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 1958801381 158 LPPELFEQLQMLLEPSSVTGNDWRKLASHLgLCGMKIRFLSCQRSPAAAILELFEEQN---GSLQELHYLMTSMERLDCA 234
Cdd:cd08781     1 LPYSIRQKLCSLLDPPNARGNDWRLLAQKL-SVDRYINYFATKPSPTEVILDLWEARNrddGALNSLAAILREMGRHDAA 79

                  ....
gi 1958801381 235 SAIQ 238
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 1958801381 158 LPPELFEQLQMLLEPSSVTGNDWRKLASHLgLCGMKIRFLSCQRSPAAAILELFEEQN---GSLQELHYLMTSMERLDCA 234
Cdd:cd08781     1 LPYSIRQKLCSLLDPPNARGNDWRLLAQKL-SVDRYINYFATKPSPTEVILDLWEARNrddGALNSLAAILREMGRHDAA 79

                  ....
gi 1958801381 235 SAIQ 238
Cdd:cd08781    80 TILE 83

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 1958801381  164 EQLQMLLEPssVTGNDWRKLASHLGLCGMKIRFLSCQ-----RSPAAAILELFEEQNG---SLQELHYLMTSMERLDCAS 235
Cdd:smart00005   6 QKLAKLLDH--PLGLDWRELARKLGLSEADIDQIRTEaprdlAEQSVQLLRLWEQREGknaTLGTLLEALRKMGRDDAVE 83

                   ...
gi 1958801381  236 AIQ 238
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 1958801381 158 LPPELFEQLQMLLEPSSVTGNDWRKLASHLgLCGMKIRFLSCQRSPAAAILELFEEQN---GSLQELHYLMTSMERLDCA 234
Cdd:cd08781     1 LPYSIRQKLCSLLDPPNARGNDWRLLAQKL-SVDRYINYFATKPSPTEVILDLWEARNrddGALNSLAAILREMGRHDAA 79

                  ....
gi 1958801381 235 SAIQ 238
Cdd:cd08781    80 TILE 83

Death domain of Nuclear Factor-KappaB precursor proteins; Death Domain (DD) of Nuclear Factor-KappaB (NF-kB) precursor proteins. 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). Two of these, NF-kB1 and NF-kB2 are produced from the processing of the precursor proteins p105 and p100, respectively. In addition to RHD, p105 and p100 contain ANK repeats and a C-terminal DD. NF-kBs are regulated by the Inhibitor of NF-kB (IkB) Kinase (IKK) complex through classical and non-canonical pathways, which differ in the IKK subunits involved and downstream targets. IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. The precursor proteins p105 and p100 function as IkBs and as NF-kB proteins after being processed by the proteasome. 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 1958801381 164 EQLQMLLEPssvtGNDWRKLASHLGLCGMkIRFLSCQRSPAAAILELFEEQNGSLQELHYLMTSMERLDCASAIQ 238
Cdd:cd08310     3 LRLCKLLDV----GKDWRELAELLGLGHL-VESIEQSSSPTKLLLDYYEAQGGTLEKLREALRALGETDAVELID 72

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 1958801381 164 EQLQMLLEPSSVTGNDWRKLASHLGLCGMKIRFLSCQRSPAAAILELFEEQNGS--LQELHYLMTSMERLD 232
Cdd:cd08312     3 KKLSLYLNPEKVVANDWRGLAELMGFDYLEIRNFERQSSPTERLLEDWETRPPGatVGNLLEILEELERKD 73

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 1958801381   5 PLAPGQTHLQLRVYFLNNTPCALQWAITNEQPHGGR-MRGPCQLFdFTGARADQCLKLKYISEG-WENVDDSSSQLVPHL 82
Cdd:pfam17217  12 PAACTSLEYSLRVYCLDDTPDALKEVVQLEKQLGGQlLEEPKTLH-FKDSTHNLRLSIHDIPPSlWKSKLFAKYQEIPFY 90

                          90       100
                  ....*....|....*....|....*
gi 1958801381  83 HIWHGKCPFRSFCF--RRKSANGNE 105
Cdd:pfam17217  91 HVWSGNQNPLHCTFtlERYSLATTE 115

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 1958801381 177 GNDWRKLASHLGLCGMKIRFLSCQ-----RSPAAAILELFEEQNGS---LQELHYLMTSMERLDCASAIQ 238
Cdd:cd01670    10 GRDWKKLARKLGLSEGDIDQIEEDnrddlKEQAYQMLERWREREGDeatLGRLIQALREIGRRDLAEKLE 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 1958801381 167 QMLLEPSsvTGNDWRKLASHLGLCGMKIRFLSCQrSPAAAILELFEEQNGSLQELHYLMTSM 228
Cdd:cd08798     7 QLLNDTQ--TDVPWMELAERLGLQSLVDTYKPTQ-SPPGSLLRSYELAGGPLQGLIEALQDM 65

Death domain found in Uncoordinated-5B; Death Domain (DD) found in Uncoordinated-5B (UNC5B). UNC5B 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. UNC5B signaling is involved in the netrin-1-induced proliferation and migration of renal proximal tubular cells. It is also required for vascular patterning during embryonic development, and its activation inhibits sprouting angiogenesis. 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 1958801381 158 LPPELFEQLQMLLEPSSVTGNDWRKLASHLGLcGMKIRFLSCQRSPAAAILELFEEQNGSLQELHYLMTSMERL 231
Cdd:cd08802     1 IPLSIRQKICNSLDAPNSRGNDWRLLAQKLSM-DRYLNYFATKASPTGVILDLWEARHQDDGDLNSLASALEEM 73