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Details on Person UniProt:P01584 IL1B

Class:Id	ReferenceGeneProduct:57238
_chainChangeLog	propeptide:1-116 added on Fri February 6 2015;chain:117-269 added on Fri February 6 2015
_displayName	UniProt:P01584 IL1B
_timestamp	2024-11-03 19:56:43
chain	propeptide:1-116 chain:117-269
checksum	9BF73C3673C6FD66
comment	FUNCTION Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). 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 (PubMed:3920526). Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells (PubMed:10653850). Plays a role in angiogenesis by inducing VEGF production synergistically with TNF and IL6 (PubMed:12794819). Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33377178, PubMed:33883744). Acts as a sensor of S.pyogenes infection in skin: cleaved and activated by pyogenes SpeB protease, leading to an inflammatory response that prevents bacterial growth during invasive skin infection (PubMed:28331908).ACTIVITY REGULATION (Microbial infection) Cleavage by S.pyogenes cysteine protease SpeB promotes its activation independently of CASP1 (PubMed:28331908, PubMed:32719155). SpeB-mediated maturation of IL1B plays a dual role depending on infection site: while IL1B inflammatory response prevents bacterial growth during invasive skin infections, it promotes streptococcal infection of the nasopharynx by disrupting colonization resistance mediated by the microbiota (PubMed:28331908, PubMed:32719155).SUBUNIT Monomer. In its precursor form, weakly interacts with full-length MEFV; the mature cytokine does not interact at all (PubMed:17431422). Interacts with integrins ITGAV:ITGBV and ITGA5:ITGB1; integrin-binding is required for IL1B signaling (PubMed:29030430). Interacts with cargo receptor TMED10; the interaction is direct and is required for the secretion of IL1B mature form (PubMed:32272059). Interacts with HSP90AB1; the interaction facilitates cargo translocation into the ERGIC (PubMed:32272059). Interacts with HSP90B1; the interaction facilitates cargo translocation into the ERGIC (PubMed:32272059).SUBCELLULAR LOCATION The precursor is cytosolic (PubMed:15192144). In response to inflammasome-activating signals, such as ATP for NLRP3 inflammasome or bacterial flagellin for NLRC4 inflammasome, cleaved and secreted (PubMed:24201029, PubMed:33377178, PubMed:33883744). Mature form is secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33883744). In contrast, the precursor form is not released, due to the presence of an acidic region that is proteolytically removed by CASP1 during maturation (PubMed:33883744). The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10 (PubMed:32272059).TISSUE SPECIFICITY Expressed in activated monocytes/macrophages (at protein level).INDUCTION By LPS (PubMed:15192144). Transcription and translation induced by M.tuberculosis and a number of different M.tuberculosis components in macrophages; EsxA is the most potent activator tested (at protein level) (PubMed:20148899). In pancreatic islets, release is increased by high glucose treatment. In pancreatic islets and macrophages, release is also increased by endocannabinoid anandamide/AEA (PubMed:23955712).PTM Activation of the IL1B precursor involves a CASP1-catalyzed proteolytic cleavage. Processing and secretion are temporarily associated.PTM (Microbial infection) Cleavage by S.pyogenes cysteine protease SpeB promotes its activation independently of CASP1.MISCELLANEOUS The 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.SIMILARITY Belongs to the IL-1 family.ONLINE INFORMATION Interleukin-1 entry
description	recommendedName: fullName evidence="22"Interleukin-1 beta shortName evidence="22"IL-1 beta alternativeName: Catabolin
geneName	IL1B IL1F2
identifier	P01584
isSequenceChanged	FALSE
keyword	3D-structure Cytokine Cytoplasm Direct protein sequencing Inflammatory response Lysosome Mitogen Proteomics identification Pyrogen Reference proteome Secreted
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
name	IL1B
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:5660998] ENSEMBL:ENSG00000125538 IL1B [Homo sapiens]
secondaryIdentifier	IL1B_HUMAN Q53X59 Q53XX2 Q7M4S7 Q7RU01 Q96HE5 Q9UCT6
sequenceLength	269
species	[Species:48887] Homo sapiens
(referenceEntity)	[EntityWithAccessionedSequence:445748] IL1B [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:448689] IL1B(1-269) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:449030] IL1B(1-116) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:449046] IL1B(117-269) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9958616] IL1B(1-27) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9987385] IL1B [endoplasmic reticulum lumen] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:P01584 IL1B (57238)