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 745750643  56 GSVVLAKMDSYPWWPGMIISEEYLPKN------MSKKPRGACLPVQFFPDNDCGWVKLSALQNLTPEMVSEALGNKRkll 129
Cdd:cd05840    1 GDLVLAKVKGYPPWPAMVLPEELLPKNvlkakkRKPKSKKTVYPVQFFPDNEYYWVSPSSLKPLTKEEIDKFLSKSK--- 77

                         90       100
                 ....*....|....*....|...
gi 745750643 130 eglrpaKLQKQLVQGYEVALDPP 152
Cdd:cd05840   78 ------RKNKDLIEAYEVALEPP 94

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 745750643  56 GSVVLAKMDSYPWWPGMIISEEYLPKN------MSKKPRGACLPVQFFPDNDCGWVKLSALQNLTPEMVSEALGNKRkll 129
Cdd:cd05840    1 GDLVLAKVKGYPPWPAMVLPEELLPKNvlkakkRKPKSKKTVYPVQFFPDNEYYWVSPSSLKPLTKEEIDKFLSKSK--- 77

                         90       100
                 ....*....|....*....|...
gi 745750643 130 eglrpaKLQKQLVQGYEVALDPP 152
Cdd:cd05840   78 ------RKNKDLIEAYEVALEPP 94

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 745750643    53 FPLGSVVLAKMDSYPWWPGMIISEEYLPKNMSK-KPRGACLPVQFFPDNDCGWVKLSALQNLT 114
Cdd:smart00293   1 FKPGDLVWAKMKGFPWWPALVISPKMTPDNIMKrKSDENLYPVLFFGDKDTAWIPSSKLFPLT 63

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 745750643  56 GSVVLAKMDSYPWWPGMIISEEYLPKN------MSKKPRGACLPVQFFPDNDCGWVKLSALQNLTPEMVSEALGNKRkll 129
Cdd:cd05840    1 GDLVLAKVKGYPPWPAMVLPEELLPKNvlkakkRKPKSKKTVYPVQFFPDNEYYWVSPSSLKPLTKEEIDKFLSKSK--- 77

                         90       100
                 ....*....|....*....|...
gi 745750643 130 eglrpaKLQKQLVQGYEVALDPP 152
Cdd:cd05840   78 ------RKNKDLIEAYEVALEPP 94

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 745750643  56 GSVVLAKMDSYPWWPGMIISEEYLPKNMSKKPRGACLPVQFFPDNDCGWVKLSALQNLTPEMVSEALGNKRK 127
Cdd:cd05162    1 GDLVWAKLKGYPWWPARVVDPEELPEEVGKKKKKGGVLVQFFGDNDYAWVKSKNIKPFEEGFKKEFKKKKKK 72

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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 745750643  56 GSVVLAKMDSYPWWPGMIISEEYLPKNM-SKKPRGACLPVQFFPDNDCGWV 105
Cdd:cd05838    3 GDIVWVKLGNYRWWPAEILHPREVPDNIqSLPHPPGEFPVRFFGSHDYYWV 53

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 745750643  52 SFPLGSVVLAKMDSYPWWPGMI----ISEEY--LPKNMSKkprgaclPVQ----FFPDN-DCGWVKLSALQNLT--PEMV 118
Cdd:cd20145    5 KYTPGSLVWAKMPGYPWWPAMVeddpDTEEFfwLDEESDI-------PTKyhvtFFDKPvSRAWVRASSIKPFTdnSNEP 77

                         90       100
                 ....*....|....*....|
gi 745750643 119 SEALGNKRKLLEGLRPAKLQ 138
Cdd:cd20145   78 NLTKKKGKKYKKRLNEAVEM 97

PWWP domain found in glyoxylate reductase 1 (GLYR1) and similar proteins; GLYR1, also called 3-hydroxyisobutyrate dehydrogenase-like protein, cytokine-like nuclear factor N-PAC, nuclear protein NP60, or nuclear protein of 60 kDa, is a putative oxidoreductase that is recruited on chromatin and promotes KDM1B demethylase activity. It recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3). GLYR1 enhances the activity of MAP2K4 and MAP2K6 kinases to phosphorylate p38-alpha. In addition to the PWWP domain, GLYR1 also contains an AT-hook and a C-terminal NAD-binding domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 745750643  53 FPLGSVVLAKMDSYPWWPGMIISEeylPKNMSKKPRGA-CLPVQFFPDNDCGWVKLSALQNLTPEMvsEALGNKRKlleg 131
Cdd:cd05836    1 FKIGDLVWAKMKGFPPWPGKIVNP---PPDLKKPPRKKkMHCVYFFGSENYAWIEDENIKPYEEFK--EEMLKSKK---- 71

                 ....*...
gi 745750643 132 lrPAKLQK 139
Cdd:cd05836   72 --SAGFKD 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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 745750643  54 PLGSVVLAKMDSYPWWPGMIISeeylPKNMSKKPrgaclpvqffPDNDCGWVK 106
Cdd:cd05835    1 KIGDLVWAKLKGSPWWPGIVVS----HKDCGQKP----------PAEGSVWVF 39

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
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 745750643  55 LGSVVLAKMDSYPWWPGMIISEEYLpKNMSKKPRGACLP-----VQFFPDNDC-GWV 105
Cdd:cd20144    1 VGDLVWAKVSGHPWWPCMVTYDPES-GLYTKIKGSGGRTyrqyhVQFFGDNGErGWV 56

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
                 ....*....|....*....|....*....|....*....|....*....|..
gi 745750643  55 LGSVVLAKMDSYPWWPGMIISEEY-----LPKNMSKKPRGacLPVQFFPDND 101
Cdd:cd20142    2 PGDVVWAKVKGYPMWPALVIDEEHaercgLEANRPGKKGT--VPVQFFGTYE 51

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
                 ....*....|....*....|....*
gi 745750643  51 RSFPLGSVVLAKMDSYPWWPGMIIS 75
Cdd:cd20140    2 RTLRVGDIVWGKIHGFPWWPGRILS 26

second 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. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 745750643  58 VVLAKMDSYPWWPGMIISEEYLPKNMSK-KPRGACLPVQFFPDNDCGWVKLSalqNLTPEMVSEAlGNKRKLLEGL 132
Cdd:cd20164    5 VVWVKVGRYRWWPAEVCHPKSIPTNIQKmKHDIGEFPVLFFGSNDYLWTHQA---RVFPYMEGDV-SSKDKMGKGV 76