1ich A: PDB entry domain

SCOP classification

• Root: SCOP hierarchy in SUPERFAMILY [ 0] (11)
• Class: All alpha proteins [ 46456] (258)
• Fold: DEATH domain [ 47985]
  • 6 helices: closed bundle; greek-key; internal pseudo twofold symmetry
• Superfamily: DEATH domain [ 47986] (4)
• Family: DEATH domain, DD [ 81312] (8)
  • Pfam 00531
• Protein:
  • Tumor necrosis factor receptor-1 death domain [74741]
• PDB Entry Domain: 1ich A: [ 71182]

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InterPro annotation

• Cross references: IPR011029 SSF47986 Protein matches
• Abstract:

  The death domain (DD) is a conserved region of about 80 residues found on death receptors, and which is required for death signalling, as well as a variety of non-apoptotic functions [11828422, 12655292]. Proteins containing this domain include the low affinity neurotrophin receptor p73, Fas, FADD (Fas-associated death domain protein), TNF-1 (tumour necrosis factor receptor-1), Pelle protein kinase, and the Tube adaptor protein [15226512].

  The induction of apoptosis also relies on the presence of a second domain, called the death effector domain. The death effector domain (DED) occurs in proteins that regulate programmed cell death, including both pro- and anti-apoptotic proteins; many of these proteins are also involved in controlling cellular activation and proliferation pathways [12719729]. Proteins containing this domain include FADD (DED N-terminal, DD C-terminal), PEA-15 (phosphoproteins enriched in astrocytes 15kDa), caspases and FLIP.

  The induction of apoptosis results in the activation of caspases, a family of aspartyl-specific cysteine proteases that are the main executioners of apoptosis. For example, the DED of FADD recruits two DED-containing caspases, caspase-8 and caspase-10, to form the death-inducing signal complex, which initiates apoptosis. Proteins containing the caspase recruitment domain (CARD) are involved in the recruitment and activation of caspases during apoptosis [12101092]. Other CARD proteins participate in NF-kappaB signalling pathways associated with innate or adaptive immune responses. Proteins containing CARD include Raidd, APAF-1 (apoptotic protease activating factor 1), procaspase 9 and iceberg (inhibitor of interleukin-1-beta generation).

  The DD shows strong structural similarity to both DED and CARD. They all display a 6-helical closed bundle fold, with greek key topology and an internal psuedo two-fold symmetry. However, despite their overall similarity in topology, each domain forms specialised interactions, typically only with members of its own subfamily, for example DED with DED.

InterPro database

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