Tumor necrosis factor receptor superfamily member 1A

Details

Name

Tumor necrosis factor receptor superfamily member 1A

Synonyms

• p55
• p60
• TNF-R1
• TNF-RI
• TNFAR
• TNFR-I
• TNFR1
• Tumor necrosis factor receptor 1
• Tumor necrosis factor receptor type I

Gene Name

TNFRSF1A

Organism

Humans

Amino acid sequence

>lcl|BSEQ0002265|Tumor necrosis factor receptor superfamily member 1A
MGLSTVPDLLLPLVLLELLVGIYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQNNSICCT
KCHKGTYLYNDCPGPGQDTDCRECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTVD
RDTVCGCRKNQYRHYWSENLFQCFNCSLCLNGTVHLSCQEKQNTVCTCHAGFFLRENECV
SCSNCKKSLECTKLCLPQIENVKGTEDSGTTVLLPLVIFFGLCLLSLLFIGLMYRYQRWK
SKLYSIVCGKSTPEKEGELEGTTTKPLAPNPSFSPTPGFTPTLGFSPVPSSTFTSSSTYT
PGDCPNFAAPRREVAPPYQGADPILATALASDPIPNPLQKWEDSAHKPQSLDTDDPATLY
AVVENVPPLRWKEFVRRLGLSDHEIDRLELQNGRCLREAQYSMLATWRRRTPRREATLEL
LGRVLRDMDLLGCLEDIEEALCGPAALPPAPSLLR

Number of residues

455

Molecular Weight

50494.3

Theoretical pI

6.62

GO Classification

Functions

tumor necrosis factor binding / tumor necrosis factor-activated receptor activity

Processes

cell surface receptor signaling pathway / cellular response to mechanical stimulus / cytokine-mediated signaling pathway / death-inducing signaling complex assembly / defense response to bacterium / establishment of protein localization to plasma membrane / extrinsic apoptotic signaling pathway via death domain receptors / I-kappaB kinase/NF-kappaB signaling / immune response / inflammatory response / intrinsic apoptotic signaling pathway in response to DNA damage / multicellular organismal development / negative regulation of inflammatory response / positive regulation of ceramide biosynthetic process / positive regulation of I-kappaB kinase/NF-kappaB signaling / positive regulation of inflammatory response / positive regulation of transcription from RNA polymerase II promoter / positive regulation of tyrosine phosphorylation of Stat1 protein / prostaglandin metabolic process / regulation of apoptotic process / regulation of cell proliferation / regulation of establishment of endothelial barrier / regulation of tumor necrosis factor-mediated signaling pathway / response to lipopolysaccharide / tumor necrosis factor-mediated signaling pathway / viral process

Components

cell surface / extracellular region / extracellular space / Golgi membrane / integral component of plasma membrane / membrane raft / mitochondrion / plasma membrane / receptor complex

General Function

Tumor necrosis factor-activated receptor activity

Specific Function

Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.

Pfam Domain Function

• TNFR_c6 (PF00020)
• Death (PF00531)

Transmembrane Regions

212-234

Cellular Location

Cell membrane

Gene sequence

>lcl|BSEQ0019072|Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)
ATGGGCCTCTCCACCGTGCCTGACCTGCTGCTGCCACTGGTGCTCCTGGAGCTGTTGGTG
GGAATATACCCCTCAGGGGTTATTGGACTGGTCCCTCACCTAGGGGACAGGGAGAAGAGA
GATAGTGTGTGTCCCCAAGGAAAATATATCCACCCTCAAAATAATTCGATTTGCTGTACC
AAGTGCCACAAAGGAACCTACTTGTACAATGACTGTCCAGGCCCGGGGCAGGATACGGAC
TGCAGGGAGTGTGAGAGCGGCTCCTTCACCGCTTCAGAAAACCACCTCAGACACTGCCTC
AGCTGCTCCAAATGCCGAAAGGAAATGGGTCAGGTGGAGATCTCTTCTTGCACAGTGGAC
CGGGACACCGTGTGTGGCTGCAGGAAGAACCAGTACCGGCATTATTGGAGTGAAAACCTT
TTCCAGTGCTTCAATTGCAGCCTCTGCCTCAATGGGACCGTGCACCTCTCCTGCCAGGAG
AAACAGAACACCGTGTGCACCTGCCATGCAGGTTTCTTTCTAAGAGAAAACGAGTGTGTC
TCCTGTAGTAACTGTAAGAAAAGCCTGGAGTGCACGAAGTTGTGCCTACCCCAGATTGAG
AATGTTAAGGGCACTGAGGACTCAGGCACCACAGTGCTGTTGCCCCTGGTCATTTTCTTT
GGTCTTTGCCTTTTATCCCTCCTCTTCATTGGTTTAATGTATCGCTACCAACGGTGGAAG
TCCAAGCTCTACTCCATTGTTTGTGGGAAATCGACACCTGAAAAAGAGGGGGAGCTTGAA
GGAACTACTACTAAGCCCCTGGCCCCAAACCCAAGCTTCAGTCCCACTCCAGGCTTCACC
CCCACCCTGGGCTTCAGTCCCGTGCCCAGTTCCACCTTCACCTCCAGCTCCACCTATACC
CCCGGTGACTGTCCCAACTTTGCGGCTCCCCGCAGAGAGGTGGCACCACCCTATCAGGGG
GCTGACCCCATCCTTGCGACAGCCCTCGCCTCCGACCCCATCCCCAACCCCCTTCAGAAG
TGGGAGGACAGCGCCCACAAGCCACAGAGCCTAGACACTGATGACCCCGCGACGCTGTAC
GCCGTGGTGGAGAACGTGCCCCCGTTGCGCTGGAAGGAATTCGTGCGGCGCCTAGGGCTG
AGCGACCACGAGATCGATCGGCTGGAGCTGCAGAACGGGCGCTGCCTGCGCGAGGCGCAA
TACAGCATGCTGGCGACCTGGAGGCGGCGCACGCCGCGGCGCGAGGCCACGCTGGAGCTG
CTGGGACGCGTGCTCCGCGACATGGACCTGCTGGGCTGCCTGGAGGACATCGAGGAGGCG
CTTTGCGGCCCCGCCGCCCTCCCGCCCGCGCCCAGTCTTCTCAGATGA

Chromosome Location

12

Locus

12p13.2

External Identifiers

Resource	Link
UniProtKB ID	P19438
UniProtKB Entry Name	TNR1A_HUMAN
GenBank Protein ID	37224
GenBank Gene ID	X55313
GenAtlas ID	TNFRSF1A
HGNC ID	HGNC:11916

General References

1. Loetscher H, Pan YC, Lahm HW, Gentz R, Brockhaus M, Tabuchi H, Lesslauer W: Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Cell. 1990 Apr 20;61(2):351-9. [Article]
2. Schall TJ, Lewis M, Koller KJ, Lee A, Rice GC, Wong GH, Gatanaga T, Granger GA, Lentz R, Raab H, et al.: Molecular cloning and expression of a receptor for human tumor necrosis factor. Cell. 1990 Apr 20;61(2):361-70. [Article]
3. Himmler A, Maurer-Fogy I, Kronke M, Scheurich P, Pfizenmaier K, Lantz M, Olsson I, Hauptmann R, Stratowa C, Adolf GR: Molecular cloning and expression of human and rat tumor necrosis factor receptor chain (p60) and its soluble derivative, tumor necrosis factor-binding protein. DNA Cell Biol. 1990 Dec;9(10):705-15. [Article]
4. Nophar Y, Kemper O, Brakebusch C, Englemann H, Zwang R, Aderka D, Holtmann H, Wallach D: Soluble forms of tumor necrosis factor receptors (TNF-Rs). The cDNA for the type I TNF-R, cloned using amino acid sequence data of its soluble form, encodes both the cell surface and a soluble form of the receptor. EMBO J. 1990 Oct;9(10):3269-78. [Article]
5. Gray PW, Barrett K, Chantry D, Turner M, Feldmann M: Cloning of human tumor necrosis factor (TNF) receptor cDNA and expression of recombinant soluble TNF-binding protein. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7380-4. [Article]
6. Fuchs P, Strehl S, Dworzak M, Himmler A, Ambros PF: Structure of the human TNF receptor 1 (p60) gene (TNFR1) and localization to chromosome 12p13 [corrected]. Genomics. 1992 May;13(1):219-24. [Article]
7. 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 TO, 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: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
8. Wang P, Yu P, Gao P, Shi T, Ma D: Discovery of novel human transcript variants by analysis of intronic single-block EST with polyadenylation site. BMC Genomics. 2009 Nov 12;10:518. doi: 10.1186/1471-2164-10-518. [Article]
9. Scherer SE, Muzny DM, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Montgomery KT, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Lovering RC, Wheeler DA, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clerc-Blankenburg KP, Davis C, Delgado O, Dinh HH, Draper H, Gonzalez-Garay ML, Havlak P, Jackson LR, Jacob LS, Kelly SH, Li L, Li Z, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Pasternak S, Perez LM, Plopper FJ, Santibanez J, Shen H, Tabor PE, Verduzco D, Waldron L, Wang Q, Williams GA, Zhang J, Zhou J, Allen CC, Amin AG, Anyalebechi V, Bailey M, Barbaria JA, Bimage KE, Bryant NP, Burch PE, Burkett CE, Burrell KL, Calderon E, Cardenas V, Carter K, Casias K, Cavazos I, Cavazos SR, Ceasar H, Chacko J, Chan SN, Chavez D, Christopoulos C, Chu J, Cockrell R, Cox CD, Dang M, Dathorne SR, David R, Davis CM, Davy-Carroll L, Deshazo DR, Donlin JE, D'Souza L, Eaves KA, Egan A, Emery-Cohen AJ, Escotto M, Flagg N, Forbes LD, Gabisi AM, Garza M, Hamilton C, Henderson N, Hernandez O, Hines S, Hogues ME, Huang M, Idlebird DG, Johnson R, Jolivet A, Jones S, Kagan R, King LM, Leal B, Lebow H, Lee S, LeVan JM, Lewis LC, London P, Lorensuhewa LM, Loulseged H, Lovett DA, Lucier A, Lucier RL, Ma J, Madu RC, Mapua P, Martindale AD, Martinez E, Massey E, Mawhiney S, Meador MG, Mendez S, Mercado C, Mercado IC, Merritt CE, Miner ZL, Minja E, Mitchell T, Mohabbat F, Mohabbat K, Montgomery B, Moore N, Morris S, Munidasa M, Ngo RN, Nguyen NB, Nickerson E, Nwaokelemeh OO, Nwokenkwo S, Obregon M, Oguh M, Oragunye N, Oviedo RJ, Parish BJ, Parker DN, Parrish J, Parks KL, Paul HA, Payton BA, Perez A, Perrin W, Pickens A, Primus EL, Pu LL, Puazo M, Quiles MM, Quiroz JB, Rabata D, Reeves K, Ruiz SJ, Shao H, Sisson I, Sonaike T, Sorelle RP, Sutton AE, Svatek AF, Svetz LA, Tamerisa KS, Taylor TR, Teague B, Thomas N, Thorn RD, Trejos ZY, Trevino BK, Ukegbu ON, Urban JB, Vasquez LI, Vera VA, Villasana DM, Wang L, Ward-Moore S, Warren JT, Wei X, White F, Williamson AL, Wleczyk R, Wooden HS, Wooden SH, Yen J, Yoon L, Yoon V, Zorrilla SE, Nelson D, Kucherlapati R, Weinstock G, Gibbs RA: The finished DNA sequence of human chromosome 12. Nature. 2006 Mar 16;440(7082):346-51. [Article]
10. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
11. Suzuki J, Tomizawa S, Arai H, Seki Y, Maruyama K, Kuroume T: Purification of two types of TNF inhibitors in the urine of the patient with chronic glomerulonephritis. Nephron. 1994;66(4):386-90. [Article]
12. Engelmann H, Novick D, Wallach D: Two tumor necrosis factor-binding proteins purified from human urine. Evidence for immunological cross-reactivity with cell surface tumor necrosis factor receptors. J Biol Chem. 1990 Jan 25;265(3):1531-6. [Article]
13. Zhu N, Khoshnan A, Schneider R, Matsumoto M, Dennert G, Ware C, Lai MM: Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosis factor (TNF) receptor 1 and enhances TNF-induced apoptosis. J Virol. 1998 May;72(5):3691-7. [Article]
14. Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J: The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation. EMBO J. 1999 Jun 1;18(11):3044-53. [Article]
15. Chan SL, Tan KO, Zhang L, Yee KS, Ronca F, Chan MY, Yu VC: F1Aalpha, a death receptor-binding protein homologous to the Caenorhabditis elegans sex-determining protein, FEM-1, is a caspase substrate that mediates apoptosis. J Biol Chem. 1999 Nov 5;274(45):32461-8. [Article]
16. Hildt E, Oess S: Identification of Grb2 as a novel binding partner of tumor necrosis factor (TNF) receptor I. J Exp Med. 1999 Jun 7;189(11):1707-14. [Article]
17. Jiang Y, Woronicz JD, Liu W, Goeddel DV: Prevention of constitutive TNF receptor 1 signaling by silencer of death domains. Science. 1999 Jan 22;283(5401):543-6. [Article]
18. Li Q, Ching AK, Chan BC, Chow SK, Lim PL, Ho TC, Ip WK, Wong CK, Lam CW, Lee KK, Chan JY, Chui YL: A death receptor-associated anti-apoptotic protein, BRE, inhibits mitochondrial apoptotic pathway. J Biol Chem. 2004 Dec 10;279(50):52106-16. Epub 2004 Oct 1. [Article]
19. Le VT, Trilling M, Hengel H: The cytomegaloviral protein pUL138 acts as potentiator of tumor necrosis factor (TNF) receptor 1 surface density to enhance ULb'-encoded modulation of TNF-alpha signaling. J Virol. 2011 Dec;85(24):13260-70. doi: 10.1128/JVI.06005-11. Epub 2011 Oct 5. [Article]
20. Gregory AP, Dendrou CA, Attfield KE, Haghikia A, Xifara DK, Butter F, Poschmann G, Kaur G, Lambert L, Leach OA, Promel S, Punwani D, Felce JH, Davis SJ, Gold R, Nielsen FC, Siegel RM, Mann M, Bell JI, McVean G, Fugger L: TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis. Nature. 2012 Aug 23;488(7412):508-11. doi: 10.1038/nature11307. [Article]
21. Banner DW, D'Arcy A, Janes W, Gentz R, Schoenfeld HJ, Broger C, Loetscher H, Lesslauer W: Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation. Cell. 1993 May 7;73(3):431-45. [Article]
22. Naismith JH, Devine TQ, Kohno T, Sprang SR: Structures of the extracellular domain of the type I tumor necrosis factor receptor. Structure. 1996 Nov 15;4(11):1251-62. [Article]
23. McDermott MF, Aksentijevich I, Galon J, McDermott EM, Ogunkolade BW, Centola M, Mansfield E, Gadina M, Karenko L, Pettersson T, McCarthy J, Frucht DM, Aringer M, Torosyan Y, Teppo AM, Wilson M, Karaarslan HM, Wan Y, Todd I, Wood G, Schlimgen R, Kumarajeewa TR, Cooper SM, Vella JP, Amos CI, Mulley J, Quane KA, Molloy MG, Ranki A, Powell RJ, Hitman GA, O'Shea JJ, Kastner DL: Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell. 1999 Apr 2;97(1):133-44. [Article]
24. Dode C, Papo T, Fieschi C, Pecheux C, Dion E, Picard F, Godeau P, Bienvenu J, Piette JC, Delpech M, Grateau G: A novel missense mutation (C30S) in the gene encoding tumor necrosis factor receptor 1 linked to autosomal-dominant recurrent fever with localized myositis in a French family. Arthritis Rheum. 2000 Jul;43(7):1535-42. [Article]
25. Aksentijevich I, Galon J, Soares M, Mansfield E, Hull K, Oh HH, Goldbach-Mansky R, Dean J, Athreya B, Reginato AJ, Henrickson M, Pons-Estel B, O'Shea JJ, Kastner DL: The tumor-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestral origins, genotype-phenotype studies, and evidence for further genetic heterogeneity of periodic fevers. Am J Hum Genet. 2001 Aug;69(2):301-14. Epub 2001 Jul 6. [Article]
26. Aganna E, Hammond L, Hawkins PN, Aldea A, McKee SA, van Amstel HK, Mischung C, Kusuhara K, Saulsbury FT, Lachmann HJ, Bybee A, McDermott EM, La Regina M, Arostegui JI, Campistol JM, Worthington S, High KP, Molloy MG, Baker N, Bidwell JL, Castaner JL, Whiteford ML, Janssens-Korpola PL, Manna R, Powell RJ, Woo P, Solis P, Minden K, Frenkel J, Yague J, Mirakian RM, Hitman GA, McDermott MF: Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes. Arthritis Rheum. 2003 Sep;48(9):2632-44. [Article]
27. Kusuhara K, Nomura A, Nakao F, Hara T: Tumour necrosis factor receptor-associated periodic syndrome with a novel mutation in the TNFRSF1A gene in a Japanese family. Eur J Pediatr. 2004 Jan;163(1):30-2. Epub 2003 Nov 11. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB03507	6-[3-(4-Morpholinyl)Propyl]-2-(3-Nitrophenyl)-5-Thioxo-5,6,-Dihydro-7h-Thienol[2',3':4,5]Pyrrolo[1,2-C]Imidazol-7-One	experimental	unknown		Details
DB11626	Tasonermin	approved	yes	agonist	Details