ID   SOCS3_CANLF             Reviewed;         225 AA.
AC   Q68AM8;
DT   15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2004, sequence version 1.
DT   25-MAY-2022, entry version 98.
DE   RecName: Full=Suppressor of cytokine signaling 3;
DE            Short=SOCS-3;
GN   Name=SOCS3;
OS   Canis lupus familiaris (Dog) (Canis familiaris).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX   NCBI_TaxID=9615;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Tsukui T., Sakaguchi M., Maeda S., Koyanagi M., Masuda K., Ohno K.,
RA   Tsujimoto H., Iwabuchi S.;
RT   "Expression analysis of suppressor of cytokine signaling 3 (SOCS3) gene in
RT   canine atopic dermatitis.";
RL   Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
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 stabilizes 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.
CC       Interacts with INSR. Interacts with BCL10; this interaction may
CC       interfere with BCL10-binding with PELI2. Interacts with NOD2 (via CARD
CC       domain); the interaction promotes NOD2 degradation.
CC       {ECO:0000250|UniProtKB:O14543, ECO:0000250|UniProtKB:O35718}.
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; AB164434; BAD42435.1; -; mRNA.
DR   RefSeq; NP_001026801.1; NM_001031631.1.
DR   AlphaFoldDB; Q68AM8; -.
DR   BMRB; Q68AM8; -.
DR   SMR; Q68AM8; -.
DR   STRING; 9612.ENSCAFP00000007917; -.
DR   PaxDb; Q68AM8; -.
DR   GeneID; 442949; -.
DR   KEGG; cfa:442949; -.
DR   CTD; 9021; -.
DR   eggNOG; KOG4566; Eukaryota.
DR   InParanoid; Q68AM8; -.
DR   OrthoDB; 1135696at2759; -.
DR   UniPathway; UPA00143; -.
DR   Proteomes; UP000002254; Unplaced.
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:0035556; P:intracellular signal transduction; IEA:InterPro.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IEA:InterPro.
DR   GO; GO:0009968; P:negative regulation of signal transduction; IEA:UniProtKB-KW.
DR   GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR   GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR   GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IEA:InterPro.
DR   GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
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   2: Evidence at transcript 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_0000181242"
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          131..162
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        131..146
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   225 AA;  24718 MW;  0EF17DFF2366A699 CRC64;
     MVTHSKFPAA GMSRPLDTSL RLKTFSSKSE YQLVVNAVCK LQESGFYWSA VTGGEANLLL
     SAEPAGTFLI RDSSDQRHFF TLSVKTQSGT KNLRIQCEGG SFSLQSDPRS TQPVPRFDCV
     LKLVHHYMPP PGAPSFPAPP TEPSSEVSEQ PPSQPLPGNP PRRAYYIYSG GEKIPLVLSR
     PLSSNVATLQ HLCRKTVNGH LDSYEKVTQL PGAIREFLDQ YDAPL