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FLASH GENE

Symbol

TNFRSF25

contributors: mct/pgu - updated : 04-12-2012

HGNC name	tumor necrosis factor receptor superfamily, member 25
HGNC id	11910

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	1p36.31      Physical location : 6.521.220 - 6.526.255
Synonym name	tumor necrosis factor receptor superfamily, member 12 (translocating chain-association membrane protein)
	death domain receptor 3 soluble form
	lymphocyte associated receptor of death
	death receptor beta
	apoptosis inducing receptor
	apoptosis-mediating receptor
	translocating chain-association membrane protein
	WSL-1 protein
Synonym symbol(s)	DR3, LARD, TRAMP, TNFRSF12, APO-3, TR3, DDR3, WSL1, WSL-LR

DNA

TYPE	functioning gene
STRUCTURE	5.04 kb     10 Exon(s)    2 Copie(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

text structure

duplicated approximatively 200kb upstream the original gene, the duplication is more prevalent in patients with rhumatoid arthritis

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed variant 1 10 - 1665 isoform 1 43.4 426 - 1997 9114039 membrane protein variant 2 10 - 1638 isoform 2 42.9 417 - 1997 9114039 shorter and distinct internal region membrane protein variant 3 9 - 1527 isoform 3 38.7 380 - 1997 9114039 frameshift secreted protein variant 4 9 - 1503 isoform 4 37.9 372 - 1997 9114039 frameshift secreted protein variant 7 5 - 1089 isoform 7 22.9 234 - 1997 9114039 lacking an intermal region secreted protein variant 12 - - 894 16.9 181 - 1997 9114039 secreted protein Drbeta - - 1669 - 426 lymphoid cell lines non Hodgkin lymphome 1997 9114039

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 blood / hematopoietic spleen       highly   thymus       highly Digestive intestine large intestine colon     Reproductive male system prostate

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic thymocyte Lymphoid/Immune lymphocyte Skeleton osteoblast

cell lineage
cell lines	lymphoid T cell and immature B cell lines
fluid/secretion

at STAGE

physiological period

fetal

Text	lung, kidney

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	four extracytoplasmic cysteine-rich pseudorepeats typical for TNFR superfamily
	a preligand assembly domain (PLAD) in CRD1 mediating ligand-independent receptor assembly and signaling
	a cytoplasmic tail with the DEATH domain
	an extracellular domain with four homologous cysteine-rich domains (CRDs)

conjugated

GlycoP

mono polymer

homomer , dimer

HOMOLOGY

Homologene

FAMILY

tumor necrosis factor receptor superfamily

CATEGORY

receptor membrane

SUBCELLULAR LOCALIZATION
text	several secreted isoforms

basic FUNCTION	inducing NFKB acitivation and apoptosis when overexpressed
	involved in the regulation of apoptosis in neuroblastoma and primitive neuroectodermal tumors
	may play a role in lymphocyte homeostasis
	may be involved in the removal of self-reactive T cells in the thymus
	has an essential role in the development of allergic lung inflammation
	potential inducible mediator of tubular inflammation and injury
	involved in atherosclerosis via the induction of proinflammatory cytokines/chemokines and decreasing plaque stability by inducing extracellular matrix degrading enzymes
	can mediate apoptosis in osteoblasts
	TNFSF15 and TNFRSF25 may play an important role in the pathophysiological process of the aged bladder

CELLULAR PROCESS	cell life, proliferation/growth
	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with BAG4
	interacts strongly via the death domains of TNFRSF1
	TNFSF15-TNFRSF25 interactions are necessary and sufficient for T cell-dependent inflammatory bowel disease
	TRADD is essential for TNFSF15/TNFRSF25 signaling
	costimulates T-cell activation, but it is unique among these receptors in that it signals through an intracytoplasmic death domain and the adapter protein TRADD (TNFR-associated death domain)

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     in neuroblastoma cell lines tumoral     --over   in primitive neuroectodermal tumors with good prognosis

Susceptibility

to rheumatoid arthritis increased in term placentas from women with pregnancies complicated by preeclampsia up-regulated in renal tubular epithelial cells and endothelial cells of some interlobular arteries during acute transplant rejection

Variant & Polymorphism other	D158G mutation increasing the risk of rheumatoid arthritis

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed blood coagulation   proatherogenic role for both TNFSF15 and TNFRSF25 that implicates this pathway as a target for the therapeutic intervention of atherosclerosis

ANIMAL & CELL MODELS