SOCS1_RAT
ID SOCS1_RAT Reviewed; 212 AA.
AC Q9QX78;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Suppressor of cytokine signaling 1;
DE Short=SOCS-1;
GN Name=Socs1;
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 [GENOMIC DNA].
RC STRAIN=Sprague-Dawley;
RA le Cam A.;
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Essential negative regulator of type I and type II interferon
CC (IFN) signaling, as well as that of other cytokines, including IL2,
CC IL4, IL6 and leukemia inhibitory factor (LIF). Downregulates cytokine
CC signaling by inhibiting the JAK/STAT signaling pathway. Acts by binding
CC to JAK proteins and to IFNGR1 and inhibiting their kinase activity. In
CC vitro, suppresses Tec protein-tyrosine activity. Regulates IFN-gamma
CC (IFNG)-mediated sensory neuron survival. Probable substrate recognition
CC component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin
CC ligase complex which mediates the ubiquitination and subsequent
CC proteasomal degradation of target proteins.
CC {ECO:0000250|UniProtKB:O15524, ECO:0000250|UniProtKB:O35716}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with multiple activated proteins of the tyrosine
CC kinase signaling pathway including JAK family kinases, TEC, KIT, GRB2
CC and VAV (By similarity). Binding to JAKs is mediated through the KIR
CC and SH2 domain to a phosphorylated tyrosine residue within the JAK JH1
CC domain (By similarity). Binds the SH3 domain of GRB2 via diproline
CC determinants in the N-terminus, and the N-terminal regulatory domain of
CC VAV (By similarity). Interacts with the Elongin BC complex (ELOB and
CC ELOC). Component of an ECS CBC(SOCS1) E3 ubiquitin-protein ligase
CC complex which contains Elongin BC, CUL5, RBX1 and SOCS1. Interacts (via
CC SH2 domain and SOCS box) with TRIM8 (By similarity). Interacts with
CC CUL2. Interacts with AXL and FGFR3 (By similarity). Interacts with
CC IGF1R (By similarity). Interacts with INSR (By similarity). Interacts
CC with DCUN1D1 (By similarity). {ECO:0000250|UniProtKB:O15524,
CC ECO:0000250|UniProtKB:O35716}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O15524}.
CC Cytoplasmic vesicle {ECO:0000250|UniProtKB:O15524}. Note=Detected in
CC perinuclear cytoplasmic vesicles upon interaction with FGFR3.
CC {ECO:0000250|UniProtKB:O15524}.
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. The Elongin BC complex binding domain is also known as BC-
CC box with the consensus [APST]-L-x(3)-C-x(3)-[AILV] and is part of the
CC SOCS box (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the SOCS1 family. {ECO:0000305}.
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DR EMBL; AJ243123; CAB64204.1; -; Genomic_DNA.
DR AlphaFoldDB; Q9QX78; -.
DR SMR; Q9QX78; -.
DR CORUM; Q9QX78; -.
DR STRING; 10116.ENSRNOP00000003458; -.
DR PaxDb; Q9QX78; -.
DR PRIDE; Q9QX78; -.
DR RGD; 69272; Socs1.
DR eggNOG; KOG4566; Eukaryota.
DR InParanoid; Q9QX78; -.
DR PhylomeDB; Q9QX78; -.
DR Reactome; R-RNO-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-RNO-877300; Interferon gamma signaling.
DR Reactome; R-RNO-877312; Regulation of IFNG signaling.
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:Q9QX78; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
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:0005159; F:insulin-like growth factor receptor binding; ISO:RGD.
DR GO; GO:0019210; F:kinase inhibitor activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISO:RGD.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IDA:MGI.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEP:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:MGI.
DR GO; GO:1905229; P:cellular response to thyrotropin-releasing hormone; IEP:RGD.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IEP:RGD.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:RGD.
DR GO; GO:0045444; P:fat cell differentiation; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0043377; P:negative regulation of CD8-positive, alpha-beta T cell differentiation; ISS:UniProtKB.
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: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:0043372; P:positive regulation of CD4-positive, alpha-beta T cell differentiation; ISS:UniProtKB.
DR GO; GO:0045591; P:positive regulation of regulatory T 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; ISO:RGD.
DR GO; GO:0010533; P:regulation of activation of Janus kinase activity; ISO:RGD.
DR GO; GO:0001817; P:regulation of cytokine production; ISO:RGD.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0060334; P:regulation of interferon-gamma-mediated signaling pathway; IEA:InterPro.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; ISO:RGD.
DR GO; GO:0042509; P:regulation of tyrosine phosphorylation of STAT protein; ISO:RGD.
DR GO; GO:0034097; P:response to cytokine; IEP:RGD.
DR GO; GO:0036017; P:response to erythropoietin; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; 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 CDD; cd10382; SH2_SOCS1; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR028411; SOCS1.
DR InterPro; IPR035861; SOCS1_SH2.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR036036; SOCS_box-like_dom_sf.
DR PANTHER; PTHR10155:SF4; PTHR10155:SF4; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF07525; SOCS_box; 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 3: Inferred from homology;
KW Cytoplasmic vesicle; Growth regulation; Nucleus; Reference proteome;
KW SH2 domain; Signal transduction inhibitor; Ubl conjugation pathway.
FT CHAIN 1..212
FT /note="Suppressor of cytokine signaling 1"
FT /id="PRO_0000181237"
FT DOMAIN 80..175
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 162..211
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 1..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 56..67
FT /note="Kinase inhibitory region (KIR)"
FT REGION 68..79
FT /note="Extended SH2 subdomain (ESS)"
FT REGION 174..183
FT /note="Interaction with Elongin BC complex"
FT /evidence="ECO:0000250"
FT COMPBIAS 21..36
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 212 AA; 23826 MW; B40419329F63FED4 CRC64;
MVARNQVAAD NAISPASEPR RRPEPSSSSS SSSPAAPRRP RPCPVVPAPA PGDTHFRTFR
SHSDYRRITR TSALLDACGF YWGPLSVHGA HERLRAEPVG TFLVRDSRQR NCFFALSVKM
ASGPTSIRVH FQAGRFHLDG SRETFDCLFE LLEHYVAAPR RMLGAPLRQR RVRPLQELCR
QRIVAAVGRE NLARIPLNPV LRDYLSSFPF QI
