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 77681981 494 ERMEERLAYIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTILIECLTKINRMDIV 573
Cdd:cd08804   1 ERTEERLAHIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLTQCLTKINRMDIV 80

                ....
gi 77681981 574 HLLE 577
Cdd:cd08804  81 HLME 84

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 77681981 494 ERMEERLAYIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTILIECLTKINRMDIV 573
Cdd:cd08804   1 ERTEERLAHIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLTQCLTKINRMDIV 80

                ....
gi 77681981 574 HLLE 577
Cdd:cd08804  81 HLME 84

Death domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77681981   497 EERLAYIADH---LGFSWTELARELDFTEEQIHQIRIENPNsLQDQSHALLKYWLERDGKHATDTILIECLTKINRMDIV 573
Cdd:pfam00531   1 RKQLDRLLDPpppLGKDWRELARKLGLSENEIDEIESENPR-LRSQTYELLRLWEQREGKNATVGTLLEALRKLGRRDAA 79

                  ....
gi 77681981   574 HLLE 577
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 77681981 494 ERMEERLAYIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTILIECLTKINRMDIV 573
Cdd:cd08804   1 ERTEERLAHIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTNLTQCLTKINRMDIV 80

                ....
gi 77681981 574 HLLE 577
Cdd:cd08804  81 HLME 84

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 77681981 494 ERMEERLAYIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTILIECLTKINRMDIV 573
Cdd:cd08803   1 ERTDIRMAIVADHLGLSWTELARELNFSVDEINQIRVENPNSLIAQSFMLLKKWVTRDGKNATTDALTSVLTKINRIDIV 80

                ....
gi 77681981 574 HLLE 577
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 77681981    497 EERLAYIADH-LGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTILIECLTKINRMDIVHL 575
Cdd:smart00005   5 RQKLAKLLDHpLGLDWRELARKLGLSEADIDQIRTEAPRDLAEQSVQLLRLWEQREGKNATLGTLLEALRKMGRDDAVEL 84

                   ...
gi 77681981    576 LET 578
Cdd:smart00005  85 LRS 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 77681981 500 LAYIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTILIECLTKINRMDIVHLLE 577
Cdd:cd01670   2 FDLVAEELGRDWKKLARKLGLSEGDIDQIEEDNRDDLKEQAYQMLERWREREGDEATLGRLIQALREIGRRDLAEKLE 79

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 77681981 489 PQDEQERMEERLAyiADHLGFSWTELARELDFTEEQIHQIrienpNSLQDQSHALLKYWLERDGkhATDTILIECLTKIN 568
Cdd:cd08311   1 PPHKQEEVEKLLN--AGREGSDWRALAGELGYSAEEIDSF-----AREADPCRALLTDWSAQDG--ATLGVLLTALRKIG 71

                ....*....
gi 77681981 569 RMDIVHLLE 577
Cdd:cd08311  72 RDDIVEILQ 80

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 77681981 497 EERLAYIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTILIECLTKIN 568
Cdd:cd08319   2 DRQLNKLAQRLGPEWEQVLLDLGLSKADIYRCKADHPYNVQSQIVEALVKWKQRQGKKATVQSLIQSLKAVE 73

Death domain of Tumor necrosis factor-Related Apoptosis-Inducing Ligand Receptors; Death Domain (DD) found in Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL) Receptors. In mammals, this family includes TRAILR1 (also called DR4 or TNFRSF10A) and TRAILR2 (also called DR5, TNFRSF10B, or KILLER). They function as receptors for the cytokine TRAIL and are involved in apoptosis signaling pathways. TRAIL preferentially induces apoptosis in cancer cells while exhibiting little toxicity in normal cells. 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 77681981 502 YIADHLGF-SWTELARELDFTEEQIHQIRIENPNSlQDQSHALLKYWLERDGKHATDTILIECLTKIN----RMDIVHLL 576
Cdd:cd08315   4 YFEDIVPFkSWKRLMRALGLSDNEIKLAEANDPGS-QEPLYQMLNKWLNKTGRKASVNTLLDALEDLGlrgaAETIADKL 82

DNA polymerase III subunits gamma and tau; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77681981   71 EEAISEDLKEGATGAEPPQTETtSESLELSEPKEAMDDE---------------GELLPDDVSEEIEDLPASDAnidSQV 135
Cdd:PRK14949 422 QAANAEAVAEADASAEPADTVE-QALDDESELLAALNAEqavilsqaqsqgfeaSSSLDADNSAVPEQIDSTAE---QSV 497

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77681981  136 IISASTETPTKEAVSTAVEEPPTTQRSDSLSTVKQTPRPAVPGpvgqlDFSPVTRSVYSGQDDESPESSpEEQKSVIEIP 215
Cdd:PRK14949 498 VNPSVTDTQVDDTSASNNSAADNTVDDNYSAEDTLESNGLDEG-----DYAQDSAPLDAYQDDYVAFSS-ESYNALSDDE 571

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77681981  216 TAPVDNVPSAESKPQIPIRTLPTLVPAPPSAEDESAfSDDFPSS-----------LDEDS-KEGGAKP-----KSKIPVK 278
Cdd:PRK14949 572 QHSANVQSAQSAAEAQPSSQSLSPISAVTTAAASLA-DDDILDAvlaardsllsdLDALSpKEGDGKKssadrKPKTPPS 650

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 77681981  279 APTQRTEWQPsPTDIPLQKTAVPQGQETLSRAPDGRSKSESDASSLDAKTKCPV 332
Cdd:PRK14949 651 RAPPASLSKP-ASSPDASQTSASFDLDPDFELATHQSVPEAALASGSAPAPPPV 703

Death Domain of p53-induced protein with a death domain; Death domain (DD) found in PIDD (p53-induced protein with a death domain) and similar proteins. PIDD is a component of the PIDDosome complex, which is an oligomeric caspase-activating complex involved in caspase-2 activation and plays a role in mediating stress-induced apoptosis. The PIDDosome complex is composed of three components, PIDD, RAIDD and caspase-2, which interact through their DDs and DD-like domains. The DD of PIDD interacts with the DD of RAIDD, which also contains a Caspase Activation and Recruitment Domain (CARD) that interacts with the caspase-2 CARD. Autoproteolysis of PIDD determines the downstream signaling event, between pro-survival NF-kB or pro-death caspase-2 activation. 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77681981 500 LAYIADHLGFSWTELARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLErdgKHATDT----ILIECLTKINRMDIVHL 575
Cdd:cd08779   5 LLSLAKELGEDWQKLALHLGVSYSRIQRIKRKNRDDLDEQILDMLFSWAK---TLPTSPdkvgLLVTALSKSGRSDLAEE 81

                ...
gi 77681981 576 LET 578
Cdd:cd08779  82 LRD 84

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 77681981 503 IADHLGfsWTE---LARELDFTEEQIHQIRIENPNSLQDQSHALLKYWLERDGKHATDTILIECLTKINR-------MDI 572
Cdd:cd08316  11 IAEIMG--WKDvkkFARKSGISETKIDEIQLDNPNDTAEQKVQLLRAWYQKHGKKGAYRTLIKTLRKAGKrakadkiQDI 88

                ..
gi 77681981 573 VH 574
Cdd:cd08316  89 IK 90