLDTSL RLKTFSSKSE YQLVVNAVRK LQESGFYWSA VTGGEANLLL 70 80 90 100 110 120 SAEPAGTFLI RDSSDQRHFF TLSVETQSGT KNLRIQCEGG SFSLQSDPRS TQPVPRFDCV 130 140 150 160 170 180 LKLVHHYMPP PGAPSFSLPP TEPSFEVQEQ PPAQALPGGT PKRAYYIYSG GEKIPLVLSR 190 200 210 220 PLSSNVATLQ HLCRKTVNGH LDSYEKVTQL PGPIREFLDQ YDAPL

References

[1]	"Endotoxin-induced inhibition of growth hormone receptor signaling in rat liver in vivo." Mao Y., Ling P.R., Fitzgibbons T.P., McCowen K.C., Frick G.P., Bistrian B.R., Smith R.J. Endocrinology 140:5505-5515(1999) [PubMed: 10579313] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Liver.
[2]	le Cam A. Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Sprague-Dawley.
[3]	"Identification of the Y985 and Y1077 motifs as SOCS3 recruitment sites in the murine leptin receptor." Eyckerman S., Broekaert D., Verhee A., Vandekerckhove J., Tavernier J. FEBS Lett. 486:33-37(2000) [PubMed: 11108838] [Abstract] Cited for: INTERACTION WITH LEPTIN.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF075383 mRNA. Translation: AAC26223.1. AJ249240 Genomic DNA. Translation: CAB56083.1.
IPI	IPI00210797.
RefSeq	NP_446017.1.
UniGene	Rn.127801
3D structure databases
HSSP	HSSP built from PDB template 1AYA based on UniProtKB P35235.
ModBase	Search...
Protein-protein interaction databases
STRING	O88583.
Genome annotation databases
Ensembl	ENSRNOT00000003940; ENSRNOP00000003940; ENSRNOG00000002946; Rattus norvegicus. [Genome view]
GeneID	89829.
KEGG	rno:89829.
UCSC	NM_053565. rat.
Organism-specific databases
CTD	89829.
RGD	621087. Socs3.
Phylogenomic databases
HOVERGEN	O88583.
Gene expression databases
ArrayExpress	O88583.
Genevestigator	O88583.
GermOnline	ENSRNOG00000002946. Rattus norvegicus.
Family and domain databases
InterPro	IPR000980. SH2. IPR001496. SOCS_C. [Graphical view]
Gene3D	G3DSA:3.30.505.10. SH2. 1 hit.
Pfam	PF00017. SH2. 1 hit. PF07525. SOCS_box. 1 hit. [Graphical view]
ProDom	PD000093. SH2. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00252. SH2. 1 hit. SM00253. SOCS. 1 hit. [Graphical view]
PROSITE	PS50001. SH2. 1 hit. PS50225. SOCS. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	617752.

Entry information

Entry name

SOCS3_RAT

Accession

Primary (citable) accession number: O88583
Secondary accession number(s): Q9QYV5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 16, 2002
Last sequence update:	November 1, 1998
Last modified:	October 13, 2009
This is version 66 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)