PWWP domain found in DNA (cytosine-5)-methyltransferase 3B (DNMT3B); DNMT3B, also called DNA methyltransferase HsaIIIB, DNA MTase HsaIIIB, or M.HsaIIIB, is required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. It 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. 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 anomalies) syndrome, a rare autosomal recessive disorder characterized by hypomethylation of classical satellite DNA.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 333440487 182 GIGDLVWGKIKGFSWWPAMVVSWKATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVSYRKAMY 261
Cdd:cd20155    1 GIGELVWGKIKGFSWWPAMVVSWRATGKRQASSGMRWLQWFGDGKFSEVSADKLVSLTAFSQHFNLSTYNKLVSYRKAMY 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 333440487 262 HALEKARVRAGKTFPSSPGDSLEDQLKPMLEWAHGGF 298
Cdd:cd20155   81 HALEVARVRAGKTFPSSPGESLEDQLKPMLDWAHGGF 117

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 333440487 510 RRPIRVLSLFDGI---ATGylvLKELGIKVGkyVASEVCEESIAVgtvkHEGNIKYVN----DVRNITKKNIEewGPFDL 582
Cdd:COG0270    1 SKKLTVIDLFAGAgglSLG---FEKAGFEVV--FAVEIDPDACET----YRANFPEAKviegDIRDIDPEELI--PDVDL 69

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 333440487 583 VIGGSPCNDLSNVNPaRKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENVVAMKVGDKRDI 648
Cdd:COG0270   70 LIGGPPCQPFSVAGK-RKGLEDPRGTLFFEFIRIVEELRPK-------AFVLENVPGLLSSDKGKT 127

PWWP domain found in DNA (cytosine-5)-methyltransferase 3B (DNMT3B); DNMT3B, also called DNA methyltransferase HsaIIIB, DNA MTase HsaIIIB, or M.HsaIIIB, is required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. It 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. 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 anomalies) syndrome, a rare autosomal recessive disorder characterized by hypomethylation of classical satellite DNA.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 333440487 182 GIGDLVWGKIKGFSWWPAMVVSWKATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVSYRKAMY 261
Cdd:cd20155    1 GIGELVWGKIKGFSWWPAMVVSWRATGKRQASSGMRWLQWFGDGKFSEVSADKLVSLTAFSQHFNLSTYNKLVSYRKAMY 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 333440487 262 HALEKARVRAGKTFPSSPGDSLEDQLKPMLEWAHGGF 298
Cdd:cd20155   81 HALEVARVRAGKTFPSSPGESLEDQLKPMLDWAHGGF 117

Cysteine rich ADD domain in DNMT3; This is a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, AD-DATRX) found in DNMT3A proteins. The ADD domains of the DNMT3 family have a decisive role in blocking DNMT activity in the areas of the genome with chromatin containing methylated H3K4. Furthermore, the ADD domain of DNMMT3A (ADD-3A) competes with the chromodomain (CD) of heterochromatin protein 1 alpha (HP1alpha, CDHP1alpha) for binding to the H3 tail. The DNA methyltransferase (DNMT) 3 family members DNMT3A and DNMT3B and the DNMT3-like non-enzymatic regulatory factor DNMT3L, are involved in de-novo establishment of DNA methylation patterns in early mammalian development.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 333440487  354 SREQMASDVANNKSSLEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDD 409
Cdd:pfam17980   1 SREQMVYEVRENKRNIEDFCLSCGSLNVHTFHPLFEGGLCQKCKDNFLETLYRYDE 56

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 333440487  184 GDLVWGKIKGFSWWPAMVVSW----KATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVS---Y 256
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVVDPeelpENVLKPKKKDGEYLVRFFGDSEFAWVKPKDLKPFDEGDEFEYLKKKKKKKKkkaF 80

                          90
                  ....*....|..
gi 333440487  257 RKAMYHALEKAR 268
Cdd:pfam00855  81 KKALEEAEEALK 92

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 333440487 513 IRVLSLFDGIATGYLVLKELGIKVgkYVASEVCEESIAVGTVKHeGNIKYVNDVRNITKKniEEWGPFDLVIGGSPCNDL 592
Cdd:cd00315    1 LRVIDLFAGIGGFRLGLEKAGFEI--VAANEIDKSAAETYEANF-PNKLIEGDITKIDEK--DFIPDIDLLTGGFPCQPF 75

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 333440487 593 SNVNpARKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENVVAMKVGDKR 646
Cdd:cd00315   76 SIAG-KRKGFEDTRGTLFFEIIRILKEKKPK-------YFLLENVKGLLTHDNG 121

DNA-methyltransferase (dcm); All proteins in this family for which functions are known are DNA-cytosine methyltransferases. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 333440487  565 DVRNITKKNIEEwgpFDLVIGGSPCNDLSnVNPARKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENV 637
Cdd:TIGR00675  48 DITKISPSDIPD---FDILLGGFPCQPFS-IAGKRKGFEDTRGTLFFEIVRILKEKKPK-------FFLLENV 109

PWWP domain found in DNA (cytosine-5)-methyltransferase 3B (DNMT3B); DNMT3B, also called DNA methyltransferase HsaIIIB, DNA MTase HsaIIIB, or M.HsaIIIB, is required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. It 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. 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 anomalies) syndrome, a rare autosomal recessive disorder characterized by hypomethylation of classical satellite DNA.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 333440487 182 GIGDLVWGKIKGFSWWPAMVVSWKATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVSYRKAMY 261
Cdd:cd20155    1 GIGELVWGKIKGFSWWPAMVVSWRATGKRQASSGMRWLQWFGDGKFSEVSADKLVSLTAFSQHFNLSTYNKLVSYRKAMY 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 333440487 262 HALEKARVRAGKTFPSSPGDSLEDQLKPMLEWAHGGF 298
Cdd:cd20155   81 HALEVARVRAGKTFPSSPGESLEDQLKPMLDWAHGGF 117

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 333440487 176 QDGKEFGIGDLVWGKIKGFSWWPAMVVSWKATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVS 255
Cdd:cd20154    1 EDGRGFGIGELVWGKLRGFSWWPGRIVSWWMTGRSRAAEGTRWVMWFGDGKFSVVCVEKLMPLSSFSSAFHQATYNKQPM 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 333440487 256 YRKAMYHALEKARVRAGKTFPSSP-------GDSLEDQLKPMLEWAHGGFKPTG 302
Cdd:cd20154   81 YRKAIYEVLQVASSRAGKLFPVCPesdesdtSKAVEVQNKQMIEWALGGFQPSG 134

ADDz domain found in DNA (cytosine-5) methyltransferases (C5-MTases) 3 like (Dnmt3l); Dnmt3l is a regulator of DNA methylation, which acts by recognizing unmethylated histone H3 tails and interacting with Dnmt3a to stimulate its de novo DNA methylation activity. The ADDz_Dnmt3l domain is located in the C-terminal region of Dnmt3l that otherwise lacks some residues required for DNA methyltransferase activity. DNA methylation is an important epigenetic mechanism involved in diverse biological processes such as embryonic development, gene expression, and genomic imprinting. Dnmt3l is also associating with HDAC1 and acts as a transcriptional repressor. The ADDz_Dnmt3l 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 333440487 368 SLEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSNTSCCRCFCVECLEVLVG 447
Cdd:cd11727    2 SIEEICICCGSLQIHTQHPLFHGGICAPCTEKFLEAFFLYDEDGYQAYCTICCSGETLLMCDDPDCTRCYCFECVDSLVG 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 333440487 448 TGTAAEAKLQEPWSCYMCLPQRCHGVLRRRKDWNVRLQAFF 488
Cdd:cd11727   82 PGTSEKVKATNNWVCFLCLPSSRSGLLQRKRKWRSQLKAFY 122

ATRX, Dnmt3 and Dnmt3l PHD-like zinc finger domain (ADDz); The ADDz zinc finger domain is present in the chromatin-associated proteins cytosine-5-methyltransferase 3 (Dnmt3) and ATRX, a SNF2 type transcription factor protein. The Dnmt3 family includes two active DNA methyltransferases, Dnmt3a and -3b, and one regulatory factor Dnmt3l. DNA methylation is an important epigenetic mechanism involved in diverse biological processes such as embryonic development, gene expression, and genomic imprinting. The ADDz 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 333440487 370 EDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSNTSCCRCFCVECLEVLVGTG 449
Cdd:cd11672    2 EDICIACGSLVVIYRHPLFQGGICKNCKKYFLSDDISYDDDGYQSYCRICCEGGNLLCCGNNFCHRCFCKECVDRLVGPG 81

                         90
                 ....*....|....*...
gi 333440487 450 TAAEAKLQEPWSCYMCLP 467
Cdd:cd11672   82 ELSTMDENNQWYCYICHP 99

Cysteine rich ADD domain in DNMT3; This is a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, AD-DATRX) found in DNMT3A proteins. The ADD domains of the DNMT3 family have a decisive role in blocking DNMT activity in the areas of the genome with chromatin containing methylated H3K4. Furthermore, the ADD domain of DNMMT3A (ADD-3A) competes with the chromodomain (CD) of heterochromatin protein 1 alpha (HP1alpha, CDHP1alpha) for binding to the H3 tail. The DNA methyltransferase (DNMT) 3 family members DNMT3A and DNMT3B and the DNMT3-like non-enzymatic regulatory factor DNMT3L, are involved in de-novo establishment of DNA methylation patterns in early mammalian development.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 333440487  354 SREQMASDVANNKSSLEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDD 409
Cdd:pfam17980   1 SREQMVYEVRENKRNIEDFCLSCGSLNVHTFHPLFEGGLCQKCKDNFLETLYRYDE 56

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 333440487 184 GDLVWGKIKGFSWWPAMVVSWKATSKRQAMS---GMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVSYRKAM 260
Cdd:cd05162    1 GDLVWAKLKGYPWWPARVVDPEELPEEVGKKkkkGGVLVQFFGDNDYAWVKSKNIKPFEEGFKKEFKKKKKKSKKFKKAV 80

                 ....*
gi 333440487 261 YHALE 265
Cdd:cd05162   81 EEAEE 85

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 333440487 181 FGIGDLVWGKIKGFSWWPAMVVSWKATSKRQamSGMRWVQWFGDGKFSEVSADKLVAL--GLFSQH 244
Cdd:cd20141    1 FNVGDLVWGQIRGFPSWPGKLVSENDVGKTN--EGKVWVSWFGDHSFGQVEPDKLKTLseGLEAHH 64

ADDz domain found in ATRX (alpha-thalassemia/mental retardation, X-linked); ADDz_ATRX is a PHD-like zinc finger domain of ATRX, which belongs to the SNF2 family of chromatin remodeling proteins. ATRX is a large chromatin-associated nuclear protein with two domains, ADDz_ATRX at the N-terminus, followed by a C-terminal ATPase/helicase domain. The ADDz_ATRX domain recognizes a specific methylated histone, and this interaction is required for heterochromatin localization of the ATRX protein. Missense mutations in either of the two ATRX domains lead to the X-linked alpha-thalassemia and mental retardation syndrome; however the mutations in the ADDz_ATRX domain produce a more severe disease phenotype that may also relate to disturbing unknown functions or interaction sites of this domain. The ADDz domain is also present in chromatin-associated proteins cytosine-5-methyltransferase 3 (Dnmt3); it 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 333440487 373 CLSCGR-----KNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSntSCCRCFCVECLEVLVG 447
Cdd:cd11726    5 CTACGEqlnhfSKEVHRHPVLKVLICKSCLKFYNSGEFSKDEDGSDEYCRWCGQGGDLICCD--FCPNVFCKKCIKRNLG 82

                         90       100
                 ....*....|....*....|
gi 333440487 448 TGTAAEAKLQEPWSCYMCLP 467
Cdd:cd11726   83 RAELSRIEESDKWKCFVCDP 102

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 333440487 178 GKEFGIGDLVWGKIKGFSWWPAMVVS-WKATSKRQAMSGMR-WVQWFGDGKFSEVSADKlvaLGLFSQHFNLATFNKLV- 254
Cdd:cd20140    1 GRTLRVGDIVWGKIHGFPWWPGRILSiTVSRDDNGELSTQEaHVSWFGSSTTSYMPCSQ---LYPFLEDFKLRYNKKKRg 77

                         90
                 ....*....|....
gi 333440487 255 SYRKAMYHALEKAR 268
Cdd:cd20140   78 PYKEAVRQALEAAK 91

C-5 cytosine-specific DNA methylase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 333440487  513 IRVLSLFDGIATGYLVLKELGIKVgkYVASEVCEESIAV-GTVKHEGNIkyvNDVRNITKKNIEEwgpFDLVIGGSPCND 591
Cdd:pfam00145   1 FKFIDLFAGIGGFRLGLEQAGFEC--VAANEIDKSAAKTyEANFPKVPI---GDITLIDIKDIPD---IDILTGGFPCQD 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 333440487  592 LSNVNpARKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENV 637
Cdd:pfam00145  73 FSIAG-KQKGFEDTRGTLFFEIIRIIKEKKPK-------AFLLENV 110

PWWP domain found in Saccharomyces cerevisiae ISWI one complex protein 4 (ScIOC4) and similar proteins; ScIOC4 functions as a component of the ISW1B complex, which acts in remodeling the chromatin by catalyzing an ATP-dependent alteration in the structure of nucleosomal DNA. The ISW1B complex acts within coding regions to control the amount of RNA polymerase II released into productive elongation and to coordinate elongation with termination and pre-mRNA processing. The family also includes Schizosaccharomyces pombe PWWP domain-containing proteins 1 and 2 (SpPDP1 and SpPDP2). SpPDP1 associates with Set9 to regulate its chromatin localization and methyltransferase activity towards H4K20. Members of this family contain a PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 333440487 184 GDLVWGKIKGFSWWPAMVVS---------WKATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALglfSQHFnLATFNKLV 254
Cdd:cd05840    1 GDLVLAKVKGYPPWPAMVLPeellpknvlKAKKRKPKSKKTVYPVQFFPDNEYYWVSPSSLKPL---TKEE-IDKFLSKS 76

                         90
                 ....*....|....
gi 333440487 255 SYR-KAMYHALEKA 267
Cdd:cd05840   77 KRKnKDLIEAYEVA 90

DNA-methyltransferase (dcm); All proteins in this family for which functions are known are DNA-cytosine methyltransferases. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 333440487  565 DVRNITKKNIEEwgpFDLVIGGSPCNDLSnVNPARKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENV 637
Cdd:TIGR00675  48 DITKISPSDIPD---FDILLGGFPCQPFS-IAGKRKGFEDTRGTLFFEIVRILKEKKPK-------FFLLENV 109

first PWWP domain found in nuclear SET domain-containing protein 2 (NSD2) and similar proteins; NSD2, also called histone-lysine N-methyltransferase NSD2, multiple myeloma SET domain-containing protein (MMSET), or protein trithorax-5 Wolf-Hirschhorn syndrome candidate 1 protein (WHSC1), is overexpressed frequently in the t(4;14) translocation in 15% to 20% of multiple myeloma. It plays important roles in cancer cell proliferation, survival, and tumor growth, through mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. It also enhances androgen receptor (AR)-mediated transcription. The principal chromatin-regulatory activity of NSD2 is dimethylation of histone H3 at lysine 36 (H3K36me2). NSD2 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, a high mobility group (HMG) box, five PHD (plant-homeodomain) zinc finger motifs, and an NSD-specific Cys-His rich domain (C5HCH). The SET domain is responsible for histone methyltransferase activity. The PWWP, HMG, and PHD domains mediate chromatin interaction and recognition of histone marks. This model corresponds to the first PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 333440487 181 FGIGDLVWGKIKGFSWWPAMVVS-----WKATSKRQAMSGMRW-VQWFGD 224
Cdd:cd20162    1 YNVGDLVWSKVSGYPWWPCMVSAdpllhSHTKLKGQKKSARQYhVQFFGD 50

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 333440487 184 GDLVWGKIKGFSWWPAMVVSWKATSKRQAM------SGMRWVQWFGDGKFSEVSADKLVAL 238
Cdd:cd20142    3 GDVVWAKVKGYPMWPALVIDEEHAERCGLEanrpgkKGTVPVQFFGTYEVARLNPKKVVGF 63

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 333440487 184 GDLVWGKIKGFSWWPAMVV---SWKATSKRQAMSGMRWVQWFGDGK 226
Cdd:cd20143    3 GDLVWAKVGTHPFWPARVVepaEQAEEVRRRCVPGSLCVYFFGPGG 48

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
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gi 333440487 181 FGIGDLVWGKIKGFSWWPAMV 201
Cdd:cd05834    1 FKPGDLVFAKVKGYPPWPARI 21

PWWP domain found in the bromodomain and PHD finger-containing (BRPF) protein family; The BRPF family of proteins includes BRPF1, BRD1/BRPF2, and BRPF3. They are scaffold proteins that form monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complexes with other regulatory subunits, such as inhibitor of growth 5 (ING5) and Esa1-associated factor 6 ortholog (EAF6). BRPF proteins have multiple domains, including a plant homeodomain (PHD) zinc finger followed by a non-canonical extended PHD (ePHD) finger, C2HC5HC2H, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain. The PHD finger binds to lysine 4 of histone H3 (K4H3), the bromodomain interacts with acetylated lysines on N-terminal tails of histones and other proteins, and the PWWP domain shows histone-binding and chromatin association properties.

                         10        20
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gi 333440487 181 FGIGDLVWGKIKGFSWWPAMVVS 203
Cdd:cd05839    1 LEPGDLVWAKCRGYPWYPAEIVD 23