TNFRSF1A

This gene encodes a member of the TNF receptor superfamily of proteins. The encoded receptor is found in membrane-bound and soluble forms that interact with membrane-bound and soluble forms, respectively, of its ligand, tumor necrosis factor alpha. Binding of membrane-bound tumor necrosis factor alpha to the membrane-bound receptor induces receptor trimerization and activation, which plays a role in cell survival, apoptosis, and inflammation. Proteolytic processing of the encoded receptor results in release of the soluble form of the receptor, which can interact with free tumor necrosis factor alpha to inhibit inflammation. Mutations in this gene underlie tumor necrosis factor receptor-associated periodic syndrome (TRAPS), characterized by fever, abdominal pain and other features. Mutations in this gene may also be associated with multiple sclerosis in human patients. [provided by RefSeq, Sep 2016]

TNFRSF1A Gene(Protein Coding) TNF Receptor Superfamily Member 1A

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.

Biological Process aortic valve development Source:BHF-UCL
Biological Process cellular response to mechanical stimulus Source:UniProtKB1 Publication
Biological Process cytokine-mediated signaling pathway Source:UniProtKB
Biological Process defense response to bacterium Source:Ensembl
Biological Process extrinsic apoptotic signaling pathway via death domain receptors Source:BHF-UCL1 Publication
Biological Process inflammatory response Source:UniProtKB
Biological Process intrinsic apoptotic signaling pathway in response to DNA damage Source:Ensembl
Biological Process negative regulation of cardiac muscle hypertrophy Source:Ensembl
Biological Process negative regulation of extracellular matrix constituent secretion Source:BHF-UCL
Biological Process negative regulation of inflammatory response Source:BHF-UCL1 Publication
Biological Process positive regulation of apoptotic process involved in morphogenesis Source:BHF-UCL
Biological Process positive regulation of I-kappaB kinase/NF-kappaB signaling Source:UniProtKB1 Publication
Biological Process positive regulation of inflammatory response Source:UniProtKB
Biological Process positive regulation of transcription by RNA polymerase II Source:BHF-UCL1 Publication
Biological Process positive regulation of tyrosine phosphorylation of STAT protein Source:BHF-UCL1 Publication
Biological Process prostaglandin metabolic process Source:InterPro
Biological Process protein localization to plasma membrane Source:UniProtKB1 Publication
Biological Process pulmonary valve development Source:BHF-UCL
Biological Process regulation of establishment of endothelial barrier Source:UniProtKB1 Publication
Biological Process regulation of tumor necrosis factor-mediated signaling pathway Source:Ensembl
Biological Process transcription by RNA polymerase II Source:Ensembl
Biological Process tumor necrosis factor-mediated signaling pathway Source:UniProtKB1 Publication

Cell membrane
Golgi apparatus membrane
Secreted
A secreted form is produced through proteolytic processing.
Isoform 4
Secreted
Lacks a Golgi-retention motif, is not membrane bound and therefore is secreted.

Periodic fever, familial, autosomal dominant (FPF):
A hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases.
Multiple sclerosis 5 (MS5):
A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheath, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease.

Extracellular: 30-211
Helical: 212-232
Cytoplasmic: 233-455

The soluble form is produced from the membrane form by proteolytic processing.
(Microbial infection) Glycosylated at Arg-376 by enteropathogenic E.coli protein NleB1 and S.typhimurium protein Ssek3: arginine GlcNAcylation prevents homotypic/heterotypic death domain interactions.