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 76880467   9 YKTGDLVFAKLKGYAHWPARIEHVTE-----PNRYQVFFFGTHETALLGPKHLFPYEESKERFGKPNKRRGFSEGLWEIE 83
Cdd:cd05834   1 FKPGDLVFAKVKGYPPWPARIDEIPEgakipKNKYPVFFYGTHETAFLKPKDLFPYEENKEKYGKPRKRKGFNEGLWEIE 80

                ..
gi 76880467  84 HD 85
Cdd:cd05834  81 NN 82

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 76880467   9 YKTGDLVFAKLKGYAHWPARIEHVTE-----PNRYQVFFFGTHETALLGPKHLFPYEESKERFGKPNKRRGFSEGLWEIE 83
Cdd:cd05834   1 FKPGDLVFAKVKGYPPWPARIDEIPEgakipKNKYPVFFYGTHETAFLKPKDLFPYEENKEKYGKPRKRKGFNEGLWEIE 80

                ..
gi 76880467  84 HD 85
Cdd:cd05834  81 NN 82

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 76880467      9 YKTGDLVFAKLKGYAHWPARIEHVTEP-----------NRYQVFFFGTHETALLGPKHLFPYE 60
Cdd:smart00293   1 FKPGDLVWAKMKGFPWWPALVISPKMTpdnimkrksdeNLYPVLFFGDKDTAWIPSSKLFPLT 63

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 76880467   9 YKTGDLVFAKLKGYAHWPARIEHVTE-----PNRYQVFFFGTHETALLGPKHLFPYEESKERFGKPNKRRGFSEGLWEIE 83
Cdd:cd05834   1 FKPGDLVFAKVKGYPPWPARIDEIPEgakipKNKYPVFFYGTHETAFLKPKDLFPYEENKEKYGKPRKRKGFNEGLWEIE 80

                ..
gi 76880467  84 HD 85
Cdd:cd05834  81 NN 82

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76880467   9 YKTGDLVFAKLKGYAHWPARIEHVTE------PNRYQVFFFGTHETALLGPKHLFPYEESKERFGKPNKRRGFSEGLWEI 82
Cdd:cd20149   1 FKPGDLVFAKMKGYPHWPARIDDIADgavkppPNKYPIFFFGTHETAFLGPKDLFPYDKYKDKYGKPNKRKGFNEGLWEI 80

                ....
gi 76880467  83 EHDP 86
Cdd:cd20149  81 QNNP 84

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 76880467   8 KYKTGDLVFAKLKGYAHWPARIEHVTE------PNRYQVFFFGTHETALLGPKHLFPYEESKERFGKPNKRRGFSEGLWE 81
Cdd:cd20150   5 EYKAGDLVFAKMKGYPHWPARIDELPEgavkppANKYPIFFFGTHETAFLGPKDLFPYKEYKDKFGKSNKRKGFNEGLWE 84

                ....*
gi 76880467  82 IEHDP 86
Cdd:cd20150  85 IENNP 89

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 76880467  12 GDLVFAKLKGYAHWPARIEHVTE----------PNRYQVFFFGTHETALLGPKHLFPYEESKERFGKPNKRRG--FSEGL 79
Cdd:cd05162   1 GDLVWAKLKGYPWWPARVVDPEElpeevgkkkkKGGVLVQFFGDNDYAWVKSKNIKPFEEGFKKEFKKKKKKSkkFKKAV 80

                ....
gi 76880467  80 WEIE 83
Cdd:cd05162  81 EEAE 84

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 76880467      9 YKTGDLVFAKLKGYAHWPARIEHVTEP-----------NRYQVFFFGTHETALLGPKHLFPYE 60
Cdd:smart00293   1 FKPGDLVWAKMKGFPWWPALVISPKMTpdnimkrksdeNLYPVLFFGDKDTAWIPSSKLFPLT 63

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
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 76880467  13 DLVFAKLKGYAHWPARIEHVtEPNRYQVFFFG-THETALLGPKHLFPYEESKERfgKPNKR 72
Cdd:cd20159   8 ELVWAKQKGFPYWPAKVIQK-EDNQYDVRFFGgHHQRAWIPKENIKPITTSPKQ--LKVKR 65

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76880467  12 GDLVFAKLKGYAHWPARIEHVTE-PNRYQ----------VFFFGTHETALLGPKHLFPYEESKERFGKPNKRRG---FSE 77
Cdd:cd05838   3 GDIVWVKLGNYRWWPAEILHPREvPDNIQslphppgefpVRFFGSHDYYWVHRGRVFLFEEGDKGSKEKSKKSLdksFKR 82

                ....
gi 76880467  78 GLWE 81
Cdd:cd05838  83 ALKE 86

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76880467  12 GDLVFAKLKGYAHWPARI------EHVTEPNRYQVFFFGTHETALLGPKHLFPYEE-----SKERFGKPNKRRGFSEGLW 80
Cdd:cd20147   1 GDLVLAKVKGFPAWPAQVsepedwGSAPDPKKVFVHFFGTQQIGFCNPGELSEFTEeikqsLLARTLKKKKGSDFSRAVK 80

                ...
gi 76880467  81 EIE 83
Cdd:cd20147  81 EIC 83

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 76880467  10 KTGDLVFAKLKGYAHWPARI-EHVT------EPNRYQVFFFGTHETALLGPKHLFPYEESKERFGKPNKRRG 74
Cdd:cd05835   1 KIGDLVWAKLKGSPWWPGIVvSHKDcgqkppAEGSVWVFWFGDHKVSEVPLDKILPFAEFFNKFYISKNSSK 72

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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 76880467  14 LVFAKLKGYAHWPARIEHvTEPNRYQVFFFGTHETALLGPKHLFPYeeSKErfgKPNKRRGFSE 77
Cdd:cd05841   9 LVWVKLDGFPFWPAKVMG-TKDGQVDVRFFGDYDRAWLPSKNVTLH--TRE---IVSTLPDSSE 66

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 76880467  12 GDLVFAKLKGYAHWPARIEHVT-------EP--NRYQVFFFGTHETALLGPKHLFPYEES-KERFGKPNK---RRGFSEG 78
Cdd:cd20153  17 GDIVWGKIHGFPWWPARVLSISlsqkedgEPswQEAKVSWFGSPTTSLLSVSKLSPFSEFfKLRFNRKKKgmyRKAITEA 96

                ....*.
gi 76880467  79 LWEIEH 84
Cdd:cd20153  97 AKAAEH 102

PWWP domain found in methyl-CpG-binding domain protein 5 (MBD5) and similar proteins; MBD5, is a methyl-CpG-binding protein that binds to heterochromatin. It does not interact with either methylated or unmethylated DNA. MBD5 acts as a transcriptional regulator responsible for 2q23.1 deletion syndrome. It belongs to the MBD family proteins, which play central roles in transcriptional regulation and development. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 76880467   9 YKTGDLVFAKLKGYAHWPARIEHVTEPNRYQ-----VFFFGTHETALLGPKHLFPYEESKERFGKPNKR 72
Cdd:cd20141   1 FNVGDLVWGQIRGFPSWPGKLVSENDVGKTNegkvwVSWFGDHSFGQVEPDKLKTLSEGLEAHHRARKR 69