Death domain of Myeloid Differentation primary response protein MyD88; Death Domain (DD) of Myeloid Differentiation primary response protein 88 (MyD88). MyD88 is an adaptor protein involved in interleukin-1 receptor (IL-1R)- and Toll-like receptor (TLR)-induced activation of nuclear factor-kappaB (NF-kB) and mitogen activated protein kinase pathways that lead to the induction of proinflammatory cytokines. It is a key component in the signaling pathway of pathogen recognition in the innate immune system. MyD88 contains an N-terminal DD and a C-terminal Toll/IL-1 Receptor (TIR) homology domain that mediates interaction with TLRs and IL-1R. 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 1478051052  29 VRRRLSLFLNVRTQVAADWTALAEEMDFEYLEIRQLETQADPTGRLLDAWQGRP-GASVGRLLELLTKLGRDDVLLELG 106
Cdd:cd08312     1 VRKKLSLYLNPEKVVANDWRGLAELMGFDYLEIRNFERQSSPTERLLEDWETRPpGATVGNLLEILEELERKDVLEDLQ 79

Death domain of Myeloid Differentation primary response protein MyD88; Death Domain (DD) of Myeloid Differentiation primary response protein 88 (MyD88). MyD88 is an adaptor protein involved in interleukin-1 receptor (IL-1R)- and Toll-like receptor (TLR)-induced activation of nuclear factor-kappaB (NF-kB) and mitogen activated protein kinase pathways that lead to the induction of proinflammatory cytokines. It is a key component in the signaling pathway of pathogen recognition in the innate immune system. MyD88 contains an N-terminal DD and a C-terminal Toll/IL-1 Receptor (TIR) homology domain that mediates interaction with TLRs and IL-1R. 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 1478051052  29 VRRRLSLFLNVRTQVAADWTALAEEMDFEYLEIRQLETQADPTGRLLDAWQGRP-GASVGRLLELLTKLGRDDVLLELG 106
Cdd:cd08312     1 VRKKLSLYLNPEKVVANDWRGLAELMGFDYLEIRNFERQSSPTERLLEDWETRPpGATVGNLLEILEELERKDVLEDLQ 79

TIR domain; The Toll/interleukin-1 receptor (TIR) homology domain is an intracellular signalling domain found in MyD88, interleukin 1 receptor and the Toll receptor. It contains three highly-conserved regions, and mediates protein-protein interactions between the Toll-like receptors (TLRs) and signal-transduction components. TIR-like motifs are also found in plant proteins thought to be involved in resistance to disease. When activated, TIR domains recruit cytoplasmic adaptor proteins MyD88 and TOLLIP (Toll interacting protein). In turn, these associate with various kinases to set off signalling cascades.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1478051052 116 FDAFICYCPSDIQ--FVQEMIRQLEQTNYrlKLCVSDRDVLPGTcvwSIASELIE--KRCRRMVVVVSDDYLQSKECDFQ 191
Cdd:pfam01582   1 YDVFLSFRGSDTRewFVSHLLKELKQKGI--KLFIDDRDLEPGE---AIAPELLSaiEKSRRSVVVLSPNYASSGWCLDE 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1478051052 192 TKFALSLspgAHQKR--LIPIKYKA-----------MKKEFPSILRFITVC----------------DYTNPCTKSWFWT 242
Cdd:pfam01582  76 LVKILEC---ALDLGqkVIPIFYEVdpsdvrkqtgsFGKAFKKHKKVLTEEkvlkwrgalnevaniwHSKSVSDESKFWK 152

                  ....*..
gi 1478051052 243 RLAKALS 249
Cdd:pfam01582 153 KIAYDIS 159

Death domain of Myeloid Differentation primary response protein MyD88; Death Domain (DD) of Myeloid Differentiation primary response protein 88 (MyD88). MyD88 is an adaptor protein involved in interleukin-1 receptor (IL-1R)- and Toll-like receptor (TLR)-induced activation of nuclear factor-kappaB (NF-kB) and mitogen activated protein kinase pathways that lead to the induction of proinflammatory cytokines. It is a key component in the signaling pathway of pathogen recognition in the innate immune system. MyD88 contains an N-terminal DD and a C-terminal Toll/IL-1 Receptor (TIR) homology domain that mediates interaction with TLRs and IL-1R. 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 1478051052  29 VRRRLSLFLNVRTQVAADWTALAEEMDFEYLEIRQLETQADPTGRLLDAWQGRP-GASVGRLLELLTKLGRDDVLLELG 106
Cdd:cd08312     1 VRKKLSLYLNPEKVVANDWRGLAELMGFDYLEIRNFERQSSPTERLLEDWETRPpGATVGNLLEILEELERKDVLEDLQ 79

TIR domain; The Toll/interleukin-1 receptor (TIR) homology domain is an intracellular signalling domain found in MyD88, interleukin 1 receptor and the Toll receptor. It contains three highly-conserved regions, and mediates protein-protein interactions between the Toll-like receptors (TLRs) and signal-transduction components. TIR-like motifs are also found in plant proteins thought to be involved in resistance to disease. When activated, TIR domains recruit cytoplasmic adaptor proteins MyD88 and TOLLIP (Toll interacting protein). In turn, these associate with various kinases to set off signalling cascades.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1478051052 116 FDAFICYCPSDIQ--FVQEMIRQLEQTNYrlKLCVSDRDVLPGTcvwSIASELIE--KRCRRMVVVVSDDYLQSKECDFQ 191
Cdd:pfam01582   1 YDVFLSFRGSDTRewFVSHLLKELKQKGI--KLFIDDRDLEPGE---AIAPELLSaiEKSRRSVVVLSPNYASSGWCLDE 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1478051052 192 TKFALSLspgAHQKR--LIPIKYKA-----------MKKEFPSILRFITVC----------------DYTNPCTKSWFWT 242
Cdd:pfam01582  76 LVKILEC---ALDLGqkVIPIFYEVdpsdvrkqtgsFGKAFKKHKKVLTEEkvlkwrgalnevaniwHSKSVSDESKFWK 152

                  ....*..
gi 1478051052 243 RLAKALS 249
Cdd:pfam01582 153 KIAYDIS 159

TIR domain; This is a family of Toll-like receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1478051052 119 FICYCPSDIQFVQEMIRQLEQTNYRlklCVSDR-DVLPGTcvwSIASELIE--KRCRRMVVVVSDDYLQSKECDFQTKFA 195
Cdd:pfam13676   2 FISYAGEDRAWAEWLADALEAAGYR---VWLDRwDIRPGD---DWVEEIEEaiENSDRVLVVLSPNYLESPWCRAEWEAA 75

                          90
                  ....*....|....*..
gi 1478051052 196 LSLSPGahQKRLIPIKY 212
Cdd:pfam13676  76 LADPEG--RKRLIPVRL 90

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1478051052  36 FLNVRTQVAADWTALAEEMDFEYLEIRQLETQA-----DPTGRLLDAWQGRPG--ASVGRLLELLTKLGRDDVLLEL 105
Cdd:cd01670     2 FDLVAEELGRDWKKLARKLGLSEGDIDQIEEDNrddlkEQAYQMLERWREREGdeATLGRLIQALREIGRRDLAEKL 78

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1478051052  41 TQVAADWTALAEEMDFEYLEIRQLETQADPTG----RLLDAWQGRPG--ASVGRLLELLTKLGRDDV 101
Cdd:cd08318    15 NKLGEQWKTLAPYLEMKDKDIRQIESDSEDMKmrakQLLVTWQDREGaqATPEILMTALNAAGLNEI 81

Death domain of Interleukin-1 Receptor-Associated Kinases; Death Domains (DDs) found in Interleukin-1 (IL-1) Receptor-Associated Kinases (IRAK1-4) and similar proteins. IRAKs are essential components of innate immunity and inflammation in mammals and other vertebrates. All four types are involved in signal transduction involving IL-1 and IL-18 receptors, Toll-like receptors, nuclear factor-kappaB, and mitogen-activated protein kinase pathways. IRAK1 and IRAK4 are active kinases while IRAK2 and IRAK-M (also called IRAK3) are inactive. In general, IRAKs are expressed ubiquitously, except for IRAK-M which is detected only in macrophages. The insect homologs, Pelle and Tube, are important components of the Toll pathway, which functions in establishing dorsoventral polarity in embryos and also in the innate immune response. Most members have an N-terminal DD followed by a kinase domain. 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 1478051052  25 LNMRVRRRLSLFLNvrTQVAADWTALAEEMDFEYLEIRQLETQAD----PTGRLLDAWQGRpGASVGRLLELLTKLG 97
Cdd:cd08309     6 LPPWVLKRLCKVLD--ALELAGWRQLASLIPYDQTDVRQIESMKQrgqsPTRELLWDWGTQ-NATVQDLVQLLTQLG 79

Death domain found in death-associated protein kinase 1; Death domain (DD) found in death-associated protein kinase 1 (DAPK1). DAPK1 is composed of several functional domains, including a kinase domain, a CaM regulatory domain, ankyrin repeats, a cytoskeletal-binding domain and a C-terminal DD. It plays important roles in a diverse range of signal transduction pathways including apoptosis, growth factor signalling, and autophagy. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. 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 1478051052  29 VRRRLSLFLNVRTQVAADWTALAeeMDFEYLE-IRQLET----QADPTGRLLDAWQGRPGASVGRLLELLTKLGRDDV 101
Cdd:cd08782     2 TRRKLARLLDPPDPMGRDWCLLA--VNLGLTDlVAKLDStsspLPSPTDRLLQEWTARPPSTIGALLRKLRELGRRDA 77

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1478051052  28 RVRRRLSLflnVRTQVAADWTALAEEMDFEYLEIRQLETQ-----ADPTGRLLDAWQGRPG--ASVGRLLELLTKLGRDD 100
Cdd:cd08804     2 RTEERLAH---IADHLGFSWTELARELDFTEEQIHQIRIEnpnslQDQSHALLKYWLERDGkhATDTNLTQCLTKINRMD 78

                  ..
gi 1478051052 101 VL 102
Cdd:cd08804    79 IV 80