Domain:AIF/PCD-8 C-term Motif | C-terminal motif of AIF (apoptosis-inducing factor) or PCD-8 which distinguishes it from other Pyridine nucleotide-disulphide oxidoreductase containing proteins without apoptotic function. | |
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Domain:Bcl-2 Domain | Bcl-2 family proteins are critical regulators of apoptosis which are conserved throughout metazoan evolution. Several members of this family share a similar protein fold consisting of a bundle of several (7-8 typically) alpha-helices. The structure of the Bcl-2 fold is similar to pore-forming domains of certain bacterial toxins, and experimental evidence has been obtained indicating that some Bcl-2 family proteins can form ion-channels or pores in synthetic lipid membranes. Regions of significant sequence homology can also be discerned, clustering in up to four Bcl-2 Homology (BH) domains, termed BH1, BH2, BH3, and BH4. Bcl-2-family proteins can be either pro-apoptotic or anti-apoptotic. A subgroup of pro-apoptotic Bcl-2 family proteins contains a BH3 domain but probably lacks structural similarity to the group of family members that share structural similarity with pore-forming proteins. These structurally diverse pro-apoptotic Bcl-2 family proteins are often referred to as "BH3-only" proteins. They dimerize with the pore-like Bcl-2 family proteins via their BH3 domain. -J.C. Reed, 2/2001 | |
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Domain:BIR Domain | The BIR domain is present in all IAP (Inhibitor of Apoptosis) family proteins. The structure of the BIR (Baculoviral IAP Repeats) domain has been solved for MIHB/c-IAP-1 (Mammalian IAP Homolog B). It consists of 4 short alpha-helices and a region of extended approximately anti-parallel structure. The domain binds Zn using 3 Cys and a His conserved across IAP proteins. | |
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Domain:Caspase Large Subunit | Caspases occur as inactive zymogens that are activated by proteolysis which (often) removes pro-domains and separates the catalytic "domain" into two subunits. The separated large and small subunit of caspase (ICE/CED-3) proteins combine to form a catalytic unit. The active site cysteine and histidine residues are harbored within this large subunit. A combination of loops from both subunits form the substrate/inhibitor binding cleft. | |
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Domain:CAspase Recruitment Domain | CARD domains have close structural homology to DED and Death domains and are found in a variety of apoptosis signalling proteins in the triggering phase of apoptosis. This domain is involved in homotypic interactions between, for example, APAF-1 and Caspase-9 (structure of the complex is solved) which leads to their oligomerization and activation. The structures, thus far, of CARD/CARD interaction reveal that the CARD domains have complimentary basic/acidic surfaces where they bind each other. The basic/acidic surfaces are on opposing faces of each CARD domain. | |
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| 0 References | 0 Multiple Sequence Alignments | 2 Diagrams | |
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Domain:Caspase Small Subunit | Caspases occur as inactive zymogens that are activated by proteolysis which removes pro-domains (often) and separates the catalytic domain into two subunits. The separated large and small subunit of caspase (ICE/CED-3) proteins combine to form a catalytic unit. The small subunit contains one of the arginine residues which bind to the required Asp in the substrate. The key determinant of caspase specificity (S4 binding site) is also part of this small subunit. | |
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Domain:Death Domain | The death domain is present in many apoptosis pathway proteins and others for which there is no known role in apoptosis. The domain is a 6 alpha helical bundle in the same structural super-family as Death Effector Domain (DED) proteins and Caspase Recruitment Domain (CARD) proteins. Several DD containing proteins serve as adaptor molecules, mediating associations between proteins that contain Death domains (homotypic DD interactions). The interaction of one DD complex, Pelle/Tube of drosophila, is "head-to-tail" between the ends of each helical bundles. The interaction of human FADD-DD/Fas-DD is proposed to be between complimentarily charged surfaces along the length of helices - similar to CARD/CARD complexes. | |
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| 0 References | 0 Multiple Sequence Alignments | 3 Diagrams | |
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Domain:Death Effector Domain | Death Effector Domains are members of the structural superfamily consisting of DED, CARD, and Death Domains. The role of the domain is to provide selective homo-/hetero- dimerization between proteins in the apoptosis pathway. Hetero-dimerization of DED domains between, for example, FADD adaptor molecules and pro-Caspase-8, are part of the pro-apoptotic signalling pathway between receptors and upstream caspase activation. DED domains alone in a protein (c-FLIP) can serve as inhibitors of Caspase-8 and -10 activation by blocking DED binding sites associated with receptors (however, they may also be initiator of apoptosis in other contexts). | |
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| 0 References | 0 Multiple Sequence Alignments | 2 Diagrams | |
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Domain:NB-ARC Domain | The NB-ARC domain is combination of a ATP binding domain which can be modeled as a classical Rossman fold followed by a helical domain. The NB-ARC domain is responsible for oligomerization and ATP dependency. In the case of APAF-1, it is the oligomerization and association of Caspase-9 and cytochrome-c that forms the apoptosome. The structure of the NB-ARC domain has not been solved. Several types of NB-ARC containing proteins are involved in apoptosis but others have diverse functions. The combination of an NB-ARC and another (apoptotic) domain is more indicative of a role in apoptosis. CED-4, APAF-1, NAC and CARD4/NOD1 all have additional CARD domains which are necessary (along with ATP binding domains) for their function in apoptosis. NAIP has additional BIR domains to a NB-ARC like domain and is also involved in apoptosis. | |
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Domain:TNFReceptor C6 | The cysteine-rich repeat is found on several cell surface receptors that are involved in apoptosis, cell cycle regulation, NFkappaB activation, immune cell activation and other processes. | |
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Domain:BAG Domain | BAG-1 protein binds Hsc70/Hsp70 ATPase domain and promotes substrate release, influencing a wide variety of cellular phenotypes including increasing resistance to apoptosis. | |
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Domain:CIDE N-terminal Domain | CIDE-B (cell death-inducing DFF45-like effector), DFF40/CAD and DFF45/ICAD proteins contain this domain, along with Drosophila homologs (DREPs). The CAD nuclease domain is involved in apoptotic DNA fragmentation and chromatin condensation (execution stage of apoptosis). The CIDE-N domains of several of these proteins bind to each other (homotypic binding and self association) which regulates their cellular roles. The domain has is an alpha/beta roll with 5 beta strands in a single sheet and two adjacent alpha helices. | |
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Domain:TRAF Domain | The TRAF domain is the portion of TRAF family adaptor proteins which bind to TNF receptor cytoplasmic domain (_after_ TNFR trimerization). The structure of the TRAF domain of TRAF2 has been solved. It forms a mushroom shaped timer, binding trimers of the CD40 receptor. The trimer binds CD40 along the outer perimeter of the mushroom cap which consists of 3 eight-stranded beta-sandwich domains. The mushroom stem is 3 helix coiled coil with each TRAF domain monomer contributing one helix. Evidence suggests that all TRAFadaptor proteins form such homotrimers and some heterotypic complexes. | |
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| 0 References | 0 Multiple Sequence Alignments | 1 Diagram | |
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