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 6753812   97 LQVAFDIVCDNVGRDWKRLARELKVSEAKMDGIEEKYPRSLSERVRESLKVWKNAEKKNASVAGLVKALRTCRLNLVADL 176
Cdd:cd08306   1 LNEAFDVICENLGRDWRQLARKLGLSETKIESISEAHPRNLREQVRQSLREWKKIKKAEATVADLIKALRDCQLNLVADL 80

                ....*
gi 6753812  177 VEEAQ 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 6753812   97 LQVAFDIVCDNVGRDWKRLARELKVSEAKMDGIEEKYPRSLSERVRESLKVWKNAEKKNASVAGLVKALRTCRLNLVADL 176
Cdd:cd08306   1 LNEAFDVICENLGRDWRQLARKLGLSETKIESISEAHPRNLREQVRQSLREWKKIKKAEATVADLIKALRDCQLNLVADL 80

                ....*
gi 6753812  177 VEEAQ 181
Cdd:cd08306  81 VEKKL 85

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 6753812      96 DLQVAFDIVCDNV-GRDWKRLARELKVSEAKMDGIEEKYPRSLSERVRESLKVWKNAEKKNASVAGLVKALRTCRLNLVA 174
Cdd:smart00005   3 LTRQKLAKLLDHPlGLDWRELARKLGLSEADIDQIRTEAPRDLAEQSVQLLRLWEQREGKNATLGTLLEALRKMGRDDAV 82

                   ....*.
gi 6753812     175 DLVEEA 180
Cdd:smart00005  83 ELLRSE 88

Death effector domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 6753812     19 DLMELKFLCRERVSKRKLERVQSGLDLFTVLLEQNDLERGHTGLLRELLASLRRHDLLQRLDDFE 83
Cdd:pfam01335  16 ELESLKFLCKDHIPKRKLEKIKSALDLFIELEKQGLLSEDNLDLLEELLRRIGRQDLLKKIEKYE 80

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 6753812   97 LQVAFDIVCDNVGRDWKRLARELKVSEAKMDGIEEKYPRSLSERVRESLKVWKNAEKKNASVAGLVKALRTCRLNLVADL 176
Cdd:cd08306   1 LNEAFDVICENLGRDWRQLARKLGLSETKIESISEAHPRNLREQVRQSLREWKKIKKAEATVADLIKALRDCQLNLVADL 80

                ....*
gi 6753812  177 VEEAQ 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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6753812    2 DPFLVLLHSLSGSLSGNDLMELKFLCRERVSKRKLERVQSGLDLFTVLLEQNDLERGHTGLLRELLASLRRHDLLQRLDD 81
Cdd:cd08336   1 DPFKVLLLEISKSLSDEELESLKFLCKDHIGKRKLEEVQSGLDLFEALEERDKLSPENTAFLRELLKSIGREDLIRKLEE 80

                ..
gi 6753812   82 FE 83
Cdd:cd08336  81 FE 82

Death domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 6753812    105 CDNVGRDWKRLARELKVSEAKMDGIEEKYPRsLSERVRESLKVWKNAEKKNASVAGLVKALRTCRLNLVADLVEE 179
Cdd:pfam00531  11 PPPLGKDWRELARKLGLSENEIDEIESENPR-LRSQTYELLRLWEQREGKNATVGTLLEALRKLGRRDAAEKIQS 84

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6753812   19 DLMELKFLCRERVSKRKLERVQSGLDLFTVLLEQNDLERGHTGLLRELLASLRRHDLLQRL 79
Cdd:cd00045  16 ELRSLKFLCKDVIPAGKLERISRGRDLFTELEKQGKISPGNLSLLEELLRSIGRRDLLEKV 76

Death effector domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 6753812      18 NDLMELKFLCRERVSKRKLErVQSGLDLFTVLLEQNDLERGHTGLLRELLASLRRHDLLQRLDD 81
Cdd:smart00031  17 EELEVLLFLCKDLIPKRKLE-IKTFLDLFSALEEQGLLSEDNLSLLAELLYRLRRLDLLRRLFG 79

Death domain associated with Ankyrins; Death Domain (DD) associated with Ankyrins. 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. Ankyrins function as adaptor proteins and they interact, through ANK repeats, with structurally diverse membrane proteins, including ion channels/pumps, calcium release channels, and cell adhesion molecules. They play critical roles in the proper expression and membrane localization of these proteins. In mammals, this family includes ankyrin-R for restricted (or ANK1), ankyrin-B for broadly expressed (or ANK2) and ankyrin-G for general or giant (or ANK3). They are expressed in different combinations in many tissues and play non-overlapping functions. 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 6753812   93 GEADLQVAfdIVCDNVGRDWKRLARELKVSEAKMDGIEEKYPRSLSERVRESLKVWKNAEKKNASVAGLVKALRT 167
Cdd:cd08317   1 HRADLRLS--DIANLLGSDWPELARELGVSEEDIDLIRSENPNSLAQQAMAMLRLWLEREGEKATGNALESALKK 73

Death effector domain, repeat 1, of Caspase-8; Death effector domain (DED) found in caspase-8 (CASP8, FLICE), repeat 1. 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 is an initiator of death receptor mediated apoptosis. Together with FADD, caspase-10, and the pseudo-caspase c-FLIP, it forms 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 also plays many important non-apoptotic functions including roles in embryonic development, cell adhesion and motility, immune cell proliferation and differentiation, T-cell activation, and NFkappaB signaling. It contains 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 6753812   19 DLMELKFLCRERVSKRKLERVQSGLDLFTVLLEQNDLERGHTGLLRELLASLRRHDLL 76
Cdd:cd08333  16 DLAALKFLSLDHIPRRKQENIKDALALFLALQEKGMLEEGNLSFLKELLFRIGRIDLL 73

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 6753812  101 FDIVcdnVGRDWKRLARELKVSEAKMDGIEEKYPRSlSERVRESLKVWKNAEKKNASVAGLVKALRTCRLNLVADLVEE 179
Cdd:cd08315   6 EDIV---PFKSWKRLMRALGLSDNEIKLAEANDPGS-QEPLYQMLNKWLNKTGRKASVNTLLDALEDLGLRGAAETIAD 80

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6753812   96 DLQVAfdIVCDNVGRDWKRLARELKVSEAKMDGIEEKYPRSLSERVRESLKVWKNAEKKNASVAGLVKAL-RTCRLNLVA 174
Cdd:cd08803   4 DIRMA--IVADHLGLSWTELARELNFSVDEINQIRVENPNSLIAQSFMLLKKWVTRDGKNATTDALTSVLtKINRIDIVT 81

                ..
gi 6753812  175 DL 176
Cdd:cd08803  82 LL 83

Death Domain of Death Receptors; Death domain (DD) found in death receptor proteins. Death receptors are members of the tumor necrosis factor (TNF) receptor superfamily, characterized by having a cytoplasmic DD. Known members of the family are Fas (CD95/APO-1), TNF-receptor 1 (TNFR1/TNFRSF1A/p55/CD120a), TNF-related apoptosis-inducing ligand receptor 1 (TRAIL-R1 /DR4), and receptor 2 (TRAIL-R2/DR5/APO-2/KILLER), as well as Death Receptor 3 (DR3/APO-3/TRAMP/WSL-1/LARD). They are involved in apoptosis signaling pathways. 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 6753812  101 FDIVCDNVGRD-WKRLARELKVSEAKMDGIEEKYPRSLSERVRESLKVWKNAEKKNASVAGLVKALR 166
Cdd:cd08784   2 ITTIAGVVPLSqWKGFVRKLGLNEAEIDEIKNDNVQDTAEAKYQMLRNWHQLTGRKAAYDTLIKDLK 68

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 6753812  104 VCDNVGRDWKRLARELKVSEAKMDGIEEKYPRSLSERVRESLKVWKNAEKKNA-SVAGLVKALR-TCRLNLVADL 176
Cdd:cd08779   8 LAKELGEDWQKLALHLGVSYSRIQRIKRKNRDDLDEQILDMLFSWAKTLPTSPdKVGLLVTALSkSGRSDLAEEL 82

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        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6753812  110 RDWKRLARELKVSEAKMDGIEEKYPRSLSERVRESLKVWKNAEKKNASVAGLVKALRTCRLNLVADLVEE 179
Cdd:cd08316  18 KDVKKFARKSGISETKIDEIQLDNPNDTAEQKVQLLRAWYQKHGKKGAYRTLIKTLRKAGKRAKADKIQD 87