TNF受容体1型

TNF受容体1型（1型TNF受容体、tumor necrosis factor receptor 1、TNFR1）、TNFRSF1A（tumor necrosis factor receptor superfamily, member 1A）またはCD120aはTNF-αを結合する膜受容体であり、普遍的に発現している^[5][6][7]。

TNFRSF1A
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 1EXT, 1FT4, 1ICH, 1NCF, 1TNR
識別子
記号	TNFRSF1A, CD120a, FPF, MS5, TBP1, TNF-R, TNF-R-I, TNF-R55, TNFAR, TNFR1, TNFR1-d2, TNFR55, TNFR60, p55, p55-R, p60, tumor necrosis factor receptor superfamily member 1A, TNF receptor superfamily member 1A
外部ID	OMIM: 191190 MGI: 1314884 HomoloGene: 828 GeneCards: TNFRSF1A
遺伝子の位置 (ヒト) 染色体 12番染色体 (ヒト)[1] バンド データ無し 開始点 6,328,757 bp[1] 終点 6,342,114 bp[1]
遺伝子の位置 (マウス) 染色体 6番染色体 (マウス)[2] バンド データ無し 開始点 125,326,325 bp[2] 終点 125,339,447 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 • 血漿タンパク結合 • tumor necrosis factor-activated receptor activity • tumor necrosis factor binding • identical protein binding 細胞の構成要素 • integral component of membrane • ゴルジ体 • 膜 • ゴルジ膜 • receptor complex • 細胞膜 • integral component of plasma membrane • 細胞外領域 • cell surface • ミトコンドリア • 脂質ラフト • 細胞外空間 • tumor necrosis factor receptor superfamily complex 生物学的プロセス • regulation of apoptotic process • prostaglandin metabolic process • 防衛反応 • positive regulation of ceramide biosynthetic process • positive regulation of inflammatory response • regulation of tumor necrosis factor-mediated signaling pathway • tumor necrosis factor-mediated signaling pathway • リポ多糖への反応 • cellular response to mechanical stimulus • death-inducing signaling complex assembly • regulation of cell population proliferation • defense response to bacterium • 免疫応答 • intrinsic apoptotic signaling pathway in response to DNA damage • positive regulation of I-kappaB kinase/NF-kappaB signaling • viral process • I-kappaB kinase/NF-kappaB signaling • negative regulation of inflammatory response • regulation of establishment of endothelial barrier • extrinsic apoptotic signaling pathway via death domain receptors • positive regulation of transcription by RNA polymerase II • シグナル伝達 • アポトーシス • 炎症反応 • 細胞表面受容体シグナル伝達経路 • positive regulation of tyrosine phosphorylation of STAT protein • protein localization to plasma membrane • サイトカイン媒介シグナル伝達経路 • 大動脈弁発生 • 肺動脈弁発生 • negative regulation of extracellular matrix constituent secretion • negative regulation of cardiac muscle hypertrophy • positive regulation of apoptotic process involved in morphogenesis 出典:Amigo / QuickGO
オルソログ
種	ヒト	マウス
Entrez	7132	21937
Ensembl	ENSG00000067182	ENSMUSG00000030341
UniProt	P19438,F5H8A6	P25118
RefSeq (mRNA)	NM_001065 NM_001346091 NM_001346092	NM_011609
RefSeq (タンパク質)	NP_001056 NP_001333020 NP_001333021	NP_035739
場所 (UCSC)	Chr 12: 6.33 – 6.34 Mb	Chr 12: 125.33 – 125.34 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

機能

TNFRSF1A遺伝子にコードされるTNFR1は、TNFR2（英語版）などとともにTNF受容体スーパーファミリー（英語版）を構成する。このタンパク質はTNF-αに対する主要な受容体の1つであり、転写因子NF-κBの活性化、アポトーシスの媒介、炎症の調節といった機能を果たす。抗アポトーシスタンパク質BAG4（英語版）やアダプタータンパク質TRADD（英語版）、TRAF2（英語版）がこの受容体と相互作用することが示されており、これらは受容体によって媒介されるシグナル伝達を調節する役割を果たしている^[8]。

臨床的意義

この受容体の細胞外ドメイン領域に生じた生殖細胞系列変異（英語版）は、TNF受容体関連周期性症候群（英語版）（TRAPS）と呼ばれる遺伝疾患との関連が示されている^[9]。この疾患の機序には受容体のクリアランスの機能不全が関係していると考えられている。

TNFRSF1A遺伝子の変異は、多発性硬化症のリスクの増大と関連している^[10]。

統合失調症や双極性障害の患者では血清中の可溶性TNFR1濃度が上昇しており^[11]、高値はより重篤な精神症状と関連している^[12]。また、血清中の高濃度は認知機能障害や認知症とも関連している^[13][14]。

相互作用

TNFRSF1Aは次に挙げる因子と相互作用することが示されている。

• BAG4（英語版）^[15][16]
• CASP10（英語版）^[17][18]
• FADD^[17][19]
• IKK2（英語版）^[20][21]
• JAK1（英語版）^[22][23]
• JAK2（英語版）^[22]
• PIP4K2B（英語版）^[24]
• PSMD2（英語版）^[25][26]
• RIPK1^{[27][28][29][30][31][32]}
• SUMO1（英語版）^[33][34]
• TRADD（英語版）^{[15][19][27][30][35][36][37]}
• TRAF2（英語版）^[19][27][35]
• TRPC4AP（英語版）^[38]
• TNF^[39][40]
• UBE2I（英語版）^[41]

出典

1. GRCh38: Ensembl release 89: ENSG00000067182 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030341 - Ensembl, May 2017
3. Human PubMed Reference:
4. Mouse PubMed Reference:
5. “Chromosomal location of the human tumor necrosis factor receptor genes”. Cytogenet Cell Genet 57 (2–3): 117–8. (November 1991). doi:10.1159/000133127. PMID 1655358.
6. “Molecular cloning and expression of a receptor for human tumor necrosis factor”. Cell 61 (2): 361–70. (June 1990). doi:10.1016/0092-8674(90)90816-W. PMID 2158863. http://www.escholarship.org/uc/item/39j2j0h2.
7. Offermanns, Stefan; Rosenthal, Walter (2008). Encyclopedia of Molecular Pharmacology, Vol. 1 (2nd ed.). Heidelberg, Germany: Springer. p. 1248. ISBN 9783540389163. https://books.google.com/books?id=iwwo5gx8aX8C
8. “Entrez Gene: TNFRSF1A tumor necrosis factor receptor superfamily, member 1A”. 2007年11月2日閲覧。
9. “Multiple sclerosis. TNFRSF1A, TRAPS and multiple sclerosis”. Nat Rev Neurol 5 (10): 528–9. (October 2009). doi:10.1038/nrneurol.2009.154. PMID 19794511.
10. International Multiple Sclerosis Genetics Consortium (2011). “The genetic association of variants in CD6, TNFRSF1A and IRF8 to multiple sclerosis: a multicenter case-control study”. PLOS ONE 6 (4): e18813. Bibcode: 2011PLoSO...618813.. doi:10.1371/journal.pone.0018813. PMC 3084233. PMID 21552549. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084233/.
11. “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.
12. “Interleukin 1 receptor antagonist and soluble tumor necrosis factor receptor 1 are associated with general severity and psychotic symptoms in schizophrenia and bipolar disorder”. Schizophr. Res. 145 (1–3): 36–42. (April 2013). doi:10.1016/j.schres.2012.12.023. PMID 23403415.
13. “Soluble TNF receptors are associated with Aβ metabolism and conversion to dementia in subjects with mild cognitive impairment”. Neurobiol. Aging 31 (11): 1877–84. (November 2010). doi:10.1016/j.neurobiolaging.2008.10.012. PMID 19070941.
14. “Higher serum sTNFR1 level predicts conversion from mild cognitive impairment to Alzheimer's disease”. J. Alzheimers Dis. 22 (4): 1305–11. (2010). doi:10.3233/JAD-2010-100921. PMID 20930310.
15. “Prevention of constitutive TNF receptor 1 signaling by silencer of death domains”. Science 283 (5401): 543–6. (1999). Bibcode: 1999Sci...283..543J. doi:10.1126/science.283.5401.543. PMID 9915703.
16. “Tumor necrosis factor receptor 1 is an ATPase regulated by silencer of death domain”. Mol. Cell. Biol. 22 (8): 2536–43. (2002). doi:10.1128/MCB.22.8.2536-2543.2002. PMC 133739. PMID 11909948. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC133739/.
17. “Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy”. J. Biol. Chem. 280 (12): 11641–7. (2005). doi:10.1074/jbc.M411781200. PMID 15659383.
18. “Fas-associated death domain protein interleukin-1beta-converting enzyme 2 (FLICE2), an ICE/Ced-3 homologue, is proximally involved in CD95- and p55-mediated death signaling”. J. Biol. Chem. 272 (10): 6578–83. (1997). doi:10.1074/jbc.272.10.6578. PMID 9045686.
19. “TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways”. Cell 84 (2): 299–308. (1996). doi:10.1016/S0092-8674(00)80984-8. PMID 8565075.
20. “Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation”. Immunity 12 (3): 301–11. (2000). doi:10.1016/S1074-7613(00)80183-1. PMID 10755617.
21. “Activation of the NF-kappaB pathway by caspase 8 and its homologs”. Oncogene 19 (39): 4451–60. (2000). doi:10.1038/sj.onc.1203812. PMID 11002417.
22. “Induction of Jak/STAT signaling by activation of the type 1 TNF receptor”. J. Immunol. 160 (6): 2742–50. (1998). doi:10.4049/jimmunol.160.6.2742. PMID 9510175.
23. “Tumor necrosis factor alpha (TNF-alpha) activates Jak1/Stat3-Stat5B signaling through TNFR-1 in human B cells”. Cell Growth Differ. 13 (1): 13–8. (2002). PMID 11801527.
24. “A novel interaction between the juxtamembrane region of the p55 tumor necrosis factor receptor and phosphatidylinositol-4-phosphate 5-kinase”. J. Biol. Chem. 272 (9): 5861–70. (1997). doi:10.1074/jbc.272.9.5861. PMID 9038203.
25. “A protein related to a proteasomal subunit binds to the intracellular domain of the p55 TNF receptor upstream to its 'death domain'”. FEBS Lett. 367 (1): 39–44. (1995). doi:10.1016/0014-5793(95)00534-G. PMID 7601280.
26. “Two-hybrid cloning of a gene encoding TNF receptor-associated protein 2, a protein that interacts with the intracellular domain of the type 1 TNF receptor: identity with subunit 2 of the 26S protease”. J. Immunol. 158 (9): 4252–9. (1997). doi:10.4049/jimmunol.158.9.4252. PMID 9126987.
27. “TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex”. Immunity 4 (4): 387–96. (1996). doi:10.1016/S1074-7613(00)80252-6. PMID 8612133.
28. “Activation of death-inducing signaling complex (DISC) by pro-apoptotic C-terminal fragment of RIP”. Oncogene 19 (39): 4491–9. (2000). doi:10.1038/sj.onc.1203796. PMID 11002422.
29. “RAIDD is a new 'death' adaptor molecule”. Nature 385 (6611): 86–9. (1997). Bibcode: 1997Natur.385...86D. doi:10.1038/385086a0. hdl:2027.42/62739. PMID 8985253. https://deepblue.lib.umich.edu/bitstream/2027.42/62739/1/385086a0.pdf.
30. “Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1)”. Biochem. J. 417 (1): 149–60. (2009). doi:10.1042/BJ20081885. PMID 18939944.
31. “Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies”. Cell 134 (4): 668–78. (2008). doi:10.1016/j.cell.2008.07.039. PMID 18724939.
32. “c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation”. J. Biol. Chem. 283 (36): 24295–9. (2008). doi:10.1074/jbc.C800128200. PMC 3259840. PMID 18621737. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259840/.
33. “The ubiquitin-homology protein, DAP-1, associates with tumor necrosis factor receptor (p60) death domain and induces apoptosis”. J. Biol. Chem. 274 (15): 10145–53. (1999). doi:10.1074/jbc.274.15.10145. PMID 10187798.
34. “Protection against Fas/APO-1- and tumor necrosis factor-mediated cell death by a novel protein, sentrin”. J. Immunol. 157 (10): 4277–81. (1996). doi:10.4049/jimmunol.157.10.4277. PMID 8906799.
35. “The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex”. Proc. Natl. Acad. Sci. U.S.A. 93 (24): 13973–8. (1996). Bibcode: 1996PNAS...9313973S. doi:10.1073/pnas.93.24.13973. PMC 19479. PMID 8943045. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC19479/.
36. “Inhibition of receptor internalization by monodansylcadaverine selectively blocks p55 tumor necrosis factor receptor death domain signaling”. J. Biol. Chem. 274 (15): 10203–12. (1999). doi:10.1074/jbc.274.15.10203. PMID 10187805.
37. “The receptor for the cytotoxic ligand TRAIL”. Science 276 (5309): 111–3. (1997). doi:10.1126/science.276.5309.111. PMID 9082980.
38. “TRUSS, a novel tumor necrosis factor receptor 1 scaffolding protein that mediates activation of the transcription factor NF-kappaB”. Mol. Cell. Biol. 23 (22): 8334–44. (2003). doi:10.1128/MCB.23.22.8334-8344.2003. PMC 262424. PMID 14585990. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC262424/.
39. “A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway”. Nat. Cell Biol. 6 (2): 97–105. (2004). doi:10.1038/ncb1086. PMID 14743216.
40. “The TNF receptor 1: a split personality complex”. Cell 114 (2): 148–50. (2003). doi:10.1016/s0092-8674(03)00561-0. PMID 12887914.
41. “hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity”. FEBS Lett. 425 (3): 431–5. (1998). doi:10.1016/S0014-5793(98)00287-7. PMID 9563508.

関連文献

• “TNF-induced signaling in apoptosis”. J. Clin. Immunol. 19 (6): 350–64. (2000). doi:10.1023/A:1020546615229. PMID 10634209.
• “TNF-R1 signaling: a beautiful pathway”. Science 296 (5573): 1634–5. (2002). Bibcode: 2002Sci...296.1634C. doi:10.1126/science.1071924. PMID 12040173.
• “Role of TNF/TNFR in autoimmunity: specific TNF receptor blockade may be advantageous to anti-TNF treatments”. Cytokine Growth Factor Rev. 13 (4–5): 315–21. (2003). doi:10.1016/S1359-6101(02)00019-9. PMID 12220546.
• “TNFRSF1A-associated periodic syndrome (TRAPS), Muckle–Wells syndrome (MWS) and renal amyloidosis”. J. Nephrol. 16 (3): 435–7. (2003). PMID 12832748.
• “The tumour necrosis factor receptor-associated periodic syndrome: current concepts”. Expert Reviews in Molecular Medicine 7 (22): 1–18. (2007). doi:10.1017/S1462399405009749. PMID 16216134.
• Rezaei N (2007). “TNF-receptor-associated periodic syndrome (TRAPS): an autosomal dominant multisystem disorder”. Clin. Rheumatol. 25 (6): 773–7. doi:10.1007/s10067-005-0198-6. PMID 16447098.

関連項目

• CD分類
• TNF受容体関連周期性症候群（英語版）

外部リンク

• TNFRSF1A protein, human - MeSH・アメリカ国立医学図書館・生命科学用語シソーラス（英語）
• Overview of all the structural information available in the PDB for UniProt: P19438 (Tumor necrosis factor receptor superfamily member 1A) at the PDBe-KB.