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tumor necrosis factor receptor superfamily member 10A; death receptor 4; TNF-related apoptosis-inducing ligand receptor 1; TRAIL receptor 1; TRAIL-R1; CD261 (TNFRSF10A, APO2, DR4, TRAILR1)
Function:
- receptor for the cytotoxic ligand TNFSF10/TRAIL
- 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 mediating apoptosis
- TRAILR1 & TRAILR2 mediate apoptosis; TRAILR3 & TRAILR4 do not
- promotes the activation of NF-kappa-B
- can interact with TRADD & RIP
Structure:
- contains 1 death domain
- contains 3 TNFR-Cys repeats
Compartment: membrane
Expression:
- widely expressed
- high levels are found in spleen, peripheral blood leukocytes, small intestine & thymus
- also expressed in K562 erythroleukemia cells, MCF7 breast carcinoma cells & activated T-cells
Pathology:
- plasma TNFRSF10A associated with loneliness [4]
General
cluster-of-differentiation antigen; cluster designation antigen; CD antigen
glycoprotein
phosphoprotein
tumor necrosis factor [TNF] receptor family
Properties
SIZE: entity length = 468 aa
MW = 50 kD
COMPARTMENT: cellular membrane
MOTIF: signal sequence {1-23}
alanine-rich region {29-32}
MOTIF: alanine residue (SEVERAL)
Ser phosphorylation site {S83}
TNFR-Cys {107-145}
MOTIF: cysteine residue {C132}
MODIFICATION: cysteine residue {C145}
cysteine residue {C145}
MODIFICATION: cysteine residue {C132}
TNFR-Cys {147-188}
MOTIF: cysteine residue {C148}
MODIFICATION: cysteine residue {C164}
N-glycosylation site {N156}
cysteine residue {C164}
MODIFICATION: cysteine residue {C148}
cysteine residue {C167}
MODIFICATION: cysteine residue {C180}
cysteine residue {C170}
MODIFICATION: cysteine residue {C188}
cysteine residue {C180}
MODIFICATION: cysteine residue {C167}
cysteine residue {C188}
MODIFICATION: cysteine residue {C170}
TNFR-Cys {189-229}
MOTIF: cysteine residue {C190}
MODIFICATION: cysteine residue {C204}
cysteine residue {C204}
MODIFICATION: cysteine residue {C190}
cysteine residue {C207}
MODIFICATION: cysteine residue {C221}
cysteine residue {C211}
MODIFICATION: cysteine residue {C229}
cysteine residue {C221}
MODIFICATION: cysteine residue {C207}
cysteine residue {C229}
MODIFICATION: cysteine residue {C211}
transmembrane domain {240-262}
death domain
NAME: death domain
SITE: 365-448
Ser phosphorylation site {S463}
Ser phosphorylation site {S466}
References
- OMIM :accession 603611
- UniProt :accession O00220
- Entrez Gene :accession 8797
- Shen C, Zhang R, Yu J, Sahakian BJ, Cheng W, Feng J.
Plasma proteomic signatures of social isolation and loneliness associated
with morbidity and mortality.
Nat Hum Behav. 2025 Jan 3.
PMID: 39753750
Databases & Figures
OMIM 603611
UniProt O00220
PFAM correlations
Entrez Gene 8797
Kegg hsa:8797
TRAIL -> caspase 8 -> bid -> smac/diablo -> IAP ...