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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370513704   5 FKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 84
Cdd:cd20151     1 FKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 80

                  ....*...
gi 1370513704  85 DNNPKVKF 92
Cdd:cd20151    81 DNNPKVKF 88

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370513704   5 FKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 84
Cdd:cd20151     1 FKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 80

                  ....*...
gi 1370513704  85 DNNPKVKF 92
Cdd:cd20151    81 DNNPKVKF 88

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370513704    5 FKPGDLIFAKMKGYPHWPARVD---EVPDGAVKPPT--NKLPIFFFGTHETAFLGPKDIFPYS 62
Cdd:smart00293   1 FKPGDLVWAKMKGFPWWPALVIspkMTPDNIMKRKSdeNLYPVLFFGDKDTAWIPSSKLFPLT 63

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370513704   5 FKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 84
Cdd:cd20151     1 FKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 80

                  ....*...
gi 1370513704  85 DNNPKVKF 92
Cdd:cd20151    81 DNNPKVKF 88

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 1370513704   5 FKPGDLIFAKMKGYPHWPARVDEVPDGAvKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 84
Cdd:cd05834     1 FKPGDLVFAKVKGYPPWPARIDEIPEGA-KIPKNKYPVFFYGTHETAFLKPKDLFPYEENKEKYGKPRKRKGFNEGLWEI 79

                  ...
gi 1370513704  85 DNN 87
Cdd:cd05834    80 ENN 82

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 1370513704   2 TRDFKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGL 81
Cdd:cd20150     3 PREYKAGDLVFAKMKGYPHWPARIDELPEGAVKPPANKYPIFFFGTHETAFLGPKDLFPYKEYKDKFGKSNKRKGFNEGL 82

                          90
                  ....*....|.
gi 1370513704  82 WEIDNNPKVKF 92
Cdd:cd20150    83 WEIENNPGVKF 93

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 1370513704   8 GDLIFAKMKGYPHWPARV---DEVPDGAVKPP--TNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKR-----KGF 77
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVvdpEELPENVLKPKkkDGEYLVRFFGDSEFAWVKPKDLKPFDEGDEFEYLKKKKkkkkkKAF 80

                          90
                  ....*....|..
gi 1370513704  78 NEGLWEIDNNPK 89
Cdd:pfam00855  81 KKALEEAEEALK 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370513704   8 GDLIFAKMKGYPHWPARVDEVPDGAV----KPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKG 76
Cdd:cd05162     1 GDLVWAKLKGYPWWPARVVDPEELPEevgkKKKKGGVLVQFFGDNDYAWVKSKNIKPFEEGFKKEFKKKKKKS 73

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 1370513704   7 PGDLIFAKMKGYPHWPARV-DEVPDGAVKPPTNK------LPIFFFGTHETAFLGPKDIFPYSEN-KEKYGKPNKRKGFN 78
Cdd:cd20142     2 PGDVVWAKVKGYPMWPALViDEEHAERCGLEANRpgkkgtVPVQFFGTYEVARLNPKKVVGFSKGlDLKYHSKCKAPVFR 81

                  ....*..
gi 1370513704  79 EGLWEID 85
Cdd:cd20142    82 QALEEAE 88

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370513704   7 PGDLIFAKMKGYPHWPARVdevpdgaVKPPTNKLPIFFFG-THETAFLGPKDIFPYSENKEKYGKPNKrKGFNEGLWE 83
Cdd:cd20159     6 PHELVWAKQKGFPYWPAKV-------IQKEDNQYDVRFFGgHHQRAWIPKENIKPITTSPKQLKVKRT-AGWNKACEE 75

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370513704   8 GDLIFAKMKGYPHWPARV---DEVPDGAVKPPT-NKLPIFFFG---THETAFLGPKDIFPYSENKEKY-GKPNKRK---- 75
Cdd:cd20143     3 GDLVWAKVGTHPFWPARVvepAEQAEEVRRRCVpGSLCVYFFGpggSRDYGWVRRSMIFPFTDDLARFqTQKIKNKkrpq 82

                  ....*...
gi 1370513704  76 GFNEGLWE 83
Cdd:cd20143    83 EFQEALEE 90

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370513704   8 GDLIFAKMKGYPHWPA----------RVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENK-EKYGKPNKRK 75
Cdd:cd05840     1 GDLVLAKVKGYPPWPAmvlpeellpkNVLKAKKRKPKSKKTVYPVQFFPDNEYYWVSPSSLKPLTKEEiDKFLSKSKRK 79

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 1370513704   5 FKPGDLIFAKMKGYPHWPARVDEVPDGA----VKPPTNKlPIF----FFGTHET-AFLGPKDIFPYSENKEKYGKPNKR- 74
Cdd:cd20145     6 YTPGSLVWAKMPGYPWWPAMVEDDPDTEeffwLDEESDI-PTKyhvtFFDKPVSrAWVRASSIKPFTDNSNEPNLTKKKg 84

                  ....*....
gi 1370513704  75 KGFNEGLWE 83
Cdd:cd20145    85 KKYKKRLNE 93

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370513704   8 GDLIFAKMKGYPHWPARVDEVP-----DGAVKPPTNKlpIFFFGTHETAFLGPKDIFPYSEN-KEKYGKpnKRKG 76
Cdd:cd20152    23 GDIVWAKIYGFPWWPARILAITvsrkdNGLLVRQEAR--ISWFGSPTTSFLALSQLAPFLENfQSRFNK--KRKG 93

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370513704   7 PGDLIFAKMKGYPHWPARV--DEVPDGAVKPPTNKLPIF------FFG-THETAFLGPKDIFPYsENKEKY 68
Cdd:cd20144     1 VGDLVWAKVSGHPWWPCMVtyDPESGLYTKIKGSGGRTYrqyhvqFFGdNGERGWVSEKSLMPF-EGKEKF 70

PWWP domain found in the bromodomain and PHD finger-containing (BRPF) protein family; The BRPF family of proteins includes BRPF1, BRD1/BRPF2, and BRPF3. They are scaffold proteins that form monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complexes with other regulatory subunits, such as inhibitor of growth 5 (ING5) and Esa1-associated factor 6 ortholog (EAF6). BRPF proteins have multiple domains, including a plant homeodomain (PHD) zinc finger followed by a non-canonical extended PHD (ePHD) finger, C2HC5HC2H, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain. The PHD finger binds to lysine 4 of histone H3 (K4H3), the bromodomain interacts with acetylated lysines on N-terminal tails of histones and other proteins, and the PWWP domain shows histone-binding and chromatin association properties.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370513704   5 FKPGDLIFAKMKGYPHWPARV-------------DEVPDGAVKPPTNKLPIF--FFGTHET 50
Cdd:cd05839     1 LEPGDLVWAKCRGYPWYPAEIvdpkdpkegngvpIPVPPDRVLKKSNEKLYLvlFFDAKRT 61

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370513704   5 FKPGDLIFAKMKGYPHWPARVDEvpdgaVKPPTNKLPIFFFGTHETAF---LGPKDIFPY-SENKEKYGKPNKRKGFNEG 80
Cdd:cd06080     1 FSKGDIVWAKYRKYPYWPAVVKS-----VYKKPKKASVLFLELPPEKKgikVSLKKLKPFdCKEKEELLEEGKESPYSED 75

                  .
gi 1370513704  81 L 81
Cdd:cd06080    76 F 76

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
                  ....*....|....*....|.
gi 1370513704   5 FKPGDLIFAKMKGYPHWPARV 25
Cdd:cd05837     1 FSPGDLVWAKLEGYPWWPSLV 21

second PWWP domain found in nuclear SET domain-containing protein 2 (NSD2) and similar proteins; NSD2, also called histone-lysine N-methyltransferase NSD2, multiple myeloma SET domain-containing protein (MMSET), or protein trithorax-5 Wolf-Hirschhorn syndrome candidate 1 protein (WHSC1), is overexpressed frequently in the t(4;14) translocation in 15% to 20% of multiple myeloma. It plays important roles in cancer cell proliferation, survival, and tumor growth, through mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. It also enhances androgen receptor (AR)-mediated transcription. The principal chromatin-regulatory activity of NSD2 is dimethylation of histone H3 at lysine 36 (H3K36me2). NSD2 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, an high mobility group (HMG) box, five PHD (plant-homeodomain) zinc finger motifs, and an NSD-specific Cys-His rich domain (C5HCH). The SET domain is responsible for histone methyltransferase activity. The PWWP, HMG, and PHD domains mediate chromatin interaction and recognition of histone marks. This model corresponds to the second PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370513704   9 DLIFAKMKGYPHWPARV---DEVPDG--AVKPPTNKLPIFFFGTHETAFLGPKDIFPYSE 63
Cdd:cd20165     4 DIIWVKLGNYRWWPAEVchpKNVPPNiqKMKHEIGEFPVFFFGSKDYYWTHQARVFPYME 63