N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor kappa B2 (NF-kappa B2); Proteins containing the Rel homology domain (RHD) are metazoan transcription factors. The RHD is composed of two structural sub-domains; this model characterizes the N-terminal RHD sub-domain of the NF-kappa B2 family of transcription factors, a class I member of the NF-kappa B family. In class I NF-kappa Bs, the RHD domain co-occurs with C-terminal ankyrin repeats. NF-kappa B2 is commonly referred to as p100 or p52 (proteolytically processed form). NF-kappa B proteins are part of a protein complex that acts as a transcription factor, which is responsible for regulating a host of cellular responses to a variety of stimuli. This complex tightly regulates the expression of a large number of genes, and is involved in processes such as adaptive and innate immunity, stress response, inflammation, cell adhesion, proliferation and apoptosis. The cytosolic NF-kappa B complex is activated via phosphorylation of the ankyrin-repeat containing inhibitory protein I-kappa B, which dissociates from the complex and exposes the nuclear localization signal of the heterodimer (NF-kappa B and REL). NF-kappa B2 is involved in the alternative NF-kappa B signaling pathway which is activated by few agonists and plays an important role in secondary lymphoid organogenesis, maturation of B-cells, and adaptive humoral immunity. p100 may also act as an I-kappa B due to its C-terminal ankyrin repeats.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017  38 PYLVIVEQPKQRGFRFRYGCEGPSHGGLPGASSEKGRKTYPTVKICNYEGPAKIEVDLVTHSDPPRAHAHSLVGKQCSEL 117
Cdd:cd07934    1 PYLVIIEQPKQRGFRFRYVCEGPSHGGLPGASSEKGRKTYPTVKICNYVGMARIEVDLVTHTDPPRVHAHSLVGKHCNES 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 118 GVCAVSVGPKDMTAQFNNLGVLHVTKKNMMEIMIQKLQRQRLRSK-PQGLTEAERRELEQEAKELKKVMDLSIVRLRFSA 196
Cdd:cd07934   81 GNCSVDVGPKDMTAQFSNLGILHVTKKNMMEILKEKLKRQKLRNTgPYKLTEAEERELEQEAKELKKVMDLSIVRLKFTA 160

                        170       180
                 ....*....|....*....|....*
gi 564334017 197 FLRASDGSFSLPLKPVISQPIHDSK 221
Cdd:cd07934  161 YLRDSNGSYTLALKPVISDPIHDSK 185

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564334017 773 ALQNLEQLLDGPEAQGSWAELAERLGLRSLVDTYRKTPSPSGSLLRSYKLAGGDLVGLLEALSDMGLHEGVRLLK 847
Cdd:cd08798    1 TLQRLEQLLNDTQTDVPWMELAERLGLQSLVDTYKPTQSPPGSLLRSYELAGGPLQGLIEALQDMGLREGVRLLR 75

N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor kappa B2 (NF-kappa B2); Proteins containing the Rel homology domain (RHD) are metazoan transcription factors. The RHD is composed of two structural sub-domains; this model characterizes the N-terminal RHD sub-domain of the NF-kappa B2 family of transcription factors, a class I member of the NF-kappa B family. In class I NF-kappa Bs, the RHD domain co-occurs with C-terminal ankyrin repeats. NF-kappa B2 is commonly referred to as p100 or p52 (proteolytically processed form). NF-kappa B proteins are part of a protein complex that acts as a transcription factor, which is responsible for regulating a host of cellular responses to a variety of stimuli. This complex tightly regulates the expression of a large number of genes, and is involved in processes such as adaptive and innate immunity, stress response, inflammation, cell adhesion, proliferation and apoptosis. The cytosolic NF-kappa B complex is activated via phosphorylation of the ankyrin-repeat containing inhibitory protein I-kappa B, which dissociates from the complex and exposes the nuclear localization signal of the heterodimer (NF-kappa B and REL). NF-kappa B2 is involved in the alternative NF-kappa B signaling pathway which is activated by few agonists and plays an important role in secondary lymphoid organogenesis, maturation of B-cells, and adaptive humoral immunity. p100 may also act as an I-kappa B due to its C-terminal ankyrin repeats.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017  38 PYLVIVEQPKQRGFRFRYGCEGPSHGGLPGASSEKGRKTYPTVKICNYEGPAKIEVDLVTHSDPPRAHAHSLVGKQCSEL 117
Cdd:cd07934    1 PYLVIIEQPKQRGFRFRYVCEGPSHGGLPGASSEKGRKTYPTVKICNYVGMARIEVDLVTHTDPPRVHAHSLVGKHCNES 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 118 GVCAVSVGPKDMTAQFNNLGVLHVTKKNMMEIMIQKLQRQRLRSK-PQGLTEAERRELEQEAKELKKVMDLSIVRLRFSA 196
Cdd:cd07934   81 GNCSVDVGPKDMTAQFSNLGILHVTKKNMMEILKEKLKRQKLRNTgPYKLTEAEERELEQEAKELKKVMDLSIVRLKFTA 160

                        170       180
                 ....*....|....*....|....*
gi 564334017 197 FLRASDGSFSLPLKPVISQPIHDSK 221
Cdd:cd07934  161 YLRDSNGSYTLALKPVISDPIHDSK 185

IPT domain of the transcription factor NFkappaB and related transcription factors. NFkappaB is considered a central regulator of stress responses, activated by different stressful conditions, including physical stress, oxidative stress, and exposure to certain chemicals. NFkappaB blocking cell apoptosis in several cell types, gives it an important role in cell proliferation and differentiation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 228 LKISRMDKTAGSVRGGDEVYLLCDKVQKDDIEVRFYEDDEN--GWQAFGDFSPTDVHKQYAIVFRTPPYHKMKIERPVTV 305
Cdd:cd01177    1 LKICRLDKTSGSVKGGDEVYLLCDKVQKEDIQVRFFEEDEEetVWEAFGDFSQTDVHRQYAIVFRTPPYHDPDITEPVKV 80

                         90       100
                 ....*....|....*....|..
gi 564334017 306 FLQLKRKRGGDVSDSKQFTYYP 327
Cdd:cd01177   81 KIQLKRPSDGERSESVPFTYVP 102

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564334017 773 ALQNLEQLLDGPEAQGSWAELAERLGLRSLVDTYRKTPSPSGSLLRSYKLAGGDLVGLLEALSDMGLHEGVRLLK 847
Cdd:cd08798    1 TLQRLEQLLNDTQTDVPWMELAERLGLQSLVDTYKPTQSPPGSLLRSYELAGGPLQGLIEALQDMGLREGVRLLR 75

ig-like, plexins, transcription factors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017   227 NLKISRMDKTAGSVRGGDEVyLLCDKVQKDDIEVRFYEddeNGWQAFGDFSPTdvhKQYAIVFRTPPYHKMKIERPVTVF 306
Cdd:smart00429   1 DPVITRISPTSGPVSGGTEI-TLCGKNLKSISVVFVEV---GVGEAPCTFSPS---SSTAIVCKTPPYHNIPGSVPVRTV 73

                           90       100
                   ....*....|....*....|.
gi 564334017   307 LQlkrkRGGDV-SDSKQFTYY 326
Cdd:smart00429  74 GL----RNGGVpSSPQPFTYV 90

Ankyrin repeats (3 copies);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017  604 HLAVHARSPECLDLLVDCGAEVEAaERQGGRTPLHLATEMEELGLVTHLVTklHANVNARTFaGNTPLHLAAGLGSPTLT 683
Cdd:pfam12796   2 HLAAKNGNLELVKLLLENGADANL-QDKNGRTALHLAAKNGHLEIVKLLLE--HADVNLKDN-GRTALHYAARSGHLEIV 77

                          90
                  ....*....|....
gi 564334017  684 RLLLKAGADIHAEN 697
Cdd:pfam12796  78 KLLLEKGADINVKD 91

Death domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017  775 QNLEQLLDGPEAQG-SWAELAERLGLRSL-VDT----YRKTPSPSGSLLRSYKLAGG---DLVGLLEALSDMGLHEGVRL 845
Cdd:pfam00531   2 KQLDRLLDPPPPLGkDWRELARKLGLSENeIDEieseNPRLRSQTYELLRLWEQREGknaTVGTLLEALRKLGRRDAAEK 81

                  ...
gi 564334017  846 LKA 848
Cdd:pfam00531  82 IQS 84

Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and TRPV6 (TRPV5/6) are two homologous members within the vanilloid subfamily of the transient receptor potential (TRP) family. TRPV5 and TRPV6 show only 30-40% homology with other members of the TRP family and have unique properties that differentiates them from other TRP channels. They mediate calcium uptake in epithelia and their expression is dramatically increased in numerous types of cancer. The structure of TRPV5/6 shows the typical topology features of all TRP family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6, which is predicted to form the Ca2+ pore, and large intracellular N- and C-terminal domains. The N-terminal domain of TRPV5/6 contains three ankyrin repeats. This structural element is present in several proteins and plays a role in protein-protein interactions. The N- and C-terminal tails of TRPV5/6 each contain an internal PDZ motif which can function as part of a molecular scaffold via interaction with PDZ-domain containing proteins. A major difference between the properties of TRPV5 and TRPV6 is in their tissue distribution: TRPV5 is predominantly expressed in the distal convoluted tubules (DCT) and connecting tubules (CNT) of the kidney, with limited expression in extrarenal tissues. In contrast, TRPV6 has a broader expression pattern such as expression in the intestine, kidney, placenta, epididymis, exocrine tissues, and a few other tissues.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 513 AQYLGVINL--TNHLHQTPLHLAVITGQTRVVSFLL-QVGADPTLLDRHGDSAVHLALRAG--AAAPDLLQAVlhsgaha 587
Cdd:cd22192    2 AQMLDELHLlqQKRISESPLLLAAKENDVQAIKKLLkCPSCDLFQRGALGETALHVAALYDnlEAAVVLMEAA------- 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 588 lPQMLHMPDFEGLYPvhlavharspecldllvdcgaeveaaerqgGRTPLHLATEMEELGLVTHLVTKLHANVNART--- 664
Cdd:cd22192   75 -PELVNEPMTSDLYQ------------------------------GETALHIAVVNQNLNLVRELIARGADVVSPRAtgt 123

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 665 ----------FAGNTPLHLAAGLGSPTLTRLLLKAGADIHAE---------------NEEPLCPLPSPPTSgSDSDSEGP 719
Cdd:cd22192  124 ffrpgpknliYYGEHPLSFAACVGNEEIVRLLIEHGADIRAQdslgntvlhilvlqpNKTFACQMYDLILS-YDKEDDLQ 202

                        250
                 ....*....|....*..
gi 564334017 720 ETDTQRNFRGHTPLDLT 736
Cdd:cd22192  203 PLDLVPNNQGLTPFKLA 219

N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor kappa B2 (NF-kappa B2); Proteins containing the Rel homology domain (RHD) are metazoan transcription factors. The RHD is composed of two structural sub-domains; this model characterizes the N-terminal RHD sub-domain of the NF-kappa B2 family of transcription factors, a class I member of the NF-kappa B family. In class I NF-kappa Bs, the RHD domain co-occurs with C-terminal ankyrin repeats. NF-kappa B2 is commonly referred to as p100 or p52 (proteolytically processed form). NF-kappa B proteins are part of a protein complex that acts as a transcription factor, which is responsible for regulating a host of cellular responses to a variety of stimuli. This complex tightly regulates the expression of a large number of genes, and is involved in processes such as adaptive and innate immunity, stress response, inflammation, cell adhesion, proliferation and apoptosis. The cytosolic NF-kappa B complex is activated via phosphorylation of the ankyrin-repeat containing inhibitory protein I-kappa B, which dissociates from the complex and exposes the nuclear localization signal of the heterodimer (NF-kappa B and REL). NF-kappa B2 is involved in the alternative NF-kappa B signaling pathway which is activated by few agonists and plays an important role in secondary lymphoid organogenesis, maturation of B-cells, and adaptive humoral immunity. p100 may also act as an I-kappa B due to its C-terminal ankyrin repeats.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017  38 PYLVIVEQPKQRGFRFRYGCEGPSHGGLPGASSEKGRKTYPTVKICNYEGPAKIEVDLVTHSDPPRAHAHSLVGKQCSEL 117
Cdd:cd07934    1 PYLVIIEQPKQRGFRFRYVCEGPSHGGLPGASSEKGRKTYPTVKICNYVGMARIEVDLVTHTDPPRVHAHSLVGKHCNES 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 118 GVCAVSVGPKDMTAQFNNLGVLHVTKKNMMEIMIQKLQRQRLRSK-PQGLTEAERRELEQEAKELKKVMDLSIVRLRFSA 196
Cdd:cd07934   81 GNCSVDVGPKDMTAQFSNLGILHVTKKNMMEILKEKLKRQKLRNTgPYKLTEAEERELEQEAKELKKVMDLSIVRLKFTA 160

                        170       180
                 ....*....|....*....|....*
gi 564334017 197 FLRASDGSFSLPLKPVISQPIHDSK 221
Cdd:cd07934  161 YLRDSNGSYTLALKPVISDPIHDSK 185

Rel homology DNA-binding domain; Proteins containing the Rel homology domain (RHD) are eukaryotic transcription factors. The RHD is composed of two structural domains. This is the N-terminal DNA-binding domain that is similar to that found in P53. The C-terminal domain has an immunoglobulin-like fold (See pfam16179) that functions as a dimerization domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017   40 LVIVEQPKQRGFRFRYGCEGPSHGGLPGASSEKGRKTYPTVKICNYEGPAKIEVDLVTHSDPPRAHAHSLVGKQCSElGV 119
Cdd:pfam00554   1 LEIVEQPKQRGMRFRYKCEGRSAGSIPGESSTRSKKTFPTVQICNYDGPAVIRVSLVTKDEPHRPHPHSLVGKDCKD-GV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017  120 CAVSVGPKDMTAQFNNLGVLHVTKKNMMEIMIQKLQrqrlrskpqgLTEAERReLEQEAKELKKVMDLSIVRLRFSAFLR 199
Cdd:pfam00554  80 CEVELGPEDMVASFQNLGIQCVKKKDVEEALKERIE----------LNIDPFN-VGFEALRQIKDMDLNVVRLCFQAFLP 148

                         170       180
                  ....*....|....*....|.
gi 564334017  200 ASDGSFSLPLKPVISQPIHDS 220
Cdd:pfam00554 149 DTRGNFTTPLPPVVSNPIYDK 169

N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of kappa B1 (NF-kappa B1); Proteins containing the Rel homology domain (RHD) are metazoan transcription factors. The RHD is composed of two structural sub-domains; this model characterizes the N-terminal RHD sub-domain of the NF-kappa B1 family of transcription factors, a class I member of the NF-kappa B family. In class I NF-kappa Bs, the RHD domain co-occurs with C-terminal ankyrin repeats. NF-kappa B1 is commonly referred to as p105 or p50 (proteolytically processed form). NF-kappa B proteins are part of a protein complex that acts as a transcription factor, which is responsible for regulating a host of cellular responses to a variety of stimuli. This complex tightly regulates the expression of a large number of genes, and is involved in processes such as adaptive and innate immunity, stress response, inflammation, cell adhesion, proliferation and apoptosis. The cytosolic NF-kappa B complex is activated via phosphorylation of the ankyrin-repeat containing inhibitory protein I-kappa B, which dissociates from the complex and exposes the nuclear localization signal of the heterodimer (NF-kappa B and REL). NF-kappa B1 is involved in the canonical NF-kappa B signaling pathway which is activated by many agonists and is essential in immune and inflammatory responses, as well as cell survival. p105 is involved in its own specific NF-kappa B signaling pathway which is also implicated in immune and inflammatory responses. p105 may also act as an I-kappa B due to its C-terminal ankyrin repeats. It is also involved in mitogen-activated protein kinase (MAPK) signaling as its degradation leads to the activation of TPL-2, a MAPK kinase kinase which activates ERK pathways.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017  38 PYLVIVEQPKQRGFRFRYGCEGPSHGGLPGASSEKGRKTYPTVKICNYEGPAKIEVDLVTHSDPPRAHAHSLVGKQCsEL 117
Cdd:cd07935    1 PYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHC-ED 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 118 GVCAVSVGPKDMTAQFNNLGVLHVTKKNMMEI----MIQKLQR---------------QRLRSKPQGLTEAERRELEQEA 178
Cdd:cd07935   80 GICTVTAGPKDMVVGFANLGILHVTKKKVFETlearMTEACKKgynpgllvhpelaylQAEGGGDRQLTEREKEIIRQAA 159

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 564334017 179 KELKKVMDLSIVRLRFSAFLRASDGSFSLPLKPVISQPIHDSK 221
Cdd:cd07935  160 VQQTKEMDLSVVRLMFTAFLPDSTGGFTRRLEPVVSDAIYDSK 202

Rel homology dimerization domain; The Rel homology domain (RHD) is composed of two structural domains, an N-terminal DNA_binding domain (pfam00554) and a C-terminal dimerization domain. This is the dimerization domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017  229 KISRMDKTAGSVRGGDEVYLLCDKVQKDDIEVRFYEDDE--NGWQAFGDFSPTDVHKQYAIVFRTPPYHKMKIERPVTVF 306
Cdd:pfam16179   1 KICRLSLCSGSVTGGEEIILLCEKVLKDDIKVRFYEEDDgqEVWEAEGDFSKTDVHRQVAIVFKTPPYRDPDITEPVTVN 80

                          90       100
                  ....*....|....*....|..
gi 564334017  307 LQLKRKRGGDVSDSKQFTYYPL 328
Cdd:pfam16179  81 IQLRRPSDKATSEPQPFTYLPL 102

IPT domain of eukaryotic transcription factors NF-kappaB/Rel, nuclear factor of activated Tcells (NFAT), and recombination signal J-kappa binding protein (RBP-Jkappa). The IPT domains in these proteins are involved in DNA binding. Most NF-kappaB/Rel proteins form homo- and heterodimers, while NFAT proteins are largely monomeric (with TonEBP being an exception). While the majority of sequence-specific DNA binding elements are found in the N-terminal domain, several are found in the IPT domain in loops adjacent to, and including, the linker region.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 228 LKISRMDKTAGSVRGGDEVYLLCDKVQKDDIEVRFYE--DDENGWQAFGDFSPTDVHkQYAIVFRTPPYHKMKIERPVTV 305
Cdd:cd00602    1 LPICRVSSLSGSVNGGDEVFLLCDKVNKPDIKVWFGEkgPGETVWEAEAMFRQEDVR-QVAIVFKTPPYHNKWITRPVQV 79

                         90       100
                 ....*....|....*....|..
gi 564334017 306 FLQLKRKRGGDVSDSKQFTYYP 327
Cdd:cd00602   80 PIQLVRPDDRKRSEPLTFTYTP 101

N-terminal sub-domain of the Rel homology domain (RHD) of the arthropod protein Relish; Proteins containing the Rel homology domain (RHD) are metazoan transcription factors. The RHD is composed of two structural sub-domains; this model characterizes the N-terminal RHD sub-domain of the arthropod Relish protein, in which the RHD domain co-occurs with C-terminal ankyrin repeats. Family members are sometimes referred to as p110 or p68 (proteolytically processed form). Relish is an NF-kappa B-like transcription factor, which plays a role in mediating innate immunity in Drosophila. It is activated via the Imd (immune deficiency) pathway, which triggers phosphorylation of Relish. IKK-dependent proteolytic cleavage of Relish (which involves Dredd) results in a smaller active form (without the C-terminal ankyrin repeats), which is transported into the nucleus and functions as a transactivator.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017  38 PYLVIVEQPKQRgFRFRYGCE-GPSHGGLPGASSEKGRKTYPTVKICNYEGPAKIEVDLVTHSDPPRA-HAHSLVGKQCs 115
Cdd:cd07884    1 PFLRIVEQPVDK-FRFRYKSEmHGTHGSLLGERSTSSKKTFPTVKLCNYRGQAVIRCSLYQADDNRRKpHVHKLVGKQG- 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 116 ELGVCAVSVGPK----DMTAQFNNLGVLHVTKKNMMEIMIQklqrqrlrskpqglteaerreleqeakelKKVMDLSIVR 191
Cdd:cd07884   79 DDDVCDPHDIEVspegDYVAMFQNMGIIHTAKKNIPEELYK-----------------------------KKNMNLNQVV 129

                        170       180       190
                 ....*....|....*....|....*....|
gi 564334017 192 LRFSAFLRASDGSFSLPLKPVISQPIHDSK 221
Cdd:cd07884  130 LRFQAFAVSANGHLRPICPPVYSNPINNLK 159

N-terminal sub-domain of the Rel homology domain (RHD) of the reticuloendotheliosis viral oncogene homolog B (RelB) protein; Proteins containing the Rel homology domain (RHD) are metazoan transcription factors. The RHD is composed of two structural sub-domains; this model characterizes the N-terminal RHD sub-domain of the RelB family of transcription factors, categorized as class II NF-kappa B family members. In class II NF-kappa Bs, the RHD domain co-occurs with a C-terminal transactivation domain (TAD). NF-kappa B proteins are part of a protein complex that acts as a transcription factor, which is responsible for regulating a host of cellular responses to a variety of stimuli. This complex tightly regulates the expression of a large number of genes, and is involved in processes such as adaptive and innate immunity, stress response, inflammation, cell adhesion, proliferation and apoptosis. The cytosolic NF-kappa B complex is activated via phosphorylation of the ankyrin-repeat containing inhibitory protein I-kappa B, which dissociates from the complex and exposes the nuclear localization signal of the heterodimer (NF-kappa B and Rel). RelB, is unable to homodimerize but is a potent transactivator in a heterodimer with NF-kappa B1 (p50) or B2 (p52). It is involved in the regulation of genes that play roles in inflammatory processes and the immune response.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017  38 PYLVIVEQPKQRGFRFRYGCEGPSHGGLPGASSEKGRKTYPTVKICNYEGPAKIEVD--LVTHSDPPRAHAHSLVGKQCS 115
Cdd:cd07886    1 PRLLITEQPKQRGMRFRYECEGRSAGSILGESSTEANKTQPAIEIQNCIGLKEVTVTvcLVWKDPPHRVHPHGLVGKDCP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 116 ElGVCAVSVGPKDMTAQ-FNNLGVLHVTKKNMMEIMIQKLQrqrLRSKPqglTEAERRELEQEakelkkvMDLSIVRLRF 194
Cdd:cd07886   81 N-GICQVTLNPHSSPRHsFSNLGIQCVRKREIEAAIETRLQ---LNIDP---FKAGSLKNHEE-------VDMNVVRLCF 146

                        170       180
                 ....*....|....*....|....*..
gi 564334017 195 SAFLRASDGsFSLPLKPVISQPIHDSK 221
Cdd:cd07886  147 QASYRDDDG-RKDCLSPVLSEPIYDKK 172

Ankyrin repeat [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 435 ALDTLQRAREYNARLFGLAQRSARALLDYGVTADARALLAGQRHLLMAQDENGDTPLHLAIIHGQTgvieqIAQVIYHAQ 514
Cdd:COG0666    1 LLLLLLLLLLLLAALLLLLLLALLLLAAALLLLLLLLLLLLLALLALALADALGALLLLAAALAGD-----LLVALLLLA 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 515 YLGVINLTNHLHQTPLHLAVITGQTRVVSFLLQVGADPTLLDRHGDSAVHLALRAGaaAPDLLQAVLHSGAHalpqmLHM 594
Cdd:COG0666   76 AGADINAKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNG--NLEIVKLLLEAGAD-----VNA 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 595 PDFEGLYPVHLAVHARSPECLDLLVDCGAEVEAAERQgGRTPLHLATEMEELGLVTHLVtKLHANVNARTFAGNTPLHLA 674
Cdd:COG0666  149 QDNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDND-GETPLHLAAENGHLEIVKLLL-EAGADVNAKDNDGKTALDLA 226

                        250       260       270
                 ....*....|....*....|....*....|.
gi 564334017 675 AGLGSPTLTRLLLKAGADIHAENEEPLCPLP 705
Cdd:COG0666  227 AENGNLEIVKLLLEAGADLNAKDKDGLTALL 257

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 564334017 773 ALQNLEQLLDGpeaQGSWAELAERLGLRSLVDTYRKTPSPSGSLLRSYKLAGGDLVGLLEALSDMGLHEGVRLL 846
Cdd:cd08310    1 TRLRLCKLLDV---GKDWRELAELLGLGHLVESIEQSSSPTKLLLDYYEAQGGTLEKLREALRALGETDAVELI 71

ankyrin-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 458 RALLDYGVTADARallagqrhllmaqDENGDTPLHLAIIHGQTgvIEQIAQVIYHaqylGV-INLTNHLHQTPLH--LAV 534
Cdd:PHA03095  67 RLLLEAGADVNAP-------------ERCGFTPLHLYLYNATT--LDVIKLLIKA----GAdVNAKDKVGRTPLHvyLSG 127

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 535 ITGQTRVVSFLLQVGADPTLLDRHGDSAVHLALRAGAAAPDLLQAVLHSGAHalpqmLHMPDFEGLYPVHlaVHARS--- 611
Cdd:PHA03095 128 FNINPKVIRLLLRKGADVNALDLYGMTPLAVLLKSRNANVELLRLLIDAGAD-----VYAVDDRFRSLLH--HHLQSfkp 200

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 612 -PECLDLLVDCGAEVEAAERqGGRTPLHLATeMEELGLVTHLVTKLHAN--VNARTFAGNTPLHLAAGLGSPTLTRLLLK 688
Cdd:PHA03095 201 rARIVRELIRAGCDPAATDM-LGNTPLHSMA-TGSSCKRSLVLPLLIAGisINARNRYGQTPLHYAAVFNNPRACRRLIA 278

                        250
                 ....*....|....*.
gi 564334017 689 AGADIHAENEEPLCPL 704
Cdd:PHA03095 279 LGADINAVSSDGNTPL 294

Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as Transcription factor ImmunoGlobin (TIG) domains. They are present in intracellular transcription factors, cell surface receptors (such as plexins and scatter factor receptors), as well as, cyclodextrin glycosyltransferase and similar enzymes. Although they are involved in DNA binding in transcription factors, their function in other proteins is unknown. In these transcription factors, IPTs form homo- or heterodimers with the exception of the nuclear factor of activated Tcells (NFAT) transcription factors which are mainly monomers.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 228 LKISRMDKTAGSVRGGDEVYLLCDKVQKD-DIEVRFYeddengwqAFGDFSPTDVHkQYAIVFRTPPYHkmkIERPVTVF 306
Cdd:cd00102    1 PVITSISPSSGPVSGGTEVTITGSNFGSGsNLRVTFG--------GGVPCSVLSVS-STAIVCTTPPYA---NPGPGPVE 68

                         90       100
                 ....*....|....*....|.
gi 564334017 307 LQLKRKRGGDVSDSKQFTYYP 327
Cdd:cd00102   69 VTVDRGNGGITSSPLTFTYVP 89

ankyrin repeat protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 538 QTRVVSFLLQVGADPTLLDRH-GDSAVHLAlrAGAAAPDLLQAVLHSGAHalpqmLHMPDFEGLYPVHLAVHARSPECLD 616
Cdd:PHA02878 146 EAEITKLLLSYGADINMKDRHkGNTALHYA--TENKDQRLTELLLSYGAN-----VNIPDKTNNSPLHHAVKHYNKPIVH 218

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 617 LLVDCGAEVEAAERQGgRTPLHLATEMEELGLVTHLVTKLHANVNAR-TFAGNTPLHLAagLGSPTLTRLLLKAGADIHA 695
Cdd:PHA02878 219 ILLENGASTDARDKCG-NTPLHISVGYCKDYDILKLLLEHGVDVNAKsYILGLTALHSS--IKSERKLKLLLEYGADINS 295

                        170
                 ....*....|.
gi 564334017 696 ENEEPLCPLPS 706
Cdd:PHA02878 296 LNSYKLTPLSS 306

ankyrin repeat protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334017 522 TNHLHQTPLHLAVITGQTRVVSFLLQVGADPTLLDRHGDSAVHLALRagAAAPDLLQAVLHSGAHalpqmLHMPDFEGLY 601
Cdd:PHA02878 164 DRHKGNTALHYATENKDQRLTELLLSYGANVNIPDKTNNSPLHHAVK--HYNKPIVHILLENGAS-----TDARDKCGNT 236

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564334017 602 PVHLAV-HARSPECLDLLVDCGAEVEAAERQGGRTPLHLATEMEElglVTHLVTKLHANVNARTFAGNTPLHLA 674
Cdd:PHA02878 237 PLHISVgYCKDYDILKLLLEHGVDVNAKSYILGLTALHSSIKSER---KLKLLLEYGADINSLNSYKLTPLSSA 307