ZU5 domain; Domain present in ZO-1 and Unc5-like netrin receptors Domain of unknown function.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569001995  108 VDHRGGCLILQDTGISLLIPPGAVTVGRQERVSLVLVWDLTDAPSLSHRQGLVSPVVACGPHGASFLKPCTLTFKHCA 185
Cdd:pfam00791   5 VDSRGGRLVLPNSGVSLLIPPGAIPEGTRIECYLAVNRDESSRPPLEEGETLLSPVVECGPPGLKFLKPVILEVPHCA 82

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 569001995  243 ARKWLQLAMFcSPLVPGQTHLQLRVYFLNNTPCALQWAITNEQPHGGR-MRGPCQLFdFTGARADQCLKLKYISEG-WEN 320
Cdd:pfam17217   1 AIKRLRLAVF-APAACTSLEYSLRVYCLDDTPDALKEVVQLEKQLGGQlLEEPKTLH-FKDSTHNLRLSIHDIPPSlWKS 78

                          90       100
                  ....*....|....*....|....*.
gi 569001995  321 VDDSSSQLVPHLHIWHGKCPFRSFCF 346
Cdd:pfam17217  79 KLFAKYQEIPFYHVWSGNQNPLHCTF 104

ZU5 domain; Domain present in ZO-1 and Unc5-like netrin receptors Domain of unknown function.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569001995  108 VDHRGGCLILQDTGISLLIPPGAVTVGRQERVSLVLVWDLTDAPSLSHRQGLVSPVVACGPHGASFLKPCTLTFKHCA 185
Cdd:pfam00791   5 VDSRGGRLVLPNSGVSLLIPPGAIPEGTRIECYLAVNRDESSRPPLEEGETLLSPVVECGPPGLKFLKPVILEVPHCA 82

Domain present in ZO-1 and Unc5-like netrin receptors; Domain of unknown function.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569001995   108 VDHRGGCLILQDTGISLLIPPGAVTVGRQERVSLVLVWDLTDAPSLSHRQGLVSPVVACGPHGASFLKPCTLTFKHCA 185
Cdd:smart00218   9 FDARGGRLRGPRTGVRLIIPPGAIPQGTRYTCYLVVHKTLSTPPPLEEGETLLSPVVECGPHGALFLRPVILEVPHCA 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569001995   423 NSVTGNDWRRLASHLGLCGMKIRFLSCQ-----RSPAAAILELFEEQNG---SLQELHYLMTSMERLDCASAIQ 488
Cdd:smart00005  13 DHPLGLDWRELARKLGLSEADIDQIRTEaprdlAEQSVQLLRLWEQREGknaTLGTLLEALRKMGRDDAVELLR 86

ZU5 domain; Domain present in ZO-1 and Unc5-like netrin receptors Domain of unknown function.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569001995  108 VDHRGGCLILQDTGISLLIPPGAVTVGRQERVSLVLVWDLTDAPSLSHRQGLVSPVVACGPHGASFLKPCTLTFKHCA 185
Cdd:pfam00791   5 VDSRGGRLVLPNSGVSLLIPPGAIPEGTRIECYLAVNRDESSRPPLEEGETLLSPVVECGPPGLKFLKPVILEVPHCA 82

Domain present in ZO-1 and Unc5-like netrin receptors; Domain of unknown function.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569001995   108 VDHRGGCLILQDTGISLLIPPGAVTVGRQERVSLVLVWDLTDAPSLSHRQGLVSPVVACGPHGASFLKPCTLTFKHCA 185
Cdd:smart00218   9 FDARGGRLRGPRTGVRLIIPPGAIPQGTRYTCYLVVHKTLSTPPPLEEGETLLSPVVECGPHGALFLRPVILEVPHCA 86

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 569001995 414 EQLQMLLEPnsvtGNDWRRLASHLGLCGMkIRFLSCQRSPAAAILELFEEQNGSLQELHYLMTSMERLDCASAIQ 488
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 569001995 414 EQLQMLLEPNSVTGNDWRRLASHLGLCGMKIRFLSCQRSPAAAILELFEEQNGS--LQELHYLMTSMERLD 482
Cdd:cd08312    3 KKLSLYLNPEKVVANDWRGLAELMGFDYLEIRNFERQSSPTERLLEDWETRPPGatVGNLLEILEELERKD 73

Death domain of p75 Neurotrophin Receptor; Death Domain (DD) found in p75 neurotrophin receptor (p75NTR, NGFR, TNFRSF16). p75NTR binds members of the neurotrophin (NT) family including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and NT3, among others. It contains an NT-binding extracellular region that bears four cysteine-rich repeats, a transmembrane domain, and an intracellular DD. p75NTR plays roles in the immune, vascular, and nervous systems, and has been shown to promote cell death or survival, and to induce neurite outgrowth or collapse depending on its ligands and co-receptors. 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 569001995 409 PPELFEQLQMLLEPNSvTGNDWRRLASHLGLCGMKIRFLSCQRSPAAAILELFEEQNGS-LQELHYLMTSMERLDCASAI 487
Cdd:cd08311    1 PPHKQEEVEKLLNAGR-EGSDWRALAGELGYSAEEIDSFAREADPCRALLTDWSAQDGAtLGVLLTALRKIGRDDIVEIL 79

                 .
gi 569001995 488 Q 488
Cdd:cd08311   80 Q 80

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 569001995 427 GNDWRRLASHLGLCGMKIRFLSCQ-----RSPAAAILELFEEQNGS---LQELHYLMTSMERLDCASAIQ 488
Cdd:cd01670   10 GRDWKKLARKLGLSEGDIDQIEEDnrddlKEQAYQMLERWREREGDeatLGRLIQALREIGRRDLAEKLE 79

Death domain of the Nuclear Factor-KappaB1 precursor protein p105; Death Domain (DD) of the Nuclear Factor-KappaB1 (NF-kB1) precursor protein p105. 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-kB1 (or p50) is produced from the processing of the precursor protein p105, which contains ANK repeats and a C-terminal DD in addition to the RHD. It is regulated by the classical (or canonical) NF-kB pathway. In the cytosol, p50 forms an inactive complex with RelA (or p65) and the Inhibitor of NF-kB (IkB). Activation is triggered by the phosphorylation and degradation of IkB, resulting in the active DNA-binding p50-RelA dimer to migrate to the nucleus. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. 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 569001995 414 EQLQMLLEPNSVTGNdWRRLASHLGLCGMKIRF-LScqRSPAAAILELFEEQNGSLQELHYLMTSMERLDCASAIQ 488
Cdd:cd08797    3 QQLYKLLESPDPDKN-WATLAQKLGLGILNNAFrLS--PSPSKTLLDNYEVSGGTVRELLAALRQMGYTEAIEVIE 75