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Interleukin-1 beta (IL-1 beta)

 IL1B_CAVPO              Reviewed;         266 AA.
Q9WVG1;
16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
01-NOV-1999, sequence version 1.
18-JUL-2018, entry version 116.
RecName: Full=Interleukin-1 beta;
Short=IL-1 beta;
Flags: Precursor;
Name=IL1B;
Cavia porcellus (Guinea pig).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia;
Hystricomorpha; Caviidae; Cavia.
NCBI_TaxID=10141;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
STRAIN=2; TISSUE=Spleen;
PubMed=10394101; DOI=10.1159/000024184;
Yoshimura T., Takeya M., Ogata H., Yamashiro S., Modi W.S.,
Gillitzer R.;
"Molecular cloning of the guinea pig GRO gene and its rapid expression
in the tissues of lipopolysaccharide-injected guinea pigs.";
Int. Arch. Allergy Immunol. 119:101-111(1999).
-!- FUNCTION: Potent proinflammatory cytokine. Initially discovered as
the major endogenous pyrogen, induces prostaglandin synthesis,
neutrophil influx and activation, T-cell activation and cytokine
production, B-cell activation and antibody production, and
fibroblast proliferation and collagen production. Promotes Th17
differentiation of T-cells. Synergizes with IL12/interleukin-12 to
induce IFNG synthesis from T-helper 1 (Th1) cells.
{ECO:0000250|UniProtKB:P01584}.
-!- SUBUNIT: Monomer. Interacts with MEFV. Interacts with integrins
ITGAV:ITGBV and ITGA5:ITGB1; integrin-binding is required for IL1B
signaling. {ECO:0000250|UniProtKB:P01584}.
-!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
{ECO:0000250|UniProtKB:P10749}. Lysosome
{ECO:0000250|UniProtKB:P01584}. Secreted, exosome
{ECO:0000250|UniProtKB:P10749}. Cytoplasmic vesicle, autophagosome
{ECO:0000250|UniProtKB:P01584}. Secreted
{ECO:0000250|UniProtKB:P10749}. Note=The precursor is cytosolic.
In response to inflammasome-activating signals, such as ATP for
NLRP3 inflammasome or bacterial flagellin for NLRC4 inflammasome,
cleaved and secreted. IL1B lacks any known signal sequence and the
pathway(s) of its secretion is(are) not yet fully understood. On
the basis of experimental results, several unconventional
secretion mechanisms have been proposed. 1. Secretion via
secretory lysosomes: a fraction of CASP1 and IL1B precursor may be
incorporated, by a yet undefined mechanism, into secretory
lysosomes that undergo Ca(2+)-dependent exocytosis with release of
mature IL1B. 2. Secretory autophagy: IL1B-containing
autophagosomes may fuse with endosomes or multivesicular bodies
(MVBs) and then merge with the plasma membrane releasing soluble
IL1B or IL1B-containing exosomes. However, autophagy impacts IL1B
production at several levels and its role in secretion is still
controversial. 3. Secretion via exosomes: ATP-activation of P2RX7
leads to the formation of MVBs containing exosomes with entrapped
IL1B, CASP1 and other inflammasome components. These MVBs undergo
exocytosis with the release of exosomes. The release of soluble
IL1B occurs after the lysis of exosome membranes. 4. Secretion by
microvesicle shedding: activation of the ATP receptor P2RX7 may
induce an immediate shedding of membrane-derived microvesicles
containing IL1B and possibly inflammasome components. The cytokine
is then released in the extracellular compartment after
microvesicle lysis. 5. Release by translocation through
permeabilized plasma membrane. This may occur in cells undergoing
pyroptosis due to sustained activation of the inflammasome. These
mechanisms may not be not mutually exclusive.
{ECO:0000250|UniProtKB:P01584, ECO:0000250|UniProtKB:P10749}.
-!- MISCELLANEOUS: IL1B production occurs in 2 steps, each being
controlled by different stimuli. First, inflammatory signals, such
as LPS, stimulate the synthesis and promote the accumulation of
cytosolic stores of pro-IL1B (priming). Then additional signals
are required for inflammasome assembly, leading to CASP1
activation, pro-IL1B processing and eventually secretion of the
active cytokine. IL1B processing and secretion are temporarily
associated. {ECO:0000250}.
-!- SIMILARITY: Belongs to the IL-1 family. {ECO:0000305}.
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EMBL; AF119622; AAD38502.1; -; mRNA.
RefSeq; NP_001166439.1; NM_001172968.1.
RefSeq; XP_013002735.1; XM_013147281.1.
ProteinModelPortal; Q9WVG1; -.
SMR; Q9WVG1; -.
STRING; 10141.ENSCPOP00000001784; -.
PRIDE; Q9WVG1; -.
Ensembl; ENSCPOT00000001999; ENSCPOP00000001784; ENSCPOG00000001975.
Ensembl; ENSCPOT00000032308; ENSCPOP00000022138; ENSCPOG00000001975.
GeneID; 100135556; -.
CTD; 3553; -.
eggNOG; ENOG410IGSZ; Eukaryota.
eggNOG; ENOG410XU2E; LUCA.
GeneTree; ENSGT00510000048687; -.
HOGENOM; HOG000246399; -.
HOVERGEN; HBG007328; -.
InParanoid; Q9WVG1; -.
OMA; QVVFSMS; -.
OrthoDB; EOG091G0GR9; -.
TreeFam; TF300203; -.
Proteomes; UP000005447; Unassembled WGS sequence.
Bgee; ENSCPOG00000001975; -.
GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
GO; GO:0070062; C:extracellular exosome; IEA:UniProtKB-SubCell.
GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
GO; GO:0005178; F:integrin binding; ISS:UniProtKB.
GO; GO:0005149; F:interleukin-1 receptor binding; IEA:InterPro.
GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
GO; GO:0000187; P:activation of MAPK activity; IEA:Ensembl.
GO; GO:0035690; P:cellular response to drug; IEA:Ensembl.
GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
GO; GO:0019221; P:cytokine-mediated signaling pathway; IEA:Ensembl.
GO; GO:0001660; P:fever generation; IEA:UniProtKB-KW.
GO; GO:0030213; P:hyaluronan biosynthetic process; IEA:Ensembl.
GO; GO:0006955; P:immune response; IEA:InterPro.
GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
GO; GO:0070487; P:monocyte aggregation; IEA:Ensembl.
GO; GO:0008285; P:negative regulation of cell proliferation; IEA:Ensembl.
GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
GO; GO:0050995; P:negative regulation of lipid catabolic process; IEA:Ensembl.
GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
GO; GO:0060559; P:positive regulation of calcidiol 1-monooxygenase activity; IEA:Ensembl.
GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IEA:Ensembl.
GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; IEA:Ensembl.
GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; IEA:Ensembl.
GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB.
GO; GO:0045086; P:positive regulation of interleukin-2 biosynthetic process; IEA:Ensembl.
GO; GO:0032757; P:positive regulation of interleukin-8 production; IEA:Ensembl.
GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IEA:Ensembl.
GO; GO:0045840; P:positive regulation of mitotic nuclear division; IEA:Ensembl.
GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; IEA:Ensembl.
GO; GO:0035505; P:positive regulation of myosin light chain kinase activity; IEA:Ensembl.
GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IEA:Ensembl.
GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IEA:Ensembl.
GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl.
GO; GO:0050766; P:positive regulation of phagocytosis; IEA:Ensembl.
GO; GO:0042102; P:positive regulation of T cell proliferation; IEA:Ensembl.
GO; GO:2000556; P:positive regulation of T-helper 1 cell cytokine production; ISS:UniProtKB.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IEA:Ensembl.
GO; GO:0043491; P:protein kinase B signaling; IEA:Ensembl.
GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
GO; GO:1903140; P:regulation of establishment of endothelial barrier; IEA:Ensembl.
GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
GO; GO:0050796; P:regulation of insulin secretion; IEA:Ensembl.
GO; GO:0050999; P:regulation of nitric-oxide synthase activity; IEA:Ensembl.
GO; GO:0030730; P:sequestering of triglyceride; IEA:Ensembl.
InterPro; IPR003296; IL-1_beta.
InterPro; IPR020877; IL-1_CS.
InterPro; IPR000975; IL-1_fam.
InterPro; IPR003502; IL-1_propep.
InterPro; IPR008996; IL1/FGF.
PANTHER; PTHR44849; PTHR44849; 1.
Pfam; PF00340; IL1; 1.
Pfam; PF02394; IL1_propep; 1.
PRINTS; PR00264; INTERLEUKIN1.
SUPFAM; SSF50353; SSF50353; 1.
PROSITE; PS00253; INTERLEUKIN_1; 1.
2: Evidence at transcript level;
Complete proteome; Cytokine; Cytoplasm; Cytoplasmic vesicle;
Inflammatory response; Lysosome; Mitogen; Pyrogen; Reference proteome;
Secreted.
PROPEP 1 114 {ECO:0000250}.
/FTId=PRO_0000015289.
CHAIN 115 266 Interleukin-1 beta.
/FTId=PRO_0000015290.
SITE 169 169 Important for interaction with integrin.
{ECO:0000250|UniProtKB:P01584}.
SITE 177 177 Important for interaction with integrin.
{ECO:0000250|UniProtKB:P01584}.
SITE 179 179 Important for interaction with integrin.
{ECO:0000250|UniProtKB:P01584}.
SITE 188 188 Important for interaction with integrin.
{ECO:0000250|UniProtKB:P01584}.
SITE 202 202 Important for interaction with integrin.
{ECO:0000250|UniProtKB:P01584}.
SEQUENCE 266 AA; 30531 MW; 46558BA16B4C529A CRC64;
MAAVPELSSE VTAYHSDENE LFFEVDGPNK MQYCFQDRDL CSLDEGIKLQ ISHQHFNKSF
RQTVSLIVAV EKLRKKLAPC TWAFQDDDLR PLLPFIFEEE PIVCDTWDEE YESDTPVPSR
NCTLHDIQHK RLVLSDPCEL KALHLNGDNL NRQVVFSMSF VQGERSDNKM PVALGLKGKN
LYLSCVMKDG KPVLQLESVD GKQYPKKKME KRFVFNKITS KSTVEFESAQ FPNWYISTSQ
AEHKPVFLGN NNGQDIIDFK LELVSS


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