Fas-associated Death Domain protein-protein interaction domain; Death domain (DD) found in FAS-associated via death domain (FADD). FADD is a component of the death-inducing signaling complex (DISC) and serves as an adaptor in the signaling pathway of death receptor proteins. It modulates apoptosis as well as non-apoptotic processes such as cell cycle progression, survival, innate immune signaling, and hematopoiesis. FADD contains an N-terminal DED and a C-terminal DD. Its DD interacts with the DD of the activated death receptor, FAS, and its DED recruits the initiator caspases, caspase-8 and -10, to the DISC complex via a homotypic interaction with the N-terminal DED of the caspase. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and they can recruit other proteins into signaling complexes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4505229   97 LCAAFNVICDNVGKDWRRLARQLKVSDTKIDSIEDRYPRNLTERVRESLRIWKNTEKENATVAHLVGALRSCQMNLVADL 176
Cdd:cd08306   1 LNEAFDVICENLGRDWRQLARKLGLSETKIESISEAHPRNLREQVRQSLREWKKIKKAEATVADLIKALRDCQLNLVADL 80

                ....*
gi 4505229  177 VQEVQ 181
Cdd:cd08306  81 VEKKL 85

Fas-associated Death Domain protein-protein interaction domain; Death domain (DD) found in FAS-associated via death domain (FADD). FADD is a component of the death-inducing signaling complex (DISC) and serves as an adaptor in the signaling pathway of death receptor proteins. It modulates apoptosis as well as non-apoptotic processes such as cell cycle progression, survival, innate immune signaling, and hematopoiesis. FADD contains an N-terminal DED and a C-terminal DD. Its DD interacts with the DD of the activated death receptor, FAS, and its DED recruits the initiator caspases, caspase-8 and -10, to the DISC complex via a homotypic interaction with the N-terminal DED of the caspase. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and they can recruit other proteins into signaling complexes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4505229   97 LCAAFNVICDNVGKDWRRLARQLKVSDTKIDSIEDRYPRNLTERVRESLRIWKNTEKENATVAHLVGALRSCQMNLVADL 176
Cdd:cd08306   1 LNEAFDVICENLGRDWRQLARKLGLSETKIESISEAHPRNLREQVRQSLREWKKIKKAEATVADLIKALRDCQLNLVADL 80

                ....*
gi 4505229  177 VQEVQ 181
Cdd:cd08306  81 VEKKL 85

Death domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4505229    101 FNVICDNV---GKDWRRLARQLKVSDTKIDSIEDRYPRnLTERVRESLRIWKNTEKENATVAHLVGALRSCQMNLVADLV 177
Cdd:pfam00531   4 LDRLLDPPpplGKDWRELARKLGLSENEIDEIESENPR-LRSQTYELLRLWEQREGKNATVGTLLEALRKLGRRDAAEKI 82

                  ..
gi 4505229    178 QE 179
Cdd:pfam00531  83 QS 84

Death effector domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 4505229     23 LKFLCLGRVGKRKLERVQSGLDLFSMLLEQNDLEPGHTELLRELLASLRRHDLLRRVDDF 82
Cdd:pfam01335  20 LKFLCKDHIPKRKLEKIKSALDLFIELEKQGLLSEDNLDLLEELLRRIGRQDLLKKIEKY 79

Fas-associated Death Domain protein-protein interaction domain; Death domain (DD) found in FAS-associated via death domain (FADD). FADD is a component of the death-inducing signaling complex (DISC) and serves as an adaptor in the signaling pathway of death receptor proteins. It modulates apoptosis as well as non-apoptotic processes such as cell cycle progression, survival, innate immune signaling, and hematopoiesis. FADD contains an N-terminal DED and a C-terminal DD. Its DD interacts with the DD of the activated death receptor, FAS, and its DED recruits the initiator caspases, caspase-8 and -10, to the DISC complex via a homotypic interaction with the N-terminal DED of the caspase. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and they can recruit other proteins into signaling complexes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4505229   97 LCAAFNVICDNVGKDWRRLARQLKVSDTKIDSIEDRYPRNLTERVRESLRIWKNTEKENATVAHLVGALRSCQMNLVADL 176
Cdd:cd08306   1 LNEAFDVICENLGRDWRQLARKLGLSETKIESISEAHPRNLREQVRQSLREWKKIKKAEATVADLIKALRDCQLNLVADL 80

                ....*
gi 4505229  177 VQEVQ 181
Cdd:cd08306  81 VEKKL 85

Death Effector Domain found in Fas-Associated via Death Domain; Death Effector Domain (DED) found in Fas-Associated via Death Domain (FADD). DEDs comprise a subfamily of the Death Domain (DD) superfamily. FADD is a component of the death-inducing signaling complex (DISC) and serves as an adaptor in the signaling pathway of death receptor proteins. It modulates apoptosis as well as non-apoptotic processes such as cell cycle progression, survival, innate immune signaling, and hematopoiesis. FADD contains an N-terminal DED and a C-terminal DD. Its DD interacts with the DD of the activated death receptor and its DED recruits the initiator caspases 8 and 10 to the DISC complex via a homotypic interaction with the N-terminal DED of the caspase. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including PYRIN and CARD (Caspase activation and recruitment domain). They serve as adaptors in signaling pathways and they can recruit other proteins into signaling complexes.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 4505229   24 KFLCLGRVGKRKLERVQSGLDLFSMLLEQNDLEPGHTELLRELLASLRRHDLLRRVDDF 82
Cdd:cd08336  23 KFLCKDHIGKRKLEEVQSGLDLFEALEERDKLSPENTAFLRELLKSIGREDLIRKLEEF 81

DEATH domain, found in proteins involved in cell death (apoptosis); Alpha-helical domain present in a variety of proteins with apoptotic functions. Some (but not all) of these domains form homotypic and heterotypic dimers.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4505229      96 DLCAAFNVICDNV-GKDWRRLARQLKVSDTKIDSIEDRYPRNLTERVRESLRIWKNTEKENATVAHLVGALRSCQMNLVA 174
Cdd:smart00005   3 LTRQKLAKLLDHPlGLDWRELARKLGLSEADIDQIRTEAPRDLAEQSVQLLRLWEQREGKNATLGTLLEALRKMGRDDAV 82

                   ....*
gi 4505229     175 DLVQE 179
Cdd:smart00005  83 ELLRS 87

Death Effector Domain: a protein-protein interaction domain; Death Effector Domains comprise a subfamily of the Death Domain (DD) superfamily. DED-containing proteins include Fas-Associated via Death Domain (FADD), Astrocyte phosphoprotein PEA-15, the initiator caspases (caspase-8 and -10), and FLICE-inhibitory protein (FLIP), among others. These proteins are prominent components of the programmed cell death (apoptosis) pathway. Some members also have non-apoptotic functions such as regulation of insulin signaling (DEDD and PEA15) and cell cycle progression (DEDD). DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including PYRIN and CARD (Caspase activation and recruitment domain). They serve as adaptors in signaling pathways and they can recruit other proteins into signaling complexes.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 4505229   23 LKFLCLGRVGKRKLERVQSGLDLFSMLLEQNDLEPGHTELLRELLASLRRHDLLRRV 79
Cdd:cd00045  20 LKFLCKDVIPAGKLERISRGRDLFTELEKQGKISPGNLSLLEELLRSIGRRDLLEKV 76

Death effector domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 4505229      24 KFLCLGRVGKRKLErVQSGLDLFSMLLEQNDLEPGHTELLRELLASLRRHDLLRRVDD 81
Cdd:smart00031  23 LFLCKDLIPKRKLE-IKTFLDLFSALEEQGLLSEDNLSLLAELLYRLRRLDLLRRLFG 79

Death Domain of Receptor-Interacting Protein 1; Death domain (DD) found in Receptor-Interacting Protein 1 (RIP1) and related proteins. RIP kinases serve as essential sensors of cellular stress. Vertebrates contain several types containing a homologous N-terminal kinase domain and varying C-terminal domains. RIP1 harbors a C-terminal DD, which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accumulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4505229  106 DNVGKDWRRLARQLKVSDTKIDSIEDRYPRN-LTERVRESLRIWKNTE-KENATVAHLVGALRSC-QMNLVADLVQ 178
Cdd:cd08777  10 ENLGKKWKRCARRLGLTEVEIEEIDHDYERDgLKEKVHQMLEKWKMKEgSKGATVGKLAKALEGCiKSDLLVSLLQ 85

Death domain of Tumor necrosis factor-Related Apoptosis-Inducing Ligand Receptors; Death Domain (DD) found in Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL) Receptors. In mammals, this family includes TRAILR1 (also called DR4 or TNFRSF10A) and TRAILR2 (also called DR5, TNFRSF10B, or KILLER). They function as receptors for the cytokine TRAIL and are involved in apoptosis signaling pathways. TRAIL preferentially induces apoptosis in cancer cells while exhibiting little toxicity in normal cells. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 4505229  110 KDWRRLARQLKVSDTKIDSIE--DRYPRnltERVRESLRIWKNTEKENATVAHLVGAL 165
Cdd:cd08315  12 KSWKRLMRALGLSDNEIKLAEanDPGSQ---EPLYQMLNKWLNKTGRKASVNTLLDAL 66

Death effector domain, repeat 2, of initator caspases 8 and 10; Death Effector Domain (DED) found in caspase-8 and caspase-10, repeat 2. Caspases are aspartate-specific cysteine proteases with functions in apoptosis and immune signaling. Initiator caspases are the first to be activated following death- or inflammation-inducing signals. Caspase-8 and -10 are the initiators of death receptor mediated apoptosis, and they play partially redundant roles. Together with FADD and the pseudo-caspase c-FLIP, they form the death-inducing signaling complex (DISC), whose formation is triggered by the activation of type 1 tumor necrosis factor (TNF) receptors such as Fas, TNF receptor 1, and TRAIL receptor. Caspase-8 and -10 also play important functions in cell adhesion and motility. They contain two N-terminal DED domains and a C-terminal caspase domain. DEDs comprise a subfamily of the Death Domain (DD) superfamily. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including PYRIN and CARD (Caspase activation and recruitment domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 4505229   24 KFLCLGRVGKRKLERVQSGLDLFSMLLEQNDLEPGHTELLRELLASLRRhDLLRRVDDF 82
Cdd:cd08334  24 KFLLSSKLPRRKLEKNKSALDVFVEMEKRGLLSEDNLDELKKILKSLRP-DLAKKINQY 81

Death Domain of Tumor Necrosis Factor Receptor 1-Associated Death Domain protein; Death domain (DD) of TRADD (TNF Receptor 1-Associated Death Domain or TNFRSF1A-associated via death domain) protein. TRADD is a central signaling adaptor for TNF-receptor 1 (TNFR1), mediating activation of Nuclear Factor -kappaB (NF-kB) and c-Jun N-terminal kinase (JNK), as well as caspase-dependent apoptosis. It also carries important immunological roles including germinal center formation, DR3-mediated T-cell stimulation, and TNFalpha-mediated inflammatory responses. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4505229  108 VGKDWRRLARQLK-----VSDTKIDSIEDRYPRN-LTERVRESLRIWKNTEKENATVAHLVGALRSCQMNLVAD 175
Cdd:cd08780  12 VGKKWKPVGRSLQkncraLRDPAIDNLAYEYDREgLYEQAYQLLRRFIQSEGKKATLQRLVQALEENGLTSLAE 85

Death domain of Nuclear Matrix Protein P84; Death domain (DD) found in the Nuclear Matrix Protein P84 (also known as HPR1 or THOC1). HPR1/p84 resides in the nuclear matrix and is part of the THO complex, also called TREX (transcription/export) complex, which functions in mRNP biogenesis at the interface between transcription and export of mRNA from the nucleus. Mice lacking THOC1 have abnormal testis development and are sterile. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4505229  103 VICDNVGKDWRRLARQLKVSDTKIDSIEDRyPRNLTERVRESLRIWKNTEKENATVAHLVGALRSCQMNLVADLV 177
Cdd:cd08318  12 VLANKLGEQWKTLAPYLEMKDKDIRQIESD-SEDMKMRAKQLLVTWQDREGAQATPEILMTALNAAGLNEIAENL 85

Death Domain of p53-induced protein with a death domain; Death domain (DD) found in PIDD (p53-induced protein with a death domain) and similar proteins. PIDD is a component of the PIDDosome complex, which is an oligomeric caspase-activating complex involved in caspase-2 activation and plays a role in mediating stress-induced apoptosis. The PIDDosome complex is composed of three components, PIDD, RAIDD and caspase-2, which interact through their DDs and DD-like domains. The DD of PIDD interacts with the DD of RAIDD, which also contains a Caspase Activation and Recruitment Domain (CARD) that interacts with the caspase-2 CARD. Autoproteolysis of PIDD determines the downstream signaling event, between pro-survival NF-kB or pro-death caspase-2 activation. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD, DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4505229  104 ICDNVGKDWRRLARQLKVSDTKIDSIEDRYPRNLTERVRESLRIWKNTEKENA-TVAHLVGALR-SCQMNLVADL 176
Cdd:cd08779   8 LAKELGEDWQKLALHLGVSYSRIQRIKRKNRDDLDEQILDMLFSWAKTLPTSPdKVGLLVTALSkSGRSDLAEEL 82

Death domain of Ankyrin-3; Death Domain (DD) of the human protein ankyrin-3 (ANK-3) and related proteins. Ankyrins are modular proteins comprising three conserved domains, an N-terminal membrane-binding domain containing ANK repeats, a spectrin-binding domain and a C-terminal DD. ANK-3, also called anykyrin-G (for general or giant), is found in neurons and at least one splice variant has been shown to be essential for propagation of action potentials as a binding partner to neurofascin and voltage-gated sodium channels. It is required for maintaining axo-dendritic polarity, and may be a genetic risk factor associated with bipolar disorder. ANK-3 may also play roles in other cell types. Mutations affecting ANK-3 pathways for Na channel localization are associated with Brugada syndrome, a potentially fatal arrythmia. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4505229  103 VICDNVGKDWRRLARQLKVSDTKIDSIEDRYPRNLTERVRESLRIWKNTEKENATVAHLVGAL 165
Cdd:cd08803   9 IVADHLGLSWTELARELNFSVDEINQIRVENPNSLIAQSFMLLKKWVTRDGKNATTDALTSVL 71

Death domain of Ankyrin-2; Death Domain (DD) of Ankyrin-2 (ANK-2) and related proteins. Ankyrins are modular proteins comprising three conserved domains, an N-terminal membrane-binding domain containing ANK repeats, a spectrin-binding domain and a C-terminal DD. ANK-2, also called ankyrin-B (for broadly expressed), is required for proper function of the Na/Ca ion exchanger-1 in cardiomyocytes, and is thought to function in linking integral membrane proteins to the underlying cytoskeleton. Human ANK-2 is associated with "Ankyrin-B syndrome", an atypical arrythmia disorder with risk of sudden cardiac death. It also plays key roles in the brain and striated muscle. Loss of ANK-2 is associated with significant nervous system defects and sarcomere disorganization. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4505229  104 ICDNVGKDWRRLARQLKVSDTKIDSIEDRYPRNLTERVRESLRIWKNTEKENATVAHLVGAL 165
Cdd:cd08804  10 IADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLTQCL 71