Tumor necrosis factor receptor 1A, N-terminal (IPR033993)

Short name: TNFRSF1A_N

Overlapping homologous superfamilies


Domain relationships



Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A, also known as type I TNFR, TNFR1, DR1, CD120a, p55) binds TNF-alpha, through the death domain (DD), and activates NF-kappaB, mediates apoptosis and activates signaling pathways controlling inflammatory, immune, and stress responses. It mediates signal transduction by interacting with antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRAF2 and TRADD that play regulatory roles [PMID: 12040173, PMID: 22374304].

The human genetic disorder called tumor necrosis factor associated periodic syndrome (TRAPS), or periodic fever syndrome, is associated with germline mutations of the extracellular domains of this receptor, possibly due to impaired receptor clearance [PMID: 23505244]. TNFRSF1A polymorphisms rs1800693 and rs4149584 are associated with elevated risk of multiple sclerosis [PMID: 23624563]. Serum levels of TNFRSF1A are elevated in schizophrenia and bipolar disorder, and high levels are also associated with cognitive impairment and dementia [PMID: 23403415, PMID: 20930310]. Patients with idiopathic recurrent acute pericarditis (IRAP), presumed to be an autoimmune process, have also been shown to carry rare mutations (R104Q and D12E) in the TNFRSF1A gene [PMID: 23745996].

This entry represents the N-terminal domain of TNFR1A. TNF-receptors are modular proteins. The N-terminal extracellular part contains a cysteine-rich region responsible for ligand-binding. This region is composed of small modules of about 40 residues containing 6 conserved cysteines; the number and type of modules can vary in different members of the family [PMID: 9538693, PMID: 8387891, PMID: 11796220].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.