PWWP domain found in PWWP domain-containing protein 2A (PWWP2A); 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 its paralog 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 1958658268 412 KMKIFSKNVSKCITPDGRTICVGDIVWAKIYGFPWWPARILTITVSRRDNGLLARQEARISWFASPTTSFLALSQLSPFL 491
Cdd:cd20152     1 KGKVFSKNVSKCVTPDGRTICVGDIVWAKIYGFPWWPARILAITVSRKDNGLLVRQEARISWFGSPTTSFLALSQLAPFL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1958658268 492 ENFQLRFNKKRKGLYRRAITEAAKAAKQLTPEVRALLTQFET 533
Cdd:cd20152    81 ENFQSRFNKKRKGLYRKAITEAAKAAKQLTPEVRALLTQFET 122

PWWP domain found in PWWP domain-containing protein 2A (PWWP2A); 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 its paralog 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 1958658268 412 KMKIFSKNVSKCITPDGRTICVGDIVWAKIYGFPWWPARILTITVSRRDNGLLARQEARISWFASPTTSFLALSQLSPFL 491
Cdd:cd20152     1 KGKVFSKNVSKCVTPDGRTICVGDIVWAKIYGFPWWPARILAITVSRKDNGLLVRQEARISWFGSPTTSFLALSQLAPFL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1958658268 492 ENFQLRFNKKRKGLYRRAITEAAKAAKQLTPEVRALLTQFET 533
Cdd:cd20152    81 ENFQSRFNKKRKGLYRKAITEAAKAAKQLTPEVRALLTQFET 122

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958658268  434 GDIVWAKIYGFPWWPARILT-------ITVSRRDNGLLARQearisWFASPTTSFLALSQLSPFL 491
Cdd:smart00293   4 GDLVWAKMKGFPWWPALVISpkmtpdnIMKRKSDENLYPVL-----FFGDKDTAWIPSSKLFPLT 63

PWWP domain found in PWWP domain-containing protein 2A (PWWP2A); 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 its paralog 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 1958658268 412 KMKIFSKNVSKCITPDGRTICVGDIVWAKIYGFPWWPARILTITVSRRDNGLLARQEARISWFASPTTSFLALSQLSPFL 491
Cdd:cd20152     1 KGKVFSKNVSKCVTPDGRTICVGDIVWAKIYGFPWWPARILAITVSRKDNGLLVRQEARISWFGSPTTSFLALSQLAPFL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1958658268 492 ENFQLRFNKKRKGLYRRAITEAAKAAKQLTPEVRALLTQFET 533
Cdd:cd20152    81 ENFQSRFNKKRKGLYRKAITEAAKAAKQLTPEVRALLTQFET 122

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        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958658268 428 GRTICVGDIVWAKIYGFPWWPARILTITVSRRDNGLLARQEARISWFASPTTSFLALSQLSPFLENFQLRFNKKRKGLYR 507
Cdd:cd20140     1 GRTLRVGDIVWGKIHGFPWWPGRILSITVSRDDNGELSTQEAHVSWFGSSTTSYMPCSQLYPFLEDFKLRYNKKKRGPYK 80

                          90
                  ....*....|..
gi 1958658268 508 RAITEAAKAAKQ 519
Cdd:cd20140    81 EAVRQALEAAKQ 92

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 1958658268 434 GDIVWAKIYGFPWWPARILTITVSRRDNGLLAR-QEARISWFASPTTSFLALSQLSPFLENFQLRFNKKRKG--LYRRAI 510
Cdd:cd05162     1 GDLVWAKLKGYPWWPARVVDPEELPEEVGKKKKkGGVLVQFFGDNDYAWVKSKNIKPFEEGFKKEFKKKKKKskKFKKAV 80

                  ....*.
gi 1958658268 511 TEAAKA 516
Cdd:cd05162    81 EEAEEA 86

PWWP domain found in DNA (cytosine-5)-methyltransferase 3A (DNMT3A); DNMT3A, also called DNA methyltransferase HsaIIIA, DNA MTase HsaIIIA, or M.HsaIIIA, is required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. It 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. It contains a PWWP domain that binds methylated histone.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958658268 427 DGRTICVGDIVWAKIYGFPWWPARILTITVSRRDNGllARQEARISWFASPTTSFLALSQLSPfLENFQLRFNK---KRK 503
Cdd:cd20154     2 DGRGFGIGELVWGKLRGFSWWPGRIVSWWMTGRSRA--AEGTRWVMWFGDGKFSVVCVEKLMP-LSSFSSAFHQatyNKQ 78

                          90
                  ....*....|....
gi 1958658268 504 GLYRRAITEAAKAA 517
Cdd:cd20154    79 PMYRKAIYEVLQVA 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958658268 433 VGDIVWAKIYGFPWWPARILTITvsrrDNGLLARQEARISWFASPTTSFLALSQLSPFLEN-FQLRFNKKRKGL 505
Cdd:cd05834     3 PGDLVFAKVKGYPPWPARIDEIP----EGAKIPKNKYPVFFYGTHETAFLKPKDLFPYEENkEKYGKPRKRKGF 72

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958658268 433 VGDIVWAKIYGFPWWPARILTITVSRRDNGLLARQEAR----ISWFASPTTSFLALSQLSPFLENFQLRFNKKRK-GLYR 507
Cdd:cd20142     2 PGDVVWAKVKGYPMWPALVIDEEHAERCGLEANRPGKKgtvpVQFFGTYEVARLNPKKVVGFSKGLDLKYHSKCKaPVFR 81

                  ....*..
gi 1958658268 508 RAITEAA 514
Cdd:cd20142    82 QALEEAE 88

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
                  ....*....|....*....|
gi 1958658268 433 VGDIVWAKIYGFPWWPARIL 452
Cdd:cd05838     2 YGDIVWVKLGNYRWWPAEIL 21

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
                  ....*....|....*...
gi 1958658268 432 CVGDIVWAKIYGFPWWPA 449
Cdd:cd20145     7 TPGSLVWAKMPGYPWWPA 24

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958658268 433 VGDIVWAKIYGFPWWPARILTITVSRRDNGLLARQEARISWFASPTT-SFLALSQLSPFLENFQLRFNKK-----RKGLY 506
Cdd:cd05837     3 PGDLVWAKLEGYPWWPSLVCNHPTTGFHKKFGKKGEVHVQFFDDPPSrAWVKAKNVKPFTGSDDKEFQKGgmffsKDPKW 82

                          90       100
                  ....*....|....*....|..
gi 1958658268 507 RRAITEAAKAAKqLTPEVRALL 528
Cdd:cd05837    83 KKAVKEADKALK-LSVEERLKL 103

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958658268 433 VGDIVWAKIYGFPWWPARIltitVSRRDNGLLARQEARISWFASPTTSFLALSQLSPF---LENFQLRFNKKRKGLYR-- 507
Cdd:cd20141     3 VGDLVWGQIRGFPSWPGKL----VSENDVGKTNEGKVWVSWFGDHSFGQVEPDKLKTLsegLEAHHRARKRTRKGRKLnn 78

                  ....*....
gi 1958658268 508 ---RAITEA 513
Cdd:cd20141    79 hleAAIQEA 87

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958658268 434 GDIVWAKIYGFPWWPARILTITvsrRDNGLLARQEARISWFASPTTSFLALSQLSPFlENFQLRFNK--KRKGL 505
Cdd:cd20148     4 GDLVFAKMKGYPHWPARIDEMP---EAAVKSTANKYQVFFFGTHETAFLGPKDLFPY-EESKEKFGKpnKRKGF 73

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958658268 434 GDIVWAKIYGFPWWPARILTI---TVSRRDNGLlarqeaRISWFASPTTSFLALSQLSPFLENfQLRFNK--KRKGL 505
Cdd:cd20151     4 GDLIFAKMKGYPHWPARVDEVpdgAVKPPTNKL------PIFFFGTHETAFLGPKDIFPYSEN-KEKYGKpnKRKGF 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 1958658268 436 IVWAKIYGFPWWPARILtitvsRRDNGLLarqEAR------ISWFasPTTSFLALSQLSPFLEnfqlrfnKKRKGLYRRA 509
Cdd:cd20160     9 LVWAKLKGFPFWPAKAL-----RVNNGQV---DVRffgahdRAWV--PVKDCYLYSKEPPTSV-------KKKKSGLDEA 71

                  ....
gi 1958658268 510 ITEA 513
Cdd:cd20160    72 MEEL 75

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
                  ....*....|....*....|
gi 1958658268 434 GDIVWAKIYGFPWWPARILT 453
Cdd:cd05840     1 GDLVLAKVKGYPPWPAMVLP 20

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
                  ....*....|....*....|..
gi 1958658268 433 VGDIVWAKIYGFPWWPARILTI 454
Cdd:cd20161     6 VGDLVWAKFSRRPWWPCRICAD 27