Q9UBH0 (I36RA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interleukin-36 receptor antagonist protein

Alternative name(s):
FIL1 delta
IL-1-related protein 3
Short name=IL-1RP3
Interleukin-1 HY1
Short name=IL-1HY1
Interleukin-1 delta
Short name=IL-1 delta
Interleukin-1 family member 5
Short name=IL-1F5
Interleukin-1 receptor antagonist homolog 1
Short name=IL-1ra homolog 1
Interleukin-1-like protein 1
Short name=IL-1L1

Gene names

Name:	IL36RN
Synonyms:	FIL1D, IL1F5, IL1HY1, IL1L1, IL1RP3
ORF Names:	UNQ1896/PRO4342

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	155 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Is a highly and a specific antagonist of the IL-1 receptor-related protein 2-mediated response to interleukin 1 family member 9 (IL1F9). Could constitute part of an independent signaling system analogous to interleukin-1 alpha (IL-1A), beta (IL-1B) receptor agonist and interleukin-1 receptor type I (IL-1R1), that is present in epithelial barriers and takes part in local inflammatory response.
Subcellular location	Secreted.
Tissue specificity	Predominantly expressed in keratinocytes but not in fibroblasts, endothelial cells or melanocytes. Detected also in the spleen, brain leukocyte and macrophage cell types. Increased in lesional psoriasis skin.
Induction	By phorbol ester (PMA) and bacterial lipopolysaccharides (LPS) treatment in macrophage cell line.
Involvement in disease	Defects in IL36RN are the cause of psoriasis generalized pustular (PSORP) [MIM:614204]. PSORP is a life-threatening disease defined by repeated flares of sudden onset consisting of diffuse erythematous skin eruption characterized by rapid coverage with pustules, high-grade fever, asthenia, marked leukocytosis, and elevated serum levels of C-reactive protein. Ref.13 Ref.14
Sequence similarities	Belongs to the IL-1 family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Molecular function	Cytokine
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cytokine activity Inferred from electronic annotation. Source: UniProtKB-KW interleukin-1 receptor antagonist activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 155	155	Interleukin-36 receptor antagonist protein		PRO_0000153642
Amino acid modifications
	Disulfide bond	8 ↔ 154		By similarity
Natural variations
	Natural variant	27	1	L → P in PSORP; expression of the protein is severely impaired compared to wild-type; the mutant protein is substantially less able to inhibit IL1RL2 signaling than wild-type. Ref.14		VAR_066646
	Natural variant	47	1	N → S. Ref.9 Corresponds to variant rs28938777 [ dbSNP | Ensembl ].		VAR_023239
	Natural variant	48	1	R → W in PSORP. Ref.13		VAR_066647
	Natural variant	113	1	S → L in PSORP. Ref.13		VAR_066648

Sequences

	Sequence		Length	Mass (Da)
	Q9UBH0 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: B96DB5EFA2612E25	FASTA	155	16,962
	10 20 30 40 50 60 MVLSGALCFR MKDSALKVLY LHNNQLLAGG LHAGKVIKGE EISVVPNRWL DASLSPVILG 70 80 90 100 110 120 VQGGSQCLSC GVGQEPTLTL EPVNIMELYL GAKESKSFTF YRRDMGLTSS FESAAYPGWF 130 140 150 LCTVPEADQP VRLTQLPENG GWNAPITDFY FQQCD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Four new members expand the IL-1 superfamily." Smith D.E., Renshaw B.R., Ketchem R.R., Kubin M., Garka K.E., Sims J.E. J. Biol. Chem. 275:1169-1175(2000) [PubMed: 10625660] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"IL1HY1: a novel interleukin-1 receptor antagonist gene." Mulero J.J., Pace A.M., Nelken S.T., Loeb D.B., Correa T.R., Drmanac R., Ford J.E. Biochem. Biophys. Res. Commun. 263:702-706(1999) [PubMed: 10512743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal skin.
[3]	"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." Barton J.L., Herbst R., Bosisio D., Higgins L., Nicklin M.J.H. Eur. J. Immunol. 30:3299-3308(2000) [PubMed: 11093146] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[4]	"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." Debets R., Timans J.C., Homey B., Zurawski S., Sana T.R., Lo S., Wagner J., Edwards G., Clifford T., Menon S., Bazan J.F., Kastelein R.A. J. Immunol. 167:1440-1446(2001) [PubMed: 11466363] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Identification and gene organization of three novel members of the IL-1 family on human chromosome 2." Busfield S.J., Comrack C.A., Yu G., Chickering T.W., Smutko J.S., Zhou H., Leiby K.R., Holmgren L.M., Gearing D.P., Pan Y. Genomics 66:213-216(2000) [PubMed: 10860666] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"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: 11991722] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cervix.
[9]	SeattleSNPs variation discovery resource Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-47.
[10]	"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: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[13]	"Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis." Onoufriadis A., Simpson M.A., Pink A.E., Di Meglio P., Smith C.H., Pullabhatla V., Knight J., Spain S.L., Nestle F.O., Burden A.D., Capon F., Trembath R.C., Barker J.N. Am. J. Hum. Genet. 89:432-437(2011) [PubMed: 21839423] [Abstract] Cited for: VARIANTS PSORP TRP-48 AND LEU-113.
[14]	"Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis." Marrakchi S., Guigue P., Renshaw B.R., Puel A., Pei X.Y., Fraitag S., Zribi J., Bal E., Cluzeau C., Chrabieh M., Towne J.E., Douangpanya J., Pons C., Mansour S., Serre V., Makni H., Mahfoudh N., Fakhfakh F. , Bodemer C., Feingold J., Hadj-Rabia S., Favre M., Genin E., Sahbatou M., Munnich A., Casanova J.L., Sims J.E., Turki H., Bachelez H., Smahi A. N. Engl. J. Med. 365:620-628(2011) [PubMed: 21848462] [Abstract] Cited for: VARIANT PSORP PRO-27, CHARACTERIZATION OF VARIANT PSORP PRO-27.
+	Additional computationally mapped references.

Web resources

Wikipedia

Interleukin-1 entry

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF201830 mRNA. Translation: AAF25210.1. AF186094 mRNA. Translation: AAF02757.1. AJ242737 mRNA. Translation: CAB59822.1. AJ242738 mRNA. Translation: CAB59823.1. AJ271338 Genomic DNA. Translation: CAB67704.1. AF216693 Genomic DNA. Translation: AAF76981.1. AF230377 mRNA. Translation: AAF91274.1. BN000002 Genomic DNA. Translation: CAD29877.1. AY359117 mRNA. Translation: AAQ89475.1. AK290249 mRNA. Translation: BAF82938.1. AY972853 Genomic DNA. Translation: AAX59031.1. AC016724 Genomic DNA. Translation: AAY14990.1. CH471217 Genomic DNA. Translation: EAW73617.1. BC024747 mRNA. Translation: AAH24747.1.
IPI	IPI00017500.
PIR	JC7104.
RefSeq	NP_036407.1. NM_012275.2. NP_775262.1. NM_173170.1.
UniGene	Hs.516301.
3D structure databases
ProteinModelPortal	Q9UBH0.
SMR	Q9UBH0. Positions 2-155.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UBH0. 4 interactions.
MINT	MINT-1194342.
STRING	Q9UBH0.
Polymorphism databases
DMDM	25008600.
Proteomic databases
PRIDE	Q9UBH0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000346807; ENSP00000259212; ENSG00000136695. ENST00000393200; ENSP00000376896; ENSG00000136695.
GeneID	26525.
KEGG	hsa:26525.
UCSC	uc002tis.1. human.
Organism-specific databases
CTD	26525.
GeneCards	GC02P113817.
H-InvDB	HIX0002388.
HGNC	HGNC:15561. IL36RN.
HPA	HPA034542.
MIM	605507. gene. 614204. phenotype.
neXtProt	NX_Q9UBH0.
PharmGKB	PA38388.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18290.
GeneTree	ENSGT00530000062899.
HOGENOM	HBG282870.
HOVERGEN	HBG052099.
InParanoid	Q9UBH0.
OMA	SVVPNRS.
OrthoDB	EOG4MKNHG.
PhylomeDB	Q9UBH0.
Gene expression databases
ArrayExpress	Q9UBH0.
Bgee	Q9UBH0.
CleanEx	HS_IL1F5.
Genevestigator	Q9UBH0.
GermOnline	ENSG00000136695. Homo sapiens.
Family and domain databases
InterPro	IPR008996. Cytokine_IL1-like. IPR003297. IL_rcpt_IL1RA. IPR020877. Interleukin-1_CS. IPR000975. Interleukin_1. [Graphical view]
KO	K05483.
Pfam	PF00340. IL1. 1 hit. [Graphical view]
PRINTS	PR00264. INTERLEUKIN1. PR01360. INTRLEUKIN1X.
SMART	SM00125. IL1. 1 hit. [Graphical view]
SUPFAM	SSF50353. Cytok_IL1_like. 1 hit.
PROSITE	PS00253. INTERLEUKIN_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	48854.
SOURCE	Search...

Entry information

Entry name

I36RA_HUMAN

Accession

Primary (citable) accession number: Q9UBH0
Secondary accession number(s): A8K2I4, Q56AT9, Q7RTZ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2002
Last sequence update:	May 1, 2000
Last modified:	January 25, 2012
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.