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IL1B_RAT
ID   IL1B_RAT                Reviewed;         268 AA.
AC   Q63264;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   03-AUG-2022, entry version 146.
DE   RecName: Full=Interleukin-1 beta;
DE            Short=IL-1 beta;
DE   Flags: Precursor;
GN   Name=Il1b {ECO:0000312|RGD:2891};
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=Macrophage;
RA   Feeser W., Freimark B.D.;
RL   Submitted (AUG-1992) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   INDUCTION BY ENDOCANNABINOID ANANDAMIDE AND HIGH GLUCOSE.
RX   PubMed=23955712; DOI=10.1038/nm.3265;
RA   Jourdan T., Godlewski G., Cinar R., Bertola A., Szanda G., Liu J., Tam J.,
RA   Han T., Mukhopadhyay B., Skarulis M.C., Ju C., Aouadi M., Czech M.P.,
RA   Kunos G.;
RT   "Activation of the Nlrp3 inflammasome in infiltrating macrophages by
RT   endocannabinoids mediates beta cell loss in type 2 diabetes.";
RL   Nat. Med. 19:1132-1140(2013).
CC   -!- FUNCTION: Potent pro-inflammatory cytokine. Initially discovered as the
CC       major endogenous pyrogen, induces prostaglandin synthesis, neutrophil
CC       influx and activation, T-cell activation and cytokine production, B-
CC       cell activation and antibody production, and fibroblast proliferation
CC       and collagen production. Promotes Th17 differentiation of T-cells.
CC       Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-
CC       helper 1 (Th1) cells. Plays a role in angiogenesis by inducing VEGF
CC       production synergistically with TNF and IL6. Involved in transduction
CC       of inflammation downstream of pyroptosis: its mature form is
CC       specifically released in the extracellular milieu by passing through
CC       the gasdermin-D (GSDMD) pore. {ECO:0000250|UniProtKB:P01584}.
CC   -!- SUBUNIT: Monomer. In its precursor form, weakly interacts with full-
CC       length MEFV; the mature cytokine does not interact at all. Interacts
CC       with integrins ITGAV:ITGBV and ITGA5:ITGB1; integrin-binding is
CC       required for IL1B signaling. Interacts with cargo receptor TMED10; the
CC       interaction is direct and is required for the secretion of IL1B mature
CC       form. Interacts with HSP90AB1; the interaction facilitates cargo
CC       translocation into the ERGIC. Interacts with HSP90B1; the interaction
CC       facilitates cargo translocation into the ERGIC.
CC       {ECO:0000250|UniProtKB:P01584}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:P01584}. Secreted
CC       {ECO:0000250|UniProtKB:P01584}. Lysosome
CC       {ECO:0000250|UniProtKB:P01584}. Secreted, extracellular exosome
CC       {ECO:0000250|UniProtKB:P10749}. Note=The precursor is cytosolic. In
CC       response to inflammasome-activating signals, such as ATP for NLRP3
CC       inflammasome or bacterial flagellin for NLRC4 inflammasome, cleaved and
CC       secreted. Mature form is secreted and released in the extracellular
CC       milieu by passing through the gasdermin-D (GSDMD) pore. In contrast,
CC       the precursor form is not released, due to the presence of an acidic
CC       region that is proteolytically removed by CASP1 during maturation. The
CC       secretion is dependent on protein unfolding and facilitated by the
CC       cargo receptor TMED10. {ECO:0000250|UniProtKB:P01584}.
CC   -!- INDUCTION: In pancreatic islets, release is increased by high glucose
CC       treatment and, to a lesser extent, by endocannabinoid anandamide/AEA.
CC       The induction is more pronounced in Zucker diabetic fatty (ZDF) rats
CC       compared to lean animals. {ECO:0000269|PubMed:23955712}.
CC   -!- MISCELLANEOUS: IL1B production occurs in 2 steps, each being controlled
CC       by different stimuli. First, inflammatory signals, such as LPS,
CC       stimulate the synthesis and promote the accumulation of cytosolic
CC       stores of pro-IL1B (priming). Then additional signals are required for
CC       inflammasome assembly, leading to CASP1 activation, pro-IL1B processing
CC       and eventually secretion of the active cytokine. IL1B processing and
CC       secretion are temporarily associated. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the IL-1 family. {ECO:0000305}.
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DR   EMBL; M98820; AAA41426.1; -; mRNA.
DR   AlphaFoldDB; Q63264; -.
DR   SMR; Q63264; -.
DR   STRING; 10116.ENSRNOP00000006308; -.
DR   PhosphoSitePlus; Q63264; -.
DR   PaxDb; Q63264; -.
DR   UCSC; RGD:2891; rat.
DR   RGD; 2891; Il1b.
DR   eggNOG; ENOG502S3E9; Eukaryota.
DR   InParanoid; Q63264; -.
DR   PhylomeDB; Q63264; -.
DR   Reactome; R-RNO-448706; Interleukin-1 processing.
DR   Reactome; R-RNO-5620971; Pyroptosis.
DR   Reactome; R-RNO-5660668; CLEC7A/inflammasome pathway.
DR   Reactome; R-RNO-9020702; Interleukin-1 signaling.
DR   PRO; PR:Q63264; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0005576; C:extracellular region; ISO:RGD.
DR   GO; GO:0005615; C:extracellular space; IDA:RGD.
DR   GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0030141; C:secretory granule; ISO:RGD.
DR   GO; GO:0031982; C:vesicle; ISO:RGD.
DR   GO; GO:0005125; F:cytokine activity; IDA:RGD.
DR   GO; GO:0005178; F:integrin binding; ISS:UniProtKB.
DR   GO; GO:0005149; F:interleukin-1 receptor binding; IEA:InterPro.
DR   GO; GO:0019904; F:protein domain specific binding; ISO:RGD.
DR   GO; GO:0002526; P:acute inflammatory response; IEP:RGD.
DR   GO; GO:0048143; P:astrocyte activation; ISO:RGD.
DR   GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD.
DR   GO; GO:0071398; P:cellular response to fatty acid; IEP:RGD.
DR   GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR   GO; GO:0097398; P:cellular response to interleukin-17; ISO:RGD.
DR   GO; GO:0071396; P:cellular response to lipid; IEP:RGD.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR   GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:RGD.
DR   GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:RGD.
DR   GO; GO:0071310; P:cellular response to organic substance; ISO:RGD.
DR   GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:RGD.
DR   GO; GO:0002439; P:chronic inflammatory response to antigenic stimulus; IEP:RGD.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:RGD.
DR   GO; GO:0050830; P:defense response to Gram-positive bacterium; ISO:RGD.
DR   GO; GO:0035234; P:ectopic germ cell programmed cell death; ISO:RGD.
DR   GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR   GO; GO:0001660; P:fever generation; IEP:RGD.
DR   GO; GO:0030213; P:hyaluronan biosynthetic process; ISO:RGD.
DR   GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR   GO; GO:0070498; P:interleukin-1-mediated signaling pathway; ISO:RGD.
DR   GO; GO:0007611; P:learning or memory; IEP:RGD.
DR   GO; GO:0050900; P:leukocyte migration; ISO:RGD.
DR   GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:RGD.
DR   GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR   GO; GO:0007613; P:memory; IMP:RGD.
DR   GO; GO:0070487; P:monocyte aggregation; ISO:RGD.
DR   GO; GO:0070164; P:negative regulation of adiponectin secretion; ISO:RGD.
DR   GO; GO:2000173; P:negative regulation of branching morphogenesis of a nerve; IDA:RGD.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR   GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR   GO; GO:1903597; P:negative regulation of gap junction assembly; ISO:RGD.
DR   GO; GO:0010629; P:negative regulation of gene expression; IDA:RGD.
DR   GO; GO:0010829; P:negative regulation of glucose transmembrane transport; ISO:RGD.
DR   GO; GO:0014050; P:negative regulation of glutamate secretion; IMP:RGD.
DR   GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISO:RGD.
DR   GO; GO:0050995; P:negative regulation of lipid catabolic process; ISO:RGD.
DR   GO; GO:0045833; P:negative regulation of lipid metabolic process; ISO:RGD.
DR   GO; GO:0043407; P:negative regulation of MAP kinase activity; ISO:RGD.
DR   GO; GO:2000178; P:negative regulation of neural precursor cell proliferation; IDA:RGD.
DR   GO; GO:0050768; P:negative regulation of neurogenesis; IDA:RGD.
DR   GO; GO:0045665; P:negative regulation of neuron differentiation; IDA:RGD.
DR   GO; GO:0050805; P:negative regulation of synaptic transmission; ISO:RGD.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:RGD.
DR   GO; GO:0030593; P:neutrophil chemotaxis; ISO:RGD.
DR   GO; GO:0030728; P:ovulation; IEP:RGD.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR   GO; GO:0048711; P:positive regulation of astrocyte differentiation; IDA:RGD.
DR   GO; GO:0060559; P:positive regulation of calcidiol 1-monooxygenase activity; ISO:RGD.
DR   GO; GO:0010942; P:positive regulation of cell death; IDA:RGD.
DR   GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR   GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR   GO; GO:0032722; P:positive regulation of chemokine production; ISO:RGD.
DR   GO; GO:0045917; P:positive regulation of complement activation; ISO:RGD.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:RGD.
DR   GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR   GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISO:RGD.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:RGD.
DR   GO; GO:0031622; P:positive regulation of fever generation; ISO:RGD.
DR   GO; GO:0010628; P:positive regulation of gene expression; IDA:RGD.
DR   GO; GO:0045687; P:positive regulation of glial cell differentiation; IDA:RGD.
DR   GO; GO:0060252; P:positive regulation of glial cell proliferation; ISO:RGD.
DR   GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISO:RGD.
DR   GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; ISO:RGD.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:RGD.
DR   GO; GO:0033092; P:positive regulation of immature T cell proliferation in thymus; IDA:RGD.
DR   GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR   GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB.
DR   GO; GO:0032743; P:positive regulation of interleukin-2 production; ISO:RGD.
DR   GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:RGD.
DR   GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:RGD.
DR   GO; GO:0046330; P:positive regulation of JNK cascade; IDA:RGD.
DR   GO; GO:0043507; P:positive regulation of JUN kinase activity; IMP:RGD.
DR   GO; GO:0050996; P:positive regulation of lipid catabolic process; ISO:RGD.
DR   GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:RGD.
DR   GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; ISO:RGD.
DR   GO; GO:0045840; P:positive regulation of mitotic nuclear division; ISO:RGD.
DR   GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; ISO:RGD.
DR   GO; GO:0035505; P:positive regulation of myosin light chain kinase activity; ISO:RGD.
DR   GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR   GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IMP:RGD.
DR   GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR   GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:RGD.
DR   GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:RGD.
DR   GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISO:RGD.
DR   GO; GO:0050766; P:positive regulation of phagocytosis; ISO:RGD.
DR   GO; GO:0031394; P:positive regulation of prostaglandin biosynthetic process; ISO:RGD.
DR   GO; GO:0032308; P:positive regulation of prostaglandin secretion; ISO:RGD.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR   GO; GO:1902680; P:positive regulation of RNA biosynthetic process; ISO:RGD.
DR   GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; IDA:RGD.
DR   GO; GO:0042102; P:positive regulation of T cell proliferation; ISO:RGD.
DR   GO; GO:2000556; P:positive regulation of T-helper 1 cell cytokine production; ISS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:RGD.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR   GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISO:RGD.
DR   GO; GO:0043491; P:protein kinase B signaling; ISO:RGD.
DR   GO; GO:0050691; P:regulation of defense response to virus by host; ISO:RGD.
DR   GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR   GO; GO:1903140; P:regulation of establishment of endothelial barrier; ISO:RGD.
DR   GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR   GO; GO:0050796; P:regulation of insulin secretion; ISO:RGD.
DR   GO; GO:0050767; P:regulation of neurogenesis; IGI:ARUK-UCL.
DR   GO; GO:0050999; P:regulation of nitric-oxide synthase activity; ISO:RGD.
DR   GO; GO:0033198; P:response to ATP; ISO:RGD.
DR   GO; GO:0009743; P:response to carbohydrate; ISO:RGD.
DR   GO; GO:0071548; P:response to dexamethasone; IEP:RGD.
DR   GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR   GO; GO:0045471; P:response to ethanol; 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:0001666; P:response to hypoxia; IEP:RGD.
DR   GO; GO:0035902; P:response to immobilization stress; IEP:RGD.
DR   GO; GO:0070555; P:response to interleukin-1; ISO:RGD.
DR   GO; GO:0033591; P:response to L-ascorbic acid; IEP:RGD.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR   GO; GO:0043278; P:response to morphine; IEP:RGD.
DR   GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR   GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD.
DR   GO; GO:0010193; P:response to ozone; IEP:RGD.
DR   GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR   GO; GO:0035634; P:response to stilbenoid; IEP:RGD.
DR   GO; GO:0033280; P:response to vitamin D; IEP:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR   GO; GO:0030730; P:sequestering of triglyceride; ISO:RGD.
DR   GO; GO:0035176; P:social behavior; IMP:RGD.
DR   GO; GO:0010573; P:vascular endothelial growth factor production; ISS:UniProtKB.
DR   GO; GO:0042060; P:wound healing; IEP:RGD.
DR   InterPro; IPR003296; IL-1_beta.
DR   InterPro; IPR020877; IL-1_CS.
DR   InterPro; IPR000975; IL-1_fam.
DR   InterPro; IPR003502; IL-1_propep.
DR   InterPro; IPR008996; IL1/FGF.
DR   PANTHER; PTHR10078; PTHR10078; 1.
DR   PANTHER; PTHR10078:SF30; PTHR10078:SF30; 1.
DR   Pfam; PF00340; IL1; 1.
DR   Pfam; PF02394; IL1_propep; 1.
DR   PRINTS; PR00264; INTERLEUKIN1.
DR   SUPFAM; SSF50353; SSF50353; 1.
DR   PROSITE; PS00253; INTERLEUKIN_1; 1.
PE   2: Evidence at transcript level;
KW   Cytokine; Cytoplasm; Inflammatory response; Lysosome; Mitogen; Pyrogen;
KW   Reference proteome; Secreted.
FT   PROPEP          1..116
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000015317"
FT   CHAIN           117..268
FT                   /note="Interleukin-1 beta"
FT                   /id="PRO_0000015318"
FT   SITE            171
FT                   /note="Important for interaction with integrin"
FT                   /evidence="ECO:0000250|UniProtKB:P01584"
FT   SITE            179
FT                   /note="Important for interaction with integrin"
FT                   /evidence="ECO:0000250|UniProtKB:P01584"
FT   SITE            190
FT                   /note="Important for interaction with integrin"
FT                   /evidence="ECO:0000250|UniProtKB:P01584"
FT   SITE            204
FT                   /note="Important for interaction with integrin"
FT                   /evidence="ECO:0000250|UniProtKB:P01584"
SQ   SEQUENCE   268 AA;  30644 MW;  109C19EBF69C242D CRC64;
     MATVPELNCE IAAFDSEEND LFFEADRPQK IKDCFQALDL GCPDESIQLQ ISQQHLDKSF
     RKAVSLIVAV EKLWQLPMSC PWSFQDEDPS TFFSFIFEEE PVLCDSWDDD DLLVCDVPIR
     QLHCRLRDEQ QKCLVLSDPC ELKALHLNGQ NISQQVVFSM SFVQGETSND KIPVALGLKG
     LNLYLSCVMK DGTPTLQLES VDPKQYPKKK MEKRFVFNKI EVKTKVEFES AQFPNWYIST
     SQAEHRPVFL GNSNGRDIVD FTMEPVSS
 
 
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