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 28559061 224 GIGDLVWGKIKGFSWWPAMVVSWKATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVSYRKAMY 303
Cdd:cd20155   1 GIGELVWGKIKGFSWWPAMVVSWRATGKRQASSGMRWLQWFGDGKFSEVSADKLVSLTAFSQHFNLSTYNKLVSYRKAMY 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 28559061 304 HALEKARVRAGKTFPSSPGDSLEDQLKPMLEWAHGGF 340
Cdd:cd20155  81 HALEVARVRAGKTFPSSPGESLEDQLKPMLDWAHGGF 117

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061 552 RRPIRVLSLFDGI---ATGylvLKELGIKVGkyVASEVCEESIAVgtvkHEGNIKYVN----DVRNITKKNIEewGPFDL 624
Cdd:COG0270   1 SKKLTVIDLFAGAgglSLG---FEKAGFEVV--FAVEIDPDACET----YRANFPEAKviegDIRDIDPEELI--PDVDL 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061 625 VIGGSPCNDLSNVNPaRKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENVVAMKVGDKRD-----ISRFLEC--- 696
Cdd:COG0270  70 LIGGPPCQPFSVAGK-RKGLEDPRGTLFFEFIRIVEELRPK-------AFVLENVPGLLSSDKGKtfeeiLKELEELgyr 141

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061 697 -NPVMIDAIKVSAA-HRARYFwgnlpgmnrpVIASKNDKLELQ----DCLEYNR-----IAKLKKVQTITTKSNSIKQGk 765
Cdd:COG0270 142 vDYKVLNAADYGVPqNRERVF----------IVGFRKDLDLFEfpepTHLKPYVtvgdaLEDLPDAHEARYLSETITAG- 210

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 28559061 766 nqlfpvvMNGKEDVL------WCT--ELERIFGFPVHYTDVSNMGRGARQklLGRSWSVPVIRHLFAPLKDYF 830
Cdd:COG0270 211 -------YGGGGRFLhpgeprRLTvrEAARLQGFPDDFKFPGSKTQAYRQ--IGNAVPPPLAEAIAKAILKAL 274

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 28559061 224 GIGDLVWGKIKGFSWWPAMVVSWKATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVSYRKAMY 303
Cdd:cd20155   1 GIGELVWGKIKGFSWWPAMVVSWRATGKRQASSGMRWLQWFGDGKFSEVSADKLVSLTAFSQHFNLSTYNKLVSYRKAMY 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 28559061 304 HALEKARVRAGKTFPSSPGDSLEDQLKPMLEWAHGGF 340
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 28559061   396 SREQMASDVANNKSSLEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDD 451
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 28559061   226 GDLVWGKIKGFSWWPAMVVSW----KATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVS---Y 298
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVVDPeelpENVLKPKKKDGEYLVRFFGDSEFAWVKPKDLKPFDEGDEFEYLKKKKKKKKkkaF 80

                          90
                  ....*....|..
gi 28559061   299 RKAMYHALEKAR 310
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 28559061 555 IRVLSLFDGIATGYLVLKELGIKVgkYVASEVCEESIAVGTVKHeGNIKYVNDVRNITKKniEEWGPFDLVIGGSPCNDL 634
Cdd:cd00315   1 LRVIDLFAGIGGFRLGLEKAGFEI--VAANEIDKSAAETYEANF-PNKLIEGDITKIDEK--DFIPDIDLLTGGFPCQPF 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061 635 SNVNpARKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENVVAMKVGDKRD-----ISRFLECN----PVMIDAIK 705
Cdd:cd00315  76 SIAG-KRKGFEDTRGTLFFEIIRILKEKKPK-------YFLLENVKGLLTHDNGNtlkviLNTLEELGynvyWKLLNASD 147

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061 706 VSAAH-RARYFW-GNLPGMN----RPVIASKNDKLELQDCLeynRIAKLKKVQTITTKSNSIKQGKNQLFPVVMNGKEDV 779
Cdd:cd00315 148 YGVPQnRERVFIiGIRKDLIlnffSPFPKPSEKKKTLKDIL---RIRDPDEPSPTLTASYGKGTGSVHPTAPDMIGKESN 224

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*..
gi 28559061 780 ---LWCTELERIFGFPVHYtDVSNMGRGARQKLLGRSWSVPVIRHLF 823
Cdd:cd00315 225 irrLTPRECARLQGFPDDF-EFPGKSVTQAYRQIGNSVPVPVAEAIA 270

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061   607 DVRNITKKNIEEwgpFDLVIGGSPCNDLSnVNPARKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENVVAMKVGD 686
Cdd:TIGR00675  48 DITKISPSDIPD---FDILLGGFPCQPFS-IAGKRKGFEDTRGTLFFEIVRILKEKKPK-------FFLLENVKGLVSHD 116

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061   687 K-RDISrflecnpVMIDAI---------KVSAA-------HRAR-------YFWGNLPgMNRPVIASKNDKLELQDCLE- 741
Cdd:TIGR00675 117 KgRTFK-------VIIETLeelgykvyyKVLNAkdfgvpqNRERiyivgfrDFDDKLN-FEFPKPIYVAKKKRIGDLLDl 188

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061   742 --------------------------------------YNRIAKLKKVQTITTK-SNSIKQGKNqlFPVVMNGKEDV--- 779
Cdd:TIGR00675 189 svdleekyylseekknglllllenmrkkegtgeqigsfYNRESKSSIIRTLSARgYTFVKGGKS--VLIVPHKSTVVhpg 266

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 28559061   780 ----LWCTELERIFGFPVHYTDvsNMGRGARQKLLGRSWSVPVIR 820
Cdd:TIGR00675 267 rirrLTPRECARLQGFPDDFKF--PVSDSQLYKQAGNAVVVPVIE 309

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 28559061 224 GIGDLVWGKIKGFSWWPAMVVSWKATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVSYRKAMY 303
Cdd:cd20155   1 GIGELVWGKIKGFSWWPAMVVSWRATGKRQASSGMRWLQWFGDGKFSEVSADKLVSLTAFSQHFNLSTYNKLVSYRKAMY 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 28559061 304 HALEKARVRAGKTFPSSPGDSLEDQLKPMLEWAHGGF 340
Cdd:cd20155  81 HALEVARVRAGKTFPSSPGESLEDQLKPMLDWAHGGF 117

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 28559061 411 LEDGCLSCGRKNP--VSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSNTSCCRCFCVECLEVLV 488
Cdd:cd11725   1 IEDICLACGSLEVseTSDHPFFEGGLCKNCKERFLECIFLFDDDGYQMYCTICGGGGEVVLCDNPDCTRVYCTECLDLLL 80

                        90       100
                ....*....|....*....|....*...
gi 28559061 489 GTGTAAEAKLQEPWSCYMCLPQRCHGVL 516
Cdd:cd11725  81 GPGAVAKILESDPWFCFLCSPESNSLLG 108

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 28559061 410 SLEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSNTSCCRCFCVECLEVLVG 489
Cdd:cd11727   2 SIEEICICCGSLQIHTQHPLFHGGICAPCTEKFLEAFFLYDEDGYQAYCTICCSGETLLMCDDPDCTRCYCFECVDSLVG 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 28559061 490 TGTAAEAKLQEPWSCYMCLPQRCHGVLRRRKDWNVRLQAFF 530
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 28559061 412 EDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSNTSCCRCFCVECLEVLVGTG 491
Cdd:cd11672   2 EDICIACGSLVVIYRHPLFQGGICKNCKKYFLSDDISYDDDGYQSYCRICCEGGNLLCCGNNFCHRCFCKECVDRLVGPG 81

                        90
                ....*....|....*...
gi 28559061 492 TAAEAKLQEPWSCYMCLP 509
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 28559061   396 SREQMASDVANNKSSLEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDD 451
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 28559061 226 GDLVWGKIKGFSWWPAMVVSWKATSKRQAMS---GMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVSYRKAM 302
Cdd:cd05162   1 GDLVWAKLKGYPWWPARVVDPEELPEEVGKKkkkGGVLVQFFGDNDYAWVKSKNIKPFEEGFKKEFKKKKKKSKKFKKAV 80

                ....*
gi 28559061 303 YHALE 307
Cdd:cd05162  81 EEAEE 85

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061 552 RRPIRVLSLFDGI---ATGylvLKELGIKVGkyVASEVCEESIAVgtvkHEGNIKYVN----DVRNITKKNIEewGPFDL 624
Cdd:COG0270   1 SKKLTVIDLFAGAgglSLG---FEKAGFEVV--FAVEIDPDACET----YRANFPEAKviegDIRDIDPEELI--PDVDL 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061 625 VIGGSPCNDLSNVNPaRKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENVVAMKVGDKRD-----ISRFLEC--- 696
Cdd:COG0270  70 LIGGPPCQPFSVAGK-RKGLEDPRGTLFFEFIRIVEELRPK-------AFVLENVPGLLSSDKGKtfeeiLKELEELgyr 141

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061 697 -NPVMIDAIKVSAA-HRARYFwgnlpgmnrpVIASKNDKLELQ----DCLEYNR-----IAKLKKVQTITTKSNSIKQGk 765
Cdd:COG0270 142 vDYKVLNAADYGVPqNRERVF----------IVGFRKDLDLFEfpepTHLKPYVtvgdaLEDLPDAHEARYLSETITAG- 210

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 28559061 766 nqlfpvvMNGKEDVL------WCT--ELERIFGFPVHYTDVSNMGRGARQklLGRSWSVPVIRHLFAPLKDYF 830
Cdd:COG0270 211 -------YGGGGRFLhpgeprRLTvrEAARLQGFPDDFKFPGSKTQAYRQ--IGNAVPPPLAEAIAKAILKAL 274

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 28559061 415 CLSCGR-----KNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTVCCEGRELLLCSntSCCRCFCVECLEVLVG 489
Cdd:cd11726   5 CTACGEqlnhfSKEVHRHPVLKVLICKSCLKFYNSGEFSKDEDGSDEYCRWCGQGGDLICCD--FCPNVFCKKCIKRNLG 82

                        90       100
                ....*....|....*....|
gi 28559061 490 TGTAAEAKLQEPWSCYMCLP 509
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 28559061 220 GKEFGIGDLVWGKIKGFSWWPAMVVS-WKATSKRQAMSGMR-WVQWFGDGKFSEVSADKlvaLGLFSQHFNLATFNKLV- 296
Cdd:cd20140   1 GRTLRVGDIVWGKIHGFPWWPGRILSiTVSRDDNGELSTQEaHVSWFGSSTTSYMPCSQ---LYPFLEDFKLRYNKKKRg 77

                        90
                ....*....|....
gi 28559061 297 SYRKAMYHALEKAR 310
Cdd:cd20140  78 PYKEAVRQALEAAK 91

C-5 cytosine-specific DNA methylase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061   555 IRVLSLFDGIATGYLVLKELGIKVgkYVASEVCEESIAV-GTVKHEGNIkyvNDVRNITKKNIEEwgpFDLVIGGSPCND 633
Cdd:pfam00145   1 FKFIDLFAGIGGFRLGLEQAGFEC--VAANEIDKSAAKTyEANFPKVPI---GDITLIDIKDIPD---IDILTGGFPCQD 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 28559061   634 LSNVNpARKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENV 679
Cdd:pfam00145  73 FSIAG-KQKGFEDTRGTLFFEIIRIIKEKKPK-------AFLLENV 110

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061   607 DVRNITKKNIEEwgpFDLVIGGSPCNDLSnVNPARKGLYEGTGRLFFEFYHLLNYSRPKegddrpfFWMFENVVAMKVGD 686
Cdd:TIGR00675  48 DITKISPSDIPD---FDILLGGFPCQPFS-IAGKRKGFEDTRGTLFFEIVRILKEKKPK-------FFLLENVKGLVSHD 116

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061   687 K-RDISrflecnpVMIDAI---------KVSAA-------HRAR-------YFWGNLPgMNRPVIASKNDKLELQDCLE- 741
Cdd:TIGR00675 117 KgRTFK-------VIIETLeelgykvyyKVLNAkdfgvpqNRERiyivgfrDFDDKLN-FEFPKPIYVAKKKRIGDLLDl 188

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061   742 --------------------------------------YNRIAKLKKVQTITTK-SNSIKQGKNqlFPVVMNGKEDV--- 779
Cdd:TIGR00675 189 svdleekyylseekknglllllenmrkkegtgeqigsfYNRESKSSIIRTLSARgYTFVKGGKS--VLIVPHKSTVVhpg 266

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 28559061   780 ----LWCTELERIFGFPVHYTDvsNMGRGARQKLLGRSWSVPVIR 820
Cdd:TIGR00675 267 rirrLTPRECARLQGFPDDFKF--PVSDSQLYKQAGNAVVVPVIE 309

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 28559061 219 DGKEFGIGDLVWGKIKGFSWWPAMVVSWKATSKRqamSGMR-----WVQWFGDGKFSEVSadkLVALGLFSQHFNlATFN 293
Cdd:cd20152  16 DGRTICVGDIVWAKIYGFPWWPARILAITVSRKD---NGLLvrqeaRISWFGSPTTSFLA---LSQLAPFLENFQ-SRFN 88

                        90
                ....*....|....*....
gi 28559061 294 KLVS--YRKAMYHALEKAR 310
Cdd:cd20152  89 KKRKglYRKAITEAAKAAK 107

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 28559061 223 FGIGDLVWGKIKGFSWWPAMVVS-----WKATSKRQAMSGMRW-VQWFGD 266
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 28559061 226 GDLVWGKIKGFSWWPAMVVSWKATSKRQAM------SGMRWVQWFGDGKFSEVSADKLVAL 280
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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28559061 226 GDLVWGKIKGFSWWPAMVV---SWKATSKRQAMSGMRWVQWFGDGK---FSEVSADKLValgLFSQhfNLATF---NKLV 296
Cdd:cd20143   3 GDLVWAKVGTHPFWPARVVepaEQAEEVRRRCVPGSLCVYFFGPGGsrdYGWVRRSMIF---PFTD--DLARFqtqKIKN 77

                        90
                ....*....|....*
gi 28559061 297 SYRKAMYH-ALEKAR 310
Cdd:cd20143  78 KKRPQEFQeALEEAK 92

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
                ....*....|....*....|.
gi 28559061 223 FGIGDLVWGKIKGFSWWPAMV 243
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
                ....*....|....*....|...
gi 28559061 223 FGIGDLVWGKIKGFSWWPAMVVS 245
Cdd:cd05839   1 LEPGDLVWAKCRGYPWYPAEIVD 23