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 5901940  431 LEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSNTSCCRCFCVECLEVLVGT 510
Cdd:cd11728   1 IEDFCLSCGRSNPATFHPLFEGGLCITCKDRFLELFYMYDDDGYQSYCTVCCEGRELLLCGNASCCRCFCVDCLEVLVGP 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 5901940  511 GTAAEAKLQEPWSCYMCLPQRCHGVLRRRKDWNVRLQAFF 550
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 5901940  431 LEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSNTSCCRCFCVECLEVLVGT 510
Cdd:cd11728   1 IEDFCLSCGRSNPATFHPLFEGGLCITCKDRFLELFYMYDDDGYQSYCTVCCEGRELLLCGNASCCRCFCVDCLEVLVGP 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 5901940  511 GTAAEAKLQEPWSCYMCLPQRCHGVLRRRKDWNVRLQAFF 550
Cdd:cd11728  81 GTAAKAKEQDPWSCYMCLPQRCYGVLKRRTDWSVRLQEFF 120

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 5901940     223 FGIGDLVWGKIKGFSWWPAMVVSWKAT----SKRQAMSGMRWVQWFGDGKFSEVSADKLVALG 281
Cdd:smart00293   1 FKPGDLVWAKMKGFPWWPALVISPKMTpdniMKRKSDENLYPVLFFGDKDTAWIPSSKLFPLT 63

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5901940  572 RRPIRVLSLFDGI---ATGylvLKELGIKVGkyVASEVCEESIAVgtvkHEGNIKYVN----DVRNITKKNIEewGPFDL 644
Cdd:COG0270   1 SKKLTVIDLFAGAgglSLG---FEKAGFEVV--FAVEIDPDACET----YRANFPEAKviegDIRDIDPEELI--PDVDL 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5901940  645 VIGGSPCNDLSNVNPaRKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENVVAMKVGDKRD-----ISRFLEC--- 716
Cdd:COG0270  70 LIGGPPCQPFSVAGK-RKGLEDPRGTLFFEFIRIVEELRPK-------AFVLENVPGLLSSDKGKtfeeiLKELEELgyr 141

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5901940  717 -NPVMIDAIKVSAA-HRARYFwgnlpgmnrpVIASKNDKLELQ----DCLEYNR-----IAKLKKVQTITTKSNSIKQGk 785
Cdd:COG0270 142 vDYKVLNAADYGVPqNRERVF----------IVGFRKDLDLFEfpepTHLKPYVtvgdaLEDLPDAHEARYLSETITAG- 210

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 5901940  786 nqlfpvvMNGKEDVL------WCT--ELERIFGFPVHYTDVSNMGRGARQklLGRSWSVPVIRHLFAPLKDYF 850
Cdd:COG0270 211 -------YGGGGRFLhpgeprRLTvrEAARLQGFPDDFKFPGSKTQAYRQ--IGNAVPPPLAEAIAKAILKAL 274

C-5 cytosine-specific DNA methylase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5901940    575 IRVLSLFDGIATGYLVLKELGIKVgkYVASEVCEESIAV-GTVKHEGNIkyvNDVRNITKKNIEEwgpFDLVIGGSPCND 653
Cdd:pfam00145   1 FKFIDLFAGIGGFRLGLEQAGFEC--VAANEIDKSAAKTyEANFPKVPI---GDITLIDIKDIPD---IDILTGGFPCQD 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 5901940    654 LSNVNpARKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENV 699
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 5901940  431 LEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSNTSCCRCFCVECLEVLVGT 510
Cdd:cd11728   1 IEDFCLSCGRSNPATFHPLFEGGLCITCKDRFLELFYMYDDDGYQSYCTVCCEGRELLLCGNASCCRCFCVDCLEVLVGP 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 5901940  511 GTAAEAKLQEPWSCYMCLPQRCHGVLRRRKDWNVRLQAFF 550
Cdd:cd11728  81 GTAAKAKEQDPWSCYMCLPQRCYGVLKRRTDWSVRLQEFF 120

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 5901940  218 QDGKEFGIGDLVWGKIKGFSWWPAMVVSWKATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVS 297
Cdd:cd20154   1 EDGRGFGIGELVWGKLRGFSWWPGRIVSWWMTGRSRAAEGTRWVMWFGDGKFSVVCVEKLMPLSSFSSAFHQATYNKQPM 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 5901940  298 YRKAMYHALEKARVRAGKTFPSSP-------GDSLEDQLKPMLEWAHGGFKPTG 344
Cdd:cd20154  81 YRKAIYEVLQVASSRAGKLFPVCPesdesdtSKAVEVQNKQMIEWALGGFQPSG 134

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 5901940  430 SLEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSNTSCCRCFCVECLEVLVG 509
Cdd:cd11729   3 NIEDICISCGSLNVTLEHPLFIGGMCQNCKNCFLECAYQYDDDGYQSYCTICCGGREVLMCGNNNCCRCFCVECVDLLVG 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 5901940  510 TGTAAEAKLQEPWSCYMCLPQRCHGVLRRRKDWNVRLQAFFTSD 553
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 5901940  225 IGDLVWGKIKGFSWWPAMVVSWKATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLaTFNKLVSYRKAMYH 304
Cdd:cd05835   2 IGDLVWAKLKGSPWWPGIVVSHKDCGQKPPAEGSVWVFWFGDHKVSEVPLDKILPFAEFFNKFYI-SKNSSKLYKKAVYE 80

                ....*....
gi 5901940  305 ALEKARVRA 313
Cdd:cd05835  81 ALKEAAERS 89

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 5901940     223 FGIGDLVWGKIKGFSWWPAMVVSWKAT----SKRQAMSGMRWVQWFGDGKFSEVSADKLVALG 281
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 5901940    226 GDLVWGKIKGFSWWPAMVVSW----KATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVS---Y 298
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVVDPeelpENVLKPKKKDGEYLVRFFGDSEFAWVKPKDLKPFDEGDEFEYLKKKKKKKKkkaF 80

                          90
                  ....*....|..
gi 5901940    299 RKAMYHALEKAR 310
Cdd:pfam00855  81 KKALEEAEEALK 92

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 5901940  435 CLSCGR-----KNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSntSCCRCFCVECLEVLVG 509
Cdd:cd11726   5 CTACGEqlnhfSKEVHRHPVLKVLICKSCLKFYNSGEFSKDEDGSDEYCRWCGQGGDLICCD--FCPNVFCKKCIKRNLG 82

                        90       100
                ....*....|....*....|
gi 5901940  510 TGTAAEAKLQEPWSCYMCLP 529
Cdd:cd11726  83 RAELSRIEESDKWKCFVCDP 102

PWWP domain found in PWWP domain-containing protein 2B (PWWP2B); PWWP2B is a paralog of PWWP2A, 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. 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 5901940  218 QDGKEFGIGDLVWGKIKGFSWWPAMVVSWKATSKRQAMSGMR--WVQWFGDGKFSEVSADKLVAlglFSQHFNLaTFN-- 293
Cdd:cd20153   9 EEGRTVSVGDIVWGKIHGFPWWPARVLSISLSQKEDGEPSWQeaKVSWFGSPTTSLLSVSKLSP---FSEFFKL-RFNrk 84

                        90
                ....*....|....*..
gi 5901940  294 KLVSYRKAMYHALEKAR 310
Cdd:cd20153  85 KKGMYRKAITEAAKAAE 101

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 5901940  575 IRVLSLFDGIATGYLVLKELGIKVgkYVASEVCEESIAVGTVKHeGNIKYVNDVRNITKKniEEWGPFDLVIGGSPCNDL 654
Cdd:cd00315   1 LRVIDLFAGIGGFRLGLEKAGFEI--VAANEIDKSAAETYEANF-PNKLIEGDITKIDEK--DFIPDIDLLTGGFPCQPF 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5901940  655 SNVNpARKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENVVAMKVGDKRD-----ISRFLECN----PVMIDAIK 725
Cdd:cd00315  76 SIAG-KRKGFEDTRGTLFFEIIRILKEKKPK-------YFLLENVKGLLTHDNGNtlkviLNTLEELGynvyWKLLNASD 147

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5901940  726 VSAAH-RARYFW-GNLPGMN----RPVIASKNDKLELQDCLeynRIAKLKKVQTITTKSNSIKQGKNQLFPVVMNGKEDV 799
Cdd:cd00315 148 YGVPQnRERVFIiGIRKDLIlnffSPFPKPSEKKKTLKDIL---RIRDPDEPSPTLTASYGKGTGSVHPTAPDMIGKESN 224

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*..
gi 5901940  800 ---LWCTELERIFGFPVHYtDVSNMGRGARQKLLGRSWSVPVIRHLF 843
Cdd:cd00315 225 irrLTPRECARLQGFPDDF-EFPGKSVTQAYRQIGNSVPVPVAEAIA 270

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 5901940  223 FGIGDLVWGKIKGFSWWPAMVVSWKATSKRQAMS-GMRWVQWFG 265
Cdd:cd05836   1 FKIGDLVWAKMKGFPPWPGKIVNPPPDLKKPPRKkKMHCVYFFG 44

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 5901940  226 GDLVWGKIKGFSWWPAMVVS---------WKATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALglfSQHFnLATFNKLV 296
Cdd:cd05840   1 GDLVLAKVKGYPPWPAMVLPeellpknvlKAKKRKPKSKKTVYPVQFFPDNEYYWVSPSSLKPL---TKEE-IDKFLSKS 76

                        90
                ....*....|....
gi 5901940  297 SYR-KAMYHALEKA 309
Cdd:cd05840  77 KRKnKDLIEAYEVA 90

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 5901940  225 IGDLVWGKIKGFSWWPAMVVS---------WKATSKRQAMsgMRWVQWFGD 266
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 5901940  223 FGIGDLVWGKIKGFSWWPAMVVSW-KATSKRQAMSGMRW-VQWFGD 266
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 5901940  226 GDLVWGKIKGFSWWPAMVVSWKaTSKRQAMSGMRWVQWFGD--------GKFSEVSADKLVAL 280
Cdd:cd20147   1 GDLVLAKVKGFPAWPAQVSEPE-DWGSAPDPKKVFVHFFGTqqigfcnpGELSEFTEEIKQSL 62

PWWP domain found in zinc finger CW-type PWWP domain protein 1 (ZCWPW1) and similar proteins; ZCWPW1 is a histone H3K4me3 reader. It is associated with late-onset Alzheimer's disease (LOAD). In addition to the PWWP domain, ZCWPW1 contains a zinc finger CW (zf-CW) domain that is a histone modification reader for the histone H3 tail with trimethylated K4. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                        10        20
                ....*....|....*....|..
gi 5901940  222 EFGIGDLVWGKIKGFSWWPAMV 243
Cdd:cd20145   5 KYTPGSLVWAKMPGYPWWPAMV 26

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.

                        10        20
                ....*....|....*....|...
gi 5901940  223 FGIGDLVWGKIKGFSWWPAMVVS 245
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.

                        10        20
                ....*....|....*....|
gi 5901940  227 DLVWGKIKGFSWWPAMVVSW 246
Cdd:cd20159   8 ELVWAKQKGFPYWPAKVIQK 27