インターロイキン-1受容体アンタゴニスト

IL1RN
PDBに登録されている構造
PDBオルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧

1ILR, 1ILT, 1IRA, 1IRP, 2IRT

識別子
記号IL1RN, DIRA, ICIL-1RA, IL-1RN, IL-1ra, IL-1ra3, IL1F3, IL1RA, IRAP, MVCD4, interleukin 1 receptor antagonist
外部IDOMIM: 147679 MGI: 96547 HomoloGene: 11163 GeneCards: IL1RN
遺伝子の位置 (ヒト)
2番染色体 (ヒト)
染色体2番染色体 (ヒト)[1]
2番染色体 (ヒト)
IL1RN遺伝子の位置
IL1RN遺伝子の位置
バンドデータ無し開始点113,099,315 bp[1]
終点113,134,016 bp[1]
遺伝子の位置 (マウス)
2番染色体 (マウス)
染色体2番染色体 (マウス)[2]
2番染色体 (マウス)
IL1RN遺伝子の位置
IL1RN遺伝子の位置
バンドデータ無し開始点24,226,865 bp[2]
終点24,241,506 bp[2]
RNA発現パターン




さらなる参照発現データ
遺伝子オントロジー
分子機能 interleukin-1 type I receptor antagonist activity
interleukin-1, type II receptor binding
血漿タンパク結合
interleukin-1, type I receptor binding
interleukin-1 type II receptor antagonist activity
interleukin-1 receptor binding
cytokine activity
interleukin-1 receptor antagonist activity
細胞の構成要素 細胞質
小胞
細胞膜
細胞内
細胞外領域
エキソソーム
細胞外空間
生物学的プロセス negative regulation of interleukin-1-mediated signaling pathway
脂質代謝
糖質コルチコイドへの反応
insulin secretion
acute-phase response
negative regulation of heterotypic cell-cell adhesion
negative regulation of cytokine-mediated signaling pathway
炎症反応
免疫応答
fever generation
regulation of signaling receptor activity
サイトカイン媒介シグナル伝達経路
neutrophil chemotaxis
positive regulation of interleukin-6 production
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of JNK cascade
interleukin-1-mediated signaling pathway
cellular response to lipopolysaccharide
出典:Amigo / QuickGO
オルソログ
ヒトマウス
Entrez
Ensembl
UniProt
RefSeq
(mRNA)
NM_000577
NM_173841
NM_173842
NM_173843
NM_001318914

NM_001379360

NM_001039701
NM_001159562
NM_031167

RefSeq
(タンパク質)
NP_000568
NP_001305843
NP_776213
NP_776214
NP_776215

NP_001366289

NP_001034790
NP_001153034
NP_112444

場所
(UCSC)
Chr 2: 113.1 – 113.13 MbChr 2: 24.23 – 24.24 Mb
PubMed検索[3][4]
ウィキデータ
閲覧/編集 ヒト閲覧/編集 マウス

インターロイキン-1受容体アンタゴニストまたはインターロイキン1受容体拮抗分子(インターロイキン1じゅようたいアンタゴニスト/きっこうぶんし、: interleukin 1 receptor antagonist、略称: IL-1Ra、IL1RNなど)は、ヒトではIL1RN遺伝子にコードされるタンパク質である[5][6]。IL-1Raは当初は"IL-1 inhibitor"と呼ばれており、1984年に2つの研究室によって独立に発見された[7]。IL-1Raは細胞表面のインターロイキン-1受容体英語版(IL-1R)に対して非生産的な結合を行う因子であり、インターロイキン-1(IL-1)ファミリーと同じ受容体に結合することでIL-1による細胞へのシグナル伝達を防ぐ役割を果たす。

機能

IL-1RaはIL-1サイトカインファミリーの一員である。IL-1Raは、免疫系細胞、上皮細胞脂肪細胞などさまざまな細胞種から分泌され、IL-1βの炎症促進作用に対する天然の阻害因子である[8]。このタンパク質はIL-1α英語版とIL-1βの活性を阻害し、さまざまなIL-1関連免疫・炎症応答を調節する。IL1RN遺伝子とその他5つの密接に関連したサイトカイン遺伝子は、2番染色体英語版上の約400 kbにわたって遺伝子クラスターを形成している。IL1RN遺伝子には、異なるアイソフォームをコードするいくつかの選択的スプライシングバリアントが報告されている[9]

臨床的意義

IL1RN遺伝子の多型は、骨粗鬆症性骨折[10]胃がん[11]のリスクの増加と関係していることが報告されている。また、IL1RN遺伝子の変異はインターロイキンI受容体拮抗分子欠損症英語版[12](DIRA)と呼ばれる希少疾患の原因となる[13]

IL1RN遺伝子の多型は統合失調症のリスクとも関係している[14][15]。統合失調症患者では血清IL-1Ra濃度の上昇がみられる[16]

アナキンラ英語版と呼ばれる、わずかに改変された組換え型IL-1Raが関節リウマチの治療に使用されている[17]。関節リウマチはIL-1が重要な役割を果たす自己免疫疾患である。アナキンラと天然型ヒトIL-1Raは、N末端メチオニン残基が1つ付加されている点で異なっている[18]

出典

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000136689 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026981 - Ensembl, May 2017
  3. ^ Human PubMed Reference:
  4. ^ Mouse PubMed Reference:
  5. ^ “The human IL-1 receptor antagonist gene (IL1RN) maps to chromosome 2q14-q21, in the region of the IL-1 alpha and IL-1 beta loci”. Genomics 13 (3): 654–7. (July 1992). doi:10.1016/0888-7543(92)90137-H. PMID 1386337. 
  6. ^ “The human interleukin-1 receptor antagonist (IL1RN) gene is located in the chromosome 2q14 region”. Genomics 15 (1): 173–6. (January 1993). doi:10.1006/geno.1993.1025. PMID 8432529. 
  7. ^ Dinarello CA (December 1994). “The interleukin-1 family: 10 years of discovery”. FASEB J. 8 (15): 1314–25. doi:10.1096/fasebj.8.15.8001745. PMID 8001745. 
  8. ^ “IL-1 receptor antagonist in metabolic diseases: Dr Jekyll or Mr Hyde?”. FEBS Lett. 580 (27): 6289–94. (November 2006). doi:10.1016/j.febslet.2006.10.061. PMID 17097645. 
  9. ^ Entrez Gene: IL1RN interleukin 1 receptor antagonist”. 2022年12月30日閲覧。
  10. ^ “Osteoporotic fractures are associated with an 86-base pair repeat polymorphism in the interleukin-1--receptor antagonist gene but not with polymorphisms in the interleukin-1beta gene”. J. Bone Miner. Res. 15 (3): 402–14. (March 2000). doi:10.1359/jbmr.2000.15.3.402. PMID 10750554. 
  11. ^ “Interleukin-1 polymorphisms associated with increased risk of gastric cancer”. Nature 404 (6776): 398–402. (March 2000). doi:10.1038/35006081. PMID 10746728. http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1131&context=publichealthresources. 
  12. ^ インターロイキンⅠ受容体拮抗分子欠損症 概要 - 小児慢性特定疾病情報センター”. www.shouman.jp. 2022年12月30日閲覧。
  13. ^ “An Autoinflammatory Disease with Deficiency of the Interleukin-1–Receptor Antagonist”. N. Engl. J. Med. 360 (23): 2426–37. (June 2009). doi:10.1056/NEJMoa0807865. PMC 2876877. PMID 19494218. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876877/. 
  14. ^ “Impact of IL-1 receptor antagonist gene polymorphism on schizophrenia and bipolar disorder”. Psychiatr. Genet. 14 (3): 165–7. (September 2004). doi:10.1097/00041444-200409000-00009. PMID 15318032. 
  15. ^ “Association between IL-1beta -511C/T and IL-1RA (86bp)n repeats polymorphisms and schizophrenia”. J Psychiatr Res 37 (6): 457–62. (2003). doi:10.1016/S0022-3956(03)00072-4. PMID 14563376. 
  16. ^ “Similar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor”. Bipolar Disord 11 (7): 726–34. (November 2009). doi:10.1111/j.1399-5618.2009.00757.x. hdl:10852/34620. PMID 19839997. 
  17. ^ “Anakinra for rheumatoid arthritis”. The Cochrane Database of Systematic Reviews (1): CD005121. (January 2009). doi:10.1002/14651858.CD005121.pub3. PMID 19160248. 
  18. ^ Kineret (anakinra) injection, for subcutaneous use”. Swedish Orphan Biovitrum. 2022年12月30日閲覧。

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