Domain

TRADD, N-terminal (IPR009095)

Short name: TRADD_N

Domain relationships

None.

Description

TRADD is a signalling adaptor protein involved in tumour necrosis factor-receptor I (TNFR1)-associated apoptosis and cell survival. The decision between apoptosis and cell survival involves the interplay between two sequential signalling complexes. The plasma membrane-bound complex I is comprised of TNFR1, TRADD, the kinase RIP1, and TRAF2, which together mediate the activation of NF-kappaB. Subsequently, complex II is formed in the cytoplasm, where TRADD and RIP1 associate with FADD and caspase-8. If NF-kappaB is activated by complex I, then complex II will associate with the caspase-8 inhibitor FLIP(L) and the cell survives, while the failure to activate NF-kappaB leads to apoptosis [PMID: 12887920].

TRADD contains two functionally separate domains, which allow the protein to couple to two distinct signaling pathways. The TRADD C-terminal death domain is responsible for its association with TNFR1, and with the death-domain proteins FADD and RIP1, which promote apoptosis. The TRADD N-terminal domain binds TRAF2 and promotes TRAF2 recruitment to TNFR1, thereby mediating the activation of NK-kappaB and JNK/AP1, which promote cell survival [PMID: 10911999]. The N-terminal TRADD domain is composed of an alpha-beta sandwich, where the beta strands form an antiparallel beta-sheet.

GO terms

Biological Process

GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling

Molecular Function

GO:0005515 protein binding
GO:0004871 signal transducer activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
SUPERFAMILY
ProDom
GENE3D
Pfam