PWWP domain found in PC4 and SFRS1-interacting protein (PSIP); 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. It contains a PWWP domain, which is necessary for DNA binding.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958776270   5 FKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 84
Cdd:cd20151     1 FKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 80

                  ....*...
gi 1958776270  85 DNNPKVKF 92
Cdd:cd20151    81 DNNPKVKF 88

PWWP domain found in PC4 and SFRS1-interacting protein (PSIP); 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. It contains a PWWP domain, which is necessary for DNA binding.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958776270   5 FKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 84
Cdd:cd20151     1 FKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 80

                  ....*...
gi 1958776270  85 DNNPKVKF 92
Cdd:cd20151    81 DNNPKVKF 88

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958776270    5 FKPGDLIFAKMKGYPHWPARVD---EVPDGAVKPPT--NKLPIFFFGTHETAFLGPKDIFPYS 62
Cdd:smart00293   1 FKPGDLVWAKMKGFPWWPALVIspkMTPDNIMKRKSdeNLYPVLFFGDKDTAWIPSSKLFPLT 63

PWWP domain found in PC4 and SFRS1-interacting protein (PSIP); 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. It contains a PWWP domain, which is necessary for DNA binding.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958776270   5 FKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 84
Cdd:cd20151     1 FKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 80

                  ....*...
gi 1958776270  85 DNNPKVKF 92
Cdd:cd20151    81 DNNPKVKF 88

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958776270   5 FKPGDLIFAKMKGYPHWPARVDEVPDGAvKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 84
Cdd:cd05834     1 FKPGDLVFAKVKGYPPWPARIDEIPEGA-KIPKNKYPVFFYGTHETAFLKPKDLFPYEENKEKYGKPRKRKGFNEGLWEI 79

                  ...
gi 1958776270  85 DNN 87
Cdd:cd05834    80 ENN 82

PWWP domain found in Hepatoma-derived growth factor-related protein 3 (HDGFL3); HDGFL3, also called HDGF-related protein 3 (HRP-3), is the only hepatoma-derived growth factor (HDGF)-related protein (HRP) family member whose expression is almost restricted to the nervous tissue. It enhances DNA synthesis and may play a role in cell proliferation. It contains a PWWP domain, which is necessary for DNA binding.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958776270   2 TRDFKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGL 81
Cdd:cd20150     3 PREYKAGDLVFAKMKGYPHWPARIDELPEGAVKPPANKYPIFFFGTHETAFLGPKDLFPYKEYKDKFGKSNKRKGFNEGL 82

                          90
                  ....*....|.
gi 1958776270  82 WEIDNNPKVKF 92
Cdd:cd20150    83 WEIENNPGVKF 93

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 1958776270   8 GDLIFAKMKGYPHWPARV---DEVPDGAVKPP--TNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKR-----KGF 77
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVvdpEELPENVLKPKkkDGEYLVRFFGDSEFAWVKPKDLKPFDEGDEFEYLKKKKkkkkkKAF 80

                          90
                  ....*....|..
gi 1958776270  78 NEGLWEIDNNPK 89
Cdd:pfam00855  81 KKALEEAEEALK 92

PWWP (Pro-Trp-Trp-Pro) domain; The PWWP domain, named for a conserved Pro-Trp-Trp-Pro motif, is a small domain consisting of 100-150 amino acids and is composed of a five-stranded antiparallel beta-barrel followed by a helical region. It is found in numerous proteins that are involved in cell division, growth, and differentiation. Most PWWP-domain proteins seem to be nuclear, often DNA-binding, proteins that function as transcription factors regulating a variety of developmental processes. PWWP domains specifically recognize DNA and histone methylated lysines at the level of the nucleosome. Based on the fact that other regions of PWWP-domain proteins are responsible for nuclear localization and DNA-binding, is likely that the PWWP domain acts as a site for protein-protein binding interactions, influencing chromatin remodeling and thereby regulating transcriptional processes. Some PWWP-domain proteins have been linked to cancer or other diseases; some are known to function as growth factors.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958776270   8 GDLIFAKMKGYPHWPARVDEVPDGAV----KPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKG 76
Cdd:cd05162     1 GDLVWAKLKGYPWWPARVVDPEELPEevgkKKKKGGVLVQFFGDNDYAWVKSKNIKPFEEGFKKEFKKKKKKS 73

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958776270   7 PGDLIFAKMKGYPHWPARV-DEVPDGAVKPPTNK------LPIFFFGTHETAFLGPKDIFPYSEN-KEKYGKPNKRKGFN 78
Cdd:cd20142     2 PGDVVWAKVKGYPMWPALViDEEHAERCGLEANRpgkkgtVPVQFFGTYEVARLNPKKVVGFSKGlDLKYHSKCKAPVFR 81

                  ....*..
gi 1958776270  79 EGLWEID 85
Cdd:cd20142    82 QALEEAE 88

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        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958776270   7 PGDLIFAKMKGYPHWPARVdevpdgaVKPPTNKLPIFFFG-THETAFLGPKDIFPYSENKEKYGKPNKrKGFNEGLWE 83
Cdd:cd20159     6 PHELVWAKQKGFPYWPAKV-------IQKEDNQYDVRFFGgHHQRAWIPKENIKPITTSPKQLKVKRT-AGWNKACEE 75

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 1958776270   8 GDLIFAKMKGYPHWPARV---DEVPDGAVKPPT-NKLPIFFFG---THETAFLGPKDIFPYSENKEKY-GKPNKRK---- 75
Cdd:cd20143     3 GDLVWAKVGTHPFWPARVvepAEQAEEVRRRCVpGSLCVYFFGpggSRDYGWVRRSMIFPFTDDLARFqTQKIKNKkrpq 82

                  ....*...
gi 1958776270  76 GFNEGLWE 83
Cdd:cd20143    83 EFQEALEE 90

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958776270   8 GDLIFAKMKGYPHWPA----------RVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENK-EKYGKPNKRK 75
Cdd:cd05840     1 GDLVLAKVKGYPPWPAmvlpeellpkNVLKAKKRKPKSKKTVYPVQFFPDNEYYWVSPSSLKPLTKEEiDKFLSKSKRK 79

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        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958776270   5 FKPGDLIFAKMKGYPHWPARVDEVPDGA----VKPPTNKlPIF----FFGTHET-AFLGPKDIFPYSENKEKYGKPNKR- 74
Cdd:cd20145     6 YTPGSLVWAKMPGYPWWPAMVEDDPDTEeffwLDEESDI-PTKyhvtFFDKPVSrAWVRASSIKPFTDNSNEPNLTKKKg 84

                  ....*....
gi 1958776270  75 KGFNEGLWE 83
Cdd:cd20145    85 KKYKKRLNE 93

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958776270   8 GDLIFAKMKGYPHWPARV-----DEVPDGAVKPPTNKlpIFFFGTHETAFLGPKDIFPYSEN-KEKYGKpnKRKGF 77
Cdd:cd20140     7 GDIVWGKIHGFPWWPGRIlsitvSRDDNGELSTQEAH--VSWFGSSTTSYMPCSQLYPFLEDfKLRYNK--KKRGP 78

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958776270  109 EAEEKETSVSKEDTDQEEKASNEDVTKAADITTPKAARRGRKRKAEKQVDTEEAGvvTAATASNVKASPKRgrpAATEVK 188
Cdd:PTZ00121  1323 KAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKKEEAK--KKADAAKKKAEEKK---KADEAK 1397

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958776270  189 IPKPRGRPKVVKQPCPSESDMVIDEDKSK----------KKGPEEKPPKKQLKKEEEGQKEEEKPRKEPDKK----EGKK 254
Cdd:PTZ00121  1398 KKAEEDKKKADELKKAAAAKKKADEAKKKaeekkkadeaKKKAEEAKKADEAKKKAEEAKKAEEAKKKAEEAkkadEAKK 1477

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958776270  255 EVESKRK--NLAKPGVTSTSDSEEDDDQEGEKQKRKGGRNFQAAHRRNMLKGQHEKEAADRKRKQEEQMETEHINPVTEK 332
Cdd:PTZ00121  1478 KAEEAKKadEAKKKAEEAKKKADEAKKAAEAKKKADEAKKAEEAKKADEAKKAEEAKKADEAKKAEEKKKADELKKAEEL 1557

                   .
gi 1958776270  333 R 333
Cdd:PTZ00121  1558 K 1558

second 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 second PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958776270   9 DLIFAKMKGYPHWPARV---DEVPDG--AVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKY--GKPNKRKGFNEGL 81
Cdd:cd20166     4 QIVWVKLGNYRWWPAEIcnpRSVPLNiqGLKHDIGDFPVFFFGSHDYYWVHQGRVFPYVEGDKSFaeGQTSINKTFKKAL 83

                  ..
gi 1958776270  82 WE 83
Cdd:cd20166    84 EE 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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958776270   5 FKPGDLIFAKMKGYPHWPARVDEVPDGaVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRK 75
Cdd:cd20141     1 FNVGDLVWGQIRGFPSWPGKLVSENDV-GKTNEGKVWVSWFGDHSFGQVEPDKLKTLSEGLEAHHRARKRT 70

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        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958776270   5 FKPGDLIFAKMKGYPHWPARV-------------DEVPDGAVKPPTNKLPIF--FFGTHET 50
Cdd:cd05839     1 LEPGDLVWAKCRGYPWYPAEIvdpkdpkegngvpIPVPPDRVLKKSNEKLYLvlFFDAKRT 61

DNA topoisomerase 2-like protein; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958776270   85 DNNPKVKFSSQQVSTKQSNASSDVEAEEKETSVSKEDTDQEEKASNEDVTKAADITTPKAARRGRKRK-AEKQVDTEEAG 163
Cdd:PTZ00108  1182 KKSSADKSKKASVVGNSKRVDSDEKRKLDDKPDNKKSNSSGSDQEDDEEQKTKPKKSSVKRLKSKKNNsSKSSEDNDEFS 1261

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958776270  164 VVTAATASNVKASPKRGRPAATEVkiPKPRGRPKVVKQPCPSESDMVIDEDKSKKKGPEEKPPKKQLKKEEEGQKEEEKP 243
Cdd:PTZ00108  1262 SDDLSKEGKPKNAPKRVSAVQYSP--PPPSKRPDGESNGGSKPSSPTKKKVKKRLEGSLAALKKKKKSEKKTARKKKSKT 1339

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1958776270  244 RKEPDKKEGKKEVESKRKNLakpgvTSTSDSEEDDDQEGEK 284
Cdd:PTZ00108  1340 RVKQASASQSSRLLRRPRKK-----KSDSSSEDDDDSEVDD 1375

second 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, an 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 second PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958776270   9 DLIFAKMKGYPHWPARV---DEVPDG--AVKPPTNKLPIFFFGTHETAFLGPKDIFPYSE 63
Cdd:cd20165     4 DIIWVKLGNYRWWPAEVchpKNVPPNiqKMKHEIGEFPVFFFGSKDYYWTHQARVFPYME 63