PWWP domain found in DNA (cytosine-5)-methyltransferase 3A (DNMT3A); DNMT3A, also called DNA methyltransferase HsaIIIA, DNA MTase HsaIIIA, or M.HsaIIIA, is required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. It modifies DNA in a non-processive manner and also methylates non-CpG sites. It may preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. DNMT3A is recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites. It contains a PWWP domain that binds methylated histone.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74200036  62 EDGRGFGIGELVWGKLRGFSWWPGRIVSWWMTGRSRAAEGTRWVMWFGDGKFSVVCVEKLMPLSSFCSAFHQATYNKQPM 141
Cdd:cd20154   1 EDGRGFGIGELVWGKLRGFSWWPGRIVSWWMTGRSRAAEGTRWVMWFGDGKFSVVCVEKLMPLSSFSSAFHQATYNKQPM 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 74200036 142 YRKAIYEVLQVASSRAGKLFPACHDSDESDSGKAVEVQNKQMIEWALGGFQPSG 195
Cdd:cd20154  81 YRKAIYEVLQVASSRAGKLFPVCPESDESDTSKAVEVQNKQMIEWALGGFQPSG 134

PWWP domain found in DNA (cytosine-5)-methyltransferase 3A (DNMT3A); DNMT3A, also called DNA methyltransferase HsaIIIA, DNA MTase HsaIIIA, or M.HsaIIIA, is required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. It modifies DNA in a non-processive manner and also methylates non-CpG sites. It may preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. DNMT3A is recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites. It contains a PWWP domain that binds methylated histone.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74200036  62 EDGRGFGIGELVWGKLRGFSWWPGRIVSWWMTGRSRAAEGTRWVMWFGDGKFSVVCVEKLMPLSSFCSAFHQATYNKQPM 141
Cdd:cd20154   1 EDGRGFGIGELVWGKLRGFSWWPGRIVSWWMTGRSRAAEGTRWVMWFGDGKFSVVCVEKLMPLSSFSSAFHQATYNKQPM 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 74200036 142 YRKAIYEVLQVASSRAGKLFPACHDSDESDSGKAVEVQNKQMIEWALGGFQPSG 195
Cdd:cd20154  81 YRKAIYEVLQVASSRAGKLFPVCPESDESDTSKAVEVQNKQMIEWALGGFQPSG 134

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 74200036    70 GELVWGKLRGFSWWPGRIVSWWMTGRS----RAAEGTRWVMWFGDGKFSVVCVEKLMPLSSFCSAFHQATYNK---QPMY 142
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVVDPEELPENvlkpKKKDGEYLVRFFGDSEFAWVKPKDLKPFDEGDEFEYLKKKKKkkkKKAF 80

                          90
                  ....*....|..
gi 74200036   143 RKAIYEVLQVAS 154
Cdd:pfam00855  81 KKALEEAEEALK 92

PWWP domain found in DNA (cytosine-5)-methyltransferase 3A (DNMT3A); DNMT3A, also called DNA methyltransferase HsaIIIA, DNA MTase HsaIIIA, or M.HsaIIIA, is required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. It modifies DNA in a non-processive manner and also methylates non-CpG sites. It may preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. DNMT3A is recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites. It contains a PWWP domain that binds methylated histone.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74200036  62 EDGRGFGIGELVWGKLRGFSWWPGRIVSWWMTGRSRAAEGTRWVMWFGDGKFSVVCVEKLMPLSSFCSAFHQATYNKQPM 141
Cdd:cd20154   1 EDGRGFGIGELVWGKLRGFSWWPGRIVSWWMTGRSRAAEGTRWVMWFGDGKFSVVCVEKLMPLSSFSSAFHQATYNKQPM 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 74200036 142 YRKAIYEVLQVASSRAGKLFPACHDSDESDSGKAVEVQNKQMIEWALGGFQPSG 195
Cdd:cd20154  81 YRKAIYEVLQVASSRAGKLFPVCPESDESDTSKAVEVQNKQMIEWALGGFQPSG 134

PWWP domain found in the DNA (cytosine-5)-methyltransferase 3 (DNMT3) family; The DNMT3 family includes DNMT3A and DNMT3B, which are required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNMT3A, also called DNA methyltransferase HsaIIIA, DNA MTase HsaIIIA, or M.HsaIIIA, modifies DNA in a non-processive manner and also methylates non-CpG sites. It may preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. DNMT3A is recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites. DNMT3B, also called DNA methyltransferase HsaIIIB, DNA MTase HsaIIIB, or M.HsaIIIB, may preferentially methylate nucleosomal DNA within the nucleosome core region. DNMT3B may function as a transcriptional co-repressor by associating with CBX4 and independently of DNA methylation. Members of this family contains a PWWP domain that is responsible for establishing DNA methylation patterns during embryogenesis and gametogenesis. In tumorigenesis, DNA methylation by DNMT3B is known to play a role in the inactivation of tumor suppressor genes. In addition, a point mutation in the PWWP domain of DNMT3B has been identified in patients with ICF (immunodeficiency, centromeric instability, and facial anomalie) syndrome , a rare autosomal recessive disorder characterized by hypomethylation of classical satellite DNA.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74200036  69 IGELVWGKLRGFSWWPGRIVSWWMTGRSRAAEGTRWVMWFGDGKFSVVCVEKLMPLSSFCSAFHQaTYNKQPMYRKAIYE 148
Cdd:cd05835   2 IGDLVWAKLKGSPWWPGIVVSHKDCGQKPPAEGSVWVFWFGDHKVSEVPLDKILPFAEFFNKFYI-SKNSSKLYKKAVYE 80

                ....*....
gi 74200036 149 VLQVASSRA 157
Cdd:cd05835  81 ALKEAAERS 89

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 74200036    70 GELVWGKLRGFSWWPGRIVSWWMTGRS----RAAEGTRWVMWFGDGKFSVVCVEKLMPLSSFCSAFHQATYNK---QPMY 142
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVVDPEELPENvlkpKKKDGEYLVRFFGDSEFAWVKPKDLKPFDEGDEFEYLKKKKKkkkKKAF 80

                          90
                  ....*....|..
gi 74200036   143 RKAIYEVLQVAS 154
Cdd:pfam00855  81 KKALEEAEEALK 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 74200036  70 GELVWGKLRGFSWWPGRIVSWWMTG---RSRAAEGTRWVMWFGDGKFSVVCVEKLMPLSSFCSAFHQATYNKQPMYRKAI 146
Cdd:cd05162   1 GDLVWAKLKGYPWWPARVVDPEELPeevGKKKKKGGVLVQFFGDNDYAWVKSKNIKPFEEGFKKEFKKKKKKSKKFKKAV 80

                ..
gi 74200036 147 YE 148
Cdd:cd05162  81 EE 82

PWWP domain found in the PWWP domain-containing protein 2 (PWWP2) family; The PWWP2 family includes PWWP2A and its paralog PWWP2B. PWWP2A is a H2A.Z-specific chromatin binding protein which may play an important role in the neural crest stem cell migration and differentiation during early development. It is also required for proper mitosis progression. PWWP2A and PWWP2B form a stable complex with NuRD subunits MTA1/2/3:HDAC1/2:RBBP4/7, but not with MBD2/3, p66alpha/beta, and CHD3/4. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74200036  64 GRGFGIGELVWGKLRGFSWWPGRIVSWWMTGRSRAAEGTRW--VMWFGDGKFSVVCVEKLMPlssFCSAFHQaTYNKQP- 140
Cdd:cd20140   1 GRTLRVGDIVWGKIHGFPWWPGRILSITVSRDDNGELSTQEahVSWFGSSTTSYMPCSQLYP---FLEDFKL-RYNKKKr 76

                        90
                ....*....|....*.
gi 74200036 141 -MYRKAIYEVLQVASS 155
Cdd:cd20140  77 gPYKEAVRQALEAAKQ 92

PWWP domain found in Arabidopsis thaliana histone-lysine N-methyltransferase trithorax-like protein ATX3, ATX4, ATX5, and similar proteins; The family includes A. thaliana ATX3 (also called protein SET domain group 14, or trithorax-homolog protein 3), ATX4 (also called protein SET domain group 16, or trithorax-homolog protein 4) and ATX5 (also called protein SET domain group 29, or trithorax-homolog protein 5), which belong to the histone-lysine methyltransferase family. They show distinct phylogenetic origins from the family of ATX1 and ATX2. They are multi-domain containing protein that consists of an N-terminal PWWP domain, a canonical plant homeodomain (PHD) domain, a non-canonical extended PHD (ePHD) domain, and a C-terminal SET domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74200036  70 GELVWGKLRGFSWWPGRIV---SWWMTGRSRAAEGTRWVMWFGDGK---FSVVCVEKLMPLSSFCSAFHQATY--NKQP- 140
Cdd:cd20143   3 GDLVWAKVGTHPFWPARVVepaEQAEEVRRRCVPGSLCVYFFGPGGsrdYGWVRRSMIFPFTDDLARFQTQKIknKKRPq 82

                        90
                ....*....|....
gi 74200036 141 MYRKAIYEVLQVAS 154
Cdd:cd20143  83 EFQEALEEAKLADA 96

PWWP domain found in hepatoma-derived growth factor (HDGF)-related protein (HRP) family; The HRP family includes hepatoma-derived growth factor (HDGF), and HDGF-related proteins (HRPs). HDGF, also called high mobility group protein 1-like 2 (HMG-1L2), is a heparin-binding protein that acts as a transcriptional repressor with mitogenic activity for fibroblasts. It is a prognostic factor in several types of cancer. HDGFL1 is also called PWWP domain-containing protein 1 (PWWP1). Its biological function remains unclear. HDGFL2, also called HDGF-related protein 2 (HRP-2), or hepatoma-derived growth factor 2 (HDGF-2), is involved in cellular growth control, through the regulation of cyclin D1 expression. HDGFL3, also called HDGF-related protein 3 (HRP-3), enhances DNA synthesis and may play a role in cell proliferation. The family also includes PC4 and SFRS1-interacting protein (PSIP) and similar proteins. PSIP, also called CLL-associated antigen KW-7, dense fine speckles 70 kDa protein (DFS 70), lens epithelium-derived growth factor (LEDGF), or transcriptional coactivator p75/p52, acts as a transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Members of the HRP family contains a PWWP domain, which is necessary for DNA binding.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74200036  67 FGIGELVWGKLRGFSWWPGRIvswwmtgrSRAAEGTRW------VMWFGDGKFSVVCVEKLMPLSSFcsAFHQATYNKQP 140
Cdd:cd05834   1 FKPGDLVFAKVKGYPPWPARI--------DEIPEGAKIpknkypVFFYGTHETAFLKPKDLFPYEEN--KEKYGKPRKRK 70

                ....*...
gi 74200036 141 MYRKAIYE 148
Cdd:cd05834  71 GFNEGLWE 78

PWWP domain found in DNA mismatch repair protein MSH6 and similar proteins; MSH6, also called G/T mismatch-binding protein (GTBP or GTMBP), MutS protein homolog 6, or MutS-alpha 160 kDa subunit (p160), is a mismatch repair protein homologous to bacterial MutS. It is a component of the post-replicative DNA mismatch repair system (MMR). It heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, it forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. Mutations in MSH6 have been linked to increased cancer susceptibility, particularly in hereditary nonpolyposis colorectal cancer in humans. MSH6 contains a PWWP domain, but its role in MSH6 remains unclear. MSH6 orthologs found in Saccharomyces cerevisiae, Caenorhabditis elegans, and Arabidopsis thaliana lack the PWWP domain. PWWP domains typically recognize DNA and histone methylated lysines.

                        10
                ....*....|....*....
gi 74200036  67 FGIGELVWGKLRGFSWWPG 85
Cdd:cd05837   1 FSPGDLVWAKLEGYPWWPS 19

PWWP domain found in Arabidopsis thaliana histone-lysine N-methyltransferase trithorax-like proteins ATX1, ATX2, and similar proteins; This family includes A. thaliana ATX1 and ATX2, which are sister paralogs originating from a segmental chromosomal duplication. They are plant counterparts of the Drosophila melanogaster trithorax (TRX) and mammalian mixed-lineage leukemia (MLL1) proteins. ATX1, also called protein SET domain group 27, or trithorax-homolog protein 1 (TRX-homolog protein 1), is a methyltransferase that trimethylates histone H3 at lysine 4 (H3K4me3). It also acts as a histone modifier and as a positive effector of gene expression. ATX1 regulates transcription from diverse classes of genes implicated in biotic and abiotic stress responses. It is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways. ATX2, also called protein SET domain group 30, or trithorax-homolog protein 2 (TRX-homolog protein 2), is involved in dimethylating histone H3 at lysine 4 (H3K4me2). Both ATX1 and ATX2 are multi-domain containing proteins that consist of an N-terminal PWWP domain, FYRN- and FYRC (DAST, domain associated with SET in trithorax) domains, a canonical plant homeodomain (PHD) domain, a non-canonical extended PHD (ePHD) domain, and a C-terminal SET domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74200036  70 GELVWGKLRGFSWWPG------RIVSWWMTGRSRAAEGTRWVMWFGDGKFSVVCVEKLMPLSS-FCSAFHQATynKQPMY 142
Cdd:cd20142   3 GDVVWAKVKGYPMWPAlvideeHAERCGLEANRPGKKGTVPVQFFGTYEVARLNPKKVVGFSKgLDLKYHSKC--KAPVF 80

                ....*..
gi 74200036 143 RKAIYEV 149
Cdd:cd20142  81 RQALEEA 87