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Suppressor of cytokine signaling 1 (SOCS-1)

 SOCS1_RAT               Reviewed;         212 AA.
Q9QX78;
16-APR-2002, integrated into UniProtKB/Swiss-Prot.
01-MAY-2000, sequence version 1.
26-FEB-2020, entry version 125.
RecName: Full=Suppressor of cytokine signaling 1;
Short=SOCS-1;
Name=Socs1;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
STRAIN=Sprague-Dawley;
le Cam A.;
Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
-!- FUNCTION: SOCS family proteins form part of a classical negative
feedback system that regulates cytokine signal transduction. SOCS1 is
involved in negative regulation of cytokines that signal through the
JAK/STAT3 pathway. Through binding to JAKs, inhibits their kinase
activity. In vitro, also suppresses Tec protein-tyrosine activity (By
similarity). Appears to be a major regulator of signaling by
interleukin 6 (IL6) and leukemia inhibitory factor (LIF). Regulates
interferon-gamma mediated sensory neuron survival. Probable substrate
recognition component of an 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 JAK2 (By similarity). SOCS1 appears to be a negative
regulator in IGF1R signaling pathway (By similarity). Interacts with
TRIM8 (By similarity). {ECO:0000250|UniProtKB:O15524,
ECO:0000250|UniProtKB:O35716}.
-!- PATHWAY: Protein modification; protein ubiquitination.
-!- SUBUNIT: Interacts with multiple activated proteins of the tyrosine
kinase signaling pathway including JAK family kinases, TEC, KIT, GRB2
and VAV (By similarity). Binding to JAKs is mediated through the KIR
and SH2 domain to a phosphorylated tyrosine residue within the JAK JH1
domain (By similarity). Binds the SH3 domain of GRB2 via diproline
determinants in the N-terminus, and the N-terminal regulatory domain of
VAV (By similarity). Interacts with the Elongin BC complex (ELOB and
ELOC). Component of an ECS CBC(SOCS1) E3 ubiquitin-protein ligase
complex which contains Elongin BC, CUL5, RBX1 and SOCS1. Interacts (via
SH2 domain and SOCS box) with TRIM8 (By similarity). Interacts with
CUL2. Interacts with AXL and FGFR3 (By similarity). Interacts with
IGF1R (By similarity). Interacts with INSR (By similarity).
{ECO:0000250|UniProtKB:O15524, ECO:0000250|UniProtKB:O35716}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O15524}.
Cytoplasmic vesicle {ECO:0000250|UniProtKB:O15524}. Note=Detected in
perinuclear cytoplasmic vesicles upon interaction with FGFR3.
{ECO:0000250|UniProtKB:O15524}.
-!- 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. The Elongin BC complex binding domain is also known as BC-
box with the consensus [APST]-L-x(3)-C-x(3)-[AILV] and is part of the
SOCS box (By similarity). {ECO:0000250}.
-!- SIMILARITY: Belongs to the SOCS1 family. {ECO:0000305}.
---------------------------------------------------------------------------
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EMBL; AJ243123; CAB64204.1; -; Genomic_DNA.
SMR; Q9QX78; -.
CORUM; Q9QX78; -.
STRING; 10116.ENSRNOP00000003458; -.
PaxDb; Q9QX78; -.
RGD; 69272; Socs1.
eggNOG; KOG4566; Eukaryota.
eggNOG; ENOG4111V4J; LUCA.
InParanoid; Q9QX78; -.
PhylomeDB; Q9QX78; -.
Reactome; R-RNO-6785807; Interleukin-4 and Interleukin-13 signaling.
Reactome; R-RNO-877300; Interferon gamma signaling.
Reactome; R-RNO-877312; Regulation of IFNG signaling.
Reactome; R-RNO-909733; Interferon alpha/beta signaling.
Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
UniPathway; UPA00143; -.
PRO; PR:Q9QX78; -.
Proteomes; UP000002494; Unplaced.
GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
GO; GO:0046935; F:1-phosphatidylinositol-3-kinase regulator activity; IBA:GO_Central.
GO; GO:0005159; F:insulin-like growth factor receptor binding; ISO:RGD.
GO; GO:0019210; F:kinase inhibitor activity; ISO:RGD.
GO; GO:0019901; F:protein kinase binding; ISO:RGD.
GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
GO; GO:0071230; P:cellular response to amino acid stimulus; ISO:RGD.
GO; GO:0071345; P:cellular response to cytokine stimulus; IDA:MGI.
GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:MGI.
GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:RGD.
GO; GO:0045444; P:fat cell differentiation; ISO:RGD.
GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
GO; GO:0043377; P:negative regulation of CD8-positive, alpha-beta T cell differentiation; ISS:UniProtKB.
GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISO:RGD.
GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; ISO:RGD.
GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; ISO:RGD.
GO; GO:0046854; P:phosphatidylinositol phosphorylation; IBA:GO_Central.
GO; GO:0043372; P:positive regulation of CD4-positive, alpha-beta T cell differentiation; ISS:UniProtKB.
GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; ISO:RGD.
GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; ISO:RGD.
GO; GO:0010533; P:regulation of activation of Janus kinase activity; ISO:RGD.
GO; GO:0050707; P:regulation of cytokine secretion; ISO:RGD.
GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
GO; GO:0060334; P:regulation of interferon-gamma-mediated signaling pathway; IEA:InterPro.
GO; GO:0001932; P:regulation of protein phosphorylation; ISO:RGD.
GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; ISO:RGD.
GO; GO:0042509; P:regulation of tyrosine phosphorylation of STAT protein; ISO: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:0032496; P:response to lipopolysaccharide; IEP:RGD.
GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
GO; GO:0032570; P:response to progesterone; IEP:RGD.
CDD; cd10382; SH2_SOCS1; 1.
Gene3D; 3.30.505.10; -; 1.
InterPro; IPR000980; SH2.
InterPro; IPR036860; SH2_dom_sf.
InterPro; IPR028411; SOCS1.
InterPro; IPR035861; SOCS1_SH2.
InterPro; IPR001496; SOCS_box.
InterPro; IPR036036; SOCS_box-like_dom_sf.
PANTHER; PTHR10155:SF4; PTHR10155:SF4; 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.
3: Inferred from homology;
Cytoplasmic vesicle; Growth regulation; Nucleus; Reference proteome;
SH2 domain; Signal transduction inhibitor; Ubl conjugation pathway.
CHAIN 1..212
/note="Suppressor of cytokine signaling 1"
/id="PRO_0000181237"
DOMAIN 80..175
/note="SH2"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
DOMAIN 162..211
/note="SOCS box"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
REGION 56..67
/note="Kinase inhibitory region (KIR)"
REGION 68..79
/note="Extended SH2 subdomain (ESS)"
REGION 174..183
/note="Interaction with Elongin BC complex"
/evidence="ECO:0000250"
COMPBIAS 26..33
/note="Poly-Ser"
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


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Pathways :
WP2292: Chemokine signaling pathway
WP116: Hedgehog Signaling Pathway
WP285: B Cell Receptor Signaling Pathway
WP1313: Insulin Signaling
WP437: EGF/EGFR Signaling Pathway
WP1381: G13 Signaling Pathway
WP65: Insulin Signaling
WP1912: Signaling by GPCR
WP8: IL-9 Signaling Pathway
WP2220: Notch signaling in Vulval Development
WP10: IL-9 Signaling Pathway
WP900: Type II interferon signaling (IFNG)
WP1103: Alpha6-Beta4 Integrin Signaling Pathway
WP1214: Notch Signaling Pathway
WP362: TGF-beta Receptor Signaling Pathway
WP1349: Wnt Signaling Pathway
WP510: MAPK Signaling Pathway
WP17: daf-2 or insulin signaling pathway
WP752: EGFR1 Signaling Pathway
WP2032: TSH signaling pathway
WP855: IL-2 Signaling Pathway
WP2380: BDNF signaling pathway
WP1047: TNF-alpha NF-kB Signaling Pathway
WP945: G13 Signaling Pathway
WP1235: Signaling of Hepatocyte Growth Factor Receptor

Related Genes :
[SOCS3 CIS3 SSI3] Suppressor of cytokine signaling 3 (SOCS-3) (Cytokine-inducible SH2 protein 3) (CIS-3) (STAT-induced STAT inhibitor 3) (SSI-3)
[Socs3 Cis3 Cish3] Suppressor of cytokine signaling 3 (SOCS-3) (Cytokine-inducible SH2 protein 3) (CIS-3) (Protein EF-10)
[Socs3 Cish3] Suppressor of cytokine signaling 3 (SOCS-3) (Cytokine-inducible SH2 protein 3)
[SOCS7 NAP4 SOCS6] Suppressor of cytokine signaling 7 (SOCS-7) (Nck, Ash and phospholipase C gamma-binding protein) (Nck-associated protein 4) (NAP-4)
[Socs7 Cish7 Nap4] Suppressor of cytokine signaling 7 (SOCS-7)
[SOCS3] Suppressor of cytokine signaling 3 (SOCS-3)
[IFNLR1 IL28RA LICR2] Interferon lambda receptor 1 (IFN-lambda receptor 1) (IFN-lambda-R1) (Cytokine receptor class-II member 12) (Cytokine receptor family 2 member 12) (CRF2-12) (Interleukin-28 receptor subunit alpha) (IL-28 receptor subunit alpha) (IL-28R-alpha) (IL-28RA) (Likely interleukin or cytokine receptor 2) (LICR2)
[SOCS3] Suppressor of cytokine signaling 3 (SOCS-3)
[UBASH3B KIAA1959 STS1] Ubiquitin-associated and SH3 domain-containing protein B (EC 3.1.3.48) (Cbl-interacting protein p70) (Suppressor of T-cell receptor signaling 1) (STS-1) (T-cell ubiquitin ligand 2) (TULA-2) (Tyrosine-protein phosphatase STS1/TULA2)
[SHO1 SSU81 YER118C] High osmolarity signaling protein SHO1 (Osmosensor SHO1) (Suppressor of SUA8-1 mutation) (Synthetic high osmolarity-sensitive protein 1)
[SOCS3] Suppressor of cytokine signaling 3 (SOCS-3)
[UBASH3A STS2] Ubiquitin-associated and SH3 domain-containing protein A (Cbl-interacting protein 4) (CLIP4) (Suppressor of T-cell receptor signaling 2) (STS-2) (T-cell ubiquitin ligand 1) (TULA-1)
[MAPK14 CSBP CSBP1 CSBP2 CSPB1 MXI2 SAPK2A] Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (Cytokine suppressive anti-inflammatory drug-binding protein) (CSAID-binding protein) (CSBP) (MAP kinase MXI2) (MAX-interacting protein 2) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha) (Stress-activated protein kinase 2a) (SAPK2a)
[MAVS IPS1 KIAA1271 VISA] Mitochondrial antiviral-signaling protein (MAVS) (CARD adapter inducing interferon beta) (Cardif) (Interferon beta promoter stimulator protein 1) (IPS-1) (Putative NF-kappa-B-activating protein 031N) (Virus-induced-signaling adapter) (VISA)
[IL27RA CRL1 TCCR WSX1 UNQ296/PRO336] Interleukin-27 receptor subunit alpha (IL-27 receptor subunit alpha) (IL-27R subunit alpha) (IL-27R-alpha) (IL-27RA) (Cytokine receptor WSX-1) (Cytokine receptor-like 1) (Type I T-cell cytokine receptor) (TCCR) (ZcytoR1)
[Crlf2 Crlm2 Tpte2 Tslpr] Cytokine receptor-like factor 2 (Cytokine receptor-like molecule 2) (CRLM-2) (Thymic stromal lymphopoietin protein receptor) (TSLP receptor) (Type I cytokine receptor delta 1)
[XCL1 LTN SCYC1] Lymphotactin (ATAC) (C motif chemokine 1) (Cytokine SCM-1) (Lymphotaxin) (SCM-1-alpha) (Small-inducible cytokine C1) (XC chemokine ligand 1)
[Xcl1 Lptn Ltn Scyc1] Lymphotactin (C motif chemokine 1) (Cytokine SCM-1) (Lymphotaxin) (Small-inducible cytokine C1)
[CRLF1 UNQ288/PRO327] Cytokine receptor-like factor 1 (Cytokine-like factor 1) (CLF-1) (ZcytoR5)
[Xcl1 Ltn Scyc1] Lymphotactin (C motif chemokine 1) (Cytokine SCM-1) (Small-inducible cytokine C1)
[IGF1R] Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain]
[Ddias Noxin] DNA damage-induced apoptosis suppressor protein (Nitric oxide-inducible gene protein)
[Crlf1 Crlm3] Cytokine receptor-like factor 1 (Cytokine receptor-like molecule 3) (CRLM-3) (Cytokine-like factor 1) (CLF-1) (Novel cytokine receptor 6) (NR6)
[S100a8 Caga Mrp8] Protein S100-A8 (Calgranulin-A) (Chemotactic cytokine CP-10) (Leukocyte L1 complex light chain) (Migration inhibitory factor-related protein 8) (MRP-8) (p8) (Pro-inflammatory S100 cytokine) (S100 calcium-binding protein A8)
[EGFR ERBB ERBB1 HER1] Epidermal growth factor receptor (EC 2.7.10.1) (Proto-oncogene c-ErbB-1) (Receptor tyrosine-protein kinase erbB-1)
[FLT3 CD135 FLK2 STK1] Receptor-type tyrosine-protein kinase FLT3 (EC 2.7.10.1) (FL cytokine receptor) (Fetal liver kinase-2) (FLK-2) (Fms-like tyrosine kinase 3) (FLT-3) (Stem cell tyrosine kinase 1) (STK-1) (CD antigen CD135)
[CCL2 MCP1 SCYA2] C-C motif chemokine 2 (HC11) (Monocyte chemoattractant protein 1) (Monocyte chemotactic and activating factor) (MCAF) (Monocyte chemotactic protein 1) (MCP-1) (Monocyte secretory protein JE) (Small-inducible cytokine A2)
[CCL4 LAG1 MIP1B SCYA4] C-C motif chemokine 4 (G-26 T-lymphocyte-secreted protein) (HC21) (Lymphocyte activation gene 1 protein) (LAG-1) (MIP-1-beta(1-69)) (Macrophage inflammatory protein 1-beta) (MIP-1-beta) (PAT 744) (Protein H400) (SIS-gamma) (Small-inducible cytokine A4) (T-cell activation protein 2) (ACT-2) [Cleaved into: MIP-1-beta(3-69)]
[CLCF1 BSF3 CLC NNT1] Cardiotrophin-like cytokine factor 1 (B-cell-stimulating factor 3) (BSF-3) (Novel neurotrophin-1) (NNT-1)
[Il11ra1 Etl2 Il11ra] Interleukin-11 receptor subunit alpha-1 (IL-11 receptor subunit alpha-1) (IL-11R subunit alpha-1) (IL-11R-alpha-1) (IL-11RA1) (Enhancer trap locus homolog 2) (Etl-2) (Novel cytokine receptor 1) (NR-1) (NR1)

Bibliography :
[32106541] MicroRNA-155 Participates in Smoke-Inhalation-Induced Acute Lung Injury through Inhibition of SOCS-1.
[32097250] Polymorphisms of SOCS-1 Are Associated With a Rapid HIV Progression Rate.
[31910343] LncRNA Upregulates Cytokine Signaling 1 by Sponging in Non-Small Cell Lung Cancer.
[31826939] Porcine Reproductive and Respiratory Syndrome Virus Enhances Self-Replication via AP-1-Dependent Induction of SOCS1.
[31780858] Mast Cell Degranulation Decreases Lipopolysaccharide-Induced Aortic Gene Expression and Systemic Levels of Interleukin-6 .
[31707448] Suppressors of cytokine signalling (SOCS)-1 inhibits neuroinflammation by regulating ROS and TLR4 in BV2 cells.
[31602891] [Effect of triptolide on Th17/Treg cells in spleen].
[31546039] Effects of short-term fasting on the resistance of Nile tilapia (Oreochromis niloticus) to Streptococcus agalactiae infection.
[31535716] Clinical correlation of liver function tests with suppression of cytokine signaling (SOCS1) gene expression in HCV infected patients: A real-world clinical experience.
[31529565] miR-155 promotes macrophage pyroptosis induced by Porphyromonas gingivalis through regulating the NLRP3 inflammasome.