PWWP domain found in Hepatoma-derived growth factor-related protein 2 (HDGFL2); 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. It contains a PWWP domain, which is necessary for DNA binding.

                       10        20        30        40        50        60        70        80
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3QBY_A       6 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKCKDKYGKPNKRKGFNEGLWEI 85
Cdd:cd20149  1 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKYKDKYGKPNKRKGFNEGLWEI 80

               ....
3QBY_A      86 QNNP 89
Cdd:cd20149 81 QNNP 84

PWWP domain found in Hepatoma-derived growth factor-related protein 2 (HDGFL2); 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. It contains a PWWP domain, which is necessary for DNA binding.

                       10        20        30        40        50        60        70        80
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3QBY_A       6 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKCKDKYGKPNKRKGFNEGLWEI 85
Cdd:cd20149  1 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKYKDKYGKPNKRKGFNEGLWEI 80

               ....
3QBY_A      86 QNNP 89
Cdd:cd20149 81 QNNP 84

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
3QBY_A          6 FKPGDLVFAKMKGYPHWPARIDD---IADGAVKPP--PNKYPIFFFGTHETAFLGPKDLFPYD 63
Cdd:smart00293  1 FKPGDLVWAKMKGFPWWPALVISpkmTPDNIMKRKsdENLYPVLFFGDKDTAWIPSSKLFPLT 63

PWWP domain found in Hepatoma-derived growth factor-related protein 2 (HDGFL2); 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. It contains a PWWP domain, which is necessary for DNA binding.

                       10        20        30        40        50        60        70        80
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3QBY_A       6 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKCKDKYGKPNKRKGFNEGLWEI 85
Cdd:cd20149  1 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKYKDKYGKPNKRKGFNEGLWEI 80

               ....
3QBY_A      86 QNNP 89
Cdd:cd20149 81 QNNP 84

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
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3QBY_A       6 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKCKDKYGKPNKRKGFNEGLWEI 85
Cdd:cd20151  1 FKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 80

               ....*...
3QBY_A      86 QNNPHASY 93
Cdd:cd20151 81 DNNPKVKF 88

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
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3QBY_A       1 GMPHAFKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKCKDKYGKPNKRKGFNE 80
Cdd:cd20150  1 PRPREYKAGDLVFAKMKGYPHWPARIDELPEGAVKPPANKYPIFFFGTHETAFLGPKDLFPYKEYKDKFGKSNKRKGFNE 80

                       90
               ....*....|...
3QBY_A      81 GLWEIQNNPHASY 93
Cdd:cd20150 81 GLWEIENNPGVKF 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3QBY_A         9 GDLVFAKMKGYPHWPARIDDIADGAV-----KPPPNKYPIFFFGTHETAFLGPKDLFPYD-----KCKDKYGKPNKRKGF 78
Cdd:pfam00855  1 GDLVWAKLKGYPWWPARVVDPEELPEnvlkpKKKDGEYLVRFFGDSEFAWVKPKDLKPFDegdefEYLKKKKKKKKKKAF 80

                         90
                 ....*....|.
3QBY_A        79 NEGLWEIQNNP 89
Cdd:pfam00855 81 KKALEEAEEAL 91

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
3QBY_A          6 FKPGDLVFAKMKGYPHWPARIDD---IADGAVKPP--PNKYPIFFFGTHETAFLGPKDLFPYD 63
Cdd:smart00293  1 FKPGDLVWAKMKGFPWWPALVISpkmTPDNIMKRKsdENLYPVLFFGDKDTAWIPSSKLFPLT 63

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        70        80
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3QBY_A       9 GDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYD-----KCKDKYGKPNKRKGFNEGLW 83
Cdd:cd20147  1 GDLVLAKVKGFPAWPAQVSEPEDWGSAPDPKKVFVHFFGTQQIGFCNPGELSEFTeeikqSLLARTLKKKKGSDFSRAVK 80

               ..
3QBY_A      84 EI 85
Cdd:cd20147 81 EI 82

second 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 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 they 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, by 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 second PWWP domain. The 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        60        70        80
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3QBY_A       9 GDLVFAKMKGYPHWPARI---DDIAD--GAVKPPPNKYPIFFFGTHETAFLGPKDLFPY---DKCKDKYGKPNKRKGFNE 80
Cdd:cd05838  3 GDIVWVKLGNYRWWPAEIlhpREVPDniQSLPHPPGEFPVRFFGSHDYYWVHRGRVFLFeegDKGSKEKSKKSLDKSFKR 82

               ....
3QBY_A      81 GLWE 84
Cdd:cd05838 83 ALKE 86

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        80
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3QBY_A       8 PGDLVFAKMKGYPHWPARIddiadgaVKPPPNKYPIFFFG-THETAFLGPKDLFPYDkcKDKYGKPNKR-KGFNEGLWEI 85
Cdd:cd20159  6 PHELVWAKQKGFPYWPAKV-------IQKEDNQYDVRFFGgHHQRAWIPKENIKPIT--TSPKQLKVKRtAGWNKACEEL 76

               .
3QBY_A      86 Q 86
Cdd:cd20159 77 K 77

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
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3QBY_A       7 KPGDLVFAKMKGYPHWPARIDDIAD-GAVKPPPNKYPIFFFGTH------ETAFLGPKDLFPYdKCKDKYGKPNKRKGFN 79
Cdd:cd05835  1 KIGDLVWAKLKGSPWWPGIVVSHKDcGQKPPAEGSVWVFWFGDHkvsevpLDKILPFAEFFNK-FYISKNSSKLYKKAVY 79

               ...
3QBY_A      80 EGL 82
Cdd:cd05835 80 EAL 82

PWWP domain found in protein BS69, protein kinase C-binding protein 1 (PRKCBP1) 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. BS69 is a multi-domain protein, containing bromo, plant homeodomain (PHD), proline-tryptophan-tryptophan-proline (PWWP), and MYeloid translocation protein 8, Nervy and DEAF-1 (MYND) domains. The specific role of the PWWP domain within BS69 is not clearly identified, but BS69 functions in chromatin remodeling, consistent with other PWWP-containing proteins. PRKCBP1, also called cutaneous T-cell lymphoma-associated antigen se14-3 (CTCL-associated antigen se14-3), Rack7, or zinc finger MYND domain-containing protein 8 (ZMYND8), is a novel receptor for activated C-kinase (RACK)-like protein that may play an important role in the activation and regulation of PKC-beta I, and the PKC signaling cascade. It also has been identified as a formin homology-2-domain containing protein 1 (FHOD1)-binding protein that may be involved in FHOD1-regulated actin polymerization and transcription. Moreover, PRKCBP1 may function as a REST co-repressor 2 (RCOR2) interacting factor. They form a RCOR2/ZMYND8 complex which might be involved in the regulation of neural differentiation. PRKCBP1 contains a PHD finger, a bromodomain, and a PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                       10        20        30        40
               ....*....|....*....|....*....|....*....|....
3QBY_A      11 LVFAKMKGYPHWPARIDDIADGAVKpppnkypIFFFGTHETAFL 54
Cdd:cd05841  9 LVWVKLDGFPFWPAKVMGTKDGQVD-------VRFFGDYDRAWL 45

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3QBY_A        6 FKPGDLVFAKMKGYPHWPARIDDIAD-------GAVKPPPNKYPIFFFGTHET-AFLGPKDLFPYDKCKDKYGKPNKR-K 76
Cdd:cd20145   6 YTPGSLVWAKMPGYPWWPAMVEDDPDteeffwlDEESDIPTKYHVTFFDKPVSrAWVRASSIKPFTDNSNEPNLTKKKgK 85

                ....*...
3QBY_A       77 GFNEGLWE 84
Cdd:cd20145  86 KYKKRLNE 93

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
                ....*....|....*....|....*....|....*....|....*....|....*....
3QBY_A        9 GDLVFAKMKGYPHWPARIDDIA-----DGAvkPPPNKYPIFFFGTHETAFLGPKDLFPY 62
Cdd:cd20153  17 GDIVWGKIHGFPWWPARVLSISlsqkeDGE--PSWQEAKVSWFGSPTTSLLSVSKLSPF 73

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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3QBY_A        8 PGDLVFAKMKGYPHWPARI--DDIADGAVKPPPNKYPIF------FFG-THETAFLGPKDLFPY-------DKCKDKYGK 71
Cdd:cd20144   1 VGDLVWAKVSGHPWWPCMVtyDPESGLYTKIKGSGGRTYrqyhvqFFGdNGERGWVSEKSLMPFegkekfeELVKELKKK 80

                ....*
3QBY_A       72 PNKRK 76
Cdd:cd20144  81 AKKKS 85

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
                ....*....|....*....
3QBY_A        6 FKPGDLVFAKMKGYPHWPA 24
Cdd:cd05837   1 FSPGDLVWAKLEGYPWWPS 19

first PWWP domain found in nuclear receptor-binding SET domain-containing protein 1 (NSD1) and similar proteins; NSD1, also called H3 Lysine-36 and H4 Lysine-20 specific histone-lysine N-methyltransferase, androgen receptor coactivator 267 kDa protein, androgen receptor-associated protein of 267 kDa, H3-K36-HMTase H4-K20-HMTase, Lysine N-methyltransferase 3B (KMT3B), or NR-binding SET domain-containing protein, is a lysine methyltransferase that preferentially methylates H3 on Lysine36 (H3-K36) and H4 on Lysine20 (H4-K20), which is primarily associated with active transcription. It plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. It can alter transcription by interacting with the protein NSD1-interacting zinc finger protein 1 (NIZP1). It also mitigates caspase-1 activation by listeriolysin o (LLO) in macrophages, and requires functional LLO for the regulation of IL-1beta secretion. Moreover, NSD1 regulates RNA polymerase II (RNAP II) recruitment to bone morphogenetic protein 4 (BMP4). NSD1 contains 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). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD domains are involved in protein-protein interactions. The model corresponds to the first PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3QBY_A        3 PHAFKPGDLVFAKMKGYPHWPARI--DDIADGAVK------PPPNKYPIFFFGT-HETAFLGPKDLFPYD 63
Cdd:cd20161   1 PVKYEVGDLVWAKFSRRPWWPCRIcaDPLLDTHSKmkvpsrRPCRQYYVETLGElTEKAWVAAKAVVPFE 70