N-terminal sub-domain of the Rel homology domain (RHD); 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 sub-domain, which may be distantly related to the DNA-binding domain found in P53. The C-terminal sub-domain has an immunoglobulin-like fold and serves as a dimerization module that also binds DNA (see cd00102). The RHD is found in NF-kappa B, nuclear factor of activated T-cells (NFAT), the tonicity-responsive enhancer binding protein (TonEBP), and the arthropod proteins Dorsal and Relish (Rel).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222564982   1 MRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRCIH 80
Cdd:cd07885    14 MRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINNYTGPGRVRISLVTKDPPHKPHPHELVGKDCKDGYYEAELSPDRCIH 93

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2222564982  81 SFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLSHPIFDNR 156
Cdd:cd07885    94 SFQNLGIQCVKKRDLEQAVSQRIQTNNNPFNVPIEEQRADYDLNAVRLCFQVTVRDPSGRLLPLPPVLSQPIYDNR 169

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 2222564982   1 MRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRCIH 80
Cdd:cd07885    14 MRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINNYTGPGRVRISLVTKDPPHKPHPHELVGKDCKDGYYEAELSPDRCIH 93

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2222564982  81 SFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLSHPIFDNR 156
Cdd:cd07885    94 SFQNLGIQCVKKRDLEQAVSQRIQTNNNPFNVPIEEQRADYDLNAVRLCFQVTVRDPSGRLLPLPPVLSQPIYDNR 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 2222564982 163 LKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYFTGP-----GWEARGSFSQADVHRQVAIVFRTPPYADPSLQAPVRV 237
Cdd:cd01177     1 LKICRLDKTSGSVKGGDEVYLLCDKVQKEDIQVRFFEEdeeetVWEAFGDFSQTDVHRQYAIVFRTPPYHDPDITEPVKV 80

                          90       100
                  ....*....|....*....|..
gi 2222564982 238 SMQLRRPSDRELSEPMEFQYLP 259
Cdd:cd01177    81 KIQLKRPSDGERSESVPFTYVP 102

ig-like, plexins, transcription factors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222564982  162 ELKICRVNRNSGSCLGGDEIfLLCDKVQKEDIEVYFTGPGWEARGSFSQAdvhRQVAIVFRTPPYADPSLQAPVRVSMQL 241
Cdd:smart00429   1 DPVITRISPTSGPVSGGTEI-TLCGKNLKSISVVFVEVGVGEAPCTFSPS---SSTAIVCKTPPYHNIPGSVPVRTVGLR 76

                           90
                   ....*....|....*..
gi 2222564982  242 RRPSdreLSEPMEFQYL 258
Cdd:smart00429  77 NGGV---PSSPQPFTYV 90

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 2222564982   1 MRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRCIH 80
Cdd:cd07885    14 MRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINNYTGPGRVRISLVTKDPPHKPHPHELVGKDCKDGYYEAELSPDRCIH 93

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2222564982  81 SFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLSHPIFDNR 156
Cdd:cd07885    94 SFQNLGIQCVKKRDLEQAVSQRIQTNNNPFNVPIEEQRADYDLNAVRLCFQVTVRDPSGRLLPLPPVLSQPIYDNR 169

N-terminal sub-domain of the Rel homology domain (RHD); 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 sub-domain, which may be distantly related to the DNA-binding domain found in P53. The C-terminal sub-domain has an immunoglobulin-like fold and serves as a dimerization module that also binds DNA (see cd00102). The RHD is found in NF-kappa B, nuclear factor of activated T-cells (NFAT), the tonicity-responsive enhancer binding protein (TonEBP), and the arthropod proteins Dorsal and Relish (Rel).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222564982   1 MRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGK-DCRDGFYEAELCPD-RC 78
Cdd:cd07827    14 HRFRYECEGRSAGSIPGENSTADRKTFPTVKLRNYNGPAKIVVSLVTKDDPPKPHPHQLVGKtDCRDGVCEVRLGPKnNM 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222564982  79 IHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVP--IEEQRGDYDLNAVRLCFQVTVRDPSG-RPLRLPPVLSHPIFDN 155
Cdd:cd07827    94 TASFNNLGIQCVRKKDVEEALGQRIQLGIDPFMVHkgPEGNASDIDLNRVRLCFQAFIEDSDGgFTLPLPPVLSNPIYDK 173

                  .
gi 2222564982 156 R 156
Cdd:cd07827   174 K 174

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 2222564982   1 MRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGK-DCRDGFYEAELCPDRCI 79
Cdd:cd07887    14 LRFRYECEGRSAGSIPGANSTSEGKTFPTIQVVNYDGRAVVVVSCVTKDEPFRPHPHNLVGKeGCKKGVCTKKINPTEMR 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222564982  80 HSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIE--EQRGDYDLNAVRLCFQVTVRDPSGRPLR-LPPVLSHPIFDNR 156
Cdd:cd07887    94 IVFQKLGIQCVKKKDVEESLKLREEINVDPFRTGFDhkDQINSIDLNVVRLCFQVFLEDENGRFTVpLPPVVSDPIYDKK 173

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 2222564982   1 MRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTG--PGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRC 78
Cdd:cd07886    14 MRFRYECEGRSAGSILGESSTEANKTQPAIEIQNCIGlkEVTVTVCLVWKDPPHRVHPHGLVGKDCPNGICQVTLNPHSS 93

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2222564982  79 I-HSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLSHPIFDNR 156
Cdd:cd07886    94 PrHSFSNLGIQCVRKREIEAAIETRLQLNIDPFKAGSLKNHEEVDMNVVRLCFQASYRDDDGRKDCLSPVLSEPIYDKK 172

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 2222564982 163 LKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYF-----TGPGWEARGSFSQADVHrQVAIVFRTPPYADPSLQAPVRV 237
Cdd:cd00602     1 LPICRVSSLSGSVNGGDEVFLLCDKVNKPDIKVWFgekgpGETVWEAEAMFRQEDVR-QVAIVFKTPPYHNKWITRPVQV 79

                          90       100
                  ....*....|....*....|..
gi 2222564982 238 SMQLRRPSDRELSEPMEFQYLP 259
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 2222564982   2 RFRYKCEGR-SAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHR-PHPHELVGKDCRDGfyeaeLCPDRCI 79
Cdd:cd07884    14 RFRYKSEMHgTHGSLLGERSTSSKKTFPTVKLCNYRGQAVIRCSLYQADDNRRkPHVHKLVGKQGDDD-----VCDPHDI 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222564982  80 H---------SFQNLGIQCVKKRDLEQAISqriqtnnnpfqvpieeQRGDYDLNAVRLCFQVTVRDPSG--RPLrLPPVL 148
Cdd:cd07884    89 EvspegdyvaMFQNMGIIHTAKKNIPEELY----------------KKKNMNLNQVVLRFQAFAVSANGhlRPI-CPPVY 151

                  ....
gi 2222564982 149 SHPI 152
Cdd:cd07884   152 SNPI 155

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 2222564982   2 RFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRCIHS 81
Cdd:cd07935    15 RFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCEDGICTVTAGPKDMVVG 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222564982  82 FQNLGIQCVKKRDLEQAISQR--------------IQTNNNPFQVPIEEQR------------------GDYDLNAVRLC 129
Cdd:cd07935    95 FANLGILHVTKKKVFETLEARmteackkgynpgllVHPELAYLQAEGGGDRqlterekeiirqaavqqtKEMDLSVVRLM 174

                         170       180
                  ....*....|....*....|....*...
gi 2222564982 130 FQVTVRDPSGR-PLRLPPVLSHPIFDNR 156
Cdd:cd07935   175 FTAFLPDSTGGfTRRLEPVVSDAIYDSK 202

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 2222564982 163 LKICRVNRNSGSCLGGDEIFLLCDKVQKE-DIEVYFTGPgwearGSFSQADVHrQVAIVFRTPPYADPSlqaPVRVSMQL 241
Cdd:cd00102     1 PVITSISPSSGPVSGGTEVTITGSNFGSGsNLRVTFGGG-----VPCSVLSVS-STAIVCTTPPYANPG---PGPVEVTV 71

                          90
                  ....*....|....*...
gi 2222564982 242 RRPSDRELSEPMEFQYLP 259
Cdd:cd00102    72 DRGNGGITSSPLTFTYVP 89

N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins and similar proteins; 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 NFAT family of transcription factors. NFAT transcription complexes are a target of calcineurin, a calcium dependent phosphatase, and activate genes that are mainly involved in cell-cell interaction. Upon de-phosphorylation of the nuclear localization signal, NFAT enters the nucleus and acts as a transcription factor; its export from the nucleus is triggered by phosphorylation via export kinases. NFATs play important roles in mediating the immune response, and are found in T cells, B Cells, NK cells, mast cells, and monocytes. NFATs are also found in various non-hematopoietic cell types, where they play roles in development. This group also contains the N-terminal RHD sub-domain of the non-calcium regulated tonicity-responsive enhancer binding protein (TonEBP), also called NFAT5. Mammalian TonEBP regulates the expression of genes in response to tonicity. It plays a pivotal role in urinary concentrating mechanisms in kidney medulla, by triggering the accumulation of osmolytes that enable renal medullary cells to tolerate high levels of urea and salt.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222564982   2 RFRYKCEGrSAGSIPGErstdTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGK-------DCRDGFYEAE-- 72
Cdd:cd07927    14 RARYETEG-SRGAVKAP----STGGFPTVKLHGYMEPVGLQVFIGTASGRLKPHAFYQVHRitgktttPCKEKIIGNTkv 88

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2222564982  73 ----LCPDRCIHS-FQNLGIQCVKKRDLEQAISQRIQTNNNpfqvpieeqrgdydlNAVRLCFQVTVRDPSGRPLRL 144
Cdd:cd07927    89 leipLEPKNNMTAtIDCAGILKLRNADIELRKGETDIKKKN---------------TRARLVFRVHIPEKDGRIVSL 150