Tumor necrosis factor receptor 1

TNFRSF1A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1EXT, 1FT4, 1ICH, 1NCF, 1TNR
Identifiers
Aliases	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
External IDs	OMIM: 191190; MGI: 1314884; HomoloGene: 828; GeneCards: TNFRSF1A; OMA:TNFRSF1A - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12p13.31 Start 6,328,757 bp[1] End 6,342,114 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 F3|6 59.32 cM Start 125,326,325 bp[2] End 125,339,447 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tendon of biceps brachii gallbladder left uterine tube epithelium of colon right coronary artery upper lobe of left lung left adrenal cortex Descending thoracic aorta pericardium blood Top expressed in granulocyte tibiofemoral joint saccule lip stroma of bone marrow otic placode esophagus calvaria otic vesicle ankle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding tumor necrosis factor-activated receptor activity tumor necrosis factor binding identical protein binding Cellular component integral component of membrane Golgi apparatus membrane Golgi membrane receptor complex plasma membrane integral component of plasma membrane extracellular region cell surface mitochondrion membrane raft extracellular space tumor necrosis factor receptor superfamily complex Biological process regulation of apoptotic process prostaglandin metabolic process defense response 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 response to lipopolysaccharide cellular response to mechanical stimulus death-inducing signaling complex assembly regulation of cell population proliferation defense response to bacterium immune response 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 signal transduction apoptotic process inflammatory response cell surface receptor signaling pathway positive regulation of tyrosine phosphorylation of STAT protein protein localization to plasma membrane cytokine-mediated signaling pathway aortic valve development pulmonary valve development negative regulation of extracellular matrix constituent secretion negative regulation of cardiac muscle hypertrophy positive regulation of apoptotic process involved in morphogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7132 21937 Ensembl ENSG00000067182 ENSMUSG00000030341 UniProt P19438 P25118 RefSeq (mRNA) NM_001065 NM_001346091 NM_001346092 NM_011609 RefSeq (protein) NP_001056 NP_001333020 NP_001333021 NP_035739 Location (UCSC) Chr 12: 6.33 – 6.34 Mb Chr 6: 125.33 – 125.34 Mb PubMed search [3] [4]
Wikidata
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Tumor necrosis factor receptor 1 (TNFR1), also known as tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and CD120a, is a ubiquitous membrane receptor that binds tumor necrosis factor-alpha (TNFα).^[5][6][7]

Function

The protein encoded by this gene is a member of the tumor necrosis factor receptor superfamily, which also contains TNFRSF1B. This protein is one of the major receptors for the tumor necrosis factor-alpha. This receptor can activate the transcription factor NF-κB, mediate apoptosis, and function as a regulator of inflammation. Antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRADD and TRAF2 have been shown to interact with this receptor, and thus play regulatory roles in the signal transduction mediated by the receptor.^[8]

Clinical significance

Germline mutations of the extracellular domains of this receptor were found to be associated with the human genetic disorder called tumor necrosis factor associated periodic syndrome (TRAPS) or periodic fever syndrome.^[9] Impaired receptor clearance is thought to be a mechanism of the disease.

Mutations in the TNFRSF1A gene are associated with elevated risk of multiple sclerosis.^[10]

Serum levels of TNFRSF1A are elevated in schizophrenia and bipolar disorder,^[11] and high levels are associated with more severe psychotic symptoms.^[12]

High serum levels are also associated with cognitive impairment and dementia.^[13][14]

Interactions

TNFRSF1A has been shown to interact with:

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

See also

• Cluster of differentiation
• TNF receptor associated periodic syndrome

References

1. GRCh38: Ensembl release 89: ENSG00000067182 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030341 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Baker E, Chen LZ, Smith CA, Callen DF, Goodwin R, Sutherland GR (November 1991). "Chromosomal location of the human tumor necrosis factor receptor genes". Cytogenetics and Cell Genetics. 57 (2–3): 117–118. doi:10.1159/000133127. PMID 1655358.
6. Schall TJ, Lewis M, Koller KJ, Lee A, Rice GC, Wong GH, et al. (April 1990). "Molecular cloning and expression of a receptor for human tumor necrosis factor". Cell. 61 (2): 361–370. doi:10.1016/0092-8674(90)90816-W. PMID 2158863. S2CID 36187863.
7. Offermanns S, Rosenthal W (2008). Encyclopedia of Molecular Pharmacology. Vol. 1 (2nd ed.). Heidelberg, Germany: Springer. p. 1248. ISBN 9783540389163.
8. "Entrez Gene: TNFRSF1A tumor necrosis factor receptor superfamily, member 1A".
9. Kümpfel T, Hohlfeld R (October 2009). "Multiple sclerosis. TNFRSF1A, TRAPS and multiple sclerosis". Nature Reviews. Neurology. 5 (10): 528–529. doi:10.1038/nrneurol.2009.154. PMID 19794511. S2CID 40665495.
10. International Multiple Sclerosis Genetics Consortium (April 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.
11. Hope S, Melle I, Aukrust P, Steen NE, Birkenaes AB, Lorentzen S, et al. (November 2009). "Similar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor". Bipolar Disorders. 11 (7): 726–734. doi:10.1111/j.1399-5618.2009.00757.x. hdl:10852/34620. PMID 19839997.
12. Hope S, Ueland T, Steen NE, Dieset I, Lorentzen S, Berg AO, et al. (April 2013). "Interleukin 1 receptor antagonist and soluble tumor necrosis factor receptor 1 are associated with general severity and psychotic symptoms in schizophrenia and bipolar disorder". Schizophrenia Research. 145 (1–3): 36–42. doi:10.1016/j.schres.2012.12.023. PMID 23403415.
13. Buchhave P, Zetterberg H, Blennow K, Minthon L, Janciauskiene S, Hansson O (November 2010). "Soluble TNF receptors are associated with Aβ metabolism and conversion to dementia in subjects with mild cognitive impairment". Neurobiology of Aging. 31 (11): 1877–1884. doi:10.1016/j.neurobiolaging.2008.10.012. PMID 19070941. S2CID 34595960.
14. Diniz BS, Teixeira AL, Ojopi EB, Talib LL, Mendonça VA, Gattaz WF, et al. (2010). "Higher serum sTNFR1 level predicts conversion from mild cognitive impairment to Alzheimer's disease". Journal of Alzheimer's Disease. 22 (4): 1305–1311. doi:10.3233/JAD-2010-100921. PMID 20930310.
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19. Hsu H, Shu HB, Pan MG, Goeddel DV (January 1996). "TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways". Cell. 84 (2): 299–308. doi:10.1016/S0092-8674(00)80984-8. PMID 8565075. S2CID 13171355.
20. Zhang SQ, Kovalenko A, Cantarella G, Wallach D (March 2000). "Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation". Immunity. 12 (3): 301–311. doi:10.1016/S1074-7613(00)80183-1. PMID 10755617.
21. Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L (September 2000). "Activation of the NF-kappaB pathway by caspase 8 and its homologs". Oncogene. 19 (39): 4451–4460. doi:10.1038/sj.onc.1203812. PMID 11002417.
22. Guo D, Dunbar JD, Yang CH, Pfeffer LM, Donner DB (March 1998). "Induction of Jak/STAT signaling by activation of the type 1 TNF receptor". Journal of Immunology. 160 (6): 2742–2750. doi:10.4049/jimmunol.160.6.2742. PMID 9510175.
23. Miscia S, Marchisio M, Grilli A, Di Valerio V, Centurione L, Sabatino G, et al. (January 2002). "Tumor necrosis factor alpha (TNF-alpha) activates Jak1/Stat3-Stat5B signaling through TNFR-1 in human B cells". Cell Growth & Differentiation. 13 (1): 13–18. PMID 11801527.
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25. Boldin MP, Mett IL, Wallach D (June 1995). "A protein related to a proteasomal subunit binds to the intracellular domain of the p55 TNF receptor upstream to its 'death domain'". FEBS Letters. 367 (1): 39–44. Bibcode:1995FEBSL.367...39B. doi:10.1016/0014-5793(95)00534-G. PMID 7601280. S2CID 21442471.
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27. Hsu H, Huang J, Shu HB, Baichwal V, Goeddel DV (April 1996). "TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex". Immunity. 4 (4): 387–396. doi:10.1016/S1074-7613(00)80252-6. PMID 8612133.
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Further reading

• Rath PC, Aggarwal BB (November 1999). "TNF-induced signaling in apoptosis". Journal of Clinical Immunology. 19 (6): 350–364. doi:10.1023/A:1020546615229. PMID 10634209. S2CID 23194856.
• Chen G, Goeddel DV (May 2002). "TNF-R1 signaling: a beautiful pathway". Science. 296 (5573): 1634–1635. Bibcode:2002Sci...296.1634C. doi:10.1126/science.1071924. PMID 12040173. S2CID 25321662.
• Kollias G, Kontoyiannis D (2003). "Role of TNF/TNFR in autoimmunity: specific TNF receptor blockade may be advantageous to anti-TNF treatments". Cytokine & Growth Factor Reviews. 13 (4–5): 315–321. doi:10.1016/S1359-6101(02)00019-9. PMID 12220546.
• Dodé C, Cuisset L, Delpech M, Grateau G (2003). "TNFRSF1A-associated periodic syndrome (TRAPS), Muckle-Wells syndrome (MWS) and renal amyloidosis". Journal of Nephrology. 16 (3): 435–437. PMID 12832748.
• Stojanov S, McDermott MF (October 2005). "The tumour necrosis factor receptor-associated periodic syndrome: current concepts". Expert Reviews in Molecular Medicine. 7 (22): 1–18. doi:10.1017/S1462399405009749. PMID 16216134. S2CID 35803989.
• Rezaei N (November 2006). "TNF-receptor-associated periodic syndrome (TRAPS): an autosomal dominant multisystem disorder". Clinical Rheumatology. 25 (6): 773–777. doi:10.1007/s10067-005-0198-6. PMID 16447098. S2CID 41808394.

External links

• TNFRSF1A+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt: P19438 (Tumor necrosis factor receptor superfamily member 1A) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.