TRADD, N-terminal domain; The N terminal domain of 'Tumour necrosis factor receptor type 1 associated death domain protein' (TRADD) folds into an alpha-beta sandwich with a four-stranded beta sheet and six alpha helices, each forming one layer of the structure. The domain allows docking of TRADD onto 'tumour necrosis factor receptor-associated factor' (TRAF): the binding is at the beta-sandwich domain, away from the coiled-coil domain. Binding ensures the recruitment of cIAPs to the signaling complex, which may be important for direct caspase-8 inhibition and the immediate suppression of apoptosis at the apical point of the cascade.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13378137    51 ESGGSPDVLQMLKIHRSDPQLIVQLRFCGRQPCGRFLRAYREGALRAALQRSLAAALAQHS-VPLQLELRAGAERLDALL 129
Cdd:pfam09034   1 DSAGGLDGYEILKIHDSDPQLIVQLKFCGVEACRRFLQSYREGALRQSLQQHLCRLLALPQeLPLETELKAGTERLDSCL 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 13378137   130 ADEERCLSCILAQQPDRLRDEELAELEDALRN 161
Cdd:pfam09034  81 DDEERCLQHIHQSKPDRLRDEEITELEQQLQS 112

TRADD, N-terminal domain; The N terminal domain of 'Tumour necrosis factor receptor type 1 associated death domain protein' (TRADD) folds into an alpha-beta sandwich with a four-stranded beta sheet and six alpha helices, each forming one layer of the structure. The domain allows docking of TRADD onto 'tumour necrosis factor receptor-associated factor' (TRAF): the binding is at the beta-sandwich domain, away from the coiled-coil domain. Binding ensures the recruitment of cIAPs to the signaling complex, which may be important for direct caspase-8 inhibition and the immediate suppression of apoptosis at the apical point of the cascade.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13378137    51 ESGGSPDVLQMLKIHRSDPQLIVQLRFCGRQPCGRFLRAYREGALRAALQRSLAAALAQHS-VPLQLELRAGAERLDALL 129
Cdd:pfam09034   1 DSAGGLDGYEILKIHDSDPQLIVQLKFCGVEACRRFLQSYREGALRQSLQQHLCRLLALPQeLPLETELKAGTERLDSCL 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 13378137   130 ADEERCLSCILAQQPDRLRDEELAELEDALRN 161
Cdd:pfam09034  81 DDEERCLQHIHQSKPDRLRDEEITELEQQLQS 112

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 13378137    212 RPLSLKDQQTFA-RSVGLKWRKVGRSLQRGCRALRDPALDSLayeyerEGLYEQAFQLLRRFVQAEGRRATLQRLVEALE 290
Cdd:smart00005   1 PELTRQKLAKLLdHPLGLDWRELARKLGLSEADIDQIRTEAP------RDLAEQSVQLLRLWEQREGKNATLGTLLEALR 74

                           90
                   ....*....|...
gi 13378137    291 ENELTSLAEDLLG 303
Cdd:smart00005  75 KMGRDDAVELLRS 87

TRADD, N-terminal domain; The N terminal domain of 'Tumour necrosis factor receptor type 1 associated death domain protein' (TRADD) folds into an alpha-beta sandwich with a four-stranded beta sheet and six alpha helices, each forming one layer of the structure. The domain allows docking of TRADD onto 'tumour necrosis factor receptor-associated factor' (TRAF): the binding is at the beta-sandwich domain, away from the coiled-coil domain. Binding ensures the recruitment of cIAPs to the signaling complex, which may be important for direct caspase-8 inhibition and the immediate suppression of apoptosis at the apical point of the cascade.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13378137    51 ESGGSPDVLQMLKIHRSDPQLIVQLRFCGRQPCGRFLRAYREGALRAALQRSLAAALAQHS-VPLQLELRAGAERLDALL 129
Cdd:pfam09034   1 DSAGGLDGYEILKIHDSDPQLIVQLKFCGVEACRRFLQSYREGALRQSLQQHLCRLLALPQeLPLETELKAGTERLDSCL 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 13378137   130 ADEERCLSCILAQQPDRLRDEELAELEDALRN 161
Cdd:pfam09034  81 DDEERCLQHIHQSKPDRLRDEEITELEQQLQS 112

Death Domain: a protein-protein interaction domain; Death Domains (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. Structural analysis of DD-DD complexes show that the domains interact with each other in many different ways. DD-containing proteins serve as adaptors in signaling pathways and they can recruit other proteins into signaling complexes. In mammals, they are prominent components of the programmed cell death (apoptosis) pathway and are found in a number of other signaling pathways. In invertebrates, they are involved in transcriptional regulation of zygotic patterning genes in insect embryogenesis, and are components of the ToII/NF-kappaB pathway, a conserved innate immune pathway in animal cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13378137 220 QTFARSVGLKWRKVGRSLQrgcraLRDPALDSLAYEYeREGLYEQAFQLLRRFVQAEGRRATLQRLVEALEENELTSLAE 299
Cdd:cd01670   3 DLVAEELGRDWKKLARKLG-----LSEGDIDQIEEDN-RDDLKEQAYQMLERWREREGDEATLGRLIQALREIGRRDLAE 76

                ..
gi 13378137 300 DL 301
Cdd:cd01670  77 KL 78

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 13378137 226 VGLKWRKVGRSLqrgcrALRDPALDSLAYEYEREGLYEQAFQLLRRFVQAEGRR-ATLQRLVEALEENELTSLAEDLL 302
Cdd:cd08777  12 LGKKWKRCARRL-----GLTEVEIEEIDHDYERDGLKEKVHQMLEKWKMKEGSKgATVGKLAKALEGCIKSDLLVSLL 84

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 13378137 226 VGLKWRKVGRSLQrgcraLRDPALDSLAYEYEREgLYEQAFQLLRRFVQAEGRRATLQRLVEALEENELtSLAEDLL 302
Cdd:cd08306  12 LGRDWRQLARKLG-----LSETKIESISEAHPRN-LREQVRQSLREWKKIKKAEATVADLIKALRDCQL-NLVADLV 81

Death domain of FAS or TNF receptor superfamily member 6; Death Domain (DD) found in the FS7-associated cell surface antigen (FAS). FAS, also known as TNFRSF6 (TNF receptor superfamily member 6), APT1, CD95, FAS1, or APO-1, together with FADD (Fas-associating via Death Domain) and caspase 8, is an integral part of the death inducing signalling complex (DISC), which plays an important role in the induction of apoptosis and is activated by binding of the ligand FasL to FAS. FAS also plays a critical role in self-tolerance by eliminating cell types (autoreactive T and B cells) that contribute to autoimmunity. 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
                ....*....|....*....|....*....|....*....|..
gi 13378137 263 EQAFQLLRRFVQAEGRRATLQRLVEALEENELTSLAEDLLGL 304
Cdd:cd08316  47 EQKVQLLRAWYQKHGKKGAYRTLIKTLRKAGKRAKADKIQDI 88