SOCS3_RAT
ID SOCS3_RAT Reviewed; 225 AA.
AC O88583; Q9QYV5;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Suppressor of cytokine signaling 3 {ECO:0000305};
DE Short=SOCS-3;
DE AltName: Full=Cytokine-inducible SH2 protein 3;
GN Name=Socs3 {ECO:0000312|RGD:621087}; Synonyms=Cish3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=10579313; DOI=10.1210/endo.140.12.7212;
RA Mao Y., Ling P.R., Fitzgibbons T.P., McCowen K.C., Frick G.P.,
RA Bistrian B.R., Smith R.J.;
RT "Endotoxin-induced inhibition of growth hormone receptor signaling in rat
RT liver in vivo.";
RL Endocrinology 140:5505-5515(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Sprague-Dawley;
RA le Cam A.;
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH LEPTIN.
RX PubMed=11108838; DOI=10.1016/s0014-5793(00)02205-5;
RA Eyckerman S., Broekaert D., Verhee A., Vandekerckhove J., Tavernier J.;
RT "Identification of the Y985 and Y1077 motifs as SOCS3 recruitment sites in
RT the murine leptin receptor.";
RL FEBS Lett. 486:33-37(2000).
CC -!- FUNCTION: SOCS family proteins form part of a classical negative
CC feedback system that regulates cytokine signal transduction. SOCS3 is
CC involved in negative regulation of cytokines that signal through the
CC JAK/STAT pathway. Inhibits cytokine signal transduction by binding to
CC tyrosine kinase receptors including IL6ST/gp130, LIF, erythropoietin,
CC insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its
CC kinase activity and regulates IL6 signaling. Suppresses fetal liver
CC erythropoiesis. Regulates onset and maintenance of allergic responses
CC mediated by T-helper type 2 cells (By similarity). Probable substrate
CC recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box
CC protein) E3 ubiquitin-protein ligase complex which mediates the
CC ubiquitination and subsequent proteasomal degradation of target
CC proteins (By similarity). {ECO:0000250|UniProtKB:O14543,
CC ECO:0000250|UniProtKB:O35718}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with multiple activated proteins of the tyrosine
CC kinase signaling pathway including IGF1 receptor, insulin receptor and
CC JAK2. Binding to JAK2 is mediated through the KIR and SH2 domains to a
CC phosphorylated tyrosine residue within the JAK2 JH1 domain. Binds
CC specific activated tyrosine residues of the leptin, EPO, IL12, GSCF and
CC gp130 receptors. Interaction with CSNK1E stabilize SOCS3 protein.
CC Component of the probable ECS(SOCS3) E3 ubiquitin-protein ligase
CC complex which contains CUL5, RNF7/RBX2, Elongin BC complex and SOCS3.
CC Interacts with CUL5, RNF7, ELOB and ELOC. Interacts with FGFR3 (By
CC similarity). Interacts with INSR (By similarity). Interacts with BCL10;
CC this interaction may interfere with BCL10-binding with PELI2 (By
CC similarity). Interacts with NOD2 (via CARD domain); the interaction
CC promotes NOD2 degradation (By similarity).
CC {ECO:0000250|UniProtKB:O14543, ECO:0000250|UniProtKB:O35718,
CC ECO:0000269|PubMed:11108838}.
CC -!- DOMAIN: The ESS and SH2 domains are required for JAK phosphotyrosine
CC binding. Further interaction with the KIR domain is necessary for
CC signal and kinase inhibition.
CC -!- DOMAIN: The SOCS box domain mediates the interaction with the Elongin
CC BC complex, an adapter module in different E3 ubiquitin ligase
CC complexes. {ECO:0000250}.
CC -!- PTM: Phosphorylated on tyrosine residues after stimulation by the
CC cytokines, IL-2, EPO or IGF1. {ECO:0000250}.
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DR EMBL; AF075383; AAC26223.1; -; mRNA.
DR EMBL; AJ249240; CAB56083.1; -; Genomic_DNA.
DR RefSeq; NP_446017.1; NM_053565.1.
DR AlphaFoldDB; O88583; -.
DR BMRB; O88583; -.
DR SMR; O88583; -.
DR BioGRID; 250151; 1.
DR STRING; 10116.ENSRNOP00000003940; -.
DR PaxDb; O88583; -.
DR GeneID; 89829; -.
DR KEGG; rno:89829; -.
DR UCSC; RGD:621087; rat.
DR CTD; 9021; -.
DR RGD; 621087; Socs3.
DR eggNOG; KOG4566; Eukaryota.
DR InParanoid; O88583; -.
DR OrthoDB; 1135696at2759; -.
DR PhylomeDB; O88583; -.
DR Reactome; R-RNO-1059683; Interleukin-6 signaling.
DR Reactome; R-RNO-877300; Interferon gamma signaling.
DR Reactome; R-RNO-877312; Regulation of IFNG signaling.
DR Reactome; R-RNO-8849474; PTK6 Activates STAT3.
DR Reactome; R-RNO-8951664; Neddylation.
DR Reactome; R-RNO-909733; Interferon alpha/beta signaling.
DR Reactome; R-RNO-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:O88583; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0046935; F:1-phosphatidylinositol-3-kinase regulator activity; IBA:GO_Central.
DR GO; GO:0035198; F:miRNA binding; ISO:RGD.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; ISO:RGD.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEP:RGD.
DR GO; GO:0097398; P:cellular response to interleukin-17; ISO:RGD.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
DR GO; GO:1905229; P:cellular response to thyrotropin-releasing hormone; IEP:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; ISO:RGD.
DR GO; GO:0009968; P:negative regulation of signal transduction; ISO:RGD.
DR GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; ISO:RGD.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0060674; P:placenta blood vessel development; ISO:RGD.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISO:RGD.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IDA:RGD.
DR GO; GO:0045595; P:regulation of cell differentiation; ISO:RGD.
DR GO; GO:0001558; P:regulation of cell growth; TAS:RGD.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0009617; P:response to bacterium; IEP:RGD.
DR GO; GO:0034097; P:response to cytokine; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0032094; P:response to food; IEP:RGD.
DR GO; GO:0010332; P:response to gamma radiation; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0009408; P:response to heat; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0032868; P:response to insulin; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0032570; P:response to progesterone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0007165; P:signal transduction; IDA:RGD.
DR GO; GO:0060708; P:spongiotrophoblast differentiation; ISO:RGD.
DR GO; GO:0060707; P:trophoblast giant cell differentiation; ISO:RGD.
DR CDD; cd10384; SH2_SOCS3; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR028414; SOCS3.
DR InterPro; IPR035863; SOCS3_SH2.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR036036; SOCS_box-like_dom_sf.
DR PANTHER; PTHR10155:SF11; PTHR10155:SF11; 1.
DR Pfam; PF00017; SH2; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00253; SOCS; 1.
DR SMART; SM00969; SOCS_box; 1.
DR SUPFAM; SSF158235; SSF158235; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50225; SOCS; 1.
PE 1: Evidence at protein level;
KW Growth regulation; Phosphoprotein; Reference proteome; SH2 domain;
KW Signal transduction inhibitor; Ubl conjugation pathway.
FT CHAIN 1..225
FT /note="Suppressor of cytokine signaling 3"
FT /id="PRO_0000181245"
FT DOMAIN 46..142
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 177..224
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 22..33
FT /note="Kinase inhibitory region (KIR)"
FT REGION 34..45
FT /note="Extended SH2 subdomain (ESS)"
FT REGION 141..160
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 75
FT /note="D -> G (in Ref. 2; CAB56083)"
FT /evidence="ECO:0000305"
FT CONFLICT 85
FT /note="E -> K (in Ref. 2; CAB56083)"
FT /evidence="ECO:0000305"
FT CONFLICT 145
FT /note="F -> S (in Ref. 2; CAB56083)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="A -> G (in Ref. 2; CAB56083)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 225 AA; 24808 MW; BC95FF2074125D8F CRC64;
MVTHSKFPAA GMSRPLDTSL RLKTFSSKSE YQLVVNAVRK LQESGFYWSA VTGGEANLLL
SAEPAGTFLI RDSSDQRHFF TLSVETQSGT KNLRIQCEGG SFSLQSDPRS TQPVPRFDCV
LKLVHHYMPP PGAPSFSLPP TEPSFEVQEQ PPAQALPGGT PKRAYYIYSG GEKIPLVLSR
PLSSNVATLQ HLCRKTVNGH LDSYEKVTQL PGPIREFLDQ YDAPL
