ADDz domain found in DNA (cytosine-5) methyltransferases (C5-MTases) 3b (Dnmt3b); ADDz_Dnmt3b is an active catalytic domain of Dnmt3b. Dnmt3b is a member of the Dnmt3 family and is a de novo DNA methyltransferases that has an N-terminal variable region followed by a conserved PWWP region and the cysteine-rich ADDz domain. DNA methylation is an important epigenetic mechanism involved in diverse biological processes such as embryonic development, gene expression, and genomic imprinting. The methyltransferase activity of Dnmt3a is not only responsible for the establishment of DNA methylation pattern, but is also essential for the inheritance of these patterns during mitosis. Dnmt3b is ubiquitously expressed in most adult tissues. The ADDz_Dnmt3 domain is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger. PHD zinc finger domains have been identified in more than 40 proteins that are mainly involved in chromatin mediated transcriptional control; the classical PHD zinc finger has a C4-H-C3 motif that spans about 50-80 amino acids. In ADDz, the conserved histidine residue of the PHD finger is replaced by a cysteine, and an additional zinc finger C2-C2 like motif is located about twenty residues upstream of the C4-C-C3 motif. A knockout of Dnmt3b has been shown to be lethal in the mouse model.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462579697 423 LEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSNTSCCRCFCVECLEVLVGT 502
Cdd:cd11728     1 IEDFCLSCGRSNPATFHPLFEGGLCITCKDRFLELFYMYDDDGYQSYCTVCCEGRELLLCGNASCCRCFCVDCLEVLVGP 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2462579697 503 GTAAEAKLQEPWSCYMCLPQRCHGVLRRRKDWNVRLQAFF 542
Cdd:cd11728    81 GTAAKAKEQDPWSCYMCLPQRCYGVLKRRTDWSVRLQEFF 120

ADDz domain found in DNA (cytosine-5) methyltransferases (C5-MTases) 3b (Dnmt3b); ADDz_Dnmt3b is an active catalytic domain of Dnmt3b. Dnmt3b is a member of the Dnmt3 family and is a de novo DNA methyltransferases that has an N-terminal variable region followed by a conserved PWWP region and the cysteine-rich ADDz domain. DNA methylation is an important epigenetic mechanism involved in diverse biological processes such as embryonic development, gene expression, and genomic imprinting. The methyltransferase activity of Dnmt3a is not only responsible for the establishment of DNA methylation pattern, but is also essential for the inheritance of these patterns during mitosis. Dnmt3b is ubiquitously expressed in most adult tissues. The ADDz_Dnmt3 domain is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger. PHD zinc finger domains have been identified in more than 40 proteins that are mainly involved in chromatin mediated transcriptional control; the classical PHD zinc finger has a C4-H-C3 motif that spans about 50-80 amino acids. In ADDz, the conserved histidine residue of the PHD finger is replaced by a cysteine, and an additional zinc finger C2-C2 like motif is located about twenty residues upstream of the C4-C-C3 motif. A knockout of Dnmt3b has been shown to be lethal in the mouse model.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462579697 423 LEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSNTSCCRCFCVECLEVLVGT 502
Cdd:cd11728     1 IEDFCLSCGRSNPATFHPLFEGGLCITCKDRFLELFYMYDDDGYQSYCTVCCEGRELLLCGNASCCRCFCVDCLEVLVGP 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2462579697 503 GTAAEAKLQEPWSCYMCLPQRCHGVLRRRKDWNVRLQAFF 542
Cdd:cd11728    81 GTAAKAKEQDPWSCYMCLPQRCYGVLKRRTDWSVRLQEFF 120

domain with conserved PWWP motif; conservation of Pro-Trp-Trp-Pro residues

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462579697  235 FGIGDLVWGKIKGFSWWPAMVVSWKAT----SKRQAMSGMRWVQWFGDGKFSEVSADKLVALG 293
Cdd:smart00293   1 FKPGDLVWAKMKGFPWWPALVISPKMTpdniMKRKSDENLYPVLFFGDKDTAWIPSSKLFPLT 63

DNA-cytosine methylase [Replication, recombination and repair];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462579697 564 RRPIRVLSLFDGI---ATGylvLKELGIKVGkyVASEVCEESIAVgtvkHEGNIKYVN----DVRNITKKNIEewGPFDL 636
Cdd:COG0270     1 SKKLTVIDLFAGAgglSLG---FEKAGFEVV--FAVEIDPDACET----YRANFPEAKviegDIRDIDPEELI--PDVDL 69

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462579697 637 VIGGSPCNDLSNVNPaRKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENVVAMKVGDKRDI 702
Cdd:COG0270    70 LIGGPPCQPFSVAGK-RKGLEDPRGTLFFEFIRIVEELRPK-------AFVLENVPGLLSSDKGKT 127

C-5 cytosine-specific DNA methylase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462579697 567 IRVLSLFDGIATGYLVLKELGIKVgkYVASEVCEESIAV-GTVKHEGNIkyvNDVRNITKKNIEEwgpFDLVIGGSPCND 645
Cdd:pfam00145   1 FKFIDLFAGIGGFRLGLEQAGFEC--VAANEIDKSAAKTyEANFPKVPI---GDITLIDIKDIPD---IDILTGGFPCQD 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2462579697 646 LSNVNpARKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENV 691
Cdd:pfam00145  73 FSIAG-KQKGFEDTRGTLFFEIIRIIKEKKPK-------AFLLENV 110

ADDz domain found in DNA (cytosine-5) methyltransferases (C5-MTases) 3b (Dnmt3b); ADDz_Dnmt3b is an active catalytic domain of Dnmt3b. Dnmt3b is a member of the Dnmt3 family and is a de novo DNA methyltransferases that has an N-terminal variable region followed by a conserved PWWP region and the cysteine-rich ADDz domain. DNA methylation is an important epigenetic mechanism involved in diverse biological processes such as embryonic development, gene expression, and genomic imprinting. The methyltransferase activity of Dnmt3a is not only responsible for the establishment of DNA methylation pattern, but is also essential for the inheritance of these patterns during mitosis. Dnmt3b is ubiquitously expressed in most adult tissues. The ADDz_Dnmt3 domain is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger. PHD zinc finger domains have been identified in more than 40 proteins that are mainly involved in chromatin mediated transcriptional control; the classical PHD zinc finger has a C4-H-C3 motif that spans about 50-80 amino acids. In ADDz, the conserved histidine residue of the PHD finger is replaced by a cysteine, and an additional zinc finger C2-C2 like motif is located about twenty residues upstream of the C4-C-C3 motif. A knockout of Dnmt3b has been shown to be lethal in the mouse model.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462579697 423 LEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSNTSCCRCFCVECLEVLVGT 502
Cdd:cd11728     1 IEDFCLSCGRSNPATFHPLFEGGLCITCKDRFLELFYMYDDDGYQSYCTVCCEGRELLLCGNASCCRCFCVDCLEVLVGP 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2462579697 503 GTAAEAKLQEPWSCYMCLPQRCHGVLRRRKDWNVRLQAFF 542
Cdd:cd11728    81 GTAAKAKEQDPWSCYMCLPQRCYGVLKRRTDWSVRLQEFF 120

ADDz domain found in DNA (cytosine-5) methyltransferases (C5-MTases) 3 (Dnmt3); Dnmt3 is a de novo DNA methyltransferase family that includes two active enzymes Dnmt3a and -3b and one regulatory factor Dnmt3l. The ADDz domain of Dnmt3 is located in the C-terminal region of Dnmt3, which is an active catalytic domain in Dnmt3a and -b, but lacks some residues for enzymatic activity in Dnmt3l. DNA methylation is an important epigenetic mechanism involved in diverse biological processes such as embryonic development, gene expression, and genomic imprinting. The ADDz_Dnmt3 domain is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger. PHD zinc finger domains have been identified in more than 40 proteins that are mainly involved in chromatin mediated transcriptional control; the classical PHD zinc finger has a C4-H-C3 motif that spans about 50-80 amino acids. In ADDz, the conserved histidine residue of the PHD finger is replaced by a cysteine, and an additional zinc finger C2-C2 like motif is located about twenty residues upstream of the C4-C-C3 motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462579697 423 LEDGCLSCGRKNP--VSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSNTSCCRCFCVECLEVLV 500
Cdd:cd11725     1 IEDICLACGSLEVseTSDHPFFEGGLCKNCKERFLECIFLFDDDGYQMYCTICGGGGEVVLCDNPDCTRVYCTECLDLLL 80

                          90       100
                  ....*....|....*....|....*...
gi 2462579697 501 GTGTAAEAKLQEPWSCYMCLPQRCHGVL 528
Cdd:cd11725    81 GPGAVAKILESDPWFCFLCSPESNSLLG 108

ADDz domain found in DNA (cytosine-5) methyltransferases (C5-MTases) 3a (Dnmt3a); Dnmt3a is a member of the Dnmt3 family and is a protein with de novo DNA methyltransferase activity. Dnmt3 family members are Dnmt3a, Dnmt3b, and Dnmt3l the non-enzymatic regulatory factor. Dnmt3a is recruited by Dnmt3l to unmethylated histone H3 and methylates the target. Dnmt3a has a variable region at the N-terminus, followed by a conserved PWWP region and the cysteine-rich ADDz domain. ADDz_Dnmt3a is an active catalytic domain of Dnmt3a. DNA methylation is an important epigenetic mechanism involved in diverse biological processes such as embryonic development, gene expression, and genomic imprinting. The methyltransferase activity of Dnmt3a is not only responsible for the establishment of DNA methylation pattern, but is also essential for the inheritance of these patterns during mitosis. The ADDz_Dnmt3 domain is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger. PHD zinc finger domains have been identified in more than 40 proteins that are mainly involved in chromatin mediated transcriptional control; the classical PHD zinc finger has a C4-H-C3 motif that spans about 50-80 amino acids. In ADDz, the conserved histidine residue of the PHD finger is replaced by a cysteine, and an additional zinc finger C2-C2 like motif is located about twenty residues upstream of the C4-C-C3 motif. A knockout of Dnmt3a has been shown to be lethal in the mouse model.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462579697 422 SLEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSNTSCCRCFCVECLEVLVG 501
Cdd:cd11729     3 NIEDICISCGSLNVTLEHPLFIGGMCQNCKNCFLECAYQYDDDGYQSYCTICCGGREVLMCGNNNCCRCFCVECVDLLVG 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2462579697 502 TGTAAEAKLQEPWSCYMCLPQRCHGVLRRRKDWNVRLQAFFTSD 545
Cdd:cd11729    83 PGAAQAAIKEDPWNCYMCGHKGTYGLLRRREDWPSRLQMFFANN 126

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 2462579697 237 IGDLVWGKIKGFSWWPAMVVSWKATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLaTFNKLVSYRKAMYH 316
Cdd:cd05835     2 IGDLVWAKLKGSPWWPGIVVSHKDCGQKPPAEGSVWVFWFGDHKVSEVPLDKILPFAEFFNKFYI-SKNSSKLYKKAVYE 80

                  ....*....
gi 2462579697 317 ALEKARVRA 325
Cdd:cd05835    81 ALKEAAERS 89

domain with conserved PWWP motif; conservation of Pro-Trp-Trp-Pro residues

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462579697  235 FGIGDLVWGKIKGFSWWPAMVVSWKAT----SKRQAMSGMRWVQWFGDGKFSEVSADKLVALG 293
Cdd:smart00293   1 FKPGDLVWAKMKGFPWWPALVISPKMTpdniMKRKSDENLYPVLFFGDKDTAWIPSSKLFPLT 63

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 2462579697 238 GDLVWGKIKGFSWWPAMVVSW----KATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVS---Y 310
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVVDPeelpENVLKPKKKDGEYLVRFFGDSEFAWVKPKDLKPFDEGDEFEYLKKKKKKKKkkaF 80

                          90
                  ....*....|..
gi 2462579697 311 RKAMYHALEKAR 322
Cdd:pfam00855  81 KKALEEAEEALK 92

PWWP domain found in methyl-CpG-binding domain protein 5 (MBD5) and similar proteins; MBD5, is a methyl-CpG-binding protein that binds to heterochromatin. It does not interact with either methylated or unmethylated DNA. MBD5 acts as a transcriptional regulator responsible for 2q23.1 deletion syndrome. It belongs to the MBD family proteins, which play central roles in transcriptional regulation and development. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462579697 235 FGIGDLVWGKIKGFSWWPAMVVSWKATSKRQamSGMRWVQWFGDGKFSEVSADKLVAL--GLFSQH 298
Cdd:cd20141     1 FNVGDLVWGQIRGFPSWPGKLVSENDVGKTN--EGKVWVSWFGDHSFGQVEPDKLKTLseGLEAHH 64

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 2462579697 232 GKEFGIGDLVWGKIKGFSWWPAMVVS-WKATSKRQAMSGMR-WVQWFGDGKFSEVSADKlvaLGLFSQHFNLATFNKLV- 308
Cdd:cd20140     1 GRTLRVGDIVWGKIHGFPWWPGRILSiTVSRDDNGELSTQEaHVSWFGSSTTSYMPCSQ---LYPFLEDFKLRYNKKKRg 77

                          90
                  ....*....|....
gi 2462579697 309 SYRKAMYHALEKAR 322
Cdd:cd20140    78 PYKEAVRQALEAAK 91

Cytosine-C5 specific DNA methylases; Methyl transfer reactions play an important role in many aspects of biology. Cytosine-specific DNA methylases are found both in prokaryotes and eukaryotes. DNA methylation, or the covalent addition of a methyl group to cytosine within the context of the CpG dinucleotide, has profound effects on the mammalian genome. These effects include transcriptional repression via inhibition of transcription factor binding or the recruitment of methyl-binding proteins and their associated chromatin remodeling factors, X chromosome inactivation, imprinting and the suppression of parasitic DNA sequences. DNA methylation is also essential for proper embryonic development and is an important player in both DNA repair and genome stability.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462579697 567 IRVLSLFDGIATGYLVLKELGIKVgkYVASEVCEESIAVGTVKHeGNIKYVNDVRNITKKniEEWGPFDLVIGGSPCNDL 646
Cdd:cd00315     1 LRVIDLFAGIGGFRLGLEKAGFEI--VAANEIDKSAAETYEANF-PNKLIEGDITKIDEK--DFIPDIDLLTGGFPCQPF 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2462579697 647 SNVNpARKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENVVAMKVGDKR 700
Cdd:cd00315    76 SIAG-KRKGFEDTRGTLFFEIIRILKEKKPK-------YFLLENVKGLLTHDNG 121

PWWP domain found in glyoxylate reductase 1 (GLYR1) and similar proteins; GLYR1, also called 3-hydroxyisobutyrate dehydrogenase-like protein, cytokine-like nuclear factor N-PAC, nuclear protein NP60, or nuclear protein of 60 kDa, is a putative oxidoreductase that is recruited on chromatin and promotes KDM1B demethylase activity. It recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3). GLYR1 enhances the activity of MAP2K4 and MAP2K6 kinases to phosphorylate p38-alpha. In addition to the PWWP domain, GLYR1 also contains an AT-hook and a C-terminal NAD-binding domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2462579697 235 FGIGDLVWGKIKGFSWWPAMVVSWKATSKRQAMS-GMRWVQWFG 277
Cdd:cd05836     1 FKIGDLVWAKMKGFPPWPGKIVNPPPDLKKPPRKkKMHCVYFFG 44

PWWP domain found in PWWP domain-containing protein 2A (PWWP2A); 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 its paralog 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 2462579697 231 DGKEFGIGDLVWGKIKGFSWWPAMVVSWKATSKRqamSGMR-----WVQWFGDGKFSEVSadkLVALGLFSQHFNlATFN 305
Cdd:cd20152    16 DGRTICVGDIVWAKIYGFPWWPARILAITVSRKD---NGLLvrqeaRISWFGSPTTSFLA---LSQLAPFLENFQ-SRFN 88

                          90
                  ....*....|....*....
gi 2462579697 306 KLVS--YRKAMYHALEKAR 322
Cdd:cd20152    89 KKRKglYRKAITEAAKAAK 107

first 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 the 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 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, through 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 first PWWP domain. This 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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462579697 237 IGDLVWGKIKGFSWWPAMVVS---------WKATSKRQAMsgMRWVQWFGD 278
Cdd:cd20144     1 VGDLVWAKVSGHPWWPCMVTYdpesglytkIKGSGGRTYR--QYHVQFFGD 49

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        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2462579697 235 FGIGDLVWGKIKGFSWWPAMVVSW-KATSKRQAMSGMRW-VQWFGD 278
Cdd:cd05837     1 FSPGDLVWAKLEGYPWWPSLVCNHpTTGFHKKFGKKGEVhVQFFDD 46

PWWP domain found in Arabidopsis thaliana protein HUA2-LIKE (HULK) family; The HULK family includes HUA2-like proteins 1-3 (HULK1-3), which are probable transcription factors that act with partial redundancy with each other. They may play diverse and essential roles in the control of plant development, physiology and flowering time. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462579697 238 GDLVWGKIKGFSWWPAMVVSWKaTSKRQAMSGMRWVQWFGD--------GKFSEVSADKLVAL 292
Cdd:cd20147     1 GDLVLAKVKGFPAWPAQVSEPE-DWGSAPDPKKVFVHFFGTqqigfcnpGELSEFTEEIKQSL 62

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
                  ....*....|....*....|....*....|....*....|....*.
gi 2462579697 238 GDLVWGKIKGFSWWPAMVV---SWKATSKRQAMSGMRWVQWFGDGK 280
Cdd:cd20143     3 GDLVWAKVGTHPFWPARVVepaEQAEEVRRRCVPGSLCVYFFGPGG 48

first PWWP domain found in nuclear SET domain-containing protein 3 (NSD3) and similar proteins; NSD3, also called histone-lysine N-methyltransferase NSD3, protein whistle, WHSC1-like 1 isoform 9 with methyltransferase activity to lysine, or Wolf-Hirschhorn syndrome candidate 1-like protein 1 (WHSC1-like protein 1, or WHSC1L1), is a lysine methyltransferase encoded by gene NSD3, which is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD3 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, five plant-homeodomain (PHD) zinc finger motifs, and an NSD-specific Cys-His rich domain (C5HCH). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD domains are involved in protein-protein interactions. This model corresponds to the first PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

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gi 2462579697 235 FGIGDLVWGKIKGFSWWPAMVVS 257
Cdd:cd20163     1 FQVGDLVWSKVGTYPWWPCMVSS 23

PWWP domain found in protein BS69 and similar proteins; Protein BS69, also called zinc finger MYND domain-containing protein 11 (ZMYND11 or ZMY11), is a ubiquitously expressed nuclear protein acting as a transcriptional co-repressor in association with various transcription factors. It was originally identified as an adenovirus 5 E1A-binding protein that inhibits E1A transactivation, as well as c-Myb transcription. It also mediates repression, at least in part, through interaction with the co-repressor N-CoR. Moreover, it interacts with Toll-interleukin 1 receptor domain (TIR)-containing adaptor molecule-1 (TICAM-1, also named TRIF) to facilitate NF-kappaB activation and type I IFN induction. It associates with PIAS1, a SUMO E3 enzyme, and Ubc9, a SUMO E2 enzyme, and plays an inhibitory role in muscle and neuronal differentiation. Moreover, BS69 regulates Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1)/C-terminal activation region 2 (CTAR2)-mediated NF-kappaB activation by interfering with the complex formation between TNFR-associated death domain protein (TRADD) and LMP1/CTAR2. It also cooperates with tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) in the regulation of EBV-derived LMP1/CTAR1-induced NF-kappaB activation. Furthermore, BS69 is involved in the p53-p21Cip1-mediated senescence pathway. BS69 contains a plant homeodomain (PHD) finger, a bromodomain, a proline-tryptophan-tryptophan-proline (PWWP) domain, and a MYeloid translocation protein 8, Nervy and DEAF-1 (MYND) domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

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gi 2462579697 239 DLVWGKIKGFSWWPAMVVSW 258
Cdd:cd20159     8 ELVWAKQKGFPYWPAKVIQK 27