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Protein

Interleukin-36 beta

Gene

IL36B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Cytokine that binds to and signals through the IL1RL2/IL-36R receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells linked to a pro-inflammatory response. Part of the IL-36 signaling system that is thought to be present in epithelial barriers and to take part in local inflammatory response; similar to the IL-1 system with which it shares the coreceptor IL1RAP. Stimulates production of interleukin-6 and interleukin-8 in synovial fibrobasts, articular chondrocytes and mature adipocytes. Induces expression of a number of antimicrobial peptides including beta-defensins 4 and 103 as well as a number of matrix metalloproteases. Seems to be involved in skin inflammatory response by acting on keratinocytes, dendritic cells and indirectly on T-cells to drive tissue infiltration, cell maturation and cell proliferation. In cultured keratinocytes induces the expression of macrophage, T-cell, and neutrophil chemokines, such as CCL3, CCL4, CCL5, CCL2, CCL17, CCL22, CL20, CCL5, CCL2, CCL17, CCL22, CXCL8, CCL20 and CXCL1, and the production of proinflammatory cytokines such as TNF-alpha, IL-8 and IL-6.6 Publications

GO - Molecular functioni

  • cytokine activity Source: GO_Central
  • interleukin-1 receptor binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-449147. Signaling by Interleukins.

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-36 beta
Alternative name(s):
FIL1 eta
Interleukin-1 eta
Short name:
IL-1 eta
Interleukin-1 family member 8
Short name:
IL-1F8
Interleukin-1 homolog 2
Short name:
IL-1H2
Gene namesi
Name:IL36B
Synonyms:IL1F8, IL1H2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:15564. IL36B.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: UniProtKB
  • extracellular space Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA38391.

Polymorphism and mutation databases

DMDMi25008595.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Propeptidei1 – 441 PublicationPRO_0000430547
Chaini5 – 164160Interleukin-36 betaPRO_0000153646Add
BLAST

Post-translational modificationi

N-terminal truncation leads to a dramatic enhancement of its activity (>1000-fold).1 Publication

Proteomic databases

PaxDbiQ9NZH7.
PRIDEiQ9NZH7.

PTM databases

iPTMnetiQ9NZH7.
PhosphoSiteiQ9NZH7.

Expressioni

Tissue specificityi

Expression at low levels in tonsil, bone marrow, heart, placenta, lung, testis and colon but not in any hematopoietic cell lines. Not detected in adipose tissue. Expressed at higher levels in psoriatic plaques than in symptomless psoriatic skin or healthy control skin. Increased levels are not detected in inflamed joint tissue.2 Publications

Inductioni

By proinflammatory cytokines IL1A, IL1B and TNF in synovial fibroblasts. By IL1A and TNF in keratinocytes. Constitutive in articular chondrocytes.1 Publication

Gene expression databases

BgeeiQ9NZH7.
CleanExiHS_IL1F8.
GenevisibleiQ9NZH7. HS.

Organism-specific databases

HPAiHPA035664.

Interactioni

GO - Molecular functioni

  • cytokine activity Source: GO_Central
  • interleukin-1 receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi118053. 1 interaction.
STRINGi9606.ENSP00000259213.

Structurei

3D structure databases

ProteinModelPortaliQ9NZH7.
SMRiQ9NZH7. Positions 9-97.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the IL-1 family.Curated

Phylogenomic databases

eggNOGiENOG410JCFD. Eukaryota.
ENOG41118F0. LUCA.
GeneTreeiENSGT00530000062899.
HOVERGENiHBG052100.
InParanoidiQ9NZH7.
KOiK05486.
OMAiFQSVSYP.
OrthoDBiEOG76MK9R.
PhylomeDBiQ9NZH7.

Family and domain databases

InterProiIPR008996. Cytokine_IL1-like.
IPR027172. IL-36_beta.
[Graphical view]
PANTHERiPTHR10078:SF24. PTHR10078:SF24. 1 hit.
SUPFAMiSSF50353. SSF50353. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NZH7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MNPQREAAPK SYAIRDSRQM VWVLSGNSLI AAPLSRSIKP VTLHLIACRD
60 70 80 90 100
TEFSDKEKGN MVYLGIKGKD LCLFCAEIQG KPTLQLKLQG SQDNIGKDTC
110 120 130 140 150
WKLVGIHTCI NLDVRESCFM GTLDQWGIGV GRKKWKSSFQ HHHLRKKDKD
160
FSSMRTNIGM PGRM
Length:164
Mass (Da):18,522
Last modified:October 1, 2000 - v1
Checksum:iF0D2099F4A357A0A
GO
Isoform 2 (identifier: Q9NZH7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     88-164: LQGSQDNIGK...RTNIGMPGRM → EKNIMDLYVE...NTNFYLDSVE

Note: No experimental confirmation available.
Show »
Length:157
Mass (Da):17,702
Checksum:i7A54F3D7557A3EE3
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti36 – 361R → C.1 Publication
Corresponds to variant rs34754959 [ dbSNP | Ensembl ].
VAR_025057

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei88 – 16477LQGSQ…MPGRM → EKNIMDLYVEKKAQKPFLFF HNKEGSTSVFQSVSYPGWFI ATSTTSGQPIFLTKERGITN NTNFYLDSVE in isoform 2. 2 PublicationsVSP_002657Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF200494 mRNA. Translation: AAF69250.1.
AF201833 mRNA. Translation: AAF25213.1.
CH471217 Genomic DNA. Translation: EAW73615.1.
BC101831 mRNA. Translation: AAI01832.1.
BC101833 mRNA. Translation: AAI01834.1.
BN000002 Genomic DNA. Translation: CAD29876.1.
DQ224343 Genomic DNA. Translation: ABA60896.1.
AC016724 Genomic DNA. Translation: AAY14989.1.
CCDSiCCDS2109.1. [Q9NZH7-1]
CCDS2110.1. [Q9NZH7-2]
RefSeqiNP_055253.2. NM_014438.4. [Q9NZH7-1]
NP_775270.1. NM_173178.2. [Q9NZH7-2]
XP_011509264.1. XM_011510962.1. [Q9NZH7-2]
UniGeneiHs.278909.

Genome annotation databases

EnsembliENST00000259213; ENSP00000259213; ENSG00000136696. [Q9NZH7-1]
ENST00000327407; ENSP00000328420; ENSG00000136696. [Q9NZH7-2]
GeneIDi27177.
KEGGihsa:27177.
UCSCiuc002tiq.2. human. [Q9NZH7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Interleukin-1 entry

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF200494 mRNA. Translation: AAF69250.1.
AF201833 mRNA. Translation: AAF25213.1.
CH471217 Genomic DNA. Translation: EAW73615.1.
BC101831 mRNA. Translation: AAI01832.1.
BC101833 mRNA. Translation: AAI01834.1.
BN000002 Genomic DNA. Translation: CAD29876.1.
DQ224343 Genomic DNA. Translation: ABA60896.1.
AC016724 Genomic DNA. Translation: AAY14989.1.
CCDSiCCDS2109.1. [Q9NZH7-1]
CCDS2110.1. [Q9NZH7-2]
RefSeqiNP_055253.2. NM_014438.4. [Q9NZH7-1]
NP_775270.1. NM_173178.2. [Q9NZH7-2]
XP_011509264.1. XM_011510962.1. [Q9NZH7-2]
UniGeneiHs.278909.

3D structure databases

ProteinModelPortaliQ9NZH7.
SMRiQ9NZH7. Positions 9-97.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118053. 1 interaction.
STRINGi9606.ENSP00000259213.

PTM databases

iPTMnetiQ9NZH7.
PhosphoSiteiQ9NZH7.

Polymorphism and mutation databases

DMDMi25008595.

Proteomic databases

PaxDbiQ9NZH7.
PRIDEiQ9NZH7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000259213; ENSP00000259213; ENSG00000136696. [Q9NZH7-1]
ENST00000327407; ENSP00000328420; ENSG00000136696. [Q9NZH7-2]
GeneIDi27177.
KEGGihsa:27177.
UCSCiuc002tiq.2. human. [Q9NZH7-1]

Organism-specific databases

CTDi27177.
GeneCardsiIL36B.
HGNCiHGNC:15564. IL36B.
HPAiHPA035664.
MIMi605508. gene.
neXtProtiNX_Q9NZH7.
PharmGKBiPA38391.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JCFD. Eukaryota.
ENOG41118F0. LUCA.
GeneTreeiENSGT00530000062899.
HOVERGENiHBG052100.
InParanoidiQ9NZH7.
KOiK05486.
OMAiFQSVSYP.
OrthoDBiEOG76MK9R.
PhylomeDBiQ9NZH7.

Enzyme and pathway databases

ReactomeiR-HSA-449147. Signaling by Interleukins.

Miscellaneous databases

GeneWikiiIL1F8.
GenomeRNAii27177.
PROiQ9NZH7.
SOURCEiSearch...

Gene expression databases

BgeeiQ9NZH7.
CleanExiHS_IL1F8.
GenevisibleiQ9NZH7. HS.

Family and domain databases

InterProiIPR008996. Cytokine_IL1-like.
IPR027172. IL-36_beta.
[Graphical view]
PANTHERiPTHR10078:SF24. PTHR10078:SF24. 1 hit.
SUPFAMiSSF50353. SSF50353. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification and initial characterization of four novel members of the interleukin-1 family."
    Kumar S., McDonnell P.C., Lehr R., Tierney L., Tzimas M.N., Griswold D.E., Capper E.A., Tal-Singer R., Wells G.I., Doyle M.L., Young P.R.
    J. Biol. Chem. 275:10308-10314(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Osteoclastoma.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
  3. "A sequence-based map of the nine genes of the human interleukin-1 cluster."
    Nicklin M.J.H., Barton J.L., Nguyen M., Fitzgerald M.G., Duff W.G., Kornman K.
    Genomics 79:718-725(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. SeattleSNPs variation discovery resource
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT CYS-36.
  5. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Lung and Placenta.
  8. "The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes."
    Magne D., Palmer G., Barton J.L., Mezin F., Talabot-Ayer D., Bas S., Duffy T., Noger M., Guerne P.A., Nicklin M.J., Gabay C.
    Arthritis Res. Ther. 8:R80-R80(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION, SUBCELLULAR LOCATION.
  9. "The effect of the interleukin-1 cytokine family members IL-1F6 and IL-1F8 on adipocyte differentiation."
    van Asseldonk E.J., Stienstra R., Koenen T.B., van Tits L.J., Joosten L.A., Tack C.J., Netea M.G.
    Obesity 18:2234-2236(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  10. "Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36alpha, IL-36beta, and IL-36gamma) or antagonist (IL-36Ra) activity."
    Towne J.E., Renshaw B.R., Douangpanya J., Lipsky B.P., Shen M., Gabel C.A., Sims J.E.
    J. Biol. Chem. 286:42594-42602(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PROCESSING.
  11. "IL-1F5, -F6, -F8, and -F9: a novel IL-1 family signaling system that is active in psoriasis and promotes keratinocyte antimicrobial peptide expression."
    Johnston A., Xing X., Guzman A.M., Riblett M., Loyd C.M., Ward N.L., Wohn C., Prens E.P., Wang F., Maier L.E., Kang S., Voorhees J.J., Elder J.T., Gudjonsson J.E.
    J. Immunol. 186:2613-2622(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  12. "Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis."
    Carrier Y., Ma H.L., Ramon H.E., Napierata L., Small C., O'Toole M., Young D.A., Fouser L.A., Nickerson-Nutter C., Collins M., Dunussi-Joannopoulos K., Medley Q.G.
    J. Invest. Dermatol. 131:2428-2437(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  13. "IL-36 promotes myeloid cell infiltration, activation, and inflammatory activity in skin."
    Foster A.M., Baliwag J., Chen C.S., Guzman A.M., Stoll S.W., Gudjonsson J.E., Ward N.L., Johnston A.
    J. Immunol. 192:6053-6061(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiIL36B_HUMAN
AccessioniPrimary (citable) accession number: Q9NZH7
Secondary accession number(s): Q3MIH0
, Q53SR6, Q7RTZ7, Q9UHA5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: October 1, 2000
Last modified: June 8, 2016
This is version 118 of the entry and version 1 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.