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 1831512980 560 LPFGVKDELARLLDMPNESHSDWRGLAKKLHYDRYLQFFASFPdcSPTSLLLDLWEASSSGSaRAVPDLLQTLRVMGRPD 639
Cdd:cd08781     1 LPYSIRQKLCSLLDPPNARGNDWRLLAQKLSVDRYINYFATKP--SPTEVILDLWEARNRDD-GALNSLAAILREMGRHD 77

                  ....*.
gi 1831512980 640 AVMVLE 645
Cdd:cd08781    78 AATILE 83

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 1831512980 403 AAKRVHLAVFGPTEMSAYRrpFELRVYCVPETGAAMESVWKQED--GSRLLCESNdfILNEKG---NLCICIEDVIPGFS 477
Cdd:pfam17217   1 AIKRLRLAVFAPAACTSLE--YSLRVYCLDDTPDALKEVVQLEKqlGGQLLEEPK--TLHFKDsthNLRLSIHDIPPSLW 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1831512980 478 CDGPEVV--EISETQHRFVAQNGLHCSLKFRPKEINGSQFSTRVIVYQ 523
Cdd:pfam17217  77 KSKLFAKyqEIPFYHVWSGNQNPLHCTFTLERYSLATTELSCKICVRQ 124

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 1831512980 560 LPFGVKDELARLLDMPNESHSDWRGLAKKLHYDRYLQFFASFPdcSPTSLLLDLWEASSSGSaRAVPDLLQTLRVMGRPD 639
Cdd:cd08781     1 LPYSIRQKLCSLLDPPNARGNDWRLLAQKLSVDRYINYFATKP--SPTEVILDLWEARNRDD-GALNSLAAILREMGRHD 77

                  ....*.
gi 1831512980 640 AVMVLE 645
Cdd:cd08781    78 AATILE 83

Death domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831512980 565 KDELARLLDMPNESHSDWRGLAKKLHYDRY-LQFFASFP--DCSPTSLLLDLWEAsSSGSARAVPDLLQTLRVMGRPDAV 641
Cdd:pfam00531   1 RKQLDRLLDPPPPLGKDWRELARKLGLSENeIDEIESENprLRSQTYELLRLWEQ-REGKNATVGTLLEALRKLGRRDAA 79

                  ....*..
gi 1831512980 642 MVLERFL 648
Cdd:pfam00531  80 EKIQSIL 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 1831512980  561 PFGVKDELARLLDMPneSHSDWRGLAKKLHY-DRYLQFFASFPDC---SPTSLLLDLWEASSSGSArAVPDLLQTLRVMG 636
Cdd:smart00005   1 PELTRQKLAKLLDHP--LGLDWRELARKLGLsEADIDQIRTEAPRdlaEQSVQLLRLWEQREGKNA-TLGTLLEALRKMG 77

                           90
                   ....*....|
gi 1831512980  637 RPDAVMVLER 646
Cdd:smart00005  78 RDDAVELLRS 87

Spondin-like TSP1 domain; This entry represents a sub-type of TSP1 domains that have an alternative disulphide binding pattern compared to the canonical TSP1 domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1831512980  16 SSWSDWSACSSSC---HRYRTRACTVPPPmNGGQPCfGDDLMTQECPAQLC 63
Cdd:pfam19028   4 SEWSEWSECSVTCgggVQTRTRTVIVEPQ-NGGRPC-PELLERRPCNLPPC 52

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 1831512980 560 LPFGVKDELARLLDMPNESHSDWRGLAKKLHYDRYLQFFASFPdcSPTSLLLDLWEASSSGSaRAVPDLLQTLRVMGRPD 639
Cdd:cd08781     1 LPYSIRQKLCSLLDPPNARGNDWRLLAQKLSVDRYINYFATKP--SPTEVILDLWEARNRDD-GALNSLAAILREMGRHD 77

                  ....*.
gi 1831512980 640 AVMVLE 645
Cdd:cd08781    78 AATILE 83

Death domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831512980 565 KDELARLLDMPNESHSDWRGLAKKLHYDRY-LQFFASFP--DCSPTSLLLDLWEAsSSGSARAVPDLLQTLRVMGRPDAV 641
Cdd:pfam00531   1 RKQLDRLLDPPPPLGKDWRELARKLGLSENeIDEIESENprLRSQTYELLRLWEQ-REGKNATVGTLLEALRKLGRRDAA 79

                  ....*..
gi 1831512980 642 MVLERFL 648
Cdd:pfam00531  80 EKIQSIL 86

Thrombospondin type 1 repeats; Type 1 repeats in thrombospondin-1 bind and activate TGF-beta.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1831512980   15 WSSWSDWSACSSSC---HRYRTRACTVPPPMNGGQPCFGDDLMTQECPAQLC 63
Cdd:smart00209   1 WSEWSEWSPCSVTCgggVQTRTRSCCSPPPQNGGGPCTGEDVETRACNEQPC 52

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831512980 560 LPFGVKDELARLLDMPNESHSDWRGLAKKLHYDRYLQFFASFPdcSPTSLLLDLWEASSSGSARaVPDLLQTLRVMGRPD 639
Cdd:cd08800     1 IPFLIRQKIISSLDPPCPRGADWRTLAQKLNLDSHLSFFASKS--SPTAMILNLWEAQHFPNGN-LSQLAAVVAEIGKQD 77

                  ....*.
gi 1831512980 640 AVMVLE 645
Cdd:cd08800    78 AMLFLV 83

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 1831512980 403 AAKRVHLAVFGPTEMSAYRrpFELRVYCVPETGAAMESVWKQED--GSRLLCESNdfILNEKG---NLCICIEDVIPGFS 477
Cdd:pfam17217   1 AIKRLRLAVFAPAACTSLE--YSLRVYCLDDTPDALKEVVQLEKqlGGQLLEEPK--TLHFKDsthNLRLSIHDIPPSLW 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1831512980 478 CDGPEVV--EISETQHRFVAQNGLHCSLKFRPKEINGSQFSTRVIVYQ 523
Cdd:pfam17217  77 KSKLFAKyqEIPFYHVWSGNQNPLHCTFTLERYSLATTELSCKICVRQ 124

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831512980 564 VKDELARLLDmpneSHSDWRGLAKKLHYDRYLQFFASFPdcSPTSLLLDLWEASSSgsarAVPDLLQTLRVMGRPDAVMV 643
Cdd:cd08310     1 TRLRLCKLLD----VGKDWRELAELLGLGHLVESIEQSS--SPTKLLLDYYEAQGG----TLEKLREALRALGETDAVEL 70

                  ..
gi 1831512980 644 LE 645
Cdd:cd08310    71 ID 72

Thrombospondin type 1 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1831512980  16 SSWSDWSACSSSC---HRYRTRACTVPPPmnGGQPCFGDDLMTQECPAQLC 63
Cdd:pfam00090   1 SPWSPWSPCSVTCgkgIQVRQRTCKSPFP--GGEPCTGDDIETQACKMDKC 49

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 1831512980 567 ELARLLdMPNESHSDWRGLAKKLHY--DRylqfFASFPDC-SPTSLLLDLWEASSSGSARAvpdLLQTLRVMGRPDAVMV 643
Cdd:cd08311     7 EVEKLL-NAGREGSDWRALAGELGYsaEE----IDSFAREaDPCRALLTDWSAQDGATLGV---LLTALRKIGRDDIVEI 78

                  ..
gi 1831512980 644 LE 645
Cdd:cd08311    79 LQ 80

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831512980 558 FRLPFGVKDELARLLDMPNEshSDWRGLAKKLHYD----RYLQFFASfPDCSPTSLLLDLWeassSGSARAVPDLLQTLR 633
Cdd:cd08309     4 RNLPPWVLKRLCKVLDALEL--AGWRQLASLIPYDqtdvRQIESMKQ-RGQSPTRELLWDW----GTQNATVQDLVQLLT 76

                  ...
gi 1831512980 634 VMG 636
Cdd:cd08309    77 QLG 79