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 1843419818  29 PYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCEDG 108
Cdd:cd07935     1 PYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCEDG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818 109 ICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGLLVHPDLAYLQAEGGGDRQLGDREKELIRQAAL 188
Cdd:cd07935    81 ICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACKKGYNPGLLVHPELAYLQAEGGGDRQLTEREKEIIRQAAV 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1843419818 189 QQTKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAIYDSK 230
Cdd:cd07935   161 QQTKEMDLSVVRLMFTAFLPDSTGGFTRRLEPVVSDAIYDSK 202

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 1843419818 802 VKLQLYKLLEIPDPDKNWATLAQKLGLGILNNAFRLSPAPSKTLMDNYEVSGGTVRELVEALRQMGYTEAIEVIQA 877
Cdd:cd08797     1 VKQQLYKLLESPDPDKNWATLAQKLGLGILNNAFRLSPSPSKTLLDNYEVSGGTVRELLAALRQMGYTEAIEVIEE 76

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 1843419818  29 PYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCEDG 108
Cdd:cd07935     1 PYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCEDG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818 109 ICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGLLVHPDLAYLQAEGGGDRQLGDREKELIRQAAL 188
Cdd:cd07935    81 ICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACKKGYNPGLLVHPELAYLQAEGGGDRQLTEREKEIIRQAAV 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1843419818 189 QQTKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAIYDSK 230
Cdd:cd07935   161 QQTKEMDLSVVRLMFTAFLPDSTGGFTRRLEPVVSDAIYDSK 202

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 1843419818 237 LKIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIRFYEEEENGGVWEGFGDFSPTDVHRQFAIVFKTPKYKDINITKPASV 316
Cdd:cd01177     1 LKICRLDKTSGSVKGGDEVYLLCDKVQKEDIQVRFFEEDEEETVWEAFGDFSQTDVHRQYAIVFRTPPYHDPDITEPVKV 80

                          90       100
                  ....*....|....*....|..
gi 1843419818 317 FVQLRRKSDLETSEPKPFLYYP 338
Cdd:cd01177    81 KIQLKRPSDGERSESVPFTYVP 102

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 1843419818 802 VKLQLYKLLEIPDPDKNWATLAQKLGLGILNNAFRLSPAPSKTLMDNYEVSGGTVRELVEALRQMGYTEAIEVIQA 877
Cdd:cd08797     1 VKQQLYKLLESPDPDKNWATLAQKLGLGILNNAFRLSPSPSKTLLDNYEVSGGTVRELLAALRQMGYTEAIEVIEE 76

Ankyrin repeats (3 copies);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818 573 LHLAVITKQEDVVEDLLRAGADLSLLDRLGNSVLHLAAKEGHDKVLSILLKHKKAALlldhpNGDGLNAIHLAMMSNSLP 652
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLLEHADVNL-----KDNGRTALHYAARSGHLE 75

                          90
                  ....*....|....*
gi 1843419818 653 CLLLLVAAGADVNAQ 667
Cdd:pfam12796  76 IVKLLLEKGADINVK 90

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818 562 INMRN-DLYQTPLHLAVITKQEDVVEDLLRAGADLSLLDRLGNSVLHLAAKEGHDKVLSILLKHKKAallLDHPNGDGLN 640
Cdd:PHA02878  160 INMKDrHKGNTALHYATENKDQRLTELLLSYGANVNIPDKTNNSPLHHAVKHYNKPIVHILLENGAS---TDARDKCGNT 236

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1843419818 641 AIHLAMMS-NSLPCLLLLVAAGADVNAQEQKSGRTALHLAVeHDNISLAgcLLLEGDAHVDSTTYDGTTPLHIA 713
Cdd:PHA02878  237 PLHISVGYcKDYDILKLLLEHGVDVNAKSYILGLTALHSSI-KSERKLK--LLLEYGADINSLNSYKLTPLSSA 307

Death domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818 803 KLQLYKLLEIPDP-DKNWATLAQKLGLGIL-NNAFRLSPA----PSKTLMDNY---EVSGGTVRELVEALRQMGYTEAIE 873
Cdd:pfam00531   1 RKQLDRLLDPPPPlGKDWRELARKLGLSENeIDEIESENPrlrsQTYELLRLWeqrEGKNATVGTLLEALRKLGRRDAAE 80

                  ....*.
gi 1843419818 874 VIQAAS 879
Cdd:pfam00531  81 KIQSIL 86

transient-receptor-potential calcium channel protein; The Transient Receptor Potential Ca2+ Channel (TRP-CC) Family (TC. 1.A.4)The TRP-CC family has also been called the store-operated calcium channel (SOC) family. The prototypical members include the Drosophila retinal proteinsTRP and TRPL (Montell and Rubin, 1989; Hardie and Minke, 1993). SOC members of the family mediate the entry of extracellular Ca2+ into cells in responseto depletion of intracellular Ca2+ stores (Clapham, 1996) and agonist stimulated production of inositol-1,4,5 trisphosphate (IP3). One member of the TRP-CCfamily, mammalian Htrp3, has been shown to form a tight complex with the IP3 receptor (TC #1.A.3.2.1). This interaction is apparently required for IP3 tostimulate Ca2+ release via Htrp3. The vanilloid receptor subtype 1 (VR1), which is the receptor for capsaicin (the ?hot? ingredient in chili peppers) and servesas a heat-activated ion channel in the pain pathway (Caterina et al., 1997), is also a member of this family. The stretch-inhibitable non-selective cation channel(SIC) is identical to the vanilloid receptor throughout all of its first 700 residues, but it exhibits a different sequence in its last 100 residues. VR1 and SICtransport monovalent cations as well as Ca2+. VR1 is about 10x more permeable to Ca2+ than to monovalent ions. Ca2+ overload probably causes cell deathafter chronic exposure to capsaicin. (McCleskey and Gold, 1999). [Transport and binding proteins, Cations and iron carrying compounds]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818 562 INMRNDLYQTPLHLAVItkqEDVVEDLLRAGADLSLLDRLGNSVLHLAAKEGHDKV---LSILLKHKKAALLLDHPNGD- 637
Cdd:TIGR00870  45 INCPDRLGRSALFVAAI---ENENLELTELLLNLSCRGAVGDTLLHAISLEYVDAVeaiLLHLLAAFRKSGPLELANDQy 121

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1843419818 638 ------GLNAIHLAMMSNSLPCLLLLVAAGADVNA 666
Cdd:TIGR00870 122 tseftpGITALHLAAHRQNYEIVKLLLERGASVPA 156

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 1843419818  29 PYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCEDG 108
Cdd:cd07935     1 PYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCEDG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818 109 ICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGLLVHPDLAYLQAEGGGDRQLGDREKELIRQAAL 188
Cdd:cd07935    81 ICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACKKGYNPGLLVHPELAYLQAEGGGDRQLTEREKEIIRQAAV 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1843419818 189 QQTKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAIYDSK 230
Cdd:cd07935   161 QQTKEMDLSVVRLMFTAFLPDSTGGFTRRLEPVVSDAIYDSK 202

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 1843419818  31 LQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCEDGIC 110
Cdd:pfam00554   1 LEIVEQPKQRGMRFRYKCEGRSAGSIPGESSTRSKKTFPTVQICNYDGPAVIRVSLVTKDEPHRPHPHSLVGKDCKDGVC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818 111 TVTAGPKDMVVGFANLGILHVTKKKVFETLEARMteacirgynpgllvhpdlaylqaegggdrQLGDREKElIRQAALQQ 190
Cdd:pfam00554  81 EVELGPEDMVASFQNLGIQCVKKKDVEEALKERI-----------------------------ELNIDPFN-VGFEALRQ 130

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1843419818 191 TKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAIYDS 229
Cdd:pfam00554 131 IKDMDLNVVRLCFQAFLPDTRGNFTTPLPPVVSNPIYDK 169

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 1843419818 237 LKIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIRFYEEEENGGVWEGFGDFSPTDVHRQFAIVFKTPKYKDINITKPASV 316
Cdd:cd01177     1 LKICRLDKTSGSVKGGDEVYLLCDKVQKEDIQVRFFEEDEEETVWEAFGDFSQTDVHRQYAIVFRTPPYHDPDITEPVKV 80

                          90       100
                  ....*....|....*....|..
gi 1843419818 317 FVQLRRKSDLETSEPKPFLYYP 338
Cdd:cd01177    81 KIQLKRPSDGERSESVPFTYVP 102

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 1843419818 238 KIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIRFYEEEENGGVWEGFGDFSPTDVHRQFAIVFKTPKYKDINITKPASVF 317
Cdd:pfam16179   1 KICRLSLCSGSVTGGEEIILLCEKVLKDDIKVRFYEEDDGQEVWEAEGDFSKTDVHRQVAIVFKTPPYRDPDITEPVTVN 80

                          90       100
                  ....*....|....*....|..
gi 1843419818 318 VQLRRKSDLETSEPKPFLYYPE 339
Cdd:pfam16179  81 IQLRRPSDKATSEPQPFTYLPL 102

N-terminal sub-domain of the Rel homology domain (RHD) of the arthropod protein Dorsal; 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 Dorsal and Dif (Dorsal-related immunity factor), and similar proteins. Dorsal and Dif are Rel-like transcription factors, which play roles in mediating innate immunity in Drosophila. They are activated via the Toll pathway. Cytoplasmic Dorsal/Dif are inactivated via forming a complex with Cactus, the Drosophila homologue of mammalian I-kappa B proteins. In response to signals, Cactus is degraded and Dorsal/Dif can be transported into the nucleus, where they act as transcription factors. Dorsal is also an essential gene in establishing the proper dorsal/ventral polarity in the developing embryo.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818  29 PYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGK-HCED 107
Cdd:cd07887     1 PYVRIVEQPTSRALRFRYECEGRSAGSIPGANSTSEGKTFPTIQVVNYDGRAVVVVSCVTKDEPFRPHPHNLVGKeGCKK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818 108 GICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARmTEACIRGYNPGlLVHPDlaylqaegggdrqlgdrekelirqaa 187
Cdd:cd07887    81 GVCTKKINPTEMRIVFQKLGIQCVKKKDVEESLKLR-EEINVDPFRTG-FDHKD-------------------------- 132

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1843419818 188 lqQTKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAIYDSK 230
Cdd:cd07887   133 --QINSIDLNVVRLCFQVFLEDENGRFTVPLPPVVSDPIYDKK 173

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 1843419818 802 VKLQLYKLLEIPDPDKNWATLAQKLGLGILNNAFRLSPAPSKTLMDNYEVSGGTVRELVEALRQMGYTEAIEVIQA 877
Cdd:cd08797     1 VKQQLYKLLESPDPDKNWATLAQKLGLGILNNAFRLSPSPSKTLLDNYEVSGGTVRELLAALRQMGYTEAIEVIEE 76

N-terminal sub-domain of the Rel homology domain (RHD) of RelA; 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 domain of the RelA family of transcription factors, categorized as a class II member of the NF-kappa B family. 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). RelA (also called p65) forms heterodimers with NF-kappa B1 (p50) and B2 (p52). RelA also forms homodimers.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818  29 PYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCEDG 108
Cdd:cd07885     1 PYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINNYTGPGRVRISLVTKDPPHKPHPHELVGKDCKDG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818 109 ICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARmteacIRGYNPGLLVHPDlaylqaegggdrqlgdrekelirqaal 188
Cdd:cd07885    81 YYEAELSPDRCIHSFQNLGIQCVKKRDLEQAVSQR-----IQTNNNPFNVPIE--------------------------- 128

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1843419818 189 QQTKEMDLSVVRLMFTAFLPDSTGSFTrRLEPVVSDAIYDSK 230
Cdd:cd07885   129 EQRADYDLNAVRLCFQVTVRDPSGRLL-PLPPVLSQPIYDNR 169

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 1843419818  29 PYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKV--IVQLVTNGKNIHLHAHSLVGKHCE 106
Cdd:cd07886     1 PRLLITEQPKQRGMRFRYECEGRSAGSILGESSTEANKTQPAIEIQNCIGLKEVtvTVCLVWKDPPHRVHPHGLVGKDCP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818 107 DGICTVT----AGPKDmvvGFANLGILHVTKKKVFETLEARMTEAcIRGYNPGllvhpdlaylqaegggdrqlgdrekel 182
Cdd:cd07886    81 NGICQVTlnphSSPRH---SFSNLGIQCVRKREIEAAIETRLQLN-IDPFKAG--------------------------- 129

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 1843419818 183 irqaALQQTKEMDLSVVRLMFTAFLPDSTGsFTRRLEPVVSDAIYDSK 230
Cdd:cd07886   130 ----SLKNHEEVDMNVVRLCFQASYRDDDG-RKDCLSPVLSEPIYDKK 172

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 1843419818 802 VKLQLYKLLeipDPDKNWATLAQKLGLGILNNAFRLSPAPSKTLMDNYEVSGGTVRELVEALRQMGYTEAIEVIQ 876
Cdd:cd08310     1 TRLRLCKLL---DVGKDWRELAELLGLGHLVESIEQSSSPTKLLLDYYEAQGGTLEKLREALRALGETDAVELID 72

Ankyrin repeats (3 copies);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818 573 LHLAVITKQEDVVEDLLRAGADLSLLDRLGNSVLHLAAKEGHDKVLSILLKHKKAALlldhpNGDGLNAIHLAMMSNSLP 652
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLLEHADVNL-----KDNGRTALHYAARSGHLE 75

                          90
                  ....*....|....*
gi 1843419818 653 CLLLLVAAGADVNAQ 667
Cdd:pfam12796  76 IVKLLLEKGADINVK 90

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818 562 INMRN-DLYQTPLHLAVITKQEDVVEDLLRAGADLSLLDRLGNSVLHLAAKEGHDKVLSILLKHKKAallLDHPNGDGLN 640
Cdd:PHA02878  160 INMKDrHKGNTALHYATENKDQRLTELLLSYGANVNIPDKTNNSPLHHAVKHYNKPIVHILLENGAS---TDARDKCGNT 236

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1843419818 641 AIHLAMMS-NSLPCLLLLVAAGADVNAQEQKSGRTALHLAVeHDNISLAgcLLLEGDAHVDSTTYDGTTPLHIA 713
Cdd:PHA02878  237 PLHISVGYcKDYDILKLLLEHGVDVNAKSYILGLTALHSSI-KSERKLK--LLLEYGADINSLNSYKLTPLSSA 307

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 1843419818 237 LKIVRMDRTAGCVTGGEEIYLLCDKVQKD-DIQIRFYEEEEnggvwegfgdFSPTDVHrQFAIVFKTPKYKDINitkPAS 315
Cdd:cd00102     1 PVITSISPSSGPVSGGTEVTITGSNFGSGsNLRVTFGGGVP----------CSVLSVS-STAIVCTTPPYANPG---PGP 66

                          90       100
                  ....*....|....*....|...
gi 1843419818 316 VFVQLRRKSDLETSEPKPFLYYP 338
Cdd:cd00102    67 VEVTVDRGNGGITSSPLTFTYVP 89

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 1843419818 806 LYKLLEIPDPDKNWATLAQKLGLGILNNAFRLSPAPSKTLMDNYEVSGGTVRELVEALRQMGYTEAIEVI 875
Cdd:cd08798     5 LEQLLNDTQTDVPWMELAERLGLQSLVDTYKPTQSPPGSLLRSYELAGGPLQGLIEALQDMGLREGVRLL 74

ankyrin-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1843419818 562 INMRNDLYQtplhlaVITKQEDV----VEDLLRAGADLSLLDRLGNSVLHLAAKEGHDKVLSILLKHKKAALLLDHPNGD 637
Cdd:PHA03095    9 IIMEAALYD------YLLNASNVtveeVRRLLAAGADVNFRGEYGKTPLHLYLHYSSEKVKDIVRLLLEAGADVNAPERC 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1843419818 638 GLNAIHLAMMSNS-LPCLLLLVAAGADVNAqEQKSGRTALH--LAVEHDNISLAGcLLLEGDAHVDSTTYDGTTPLHI 712
Cdd:PHA03095   83 GFTPLHLYLYNATtLDVIKLLIKAGADVNA-KDKVGRTPLHvyLSGFNINPKVIR-LLLRKGADVNALDLYGMTPLAV 158

Ankyrin repeats (3 copies);