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 1239290983  670 ERIEERLAYIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLVECLTKINRMDIV 749
Cdd:cd08804      1 ERTEERLAHIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLTQCLTKINRMDIV 80

                   ....
gi 1239290983  750 HLME 753
Cdd:cd08804     81 HLME 84

Neuroendocrine-specific golgi protein P55 (NESP55); This family consists of several mammalian neuroendocrine-specific golgi protein P55 (NESP55) sequences. NESP55 is a novel member of the chromogranin family and is a soluble, acidic, heat-stable secretory protein that is expressed exclusively in endocrine and nervous tissues, although less widely than chromogranins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239290983  826 TFQDGVPKTEGDSSATALFPQTHKEQVQQDFSGKMQDLPEESSLEYQQEYFVTTPGTET-------SETQKAMIVPSSPS 898
Cdd:pfam06390   62 SFLNAHHRSAAAAAAAQVFPEPSEPESDHEDEDFEPELARPECLEYDEDDFDTETDSETepesdieSETEFETEPETEPD 141

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239290983  899 KTPE-EVSTPAEEEK--------------------LYLQTPTSSERGGSPIIQEPEEPSEHRE------ESSPR--KTSL 949
Cdd:pfam06390  142 TAPTtEPETEPEDEPgpvvpkgatfhqslterlhaLKLQSADASPRRAPPSTQEPESAREGEEpergplDKDPRdpEEEE 221

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1239290983  950 VIVESADNQPETCErldEDAAFEKGDDMPEIPPE 983
Cdd:pfam06390  222 EEKEEEKQQPHRCK---PKKPARRRDPSPESPPK 252

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 1239290983  670 ERIEERLAYIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLVECLTKINRMDIV 749
Cdd:cd08804      1 ERTEERLAHIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLTQCLTKINRMDIV 80

                   ....
gi 1239290983  750 HLME 753
Cdd:cd08804     81 HLME 84

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239290983  191 VSFMVDARGGAMRGCrHNGLRIIIPPRKCTAPTRVTCRLVKRHRLATMPPMVEGEGLASRLIEVGPSGAQFLGPVIVEIP 270
Cdd:pfam00791    1 VSGLVDSRGGRLVLP-NSGVSLLIPPGAIPEGTRIECYLAVNRDESSRPPLEEGETLLSPVVECGPPGLKFLKPVILEVP 79

                           90
                   ....*....|....*...
gi 1239290983  271 HFAALRGKERELVVLRSE 288
Cdd:pfam00791   80 HCASLRPEEWEIVLKRSD 97

Death domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239290983  673 EERLAYIADH---LGFSWTELARELDFTEEQIHQIRIENPNsLQDQSHALLKYWLERDGKHATDTNLVECLTKINRMDIV 749
Cdd:pfam00531    1 RKQLDRLLDPpppLGKDWRELARKLGLSENEIDEIESENPR-LRSQTYELLRLWEQREGKNATVGTLLEALRKLGRRDAA 79

                   ....
gi 1239290983  750 HLME 753
Cdd:pfam00531   80 EKIQ 83

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 1239290983  670 ERIEERLAYIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLVECLTKINRMDIV 749
Cdd:cd08804      1 ERTEERLAHIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLTQCLTKINRMDIV 80

                   ....
gi 1239290983  750 HLME 753
Cdd:cd08804     81 HLME 84

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239290983  191 VSFMVDARGGAMRGCrHNGLRIIIPPRKCTAPTRVTCRLVKRHRLATMPPMVEGEGLASRLIEVGPSGAQFLGPVIVEIP 270
Cdd:pfam00791    1 VSGLVDSRGGRLVLP-NSGVSLLIPPGAIPEGTRIECYLAVNRDESSRPPLEEGETLLSPVVECGPPGLKFLKPVILEVP 79

                           90
                   ....*....|....*...
gi 1239290983  271 HFAALRGKERELVVLRSE 288
Cdd:pfam00791   80 HCASLRPEEWEIVLKRSD 97

Death domain of Ankyrin-3; Death Domain (DD) of the human protein ankyrin-3 (ANK-3) 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-3, also called anykyrin-G (for general or giant), is found in neurons and at least one splice variant has been shown to be essential for propagation of action potentials as a binding partner to neurofascin and voltage-gated sodium channels. It is required for maintaining axo-dendritic polarity, and may be a genetic risk factor associated with bipolar disorder. ANK-3 may also play roles in other cell types. Mutations affecting ANK-3 pathways for Na channel localization are associated with Brugada syndrome, a potentially fatal arrythmia. 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 1239290983  670 ERIEERLAYIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLVECLTKINRMDIV 749
Cdd:cd08803      1 ERTDIRMAIVADHLGLSWTELARELNFSVDEINQIRVENPNSLIAQSFMLLKKWVTRDGKNATTDALTSVLTKINRIDIV 80

                   ....
gi 1239290983  750 HLME 753
Cdd:cd08803     81 TLLE 84

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 1239290983   669 QERIEERLAYIADH-LGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLVECLTKINRMD 747
Cdd:smart00005    1 PELTRQKLAKLLDHpLGLDWRELARKLGLSEADIDQIRTEAPRDLAEQSVQLLRLWEQREGKNATLGTLLEALRKMGRDD 80

                    ....*..
gi 1239290983   748 IVHLMET 754
Cdd:smart00005   81 AVELLRS 87

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 1239290983  676 LAYIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLVECLTKINRMDIVHLME 753
Cdd:cd01670      2 FDLVAEELGRDWKKLARKLGLSEGDIDQIEEDNRDDLKEQAYQMLERWREREGDEATLGRLIQALREIGRRDLAEKLE 79

Death domain of RIP-associated ICH-1 homologous protein with a death domain; Death domain (DD) of RAIDD (RIP-associated ICH-1 homologous protein with a death domain), also known as CRADD (Caspase and RIP adaptor). RAIDD is an adaptor protein that together with the p53-inducible protein PIDD and caspase-2, forms the PIDDosome complex, which is required for caspase-2 activation and plays a role in mediating stress-induced apoptosis. RAIDD contains an N-terminal Caspase Activation and Recruitment Domain (CARD), which interacts with the caspase-2 CARD, and a C-terminal DD, which interacts with the DD of PIDD. 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, 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 1239290983  673 EERLAYIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLVECLTKIN 744
Cdd:cd08319      2 DRQLNKLAQRLGPEWEQVLLDLGLSKADIYRCKADHPYNVQSQIVEALVKWKQRQGKKATVQSLIQSLKAVE 73

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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239290983  669 QERIEErlayIADHLGFSWTELARELDFTEEQIHQIRiENPNSLQDQSHALLKYWLERDGKHATDTNLVECLTKINRMDI 748
Cdd:cd08318      7 SEQIDV----LANKLGEQWKTLAPYLEMKDKDIRQIE-SDSEDMKMRAKQLLVTWQDREGAQATPEILMTALNAAGLNEI 81

Death Domain of Death Receptors; Death domain (DD) found in death receptor proteins. Death receptors are members of the tumor necrosis factor (TNF) receptor superfamily, characterized by having a cytoplasmic DD. Known members of the family are Fas (CD95/APO-1), TNF-receptor 1 (TNFR1/TNFRSF1A/p55/CD120a), TNF-related apoptosis-inducing ligand receptor 1 (TRAIL-R1 /DR4), and receptor 2 (TRAIL-R2/DR5/APO-2/KILLER), as well as Death Receptor 3 (DR3/APO-3/TRAMP/WSL-1/LARD). They are involved in apoptosis signaling pathways. 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 1239290983  686 SWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLVECLtkiNRMDIVHLME 753
Cdd:cd08784     13 QWKGFVRKLGLNEAEIDEIKNDNVQDTAEAKYQMLRNWHQLTGRKAAYDTLIKDL---KKMNLCTLAE 77

Death Domain of Receptor-Interacting Protein 1; Death domain (DD) found in Receptor-Interacting Protein 1 (RIP1) and related proteins. RIP kinases serve as essential sensors of cellular stress. Vertebrates contain several types containing a homologous N-terminal kinase domain and varying C-terminal domains. RIP1 harbors a C-terminal DD, which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accumulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. 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 1239290983  673 EERLAYIADHLGFSWTELARELDFTEEQIHQIRIE-NPNSLQDQSHALLKYWLERDG-KHATDTNLVECLTKINRMDIVH 750
Cdd:cd08777      2 EKHLDLLRENLGKKWKRCARRLGLTEVEIEEIDHDyERDGLKEKVHQMLEKWKMKEGsKGATVGKLAKALEGCIKSDLLV 81

                   ..
gi 1239290983  751 LM 752
Cdd:cd08777     82 SL 83

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1239290983  687 WTELARELDFTEEQIHQIRIENpnslqDQSHALLKYWLERDgKHATDTNLVECLTKINRMDIVH 750
Cdd:cd08312     19 WRGLAELMGFDYLEIRNFERQS-----SPTERLLEDWETRP-PGATVGNLLEILEELERKDVLE 76

Death domain of FAS or TNF receptor superfamily member 6; Death Domain (DD) found in the FS7-associated cell surface antigen (FAS). FAS, also known as TNFRSF6 (TNF receptor superfamily member 6), APT1, CD95, FAS1, or APO-1, together with FADD (Fas-associating via Death Domain) and caspase 8, is an integral part of the death inducing signalling complex (DISC), which plays an important role in the induction of apoptosis and is activated by binding of the ligand FasL to FAS. FAS also plays a critical role in self-tolerance by eliminating cell types (autoreactive T and B cells) that contribute to autoimmunity. 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 1239290983  672 IEERLAYIADHLGfsWTE---LARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLVECLTKINR--- 745
Cdd:cd08316      4 LSKHIPDIAEIMG--WKDvkkFARKSGISETKIDEIQLDNPNDTAEQKVQLLRAWYQKHGKKGAYRTLIKTLRKAGKrak 81

                   ....*....
gi 1239290983  746 ----MDIVH 750
Cdd:cd08316     82 adkiQDIIK 90