O95760 (IL33_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interleukin-33
Short name=IL-33

Alternative name(s):
Interleukin-1 family member 11
Short name=IL-1F11
Nuclear factor from high endothelial venules
Short name=NF-HEV

Gene names

Name:	IL33
Synonyms:	C9orf26, IL1F11, NFHEV

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	270 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cytokine that binds to and signals through IL1RL1/ST2 and its stimulation recruits MYD88, IRAK1, IRAK4, and TRAF6, followed by phosphorylation of MAPK3/ERK1 and/or MAPK1/ERK2, MAPK14, and MAPK8. Induces T-helper type 2-associated cytokines. Ref.3
Subcellular location	Secreted Ref.1 Ref.3.
Tissue specificity	Expressed at high level in high endothelial venules found in tonsils, Peyer patches and mesenteric lymph nodes. Almost undetectable in placenta.
Post-translational modification	Proteolytically converted to a mature form by CASP1 in vitro and calpains in vivo.
Sequence similarities	Belongs to the IL-1 family. Highly divergent.
Caution	Was originally (Ref.1) thought to one of the key factors that controls the specialized post-capillary high endothelial venules (HEV) phenotype found in organized secondary lymphoid tissue and to be nuclear localized.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Cytokine
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	positive regulation of chemokine secretion Inferred from direct assay PubMed 19841166. Source: BHF-UCL positive regulation of inflammatory response Inferred from sequence or structural similarity PubMed 19841166. Source: BHF-UCL positive regulation of macrophage activation Inferred from direct assay PubMed 19841166. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity PubMed 19841166. Source: BHF-UCL
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cytokine activity Inferred from direct assay PubMed 19841166. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IL1RL1	Q01638	2	EBI-724057,EBI-993762

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95760-1)

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.

Isoform 2 (identifier: O95760-2)

The sequence of this isoform differs from the canonical sequence as follows:
     115-156: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Propeptide

1 – 111

111

PRO_0000248845

Chain

112 – 270

159

Interleukin-33

PRO_0000096790

Natural variations

Alternative sequence

115 – 156

42

Missing in isoform 2.

VSP_042728

Natural variant

263

1

I → M.
Corresponds to variant rs16924241 [ dbSNP | Ensembl ].

VAR_049576

Secondary structure

1

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270

Helix Strand Turn

Details...

Beta strand

118 – 128

11

Turn

129 – 131

3

Beta strand

132 – 138

7

Beta strand

143 – 149

7

Beta strand

159 – 165

7

Turn

170 – 172

3

Beta strand

182 – 197

16

Turn

198 – 201

4

Beta strand

202 – 207

6

Turn

214 – 216

3

Beta strand

218 – 222

5

Beta strand

224 – 226

3

Beta strand

228 – 234

7

Beta strand

244 – 246

3

Helix

261 – 263

3

Beta strand

265 – 268

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 7C158069196EF636	FASTA	270	30,759
	10 20 30 40 50 60 MKPKMKYSTN KISTAKWKNT ASKALCFKLG KSQQKAKEVC PMYFMKLRSG LMIKKEACYF 70 80 90 100 110 120 RRETTKRPSL KTGRKHKRHL VLAACQQQST VECFAFGISG VQKYTRALHD SSITGISPIT 130 140 150 160 170 180 EYLASLSTYN DQSITFALED ESYEIYVEDL KKDEKKDKVL LSYYESQHPS NESGDGVDGK 190 200 210 220 230 240 MLMVTLSPTK DFWLHANNKE HSVELHKCEK PLPDQAFFVL HNMHSNCVSF ECKTDPGVFI 250 260 270 GVKDNHLALI KVDSSENLCT ENILFKLSET
	Isoform 2 [UniParc]. Checksum: D48B2E3078CFA6C8	FASTA	228	25,930
	10 20 30 40 50 60 MKPKMKYSTN KISTAKWKNT ASKALCFKLG KSQQKAKEVC PMYFMKLRSG LMIKKEACYF 70 80 90 100 110 120 RRETTKRPSL KTGRKHKRHL VLAACQQQST VECFAFGISG VQKYTRALHD SSITDKVLLS 130 140 150 160 170 180 YYESQHPSNE SGDGVDGKML MVTLSPTKDF WLHANNKEHS VELHKCEKPL PDQAFFVLHN 190 200 210 220 MHSNCVSFEC KTDPGVFIGV KDNHLALIKV DSSENLCTEN ILFKLSET

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venules." Baekkevold E.S., Roussigne M., Yamanaka T., Johansen F.-E., Jahnsen F.L., Amalric F., Brandtzaeg P., Erard M., Haraldsen G., Girard J.-P. Am. J. Pathol. 163:69-79(2003) [PubMed: 12819012] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, SUBCELLULAR LOCATION. Tissue: Endothelial cell.
[2]	"Identification of genes differentially expressed in canine vasospastic cerebral arteries after subarachnoid hemorrhage." Onda H., Kasuya H., Takakura K., Hori T., Imaizumi T., Takeuchi T., Inoue I., Takeda J. J. Cereb. Blood Flow Metab. 19:1279-1288(1999) [PubMed: 10566975] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST 2 and induces T helper type 2-associated cytokines." Schmitz J., Owyang A., Oldham E., Song Y., Murphy E., McClanahan T.K., Zurawski G., Moshrefi M., Qin J., Li X., Gorman D.M., Bazan J.F., Kastelein R.A. Immunity 23:479-490(2005) [PubMed: 16286016] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, FUNCTION.
[4]	"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] (ISOFORM 2). Tissue: Trachea.
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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] (ISOFORM 1). Tissue: Brain.
[9]	"Mature interleukin-33 is produced by calpain-mediated cleavage in vivo." Hayakawa M., Hayakawa H., Matsuyama Y., Tamemoto H., Okazaki H., Tominaga S. Biochem. Biophys. Res. Commun. 387:218-222(2009) [PubMed: 19596270] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB024518 mRNA. Translation: BAA75892.1.
AY905581 mRNA. Translation: AAX86998.1.
AK303943 mRNA. Translation: BAG64871.1.
CR407619 mRNA. Translation: CAG28547.1.
AL353741 Genomic DNA. Translation: CAI16003.1.
CH471071 Genomic DNA. Translation: EAW58748.1.
CH471071 Genomic DNA. Translation: EAW58750.1.
CH471071 Genomic DNA. Translation: EAW58751.1.
BC047085 mRNA. Translation: AAH47085.1.

IPI

IPI00027628.
IPI00908682.

RefSeq

NP_001186569.1. NM_001199640.1.
NP_001186570.1. NM_001199641.1.
NP_254274.1. NM_033439.3.

UniGene

Hs.731660.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KLL	NMR	-	A	111-270	[»]

ProteinModelPortal

O95760.

SMR

O95760. Positions 111-270.

ModBase

Search...

Protein-protein interaction databases

IntAct

O95760. 2 interactions.

MINT

MINT-1423224.

STRING

O95760.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000381434; ENSP00000370842; ENSG00000137033.
ENST00000429607; ENSP00000399586; ENSG00000137033.
ENST00000456383; ENSP00000414238; ENSG00000137033.

GeneID

90865.

KEGG

hsa:90865.

UCSC

uc003zjt.3. human.

Organism-specific databases

CTD

90865.

GeneCards

GC09P006206.

H-InvDB

HIX0007908.

HGNC

HGNC:16028. IL33.

HPA

CAB007057.
HPA024426.

MIM

608678. gene.

neXtProt

NX_O95760.

PharmGKB

PA162392005.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG41297.

GeneTree

ENSGT00390000005185.

HOGENOM

HOG000070215.

HOVERGEN

HBG081791.

InParanoid

O95760.

KO

K12967.

OMA

GVKDNHL.

OrthoDB

EOG4FXR8C.

PhylomeDB

O95760.

Gene expression databases

ArrayExpress

O95760.

Bgee

O95760.

CleanEx

HS_IL33.

Genevestigator

O95760.

GermOnline

ENSG00000137033. Homo sapiens.

Family and domain databases

ProtoNet

Search...

Other

EvolutionaryTrace

O95760.

NextBio

77016.

SOURCE

Search...

Entry information

Entry name

IL33_HUMAN

Accession

Primary (citable) accession number: O95760
Secondary accession number(s): B4E1Q9, D3DRI5, Q2YEJ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2005
Last sequence update:	May 1, 1999
Last modified:	May 16, 2012
This is version 82 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.