ID   SOCS3_CHICK             Reviewed;         209 AA.
AC   Q90X67;
DT   16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   03-AUG-2022, entry version 112.
DE   RecName: Full=Suppressor of cytokine signaling 3;
DE            Short=SOCS-3;
GN   Name=SOCS3;
OS   Gallus gallus (Chicken).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC   Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC   Phasianinae; Gallus.
OX   NCBI_TaxID=9031;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Wang X., Tang J., Cogburn L.A.;
RT   "Chicken suppressors of cytokine signaling 3 (SOCS-3) has strictly
RT   conserved SH2 and SOCS box but lack interlink between domains.";
RL   Submitted (SEP-2001) 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       EPO receptor. Binding to JAK is mediated through the KIR and SH2
CC       domains to a phosphorylated tyrosine residue within the JAK JH1 domain.
CC       Binds specific activated tyrosine residues of the leptin, EPO and gp130
CC       receptors. {ECO:0000250}.
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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AF424806; AAL23933.1; -; mRNA.
DR   RefSeq; NP_989931.1; NM_204600.1.
DR   AlphaFoldDB; Q90X67; -.
DR   SMR; Q90X67; -.
DR   STRING; 9031.ENSGALP00000042295; -.
DR   PaxDb; Q90X67; -.
DR   GeneID; 395299; -.
DR   KEGG; gga:395299; -.
DR   CTD; 9021; -.
DR   VEuPathDB; HostDB:geneid_395299; -.
DR   eggNOG; KOG4566; Eukaryota.
DR   InParanoid; Q90X67; -.
DR   OrthoDB; 1135696at2759; -.
DR   PhylomeDB; Q90X67; -.
DR   UniPathway; UPA00143; -.
DR   PRO; PR:Q90X67; -.
DR   Proteomes; UP000000539; 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..209
FT                   /note="Suppressor of cytokine signaling 3"
FT                   /id="PRO_0000181246"
FT   DOMAIN          46..142
FT                   /note="SH2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT   DOMAIN          161..208
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)"
SQ   SEQUENCE   209 AA;  23176 MW;  3B98E5B787C35371 CRC64;
     MVTHSKFPAA GMSRPLDTSL RLKTFSSKSE YQLVVNTVRK LQESGFYWST VTGGEANVLL
     SAEPAGTFLI RDSSDQRHFF TLSVKTESGT KNLRIQCEGG SFSLQSDPRS SQPVPRFDCV
     LKLVHHYMPP TPCAGPKQPG GALHPKRTYY IYSGGEKIPL VLSRPLSSSV STLQHLCRKT
     VNGHLDSYEK MTQLPAPIKE FLDQYDAPL