Death Domain Superfamily of protein-protein interaction domains; The Death Domain (DD) superfamily includes the DD, Pyrin, CARD (Caspase activation and recruitment domain) and DED (Death Effector Domain) families. 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. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes. They are prominent components of the programmed cell death (apoptosis) pathway and are found in a number of other signaling pathways including those that impact innate immunity, inflammation, differentiation, and cancer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2048774907 408 LPPELFEQLQMLLEPSSVTGNDWRKLASHLgLCGMKIRFLSCQRSPAAAILELFEEQN---GSLQELHYLMTSMERLDCA 484
Cdd:cd08781     1 LPYSIRQKLCSLLDPPNARGNDWRLLAQKL-SVDRYINYFATKPSPTEVILDLWEARNrddGALNSLAAILREMGRHDAA 79

                  ....
gi 2048774907 485 SAIQ 488
Cdd:cd08781    80 TILE 83

Death domain found in Uncoordinated-5 homolog family; Death Domain (DD) found in Uncoordinated-5 (UNC-5) homolog family, which includes Unc5A, B, C and D in vertebrates. UNC5 proteins are receptors for secreted netrins (netrin-1, -3 and -4) that are involved in diverse processes like axonal guidance, neuronal migration, blood vessel patterning, and apoptosis. They are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD. 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 2048774907 408 LPPELFEQLQMLLEPSSVTGNDWRKLASHLgLCGMKIRFLSCQRSPAAAILELFEEQN---GSLQELHYLMTSMERLDCA 484
Cdd:cd08781     1 LPYSIRQKLCSLLDPPNARGNDWRLLAQKL-SVDRYINYFATKPSPTEVILDLWEARNrddGALNSLAAILREMGRHDAA 79

                  ....
gi 2048774907 485 SAIQ 488
Cdd:cd08781    80 TILE 83

Death domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2048774907 414 EQLQMLLEPSSVTGNDWRKLASHLGLCGMKIRFLSCQ----RSPAAAILELFEEQ---NGSLQELHYLMTSMERLDCASA 486
Cdd:pfam00531   2 KQLDRLLDPPPPLGKDWRELARKLGLSENEIDEIESEnprlRSQTYELLRLWEQRegkNATVGTLLEALRKLGRRDAAEK 81

                  ....*
gi 2048774907 487 IQNYL 491
Cdd:pfam00531  82 IQSIL 86

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 2048774907  414 EQLQMLLEPssVTGNDWRKLASHLGLCGMKIRFLSCQ-----RSPAAAILELFEEQNG---SLQELHYLMTSMERLDCAS 485
Cdd:smart00005   6 QKLAKLLDH--PLGLDWRELARKLGLSEADIDQIRTEaprdlAEQSVQLLRLWEQREGknaTLGTLLEALRKMGRDDAVE 83

                   ...
gi 2048774907  486 AIQ 488
Cdd:smart00005  84 LLR 86

Death domain found in Uncoordinated-5 homolog family; Death Domain (DD) found in Uncoordinated-5 (UNC-5) homolog family, which includes Unc5A, B, C and D in vertebrates. UNC5 proteins are receptors for secreted netrins (netrin-1, -3 and -4) that are involved in diverse processes like axonal guidance, neuronal migration, blood vessel patterning, and apoptosis. They are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD. 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 2048774907 408 LPPELFEQLQMLLEPSSVTGNDWRKLASHLgLCGMKIRFLSCQRSPAAAILELFEEQN---GSLQELHYLMTSMERLDCA 484
Cdd:cd08781     1 LPYSIRQKLCSLLDPPNARGNDWRLLAQKL-SVDRYINYFATKPSPTEVILDLWEARNrddGALNSLAAILREMGRHDAA 79

                  ....
gi 2048774907 485 SAIQ 488
Cdd:cd08781    80 TILE 83

Death domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2048774907 414 EQLQMLLEPSSVTGNDWRKLASHLGLCGMKIRFLSCQ----RSPAAAILELFEEQ---NGSLQELHYLMTSMERLDCASA 486
Cdd:pfam00531   2 KQLDRLLDPPPPLGKDWRELARKLGLSENEIDEIESEnprlRSQTYELLRLWEQRegkNATVGTLLEALRKLGRRDAAEK 81

                  ....*
gi 2048774907 487 IQNYL 491
Cdd:pfam00531  82 IQSIL 86

UPA domain; The UPA domain is conserved in UNC5, PIDD, and Ankyrins. It has a beta sandwich structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2048774907 243 ARKWLQLAMFcSPLAPGQTHLQLRVYFLNNTPCALQWAITNEQPHGGR-MRGPCQLFdFTGARADQCLKLKYISEG-WEN 320
Cdd:pfam17217   1 AIKRLRLAVF-APAACTSLEYSLRVYCLDDTPDALKEVVQLEKQLGGQlLEEPKTLH-FKDSTHNLRLSIHDIPPSlWKS 78

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 2048774907 321 VDDSSSQLVPHLHIWHGKCPFRSFCF--RRKSANGNE 355
Cdd:pfam17217  79 KLFAKYQEIPFYHVWSGNQNPLHCTFtlERYSLATTE 115

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 2048774907 414 EQLQMLLEPSSVTGNDWRKLASHLGLCGMKIRFLSCQRSPAAAILELFEEQNGS--LQELHYLMTSMERLD 482
Cdd:cd08312     3 KKLSLYLNPEKVVANDWRGLAELMGFDYLEIRNFERQSSPTERLLEDWETRPPGatVGNLLEILEELERKD 73

Death domain found in Uncoordinated-5C; Death Domain (DD) found in Uncoordinated-5C (UNC5C). UNC5C is part of the UNC-5 homolog family. It is a receptor for the secreted netrin-1 and plays a role in axonal guidance, angiogenesis, and apoptosis. UNC5C plays a critical role in the development of spinal accessory motor neurons. Methylation of the UNC5C gene is associated with early stages of colorectal carcinogenesis. UNC5 proteins are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD. 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 2048774907 408 LPPELFEQLQMLLEPSSVTGNDWRKLASHLGLcGMKIRFLSCQRSPAAAILELFEEQN---GSLQELHYLMTSMERLD 482
Cdd:cd08799     1 IPLSIRQKLCGSLDAPQTRGNDWRMLAHKLNL-DRYLNYFATKSSPTGVILDLWEAQHfpdGNLSRLAAVLEEMGRHE 77

Death domain found in Uncoordinated-5A; Death Domain (DD) found in Uncoordinated-5A (UNC5A). UNC5A is part of the UNC-5 homolog family. It is a receptor for the secreted netrin-1 and plays a critical role in neuronal development and differentiation, as well as axon-guidance. It also plays a role in regulating apoptosis in non-neuronal cells as a downstream target of p53. UNC5 proteins are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD. 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 2048774907 420 LEPSSVTGNDWRKLASHLGLcGMKIRFLSCQRSPAAAILELFEEQ---NGSLQELHYLMTSMERLDCA 484
Cdd:cd08800    13 LDPPCPRGADWRTLAQKLNL-DSHLSFFASKSSPTAMILNLWEAQhfpNGNLSQLAAVVAEIGKQDAM 79

Death domain of the Nuclear Factor-KappaB2 precursor protein p100; Death Domain (DD) of the Nuclear Factor-KappaB2 (NF-kB2) precursor protein p100. The NF-kB family of transcription factors play a central role in cardiovascular growth, stress response, and inflammation by controlling the expression of a network of different genes. There are five NF-kB proteins, all containing an N-terminal REL Homology Domain (RHD). NF-kB2 (or p52) is produced from the processing of the precursor protein p100, which contains ANK repeats and a C-terminal DD in addition to the RHD. It is regulated by the non-canonical NF-kB pathway. The p100 precursor is cytosolic and interacts with RelB. Upon phosphorylation by IKKalpha, p100 is processed to its 52kDa active, DNA-binding form and the p52/RelB complex is translocated into the nucleus. The non-canonical pathway plays a role in adaptive immunity and lymphorganogenesis. 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 2048774907 417 QMLLEPSsvTGNDWRKLASHLGLCGMKIRFLSCQrSPAAAILELFEEQNGSLQELHYLMTSM 478
Cdd:cd08798     7 QLLNDTQ--TDVPWMELAERLGLQSLVDTYKPTQ-SPPGSLLRSYELAGGPLQGLIEALQDM 65