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Interleukin 36 receptor antagonist

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From Wikipedia, the free encyclopedia

(Redirected fromIL-36Ra)

Protein-coding gene in the species Homo sapiens

IL36RN

Available structures

PDB

Ortholog search:PDBe RCSB

List of PDB id codes
4P0J,4P0K,4P0L

Identifiers

Aliases

IL36RN, FIL1, FIL1(DELTA), FIL1D, IL1F5, IL1HY1, IL1L1, IL1RP3, IL36RA, PSORP, IL-36Ra, PSORS14, interleukin 36 receptor antagonist

External IDs

OMIM:605507;MGI:1859325;HomoloGene:10453;GeneCards:IL36RN;OMA:IL36RN - orthologs

Gene location (Human)

Chr.	Chromosome 2 (human)^[1]

Band	2q14.1	Start	113,058,638bp^[1]
Band	2q14.1	End	113,065,382bp^[1]

Gene location (Mouse)

Chr.	Chromosome 2 (mouse)^[2]

Band	2 A3\|2 16.31 cM	Start	24,166,966bp^[2]
Band	2 A3\|2 16.31 cM	End	24,173,438bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

amniotic fluid

skin of arm

gums

gingival epithelium

skin of leg

skin of abdomen

cervix epithelium

oral cavity

buccal mucosa cell

cartilage tissue

Top expressed in

esophagus

skin of external ear

skin of back

umbilical cord

skin of abdomen

parotid gland

superior surface of tongue

lumbar subsegment of spinal cord

epidermis

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	cytokine activity protein binding interleukin-1 receptor binding interleukin-1 receptor antagonist activity
Cellular component	extracellular space extracellular region
Biological process	negative regulation of interleukin-6 production negative regulation of cytokine-mediated signaling pathway innate immune response negative regulation of interleukin-17 production antifungal humoral response immune system process inflammatory response immune response regulation of signaling receptor activity cytokine-mediated signaling pathway neutrophil chemotaxis positive regulation of interleukin-6 production positive regulation of I-kappaB kinase/NF-kappaB signaling positive regulation of JNK cascade cellular response to lipopolysaccharide
Sources:Amigo /QuickGO

Orthologs

Species

Human

Mouse

Entrez


26525


54450

Ensembl


ENSG00000136695


ENSMUSG00000026983

UniProt


Q9UBH0


Q9QYY1

RefSeq (mRNA)


NM_173170 NM_012275


NM_001146087 NM_001146088 NM_019451

RefSeq (protein)


NP_036407 NP_775262


NP_001139559 NP_001139560 NP_062324

Location (UCSC)

Chr 2: 113.06 – 113.07 Mb

Chr 2: 24.17 – 24.17 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Interleukin 36 receptor antagonist (IL-36RA) is a member of theinterleukin-36 family ofcytokines. It was previously namedInterleukin-1 family member 5 (IL1F5).^[5]^[6]^[7]^[8]

The protein is known to inhibit the effects of Interleukin-36 cytokines (IL-36α,IL-36β andIL-36γ) via competing with their receptorIL-36R/IL1RL2 and thereby inhibiting their proinflammatory effects.^[9]

Roles in disease

[edit]

Mutations in the IL-36RN gene resulting in a decrease or production of defective IL-36RA protein have been shown to cause inflammatory skin diseases includinggeneralised pustular psoriasis,acrodermatitis continua suppurativa Hallopeau (ACH) andacute generalized exanthematous pustulosis (AGEP).^[10]

References

[edit]

^^a ^b ^cGRCh38: Ensembl release 89: ENSG00000136695 –Ensembl, May 2017
^^a ^b ^cGRCm38: Ensembl release 89: ENSMUSG00000026983 –Ensembl, May 2017
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Smith DE, Renshaw BR, Ketchem RR, Kubin M, Garka KE, Sims JE (Feb 2000)."Four new members expand the interleukin-1 superfamily".J Biol Chem.275 (2):1169–75.doi:10.1074/jbc.275.2.1169.PMID 10625660.
^Mulero JJ, Pace AM, Nelken ST, Loeb DB, Correa TR, Drmanac R, Ford JE (Nov 1999). "IL1HY1: A novel interleukin-1 receptor antagonist gene".Biochem Biophys Res Commun.263 (3):702–6.doi:10.1006/bbrc.1999.1440.PMID 10512743.
^Sims JE, Nicklin MJ, Bazan JF, Barton JL, Busfield SJ, Ford JE, Kastelein RA, Kumar S, Lin H, Mulero JJ, Pan J, Pan Y, Smith DE, Young PR (Sep 2001). "A new nomenclature for IL-1-family genes".Trends Immunol.22 (10):536–7.doi:10.1016/S1471-4906(01)02040-3.PMID 11574262.
^"Entrez Gene: IL36RN interleukin 36 receptor antagonist".
^Towne, JE; Garka, KE; Renshaw, BR; Virca, GD; Sims, JE (2 April 2004)."Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs".The Journal of Biological Chemistry.279 (14):13677–88.doi:10.1074/jbc.M400117200.PMID 14734551.
^Navarini, AA; Valeyrie-Allanore, L; Setta-Kaffetzi, N; Barker, JN; Capon, F; Creamer, D; Roujeau, JC; Sekula, P; Simpson, MA; Trembath, RC; Mockenhaupt, M; Smith, CH (July 2013)."Rare variations in IL36RN in severe adverse drug reactions manifesting as acute generalized exanthematous pustulosis".The Journal of Investigative Dermatology.133 (7):1904–7.doi:10.1038/jid.2013.44.PMID 23358093.

Nicklin MJ, Weith A, Duff GW (1994). "A physical map of the region encompassing the human interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist genes".Genomics.19 (2):382–4.doi:10.1006/geno.1994.1076.PMID 8188271.
Nothwang HG, Strahm B, Denich D, et al. (1997). "Molecular cloning of the interleukin-1 gene cluster: construction of an integrated YAC/PAC contig and a partial transcriptional map in the region of chromosome 2q13".Genomics.41 (3):370–8.doi:10.1006/geno.1997.4654.PMID 9169134.
Kumar S, McDonnell PC, Lehr R, et al. (2000)."Identification and initial characterization of four novel members of the interleukin-1 family".J. Biol. Chem.275 (14):10308–14.doi:10.1074/jbc.275.14.10308.PMID 10744718.
Busfield SJ, Comrack CA, Yu G, et al. (2000). "Identification and gene organization of three novel members of the IL-1 family on human chromosome 2".Genomics.66 (2):213–6.doi:10.1006/geno.2000.6184.PMID 10860666.
Mulero JJ, Nelken ST, Ford JE (2000). "Organization of the human interleukin-1 receptor antagonist gene IL1HY1".Immunogenetics.51 (6):425–8.doi:10.1007/s002510050640.PMID 10866108.S2CID 37207859.
Barton JL, Herbst R, Bosisio D, et al. (2001)."A tissue specific IL-1 receptor antagonist homolog from the IL-1 cluster lacks IL-1, IL-1ra, IL-18 and IL-18 antagonist activities".Eur. J. Immunol.30 (11):3299–308.doi:10.1002/1521-4141(200011)30:11<3299::AID-IMMU3299>3.0.CO;2-S.PMID 11093146.
Pan G, Risser P, Mao W, et al. (2001). "IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL-1Rrp".Cytokine.13 (1):1–7.doi:10.1006/cyto.2000.0799.PMID 11145836.
Lin H, Ho AS, Haley-Vicente D, et al. (2001)."Cloning and characterization of IL-1HY2, a novel interleukin-1 family member".J. Biol. Chem.276 (23):20597–602.doi:10.1074/jbc.M010095200.PMID 11278614.
Debets R, Timans JC, Homey B, et al. (2001)."Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2".J. Immunol.167 (3):1440–6.doi:10.4049/jimmunol.167.3.1440.PMID 11466363.
Tazi-Ahnini R, Cox A, McDonagh AJ, et al. (2002). "Genetic analysis of the interleukin-1 receptor antagonist and its homologue IL-1L1 in alopecia areata: strong severity association and possible gene interaction".Eur. J. Immunogenet.29 (1):25–30.doi:10.1046/j.1365-2370.2002.00271.x.PMID 11841485.
Nicklin MJ, Barton JL, Nguyen M, et al. (2002). "A sequence-based map of the nine genes of the human interleukin-1 cluster".Genomics.79 (5):718–25.doi:10.1006/geno.2002.6751.PMID 11991722.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003)."Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences".Proc. Natl. Acad. Sci. U.S.A.99 (26):16899–903.Bibcode:2002PNAS...9916899M.doi:10.1073/pnas.242603899.PMC 139241.PMID 12477932.
Clark HF, Gurney AL, Abaya E, et al. (2003)."The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment".Genome Res.13 (10):2265–70.doi:10.1101/gr.1293003.PMC 403697.PMID 12975309.
Zee RY, Fernandez-Ortiz A, Macaya C, et al. (2004). "IL-1 cluster genes and occurrence of post-percutaneous transluminal coronary angioplasty restenosis: a prospective, angiography-based evaluation".Atherosclerosis.171 (2):259–64.doi:10.1016/S0021-9150(03)00294-6.PMID 14644395.
Ota T, Suzuki Y, Nishikawa T, et al. (2004)."Complete sequencing and characterization of 21,243 full-length human cDNAs".Nat. Genet.36 (1):40–5.doi:10.1038/ng1285.PMID 14702039.
Colland F, Jacq X, Trouplin V, et al. (2004)."Functional Proteomics Mapping of a Human Signaling Pathway".Genome Res.14 (7):1324–32.doi:10.1101/gr.2334104.PMC 442148.PMID 15231748.
Gerhard DS, Wagner L, Feingold EA, et al. (2004)."The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)".Genome Res.14 (10B):2121–7.doi:10.1101/gr.2596504.PMC 528928.PMID 15489334.
Macleod, T; Doble, R; McGonagle, D; Wasson, CW; Alase, A; Stacey, M; Wittmann, M (22 April 2016)."Neutrophil Elastase-mediated proteolysis activates the anti-inflammatory cytokine IL-36 Receptor antagonist".Scientific Reports.6: 24880.Bibcode:2016NatSR...624880M.doi:10.1038/srep24880.PMC 4840362.PMID 27101808.

v t e PDB gallery
1md6: High resolution crystal structure of murine IL-1F5 reveals unique loop conformation for specificity

Cell signaling:cytokines

By family

Chemokine

CCL	CCL1 CCL2/MCP1 CCL3/MIP1α CCL4/MIP1β CCL5/RANTES CCL6 CCL7 CCL8 CCL9 CCL11 CCL12 CCL13 CCL14 CCL15 CCL16 CCL17 CCL18/PARC/DCCK1/AMAC1/MIP4 CCL19 CCL20 CCL21 CCL22 CCL23 CCL24 CCL25 CCL26 CCL27 CCL28
CXCL	CXCL1/KC CXCL2 CXCL3 CXCL4 CXCL5 CXCL6 CXCL7 CXCL8/IL8 CXCL9 CXCL10 CXCL11 CXCL12 CXCL13 CXCL14 CXCL15 CXCL16 CXCL17
CX3CL	CX3CL1
XCL	XCL1 XCL2

TNF

Interleukin

Type I
(grouped by
receptor
subunit)

γ chain	IL2/IL15 IL4/IL13 IL7 IL9 IL21
β chain	IL3 IL5 GMCSF
IL6 like/gp130	IL6 IL11 IL27 IL30 IL31 +non ILOSM LIF CNTF CTF1
IL12 family/IL12RB1	IL12 IL23 IL27 IL35
Other	IL14 IL16 IL32 IL34

Type II

IL10 family

Interferon

I	IFNA1 IFNA2 IFNA4 IFNA5 IFNA6 IFNA7 IFNA8 IFNA10 IFNA13 IFNA14 IFNA16 IFNA17 IFNA21 IFNB1 IFNK IFNW1
II	IFNG

Ig superfamily

IL17 family

IL17/IL25 (IL17A)

Other

By function/
cell

proinflammatory cytokine
- IL1
- TNFA

Monokine
Lymphokine
- T_h1
  - IFNγ
  - TNFβ
- T_h2
  - IL4
  - IL5
  - IL6
  - IL10
  - IL13

Interleukin receptor modulators

IL-1

Decoy receptors:Rilonacept (IL-1 Trap)

IL-2

IL-3

IL-4

Antagonists:Pitrakinra

Antibodies:Dupilumab
Pascolizumab

IL-5

Agonists:Interleukin 5

Antagonists:YM-90709

Antisense oligonucleotides:TPI ASM8

IL-6

Agonists:Atexakin alfa
Interleukin 6

IL-7

Agonists:Interleukin 7

IL-8

See CXCR1 (IL-8Rα) and CXCR2 (IL-8Rβ)here instead.

IL-9

Agonists:Interleukin 9

Antibodies:Enokizumab

IL-10

Agonists:Ilodecakin
Interleukin 10 (CSIF)

IL-11

Agonists:Interleukin 11 (AGIF)
Oprelvekin

IL-12

Agonists:Edodekin alfa
Interleukin 12

Antibodies:Briakinumab
Ustekinumab

IL-13

IL-15

Agonists:ALT-803
Interleukin 15

IL-17

Agonists:Interleukin 17 (A,B,C,D,E (interleukin 25),F)

IL-18

Binding proteins:IL18BP

IL-20

Antibodies:Fletikumab (against IL-20)

IL-21

Agonists:Denenicokin
Interleukin 21

Antibodies:NNC0114-0005
NNC0114-0006

IL-22

Agonists:Interleukin 22

Antibodies:Fezakinumab (against IL-22)

IL-23

Agonists:Interleukin 23 (SGRF)

IL-27

Agonists:Interleukin 27 (interleukin 30)

IL-28

IL-31

Agonists:Interleukin 31

IL1RL1

Agonists:Interleukin 33

IL1RL2

Agonists:Interleukin 36 (α,β,γ)
Interleukin 38

Antagonists:IL-36RA

Others

JAK	Seehere instead.
Others	Interleukin 14 (taxilin alpha, HMW-BCGF) Interleukin 16 (signals throughCD4) Interleukin 24 (signals throughIL-22Rα1/IL-20Rβ heterodimer) Interleukin 26 (signals throughIL-20Rα/IL-10Rβ heterodimer) Interleukin 32 Interleukin 34 (signals throughM-CSFR/CSF1R) Interleukin 35 Unsorted:Efavaleukin alfa Efineptakin alfa

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Roles in disease

References

Further reading