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 30695719   25 GDLVLAKVKGFPAWPAVVDEPEKWGHSADSKKVTVHFFGTQQIAFCNHGDVESFTEEKKQSLLTR--RHAKGSDFVRAVK 102
Cdd:cd20147    1 GDLVLAKVKGFPAWPAQVSEPEDWGSAPDPKKVFVHFFGTQQIGFCNPGELSEFTEEIKQSLLARtlKKKKGSDFSRAVK 80

                         90
                 ....*....|..
gi 30695719  103 EITESYEKLKQQ 114
Cdd:cd20147   81 EICELYEERKGQ 92

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 30695719   25 GDLVLAKVKGFPAWPAVVDEPEKWGHSADSKKVTVHFFGTQQIAFCNHGDVESFTEEKKQSLLTR--RHAKGSDFVRAVK 102
Cdd:cd20147    1 GDLVLAKVKGFPAWPAQVSEPEDWGSAPDPKKVFVHFFGTQQIGFCNPGELSEFTEEIKQSLLARtlKKKKGSDFSRAVK 80

                         90
                 ....*....|..
gi 30695719  103 EITESYEKLKQQ 114
Cdd:cd20147   81 EICELYEERKGQ 92

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 30695719     25 GDLVLAKVKGFPAWPAVVDEPEKWGHSADSKK-----VTVHFFGTQQIAFCNHGDVESFTEEKKQSLLTRRHAKGS--DF 97
Cdd:pfam00855    1 GDLVWAKLKGYPWWPARVVDPEELPENVLKPKkkdgeYLVRFFGDSEFAWVKPKDLKPFDEGDEFEYLKKKKKKKKkkAF 80

                           90
                   ....*....|..
gi 30695719     98 VRAVKEITESYE 109
Cdd:pfam00855   81 KKALEEAEEALK 92

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*..
gi 30695719      23 KVGDLVLAKVKGFPAWPAVVDEPEKWGHS-----ADSKKVTVHFFGT 64
Cdd:smart00293    2 KPGDLVWAKMKGFPWWPALVISPKMTPDNimkrkSDENLYPVLFFGD 48

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 30695719   25 GDLVLAKVKGFPAWPAVVDEPEKWGHSADSKKVTVHFFGTQQIAFCNHGDVESFTEEKKQSLLTR--RHAKGSDFVRAVK 102
Cdd:cd20147    1 GDLVLAKVKGFPAWPAQVSEPEDWGSAPDPKKVFVHFFGTQQIGFCNPGELSEFTEEIKQSLLARtlKKKKGSDFSRAVK 80

                         90
                 ....*....|..
gi 30695719  103 EITESYEKLKQQ 114
Cdd:cd20147   81 EICELYEERKGQ 92

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 30695719     25 GDLVLAKVKGFPAWPAVVDEPEKWGHSADSKK-----VTVHFFGTQQIAFCNHGDVESFTEEKKQSLLTRRHAKGS--DF 97
Cdd:pfam00855    1 GDLVWAKLKGYPWWPARVVDPEELPENVLKPKkkdgeYLVRFFGDSEFAWVKPKDLKPFDEGDEFEYLKKKKKKKKkkAF 80

                           90
                   ....*....|..
gi 30695719     98 VRAVKEITESYE 109
Cdd:pfam00855   81 KKALEEAEEALK 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        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30695719   23 KVGDLVLAKVKGFPAWPAVVDEPEKwGHSADSKKVTVHFFGTQQIAFCNHGDVESFTEEK-KQSLLTRRhaKGsdFVRAV 101
Cdd:cd05834    2 KPGDLVFAKVKGYPPWPARIDEIPE-GAKIPKNKYPVFFYGTHETAFLKPKDLFPYEENKeKYGKPRKR--KG--FNEGL 76

                 ...
gi 30695719  102 KEI 104
Cdd:cd05834   77 WEI 79

PWWP domain found in Hepatoma-derived growth factor (HDGF); 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 contains a PWWP domain, which is necessary for DNA binding.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 30695719   22 WKVGDLVLAKVKGFPAWPAVVDEPEKWGHSADSKKVTVHFFGTQQIAFCNHGDVESFTEEKKQ 84
Cdd:cd20148    1 YKCGDLVFAKMKGYPHWPARIDEMPEAAVKSTANKYQVFFFGTHETAFLGPKDLFPYEESKEK 63

CID domain; This domain binds to the phosphorylated C-terminal domain (CTD) of RNA polymerase II. This domain is known as the CTD-interacting domain (CID).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30695719    851 ESFETALDSLVRTKETIGRATRLAMDLAKFgvsAKAM-EILAHTLeSESNLQRRVDLFFLVDSIAQCSKGLNGDaggVYL 929
Cdd:pfam04818    1 EALEKKLSSLNNSQESIQTLSKWILFHRKH---AKAIvEVWEKYL-KKAKPEKKLHLLYLANDVLQNSRKKGKS---EFA 73

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 30695719    930 SSIQAMLPRLLTAAVPAGAttQENRKQCLKVLRLWLERRILPESIV 975
Cdd:pfam04818   74 DAFEPVLPEAFASAYKKCD--EKLKKKLERLLNIWEERNVFSPEVI 117

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 30695719   21 EWKVGDLVLAKVKGFPAWPAVVDEPEKWGHSADSKKVTVHFFGTQQIAFCNHGDVESFTEEKKQ 84
Cdd:cd20150    5 EYKAGDLVFAKMKGYPHWPARIDELPEGAVKPPANKYPIFFFGTHETAFLGPKDLFPYKEYKDK 68

PWWP domain found in Saccharomyces cerevisiae ISWI one complex protein 4 (ScIOC4) and similar proteins; ScIOC4 functions as a component of the ISW1B complex, which acts in remodeling the chromatin by catalyzing an ATP-dependent alteration in the structure of nucleosomal DNA. The ISW1B complex acts within coding regions to control the amount of RNA polymerase II released into productive elongation and to coordinate elongation with termination and pre-mRNA processing. The family also includes Schizosaccharomyces pombe PWWP domain-containing proteins 1 and 2 (SpPDP1 and SpPDP2). SpPDP1 associates with Set9 to regulate its chromatin localization and methyltransferase activity towards H4K20. Members of this family contain a PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30695719   25 GDLVLAKVKGFPAWPAVVDEPE-------KWGHSADSKKVT---VHFFGTQQIAFCNHGDVESFTEEKKQSLLTRRHAKG 94
Cdd:cd05840    1 GDLVLAKVKGYPPWPAMVLPEEllpknvlKAKKRKPKSKKTvypVQFFPDNEYYWVSPSSLKPLTKEEIDKFLSKSKRKN 80

                 ....*....
gi 30695719   95 SDFVRAVKE 103
Cdd:cd05840   81 KDLIEAYEV 89

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 30695719   22 WKVGDLVLAKVKGFPAWPAVVDEPEKWGHSADSKKVTVHFFGTQQIAFCNHGDVESFTEEKKQ 84
Cdd:cd20149    1 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKYKDK 63

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 30695719   24 VGDLVLAKVKGFPAWPAVV-------DEPEKWGHSAdsKKVTVHFFGTQQIAFCNHGDVESFTEEKKQSLLTRRHAKGSD 96
Cdd:cd05838    2 YGDIVWVKLGNYRWWPAEIlhprevpDNIQSLPHPP--GEFPVRFFGSHDYYWVHRGRVFLFEEGDKGSKEKSKKSLDKS 79

                         90
                 ....*....|....*..
gi 30695719   97 FVRAVKEITESYEKLKQ 113
Cdd:cd05838   80 FKRALKEANEAFRELKA 96

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30695719   27 LVLAKVKGFPAWPAVVDEPEkwghsadSKKVTVHFFGTQQIAFCNHGDVESFTEEKKQSLLTRRHAK-GSDFVRAVKEIT 105
Cdd:cd05841    9 LVWVKLDGFPFWPAKVMGTK-------DGQVDVRFFGDYDRAWLPSKNVTLHTREIVSTLPDSSESKdKRTLKKAIKELE 81

                 ....*...
gi 30695719  106 ESYEKLKQ 113
Cdd:cd05841   82 RHIALLRQ 89

PWWP domain found in DNA mismatch repair protein MSH6 and similar proteins; MSH6, also called G/T mismatch-binding protein (GTBP or GTMBP), MutS protein homolog 6, or MutS-alpha 160 kDa subunit (p160), is a mismatch repair protein homologous to bacterial MutS. It is a component of the post-replicative DNA mismatch repair system (MMR). It heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, it forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. Mutations in MSH6 have been linked to increased cancer susceptibility, particularly in hereditary nonpolyposis colorectal cancer in humans. MSH6 contains a PWWP domain, but its role in MSH6 remains unclear. MSH6 orthologs found in Saccharomyces cerevisiae, Caenorhabditis elegans, and Arabidopsis thaliana lack the PWWP domain. PWWP domains typically recognize DNA and histone methylated lysines.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 30695719   23 KVGDLVLAKVKGFPAWPAVV-DEP--EKWGHSADSKKVTVHFFG 63
Cdd:cd05837    2 SPGDLVWAKLEGYPWWPSLVcNHPttGFHKKFGKKGEVHVQFFD 45

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30695719   26 DLVLAKVKGFPAWPAVVDEPEkwghsadSKKVTVHFFG-TQQIAFCNHGDVESFTEEKKQSLLTRrhakGSDFVRAVKEI 104
Cdd:cd20159    8 ELVWAKQKGFPYWPAKVIQKE-------DNQYDVRFFGgHHQRAWIPKENIKPITTSPKQLKVKR----TAGWNKACEEL 76

                 ....*...
gi 30695719  105 TESYEKLK 112
Cdd:cd20159   77 KKHQELLE 84

CTD kinase subunit gamma CTK3; The C-terminal domain kinase (CTDK-1), is a three-subunit complex comprised of Ctk1, Ctk2, and Ctk3, that plays a key role in regulation of transcription and translation and in coordinating these two processes. Both Ctk2 and Ctk3 are regulated at the level of protein turnover, and are unstable proteins processed through a ubiquitin-proteasome pathway. Their physical interaction is required to protect both subunits from degradation, and both Ctk2 and Ctk3 are required for Ctk1 CTD kinase activation. The mammalian P-TEFb is mirrored by the combined complexes in yeast of the CTDK1 and the Bur1/2.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30695719    853 FETALDSLVRTKETIGRATRLAM---DLAKFGVSAkameILaHTLESeSNLQRRVDLFFLVDSI-AQCSKglNGDAGGVY 928
Cdd:pfam12243    9 FSQLLRKLNASVQSLQKAAHFALknrDLEEDLHSC----IL-EQLER-GDLNTRANIFYFIDTLcEESLK--NGQSGKPY 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 30695719    929 LSSIQAMLPRLLTAAVPAGATTQENRKQCLKVLRLWLERRIL 970
Cdd:pfam12243   81 VRSLKRDIPRLVDSVAPDDGSGAANVKSVRKILQSLKLKSLL 122

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
                 ....*....|....*....|....*....|....*....|....*...
gi 30695719   25 GDLVLAKVKGFPAWPAVVDE-PEK----WGHSaDSKKVT---VHFFGT 64
Cdd:cd20145    9 GSLVWAKMPGYPWWPAMVEDdPDTeeffWLDE-ESDIPTkyhVTFFDK 55