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FLASH GENE

Symbol

TNFRSF1A

contributors: mct/pgu - updated : 07-06-2017

HGNC name	tumor necrosis factor receptor superfamily, member 1A
HGNC id	11916

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	13.36 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001065 10 - 2258 55 455 predominant form in serum and pulmonary epithelium fluid 2004 14745008 exosome-associated TNFR1 TNFR1S - splicing - 28 - - 2004 14745008 cleaved ectodomain

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       highly   intestine large intestine colon   highly Lymphoid/Immune spleen         Nervous brain         Reproductive female system placenta     highly Respiratory lung

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Connective adipose     highly

cell lineage
cell lines
fluid/secretion	serum, pulmonary epithelium fluid

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an extracytoplasmic cysteine-rich pseudorepeats typical for the TNFR superfamily
	a preligand assembly domain (PLAD) in CRD1 mediating ligand-independent receptor assembly
	a small cytoplasmic domain with the serine/threonine kinase
	a DEATH domain, involved in the induction of A-Smase
	a N-Smase activation domain (NSD) is both necessary and sufficient for activation of N-Smase
	contains a membrane-proximal sequence that targets the receptor to caveolae/lipid rafts

mono polymer

homomer , trimer

HOMOLOGY

interspecies

homolog to murine Tnfrsf1a (73 pc)

Homologene

FAMILY

tumor necrosis factor receptor superfamily

CATEGORY

signaling cytokine , receptor

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
text	release in exosome-like vesicles

basic FUNCTION	involved at least in two independent pathways
	acidic sphingomyelinase controlling expression of multiple TNF-responsive genes, including the apoptotic pathway
	neutral sphingomyelinase critical for the inflammatory and proliferative responses induced by TNF
	plays a key role in the initiation of inflammation, host defense, apoptosis, and cell survival through its ability to activate NFKB, mitogen-activated protein kinases, caspase-8, and other signaling responses
	endogenous TNFRSF1B/TNFRSF1A signaling pathway in polymicrobial sepsis reduces neutrophil recruitment contributing to mortality
	potential role as a positive T-cell costimulatory molecule that is important for timely T-cell activation and effector cytokine production and the development of primary immune responses
	important for the development of secondary lymphoid organs during embryonic life, and is required for the formation of splenic compartments during adult, but not embryonic life
	is predominantly associated with neurodegeneration
	TNFRSF1A, TNFRSF1B were required for IRF1-IFNB signaling and, in human endothelial cells
	TNFRSF1A, TNFRSF1B activities are required for the TNF-induced proinflammatory response

CELLULAR PROCESS	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

with EED recruited to the TNFRSF1A•NSMAF•RACK1-complex

INTERACTION

DNA

RNA

small molecule

protein	interacted with only TRPC4AP, TRAF2, and IKBKG
	IGFBP5 interacts with TNFRSF1A through its N- and L-domains, and L-domain of IGFBP5 is a novel TNFRSF1A ligand that functions as a competitive TNF inhibitor JNK pathway)
	IL32-mediated activity may be dependent on TNFRSF1A
	is a novel UPR-regulated gene in response to severe hypoxia and ER stress, which is actively involved in the release of TNFRSF1A under these conditions
	NDN is implicated through the TNFRSF1A pathway in the developmental death of motoneurons
	TRAF2 is critical for either TNFRSF1A- or TNFRSF1B-mediated activation of NFKB and mitogen-activated protein kinase (MAPK) signaling, as well as for target gene expression
	TRADD is an adapter molecule that bridges the interaction between TNFRSF1A and receptor-interacting serine/threonine-protein kinase 1 (RIPK1)
	HACE1 is a central gatekeeper of TNFRSF1A-induced cell fate
	TRADD is an adaptor for TNFRSF1A-induced apoptosis and NFKB1 activation
	LYPLA2 is involved in TNFRSF1A depalmitoylation and TNF induced NFkB1 activation
	promotes neurodegenerative process through augmenting astrocytic tumor necrosis factor receptor (TNFRSF1A) signaling

cell & other

REGULATION

Other

extracellular release regulated by RBMX associates with ERAP1 in airway epithelial and vascular endothelial cells

ASSOCIATED DISORDERS

corresponding disease(s)

TRAPS

related resource

INFEVERS: The repertory of Familial Mediterranean Fever (FMF) and Hereditary Inflammatory Disorders Mutations

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       MVK (V377I) mutation and TNFRSF1A (R92Q) mutation with phenotype resembled a mixture of variant-type HIDS and TRAPS constitutional     --over   in fulminant hepatic failure cases in relation to acute viral hepatitis cases

Susceptibility

to myocardial infarction and carotid intima-media thickness to systemic lupus erythematosus to tuberculosis to hepatocellular carcinoma

Variant & Polymorphism other	R92Q increasing the risk of atherosclerosis
	T61I and R104Q, are associated with systemic lupus erythematosus
	polymorphisms increasing the risk of hepatocellular carcinoma

Candidate gene	could be a modifier gene in cystic fibrosis
Marker
Therapy target
	System Type Disorder Pubmed immunology inflammatory   interfering with the TNFRSF1A pathway offers the possibility to selectively block the formation of ectopic lymphoid tissue, opening a new perspective for the treatment of autoimmune and inflammatory diseases immunology inflammatory   potential therapeutic target in fulminant hepatic failure cases in relation to acute viral hepatitis cases

ANIMAL & CELL MODELS