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Suppressor of cytokine signaling 3 (SOCS-3) (Cytokine-inducible SH2 protein 3)

 SOCS3_RAT               Reviewed;         225 AA.
O88583; Q9QYV5;
16-APR-2002, integrated into UniProtKB/Swiss-Prot.
01-NOV-1998, sequence version 1.
28-FEB-2018, entry version 126.
RecName: Full=Suppressor of cytokine signaling 3;
AltName: Full=Cytokine-inducible SH2 protein 3;
Name=Socs3; Synonyms=Cish3;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
STRAIN=Sprague-Dawley; TISSUE=Liver;
PubMed=10579313; DOI=10.1210/endo.140.12.7212;
Mao Y., Ling P.R., Fitzgibbons T.P., McCowen K.C., Frick G.P.,
Bistrian B.R., Smith R.J.;
"Endotoxin-induced inhibition of growth hormone receptor signaling in
rat liver in vivo.";
Endocrinology 140:5505-5515(1999).
le Cam A.;
Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
PubMed=11108838; DOI=10.1016/S0014-5793(00)02205-5;
Eyckerman S., Broekaert D., Verhee A., Vandekerckhove J.,
Tavernier J.;
"Identification of the Y985 and Y1077 motifs as SOCS3 recruitment
sites in the murine leptin receptor.";
FEBS Lett. 486:33-37(2000).
-!- 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: 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, ELOB and ELOC. Interacts with FGFR3 (By similarity).
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 (By similarity).
{ECO:0000250|UniProtKB:O14543, ECO:0000250|UniProtKB:O35718,
-!- 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. {ECO:0000250}.
-!- PTM: Phosphorylated on tyrosine residues after stimulation by the
cytokines, IL-2, EPO or IGF1. {ECO:0000250}.
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
Distributed under the Creative Commons Attribution-NoDerivs License
EMBL; AF075383; AAC26223.1; -; mRNA.
EMBL; AJ249240; CAB56083.1; -; Genomic_DNA.
RefSeq; NP_446017.1; NM_053565.1.
UniGene; Rn.127801; -.
ProteinModelPortal; O88583; -.
SMR; O88583; -.
BioGrid; 250151; 1.
STRING; 10116.ENSRNOP00000003940; -.
PaxDb; O88583; -.
GeneID; 89829; -.
KEGG; rno:89829; -.
UCSC; RGD:621087; rat.
CTD; 9021; -.
RGD; 621087; Socs3.
eggNOG; KOG4566; Eukaryota.
eggNOG; ENOG4111V4J; LUCA.
HOGENOM; HOG000236320; -.
HOVERGEN; HBG105645; -.
InParanoid; O88583; -.
KO; K04696; -.
PhylomeDB; O88583; -.
UniPathway; UPA00143; -.
PRO; PR:O88583; -.
Proteomes; UP000002494; Unplaced.
GO; GO:0005737; C:cytoplasm; IDA:RGD.
GO; GO:0001784; F:phosphotyrosine residue binding; ISO:RGD.
GO; GO:0004860; F:protein kinase inhibitor activity; IBA:GO_Central.
GO; GO:0007568; P:aging; IEP:RGD.
GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; ISO:RGD.
GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
GO; GO:0035556; P:intracellular signal transduction; IDA:RGD.
GO; GO:0007259; P:JAK-STAT cascade; IDA:RGD.
GO; GO:0043066; P:negative regulation of apoptotic process; IEA:InterPro.
GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISO:RGD.
GO; GO:0046426; P:negative regulation of JAK-STAT cascade; ISO:RGD.
GO; GO:0006469; P:negative regulation of protein kinase activity; IBA:GO_Central.
GO; GO:0009968; P:negative regulation of signal transduction; ISO:RGD.
GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; ISO:RGD.
GO; GO:0060674; P:placenta blood vessel development; ISO:RGD.
GO; GO:0045597; P:positive regulation of cell differentiation; ISO:RGD.
GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
GO; GO:0045595; P:regulation of cell differentiation; ISO:RGD.
GO; GO:0001558; P:regulation of cell growth; TAS:RGD.
GO; GO:0001932; P:regulation of protein phosphorylation; ISO:RGD.
GO; GO:0009617; P:response to bacterium; IEP:RGD.
GO; GO:0034097; P:response to cytokine; IEP:RGD.
GO; GO:0042493; P:response to drug; IEP:RGD.
GO; GO:0032355; P:response to estradiol; IEP:RGD.
GO; GO:0032094; P:response to food; IEP:RGD.
GO; GO:0010332; P:response to gamma radiation; IEP:RGD.
GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
GO; GO:0009408; P:response to heat; IEP:RGD.
GO; GO:0009725; P:response to hormone; IEP:RGD.
GO; GO:0001666; P:response to hypoxia; IEP:RGD.
GO; GO:0032868; P:response to insulin; IEP:RGD.
GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
GO; GO:0032570; P:response to progesterone; IEP:RGD.
GO; GO:0007165; P:signal transduction; IDA:RGD.
GO; GO:0060708; P:spongiotrophoblast differentiation; ISO:RGD.
GO; GO:0060707; P:trophoblast giant cell differentiation; ISO:RGD.
CDD; cd10384; SH2_SOCS3; 1.
InterPro; IPR000980; SH2.
InterPro; IPR036860; SH2_dom_sf.
InterPro; IPR028414; SOCS3.
InterPro; IPR035863; SOCS3_SH2.
InterPro; IPR001496; SOCS_box.
InterPro; IPR036036; SOCS_box-like_dom_sf.
PANTHER; PTHR44534; PTHR44534; 1.
Pfam; PF00017; SH2; 1.
Pfam; PF07525; SOCS_box; 1.
SMART; SM00252; SH2; 1.
SMART; SM00253; SOCS; 1.
SMART; SM00969; SOCS_box; 1.
SUPFAM; SSF158235; SSF158235; 1.
SUPFAM; SSF55550; SSF55550; 1.
PROSITE; PS50001; SH2; 1.
PROSITE; PS50225; SOCS; 1.
1: Evidence at protein level;
Complete proteome; Growth regulation; Phosphoprotein;
Reference proteome; SH2 domain; Signal transduction inhibitor;
Ubl conjugation pathway.
CHAIN 1 225 Suppressor of cytokine signaling 3.
DOMAIN 46 142 SH2. {ECO:0000255|PROSITE-
DOMAIN 177 224 SOCS box. {ECO:0000255|PROSITE-
REGION 22 33 Kinase inhibitory region (KIR).
REGION 34 45 Extended SH2 subdomain (ESS).
CONFLICT 75 75 D -> G (in Ref. 2; CAB56083).
CONFLICT 85 85 E -> K (in Ref. 2; CAB56083).
CONFLICT 145 145 F -> S (in Ref. 2; CAB56083).
CONFLICT 164 164 A -> G (in Ref. 2; CAB56083).
SEQUENCE 225 AA; 24808 MW; BC95FF2074125D8F CRC64;

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