PWWP domain; The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif. The domain binds to Histone-4 methylated at lysine-20, H4K20me, suggesting that it is methyl-lysine recognition motif. Removal of two conserved aromatic residues in a hydrophobic cavity created by this domain within the full-length protein, Pdp1, abolishes the interaction o f the protein with H4K20me3. In fission yeast, Set9 is the sole enzyme that catalyzes all three states of H4K20me, and Set9-mediated H4K20me is required for efficient recruitment of checkpoint protein Crb2 to sites of DNA damage. The methylation of H4K20 is involved in a diverse array of cellular processes, such as organizing higher-order chromatin, maintaining genome stability, and regulating cell-cycle progression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301102939   12 WYILEGYPWWPVYICDVFKLRPTLhllgsghkkilkKARDFPEDFIVVYYFGSHDFSLVGLKKgvLRPWDCAQKDQFLKG 91
Cdd:pfam00855   5 WAKLKGYPWWPARVVDPEELPENV------------LKPKKKDGEYLVRFFGDSEFAWVKPKD--LKPFDEGDEFEYLKK 70

                          90       100
                  ....*....|....*....|....*..
gi 301102939   92 hpqhlAKKKGVMEDLTEAVQEVEEYLS 118
Cdd:pfam00855  71 -----KKKKKKKKAFKKALEEAEEALK 92

DEK C terminal domain; DEK is a chromatin associated protein that is linked with cancers and autoimmune disease. This domain is found at the C terminal of DEK and is of clinical importance since it can reverse the characteriztic abnormal DNA-mutagen sensitivity in fibroblasts from ataxia-telangiectasia (A-T) patients. The structure of this domain shows it to be homologous to the E2F/DP transcription factor family. This domain is also found in chitin synthase proteins like Swiss:Q8TF96, and in protein phosphatases such as Swiss:Q6NN85.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 301102939  251 LEKEIRWILVNCPFEEMTTKTVRKLLEDRLHMDLRHHKASIKE 293
Cdd:pfam08766   6 IREAIREILRTADLETVTKKQVRKQLEERLGVDLSERKAFINA 48

PWWP domain; The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif. The domain binds to Histone-4 methylated at lysine-20, H4K20me, suggesting that it is methyl-lysine recognition motif. Removal of two conserved aromatic residues in a hydrophobic cavity created by this domain within the full-length protein, Pdp1, abolishes the interaction o f the protein with H4K20me3. In fission yeast, Set9 is the sole enzyme that catalyzes all three states of H4K20me, and Set9-mediated H4K20me is required for efficient recruitment of checkpoint protein Crb2 to sites of DNA damage. The methylation of H4K20 is involved in a diverse array of cellular processes, such as organizing higher-order chromatin, maintaining genome stability, and regulating cell-cycle progression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301102939   12 WYILEGYPWWPVYICDVFKLRPTLhllgsghkkilkKARDFPEDFIVVYYFGSHDFSLVGLKKgvLRPWDCAQKDQFLKG 91
Cdd:pfam00855   5 WAKLKGYPWWPARVVDPEELPENV------------LKPKKKDGEYLVRFFGDSEFAWVKPKD--LKPFDEGDEFEYLKK 70

                          90       100
                  ....*....|....*....|....*..
gi 301102939   92 hpqhlAKKKGVMEDLTEAVQEVEEYLS 118
Cdd:pfam00855  71 -----KKKKKKKKAFKKALEEAEEALK 92

PWWP (Pro-Trp-Trp-Pro) domain; The PWWP domain, named for a conserved Pro-Trp-Trp-Pro motif, is a small domain consisting of 100-150 amino acids and is composed of a five-stranded antiparallel beta-barrel followed by a helical region. It is found in numerous proteins that are involved in cell division, growth, and differentiation. Most PWWP-domain proteins seem to be nuclear, often DNA-binding, proteins that function as transcription factors regulating a variety of developmental processes. PWWP domains specifically recognize DNA and histone methylated lysines at the level of the nucleosome. Based on the fact that other regions of PWWP-domain proteins are responsible for nuclear localization and DNA-binding, is likely that the PWWP domain acts as a site for protein-protein binding interactions, influencing chromatin remodeling and thereby regulating transcriptional processes. Some PWWP-domain proteins have been linked to cancer or other diseases; some are known to function as growth factors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301102939  12 WYILEGYPWWPVYICDVFKLRPtlhllgsghkkilKKARDFPEDFIVVYYFGSHDFSLVGLKKgvLRPWDCAQKDQFLkg 91
Cdd:cd05162    5 WAKLKGYPWWPARVVDPEELPE-------------EVGKKKKKGGVLVQFFGDNDYAWVKSKN--IKPFEEGFKKEFK-- 67

                         90       100
                 ....*....|....*....|....*
gi 301102939  92 hpqhlaKKKGVMEDLTEAVQEVEEY 116
Cdd:cd05162   68 ------KKKKKSKKFKKAVEEAEEA 86

TFIIS helical bundle-like domain; Mediator is a large complex of up to 33 proteins that is conserved from plants to fungi to humans - the number and representation of individual subunits varying with species {1-2]. It is arranged into four different sections, a core, a head, a tail and a kinase-activity part, and the number of subunits within each of these is what varies with species. Overall, Mediator regulates the transcriptional activity of RNA polymerase II but it would appear that each of the four different sections has a slightly different function. Mediator exists in two major forms in human cells: a smaller form that interacts strongly with pol II and activates transcription, and a large form that does not interact strongly with pol II and does not directly activate transcription. Notably, the 'small' and 'large' Mediator complexes differ in their subunit composition: the Med26 subunit preferentially associates with the small, active complex, whereas cdk8, cyclin C, Med12 and Med13 associate with the large Mediator complex. This family includesthe C terminal region of a number of eukaryotic hypothetical proteins which are homologous to the Saccharomyces cerevisiae protein IWS1. IWS1 is known to be an Pol II transcription elongation factor and interacts with Spt6 and Spt5.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 301102939  448 CLNQLGEMPLTIDHLKKTGIARAVSKLRQH-GNDKVSAKAHELRQKWIKQI 497
Cdd:pfam08711   2 LLKKLEKLPVTLELLKSTGIGKVVNKLRKHkENPEIKKLAKELVKKWKRLV 52

transcription elongation factor S-II; This model represents eukaryotic transcription elongation factor S-II. This protein allows stalled RNA transcription complexes to perform a cleavage of the nascent RNA and restart at the newly generated 3-prime end.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301102939  426 EEILELKLKVENAdTSHDEMLVCLN---QLGEMPLTIDHLKKTGIARAVSKLRQHGNDKVSAKAHELRQKWIKQINEQSA 502
Cdd:TIGR01385   2 AEVASHAKALDKN-KSSKNVEQCLDilhQLKEFPPTEELLQETKVGVKVNKLRKHPNEDISKLAKKIIKSWKKVVDKNKS 80

                  ..
gi 301102939  503 DH 504
Cdd:TIGR01385  81 DH 82

PWWP domain; The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif. The domain binds to Histone-4 methylated at lysine-20, H4K20me, suggesting that it is methyl-lysine recognition motif. Removal of two conserved aromatic residues in a hydrophobic cavity created by this domain within the full-length protein, Pdp1, abolishes the interaction o f the protein with H4K20me3. In fission yeast, Set9 is the sole enzyme that catalyzes all three states of H4K20me, and Set9-mediated H4K20me is required for efficient recruitment of checkpoint protein Crb2 to sites of DNA damage. The methylation of H4K20 is involved in a diverse array of cellular processes, such as organizing higher-order chromatin, maintaining genome stability, and regulating cell-cycle progression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301102939   12 WYILEGYPWWPVYICDVFKLRPTLhllgsghkkilkKARDFPEDFIVVYYFGSHDFSLVGLKKgvLRPWDCAQKDQFLKG 91
Cdd:pfam00855   5 WAKLKGYPWWPARVVDPEELPENV------------LKPKKKDGEYLVRFFGDSEFAWVKPKD--LKPFDEGDEFEYLKK 70

                          90       100
                  ....*....|....*....|....*..
gi 301102939   92 hpqhlAKKKGVMEDLTEAVQEVEEYLS 118
Cdd:pfam00855  71 -----KKKKKKKKAFKKALEEAEEALK 92

PWWP (Pro-Trp-Trp-Pro) domain; The PWWP domain, named for a conserved Pro-Trp-Trp-Pro motif, is a small domain consisting of 100-150 amino acids and is composed of a five-stranded antiparallel beta-barrel followed by a helical region. It is found in numerous proteins that are involved in cell division, growth, and differentiation. Most PWWP-domain proteins seem to be nuclear, often DNA-binding, proteins that function as transcription factors regulating a variety of developmental processes. PWWP domains specifically recognize DNA and histone methylated lysines at the level of the nucleosome. Based on the fact that other regions of PWWP-domain proteins are responsible for nuclear localization and DNA-binding, is likely that the PWWP domain acts as a site for protein-protein binding interactions, influencing chromatin remodeling and thereby regulating transcriptional processes. Some PWWP-domain proteins have been linked to cancer or other diseases; some are known to function as growth factors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301102939  12 WYILEGYPWWPVYICDVFKLRPtlhllgsghkkilKKARDFPEDFIVVYYFGSHDFSLVGLKKgvLRPWDCAQKDQFLkg 91
Cdd:cd05162    5 WAKLKGYPWWPARVVDPEELPE-------------EVGKKKKKGGVLVQFFGDNDYAWVKSKN--IKPFEEGFKKEFK-- 67

                         90       100
                 ....*....|....*....|....*
gi 301102939  92 hpqhlaKKKGVMEDLTEAVQEVEEY 116
Cdd:cd05162   68 ------KKKKKSKKFKKAVEEAEEA 86

TFIIS helical bundle-like domain; Mediator is a large complex of up to 33 proteins that is conserved from plants to fungi to humans - the number and representation of individual subunits varying with species {1-2]. It is arranged into four different sections, a core, a head, a tail and a kinase-activity part, and the number of subunits within each of these is what varies with species. Overall, Mediator regulates the transcriptional activity of RNA polymerase II but it would appear that each of the four different sections has a slightly different function. Mediator exists in two major forms in human cells: a smaller form that interacts strongly with pol II and activates transcription, and a large form that does not interact strongly with pol II and does not directly activate transcription. Notably, the 'small' and 'large' Mediator complexes differ in their subunit composition: the Med26 subunit preferentially associates with the small, active complex, whereas cdk8, cyclin C, Med12 and Med13 associate with the large Mediator complex. This family includesthe C terminal region of a number of eukaryotic hypothetical proteins which are homologous to the Saccharomyces cerevisiae protein IWS1. IWS1 is known to be an Pol II transcription elongation factor and interacts with Spt6 and Spt5.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 301102939  448 CLNQLGEMPLTIDHLKKTGIARAVSKLRQH-GNDKVSAKAHELRQKWIKQI 497
Cdd:pfam08711   2 LLKKLEKLPVTLELLKSTGIGKVVNKLRKHkENPEIKKLAKELVKKWKRLV 52

transcription elongation factor S-II; This model represents eukaryotic transcription elongation factor S-II. This protein allows stalled RNA transcription complexes to perform a cleavage of the nascent RNA and restart at the newly generated 3-prime end.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301102939  426 EEILELKLKVENAdTSHDEMLVCLN---QLGEMPLTIDHLKKTGIARAVSKLRQHGNDKVSAKAHELRQKWIKQINEQSA 502
Cdd:TIGR01385   2 AEVASHAKALDKN-KSSKNVEQCLDilhQLKEFPPTEELLQETKVGVKVNKLRKHPNEDISKLAKKIIKSWKKVVDKNKS 80

                  ..
gi 301102939  503 DH 504
Cdd:TIGR01385  81 DH 82

second PWWP domain found in nuclear receptor-binding SET domain-containing (NSD) proteins; The nuclear receptor binding SET domain (NSD) protein family consists of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1, that are critical in maintaining chromatin integrity. Reducing NSD activity through specific lysine-HMTase inhibitors appears promising in suppressing cancer growth. NSD proteins have specific mono- and dimethylase activities for H3K36, and they play nonredundant roles during development. NSD1 plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. NSD2 is involved in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. NSD3 is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD proteins contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (C5HCH). This model corresponds to the second PWWP domain. The family also includes Drosophila melanogaster maternal-effect sterile 4 (dMes4) that may act as a histone-lysine N-methyltransferase required for wing morphogenesis. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301102939   4 EIVpnsvgWYILEGYPWWPVYICDVFKLrPtlhllgsghKKILKKAR---DFPedfivVYYFGSHDFSLVGlKKGVLRpw 80
Cdd:cd05838    4 DIV-----WVKLGNYRWWPAEILHPREV-P---------DNIQSLPHppgEFP-----VRFFGSHDYYWVH-RGRVFL-- 60

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 301102939  81 dcaqkdqFLKGHPQHLAKKKGVMEDL-TEAVQEVEEY 116
Cdd:cd05838   61 -------FEEGDKGSKEKSKKSLDKSfKRALKEANEA 90