Lens epithelium-derived growth factor (LEDGF); LEDGF is a chromatin-associated protein that protects cells from stress-induced apoptosis. It is the binding partner of HIV-1 integrase in human cells. The integrase binding domain (IBD) of LEDGF is a compact right-handed bundle composed of five alpha-helices. The residues essential for the interaction with the integrase are present in the inter-helical loop regions of the bundle structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19424218   468 EERLQKLHSEIKFALKVDNPDVRRCLSALEELGTLQVTSQILQKNTDVVATLKKIRRYKAN------------------K 529
Cdd:pfam11467   1 ERKLQELDLDIKSCLKLDNADVDKCLEALDELKSLQVTPLMLKKNPECVETIKKLRRYVGNleewkmdeeeeaefkekaQ 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 19424218   530 DVMAKAAEVYTRLKSRVLGPKVEALQKVNKAGAEKE 565
Cdd:pfam11467  81 LIRDKATEIYNKFKSLFLVPEGEVNFWPDFNEEVKE 116

Lens epithelium-derived growth factor (LEDGF); LEDGF is a chromatin-associated protein that protects cells from stress-induced apoptosis. It is the binding partner of HIV-1 integrase in human cells. The integrase binding domain (IBD) of LEDGF is a compact right-handed bundle composed of five alpha-helices. The residues essential for the interaction with the integrase are present in the inter-helical loop regions of the bundle structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19424218   468 EERLQKLHSEIKFALKVDNPDVRRCLSALEELGTLQVTSQILQKNTDVVATLKKIRRYKAN------------------K 529
Cdd:pfam11467   1 ERKLQELDLDIKSCLKLDNADVDKCLEALDELKSLQVTPLMLKKNPECVETIKKLRRYVGNleewkmdeeeeaefkekaQ 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 19424218   530 DVMAKAAEVYTRLKSRVLGPKVEALQKVNKAGAEKE 565
Cdd:pfam11467  81 LIRDKATEIYNKFKSLFLVPEGEVNFWPDFNEEVKE 116

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 19424218     8 GDLVFAKMKGYPHWPARI---DDIADGAVKPP--PNKYPIFFFGTHETAFLGPKDLFPYD-----KCKDKYGKPNKRKGF 77
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVvdpEELPENVLKPKkkDGEYLVRFFGDSEFAWVKPKDLKPFDegdefEYLKKKKKKKKKKAF 80

                          90
                  ....*....|.
gi 19424218    78 NEGLWEIQNNP 88
Cdd:pfam00855  81 KKALEEAEEAL 91

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 19424218   5 FKPGDLVFAKMKGYPHWPARIDDIADGAvKPPPNKYPIFFFGTHETAFLGPKDLFPYDKCKDKYGKPNKRKGFNEGLWEI 84
Cdd:cd05834   1 FKPGDLVFAKVKGYPPWPARIDEIPEGA-KIPKNKYPVFFYGTHETAFLKPKDLFPYEENKEKYGKPRKRKGFNEGLWEI 79

                ...
gi 19424218  85 QNN 87
Cdd:cd05834  80 ENN 82

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19424218   5 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKCKDKYGKPNKRKGFNEGLWEI 84
Cdd:cd20148   1 YKCGDLVFAKMKGYPHWPARIDEMPEAAVKSTANKYQVFFFGTHETAFLGPKDLFPYEESKEKFGKPNKRKGFSEGLWEI 80

                ....
gi 19424218  85 QNNP 88
Cdd:cd20148  81 ENNP 84

Lens epithelium-derived growth factor (LEDGF); LEDGF is a chromatin-associated protein that protects cells from stress-induced apoptosis. It is the binding partner of HIV-1 integrase in human cells. The integrase binding domain (IBD) of LEDGF is a compact right-handed bundle composed of five alpha-helices. The residues essential for the interaction with the integrase are present in the inter-helical loop regions of the bundle structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19424218   468 EERLQKLHSEIKFALKVDNPDVRRCLSALEELGTLQVTSQILQKNTDVVATLKKIRRYKAN------------------K 529
Cdd:pfam11467   1 ERKLQELDLDIKSCLKLDNADVDKCLEALDELKSLQVTPLMLKKNPECVETIKKLRRYVGNleewkmdeeeeaefkekaQ 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 19424218   530 DVMAKAAEVYTRLKSRVLGPKVEALQKVNKAGAEKE 565
Cdd:pfam11467  81 LIRDKATEIYNKFKSLFLVPEGEVNFWPDFNEEVKE 116

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19424218      5 FKPGDLVFAKMKGYPHWPARIDD---IADGAVKPP--PNKYPIFFFGTHETAFLGPKDLFPYD 62
Cdd:smart00293   1 FKPGDLVWAKMKGFPWWPALVISpkmTPDNIMKRKsdENLYPVLFFGDKDTAWIPSSKLFPLT 63

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 19424218   8 GDLVFAKMKGYPHWPARIDDIADGAV----KPPPNKYPIFFFGTHETAFLGPKDLFPYDKCKDKYGKPNKRKG 76
Cdd:cd05162   1 GDLVWAKLKGYPWWPARVVDPEELPEevgkKKKKGGVLVQFFGDNDYAWVKSKNIKPFEEGFKKEFKKKKKKS 73

PWWP domain found in protein kinase C-binding protein 1 (PRKCBP1) and similar 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 plant homeodomain (PHD) finger, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19424218   6 KPGDLVFAKMKGYPHWPARIDDIADGAVKpppnkypIFFFGTHETAFLGPKDLFPYDKcKDKYGKPNKRKGFNEGLWEIQ 85
Cdd:cd20160   5 KPHLLVWAKLKGFPFWPAKALRVNNGQVD-------VRFFGAHDRAWVPVKDCYLYSK-EPPTSVKKKKSGLDEAMEELE 76

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 19424218   8 GDLVFAKMKGYPHWPA----------RIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDK--CKDKYGKPNKRK 75
Cdd:cd05840   1 GDLVLAKVKGYPPWPAmvlpeellpkNVLKAKKRKPKSKKTVYPVQFFPDNEYYWVSPSSLKPLTKeeIDKFLSKSKRKN 80

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 19424218   7 PGDLVFAKMKGYPHWPARIddiadgaVKPPPNKYPIFFFG-THETAFLGPKDLFPYDkcKDKYGKPNKR-KGFNEGLWEI 84
Cdd:cd20159   6 PHELVWAKQKGFPYWPAKV-------IQKEDNQYDVRFFGgHHQRAWIPKENIKPIT--TSPKQLKVKRtAGWNKACEEL 76

                .
gi 19424218  85 Q 85
Cdd:cd20159  77 K 77

PWWP domain found in zinc finger CW-type PWWP domain protein 2 (ZCWPW2) and similar proteins; ZCWPW2 is a histone H3K4me3 reader. In addition to the PWWP domain, ZCWPW2 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 19424218   5 FKPGDLVFAKMKGYPHWPARI--DDIADGAVK----PPPNKYPIFFFGT-HETAFLGPKDLFPYD-KCKDKYGKPNKRK 75
Cdd:cd20146   9 LPLGSLVWAKMTGYPRWPAILtpDPICGEYVDydedGEVEKYHVEFLGKpHSHAWISAKSVEPYNsNTKTPKCKTKKSK 87

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
                ....*....|....*....|....*....|....*....|....
gi 19424218  10 LVFAKMKGYPHWPARIDDIADGAVKpppnkypIFFFGTHETAFL 53
Cdd:cd05841   9 LVWVKLDGFPFWPAKVMGTKDGQVD-------VRFFGDYDRAWL 45

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19424218   7 PGDLVFAKMKGYPHWPARI--DDIADGAVKPPPNKYPIF------FFG-THETAFLGPKDLFPY-------DKCKDKYGK 70
Cdd:cd20144   1 VGDLVWAKVSGHPWWPCMVtyDPESGLYTKIKGSGGRTYrqyhvqFFGdNGERGWVSEKSLMPFegkekfeELVKELKKK 80

                ....*
gi 19424218  71 PNKRK 75
Cdd:cd20144  81 AKKKS 85

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
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 19424218   8 GDLVFAKMKGYPHWPARI---DDIADGAVKPP-PNKYPIFFFG---THETAFLGPKDLFPY 61
Cdd:cd20143   3 GDLVWAKVGTHPFWPARVvepAEQAEEVRRRCvPGSLCVYFFGpggSRDYGWVRRSMIFPF 63

PWWP domain found in mutated melanoma-associated antigen 1 (MUM-1) and similar proteins; MUM-1, also called PWWP domain-containing DNA repair factor 3A (PWWP3A), or protein expandere (EXPAND1), is a melanoma-associated antigen (MAA) that belongs to the mutated or aberrantly expressed type of MAAs, along with antigens such as CDK4, beta-catenin, gp100-in4, p15, and N-acetylglucosaminyltransferase V. It is highly expressed in several types of human cancers and involved in the DNA damage response pathway by contributing to the maintenance of chromatin architecture. MUM-1 is recruited to the vicinity of DNA breaks by TP53BP1 and plays an accessory role to facilitate damage-induced chromatin changes and promoting chromatin relaxation. It is required for efficient DNA repair and cell survival following DNA damage. This subfamily also includes mutated melanoma-associated antigen 1-like protein 1 (MUM1L1), also called MUM1-like protein 1, or PWWP domain-containing DNA repair factor 3B (PWWP3B). Its biological function remains unclear. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 19424218   5 FKPGDLVFAKMKGYPHWPARIDDiadgaVKPPPNKYPIFFFGTHETAF---LGPKDLFPYDkCKDK 67
Cdd:cd06080   1 FSKGDIVWAKYRKYPYWPAVVKS-----VYKKPKKASVLFLELPPEKKgikVSLKKLKPFD-CKEK 60

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
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 19424218   8 GDLVFAKMKGYPHWPARIDDIA-----DGAvkPPPNKYPIFFFGTHETAFLGPKDLFPY 61
Cdd:cd20153  17 GDIVWGKIHGFPWWPARVLSISlsqkeDGE--PSWQEAKVSWFGSPTTSLLSVSKLSPF 73