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Protein

Interleukin-1 beta

Gene

IL1B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (PubMed:10653850).2 Publications

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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei120Involved in receptor binding1
Sitei171Important for interaction with integrin1 Publication1
Sitei179Important for interaction with integrin1 Publication1
Sitei181Important for interaction with integrin1 Publication1
Sitei190Important for interaction with integrin1 Publication1
Sitei204Important for interaction with integrin1 Publication1

GO - Molecular functioni

  • cytokine activity Source: BHF-UCL
  • integrin binding Source: UniProtKB
  • interleukin-1 receptor binding Source: GO_Central
  • protein domain specific binding Source: UniProtKB

GO - Biological processi

  • activation of MAPK activity Source: BHF-UCL
  • apoptotic process Source: ProtInc
  • cell-cell signaling Source: ProtInc
  • cellular response to drug Source: MGI
  • cellular response to mechanical stimulus Source: UniProtKB
  • cellular response to organic cyclic compound Source: UniProtKB
  • cellular response to organic substance Source: MGI
  • cytokine-mediated signaling pathway Source: BHF-UCL
  • ectopic germ cell programmed cell death Source: Ensembl
  • embryo implantation Source: BHF-UCL
  • extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  • fever generation Source: GO_Central
  • hyaluronan biosynthetic process Source: UniProtKB
  • immune response Source: InterPro
  • inflammatory response Source: UniProtKB
  • interleukin-1 beta production Source: Ensembl
  • interleukin-1-mediated signaling pathway Source: Reactome
  • interleukin-6 production Source: Ensembl
  • lipopolysaccharide-mediated signaling pathway Source: UniProtKB
  • MAPK cascade Source: UniProtKB
  • monocyte aggregation Source: UniProtKB
  • negative regulation of adiponectin secretion Source: BHF-UCL
  • negative regulation of cell proliferation Source: BHF-UCL
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
  • negative regulation of glucose transmembrane transport Source: BHF-UCL
  • negative regulation of insulin receptor signaling pathway Source: BHF-UCL
  • negative regulation of lipid catabolic process Source: BHF-UCL
  • negative regulation of lipid metabolic process Source: BHF-UCL
  • negative regulation of MAP kinase activity Source: BHF-UCL
  • negative regulation of synaptic transmission Source: ARUK-UCL
  • neutrophil chemotaxis Source: Ensembl
  • positive regulation of angiogenesis Source: BHF-UCL
  • positive regulation of calcidiol 1-monooxygenase activity Source: BHF-UCL
  • positive regulation of cell adhesion molecule production Source: BHF-UCL
  • positive regulation of cell division Source: UniProtKB-KW
  • positive regulation of cell migration Source: BHF-UCL
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of chemokine biosynthetic process Source: Ensembl
  • positive regulation of DNA binding transcription factor activity Source: BHF-UCL
  • positive regulation of epithelial to mesenchymal transition Source: BHF-UCL
  • positive regulation of fever generation Source: BHF-UCL
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of granulocyte macrophage colony-stimulating factor production Source: BHF-UCL
  • positive regulation of heterotypic cell-cell adhesion Source: UniProtKB
  • positive regulation of histone acetylation Source: BHF-UCL
  • positive regulation of histone phosphorylation Source: BHF-UCL
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  • positive regulation of interferon-gamma production Source: BHF-UCL
  • positive regulation of interleukin-2 biosynthetic process Source: BHF-UCL
  • positive regulation of interleukin-6 biosynthetic process Source: Ensembl
  • positive regulation of interleukin-6 production Source: BHF-UCL
  • positive regulation of interleukin-6 secretion Source: Ensembl
  • positive regulation of interleukin-8 production Source: UniProtKB
  • positive regulation of JNK cascade Source: ARUK-UCL
  • positive regulation of lipid catabolic process Source: BHF-UCL
  • positive regulation of membrane protein ectodomain proteolysis Source: BHF-UCL
  • positive regulation of mitotic nuclear division Source: BHF-UCL
  • positive regulation of monocyte chemotactic protein-1 production Source: UniProtKB
  • positive regulation of myosin light chain kinase activity Source: BHF-UCL
  • positive regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  • positive regulation of NIK/NF-kappaB signaling Source: BHF-UCL
  • positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
  • positive regulation of p38MAPK cascade Source: ARUK-UCL
  • positive regulation of phagocytosis Source: AgBase
  • positive regulation of prostaglandin secretion Source: BHF-UCL
  • positive regulation of protein export from nucleus Source: BHF-UCL
  • positive regulation of protein phosphorylation Source: BHF-UCL
  • positive regulation of T cell mediated immunity Source: BHF-UCL
  • positive regulation of T cell proliferation Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: Ensembl
  • positive regulation of vascular endothelial growth factor production Source: BHF-UCL
  • positive regulation of vascular endothelial growth factor receptor signaling pathway Source: BHF-UCL
  • protein kinase B signaling Source: UniProtKB
  • regulation of defense response to virus by host Source: Ensembl
  • regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  • regulation of establishment of endothelial barrier Source: UniProtKB
  • regulation of I-kappaB kinase/NF-kappaB signaling Source: BHF-UCL
  • regulation of insulin secretion Source: BHF-UCL
  • regulation of nitric-oxide synthase activity Source: UniProtKB
  • response to ATP Source: Ensembl
  • response to carbohydrate Source: Ensembl
  • sequestering of triglyceride Source: BHF-UCL
  • signal transduction Source: ProtInc
  • smooth muscle adaptation Source: BHF-UCL

Keywordsi

Molecular functionCytokine, Mitogen, Pyrogen
Biological processInflammatory response

Enzyme and pathway databases

ReactomeiR-HSA-448706 Interleukin-1 processing
R-HSA-5660668 CLEC7A/inflammasome pathway
R-HSA-6783783 Interleukin-10 signaling
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-9020702 Interleukin-1 signaling
SignaLinkiP01584
SIGNORiP01584

Protein family/group databases

TCDBi1.A.109.1.2 the interleukin 1 (il1) family

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-1 beta1 Publication
Short name:
IL-1 beta1 Publication
Alternative name(s):
Catabolin
Gene namesi
Name:IL1BImported
Synonyms:IL1F2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000125538.11
HGNCiHGNC:5992 IL1B
MIMi147720 gene
neXtProtiNX_P01584

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Lysosome, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi27D → A: Loss of activation by CASP1; when associated with A-116. 1 Publication1
Mutagenesisi116D → A: Loss of activation by CASP1; when associated with A-27. 1 Publication1
Mutagenesisi171K → E: Suppression of integrin binding; when associated with K-244. Markedly reduced activity; when associated with E-190; E-204 and C-233. 1 Publication1
Mutagenesisi179K → E: Suppression of integrin binding; when associated with E-181 and K-244. Markedly reduced activity; when associated with E-181; E-190; E-204 and C-233. 1 Publication1
Mutagenesisi181K → E: Suppression of integrin binding; when associated with E-179 and K-244. Markedly reduced activity; when associated with E-179; E-190; E-204 and C-233. 1 Publication1
Mutagenesisi190K → E: Suppression of integrin binding; when associated with K-244. Markedly reduced activity; when associated with E-171; E-204 and C-233. Markedly reduced activity; when associated with E-179; E-181; E-204 and C-233. 1 Publication1
Mutagenesisi204K → E: Suppression of integrin binding; when associated with K-244. Markedly reduced activity; when associated with E-171; E-190 and C-233. Markedly reduced activity; when associated with E-179; E-181; E-190 and C-233. 1 Publication1
Mutagenesisi221E → K: Enhanced integrin binding. 1 Publication1
Mutagenesisi233F → C: No effect on binding to IL1R or on IL1B activity. Markedly reduced activity; when associated with E-171; E-190 and E-204. Markedly reduced activity; when associated with E-179; E-181; E-190 and E-204. 1 Publication1
Mutagenesisi244E → K: Increased affinity for integrin ITGAV:ITGB3. Suppression of integrin binding; when associated with E-171; E-190 or E-204. Suppression of integrin binding; when associated with E-179 and E-181. 1 Publication1

Organism-specific databases

DisGeNETi3553
MalaCardsiIL1B
OpenTargetsiENSG00000125538
PharmGKBiPA29808

Chemistry databases

ChEMBLiCHEMBL1909490
DrugBankiDB05250 681323
DB05066 AV411
DB06168 Canakinumab
DB05442 Etiprednol dicloacetate
DB05260 Gallium nitrate
DB05767 HMPL-004
DB01017 Minocycline
DB06372 Rilonacept
DB05412 SCIO-469
DB05133 VP025
DB05470 VX-702
DB05507 VX-765
DB06062 XOMA 052

Polymorphism and mutation databases

BioMutaiIL1B
DMDMi62906858

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000153011 – 116Removed in mature form; by CASP12 PublicationsAdd BLAST116
ChainiPRO_0000015302117 – 269Interleukin-1 beta1 PublicationAdd BLAST153

Post-translational modificationi

Activation of the IL1B precursor involves a CASP1-catalyzed proteolytic cleavage. Processing and secretion are temporarily associated.1 Publication

Proteomic databases

MaxQBiP01584
PaxDbiP01584
PeptideAtlasiP01584
PRIDEiP01584
ProteomicsDBi51391

PTM databases

iPTMnetiP01584
PhosphoSitePlusiP01584
SwissPalmiP01584

Miscellaneous databases

PMAP-CutDBiP01584

Expressioni

Tissue specificityi

Expressed in activated monocytes/macrophages (at protein level).1 Publication

Inductioni

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).3 Publications

Gene expression databases

BgeeiENSG00000125538
CleanExiHS_IL1B
ExpressionAtlasiP01584 baseline and differential
GenevisibleiP01584 HS

Interactioni

Subunit structurei

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).3 Publications

GO - Molecular functioni

  • cytokine activity Source: BHF-UCL
  • integrin binding Source: UniProtKB
  • interleukin-1 receptor binding Source: GO_Central
  • protein domain specific binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109769, 15 interactors
DIPiDIP-474N
IntActiP01584, 7 interactors
STRINGi9606.ENSP00000263341

Chemistry databases

BindingDBiP01584

Structurei

Secondary structure

1269
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi121 – 128Combined sources8
Beta strandi133 – 137Combined sources5
Beta strandi138 – 140Combined sources3
Beta strandi141 – 145Combined sources5
Helixi149 – 154Combined sources6
Beta strandi158 – 162Combined sources5
Beta strandi172 – 178Combined sources7
Turni179 – 181Combined sources3
Beta strandi183 – 190Combined sources8
Beta strandi193 – 200Combined sources8
Turni203 – 205Combined sources3
Helixi213 – 215Combined sources3
Beta strandi217 – 222Combined sources6
Beta strandi225 – 233Combined sources9
Beta strandi237 – 240Combined sources4
Beta strandi242 – 247Combined sources6
Beta strandi249 – 252Combined sources4
Turni254 – 257Combined sources4
Beta strandi262 – 266Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1HIBX-ray2.40A117-269[»]
1I1BX-ray2.00A117-269[»]
1IOBX-ray2.00A117-269[»]
1ITBX-ray2.50A117-269[»]
1L2HX-ray1.54A117-269[»]
1S0LX-ray2.34A117-269[»]
1T4QX-ray2.10A117-269[»]
1TOOX-ray2.10A117-269[»]
1TP0X-ray2.20A117-269[»]
1TWEX-ray2.10A117-269[»]
1TWMX-ray2.26A117-269[»]
21BIX-ray2.00A117-269[»]
2I1BX-ray2.00A117-269[»]
2KH2NMR-A117-269[»]
2NVHX-ray1.53A117-269[»]
31BIX-ray2.00A117-269[»]
3LTQX-ray2.10A117-269[»]
3O4OX-ray3.30A117-269[»]
3POKX-ray1.70A117-269[»]
41BIX-ray2.90A117-269[»]
4DEPX-ray3.10A/D117-269[»]
4G6JX-ray2.03A117-269[»]
4G6MX-ray1.81A118-267[»]
4GAFX-ray2.15A117-269[»]
4GAIX-ray1.49A/B117-269[»]
4I1BX-ray2.00A117-269[»]
5BVPX-ray2.20I117-269[»]
5I1BX-ray2.10A117-269[»]
5MVZX-ray2.15U/V117-269[»]
6I1BNMR-A117-269[»]
7I1BNMR-A117-269[»]
9ILBX-ray2.28A117-269[»]
ProteinModelPortaliP01584
SMRiP01584
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01584

Family & Domainsi

Sequence similaritiesi

Belongs to the IL-1 family.Curated

Phylogenomic databases

eggNOGiENOG410IGSZ Eukaryota
ENOG410XU2E LUCA
GeneTreeiENSGT00510000048687
HOVERGENiHBG007328
InParanoidiP01584
KOiK04519
OMAiQVVFSMS
OrthoDBiEOG091G0GR9
PhylomeDBiP01584
TreeFamiTF300203

Family and domain databases

InterProiView protein in InterPro
IPR003296 IL-1_beta
IPR020877 IL-1_CS
IPR000975 IL-1_fam
IPR003502 IL-1_propep
IPR008996 IL1/FGF
PANTHERiPTHR44849 PTHR44849, 1 hit
PfamiView protein in Pfam
PF00340 IL1, 1 hit
PF02394 IL1_propep, 1 hit
PRINTSiPR00264 INTERLEUKIN1
SUPFAMiSSF50353 SSF50353, 1 hit
PROSITEiView protein in PROSITE
PS00253 INTERLEUKIN_1, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P01584-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEVPELASE MMAYYSGNED DLFFEADGPK QMKCSFQDLD LCPLDGGIQL
60 70 80 90 100
RISDHHYSKG FRQAASVVVA MDKLRKMLVP CPQTFQENDL STFFPFIFEE
110 120 130 140 150
EPIFFDTWDN EAYVHDAPVR SLNCTLRDSQ QKSLVMSGPY ELKALHLQGQ
160 170 180 190 200
DMEQQVVFSM SFVQGEESND KIPVALGLKE KNLYLSCVLK DDKPTLQLES
210 220 230 240 250
VDPKNYPKKK MEKRFVFNKI EINNKLEFES AQFPNWYIST SQAENMPVFL
260
GGTKGGQDIT DFTMQFVSS
Length:269
Mass (Da):30,748
Last modified:April 26, 2005 - v2
Checksum:i9BF73C3673C6FD66
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6E → K in AAA36106 (PubMed:6083565).Curated1
Sequence conflicti6E → K in AAA59136 (PubMed:6083565).Curated1
Sequence conflicti6E → K in CAG28607 (Ref. 9) Curated1
Sequence conflicti124C → A AA sequence (PubMed:3920526).Curated1
Sequence conflicti155Q → D AA sequence (PubMed:3920526).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073951141E → N Requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant dbSNP:rs144640380Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02770 mRNA Translation: AAA36106.1
M54933 mRNA Translation: AAA59136.1 Sequence problems.
X02532 mRNA Translation: CAA26372.1
X04500 Genomic DNA Translation: CAA28185.1
M15330 mRNA Translation: AAA59135.1
M15840 Genomic DNA Translation: AAA74137.1
X56087 mRNA Translation: CAA39567.1
BN000002 Genomic DNA Translation: CAD29872.1
BT007213 mRNA Translation: AAP35877.1
CR407679 mRNA Translation: CAG28607.1
AY137079 Genomic DNA Translation: AAM88883.1
AC079753 Genomic DNA Translation: AAX88888.1
CH471217 Genomic DNA Translation: EAW73605.1
BC008678 mRNA Translation: AAH08678.1
CCDSiCCDS2102.1
PIRiA21851
A25542 ICHU1B
RefSeqiNP_000567.1, NM_000576.2
UniGeneiHs.126256

Genome annotation databases

EnsembliENST00000263341; ENSP00000263341; ENSG00000125538
GeneIDi3553
KEGGihsa:3553
UCSCiuc002tii.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIL1B_HUMAN
AccessioniPrimary (citable) accession number: P01584
Secondary accession number(s): Q53X59
, Q53XX2, Q7M4S7, Q7RU01, Q96HE5, Q9UCT6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: April 26, 2005
Last modified: June 20, 2018
This is version 222 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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