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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 756761804   5 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKCKDKYGKPNKRKGFNEGLWEI 84
Cdd:cd20149    1 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKYKDKYGKPNKRKGFNEGLWEI 80

                 ....
gi 756761804  85 QNNP 88
Cdd:cd20149   81 QNNP 84

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 756761804  378 EELEDEEPVKK----RSRKARGRGTPSSSDSEPEGELGKEGKKLAKKSQLPGSESARKPGQKEKRGRPDEKPRARPVKVE 453
Cdd:PTZ00121 1246 EEERNNEEIRKfeeaRMAHFARRQAAIKAEEARKADELKKAEEKKKADEAKKAEEKKKADEAKKKAEEAKKADEAKKKAE 1325

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 756761804  454 RTRKRSEGLSLERKGEKKKEPSVEERLQKLHSEIKFALKVDNPDVRKCLSALEELGTLQVTSQILQKNTDVVatlKKIRR 533
Cdd:PTZ00121 1326 EAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKKEEAKKKADAAKKKAEEKKKADEAK---KKAEE 1402

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 756761804  534 YKANKDVMAKAAEvyTRLKSRVLGPKVEALQKVN---KAGAEKERAD--NEKLEEQPGEQAPRELAEDEPSTDRSAPVNG 608
Cdd:PTZ00121 1403 DKKKADELKKAAA--AKKKADEAKKKAEEKKKADeakKKAEEAKKADeaKKKAEEAKKAEEAKKKAEEAKKADEAKKKAE 1480

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 756761804  609 EAtsQKGENMEDRAQEDGQDSEDGPRGGSSEELHDSPRdNSDPAKPGNERQDHERTRLASE 669
Cdd:PTZ00121 1481 EA--KKADEAKKKAEEAKKKADEAKKAAEAKKKADEAK-KAEEAKKADEAKKAEEAKKADE 1538

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 756761804   5 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKCKDKYGKPNKRKGFNEGLWEI 84
Cdd:cd20149    1 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKYKDKYGKPNKRKGFNEGLWEI 80

                 ....
gi 756761804  85 QNNP 88
Cdd:cd20149   81 QNNP 84

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 756761804     5 FKPGDLVFAKMKGYPHWPARIDD---IADGAVKPP--PNKYPIFFFGTHETAFLGPKDLFPYD 62
Cdd:smart00293   1 FKPGDLVWAKMKGFPWWPALVISpkmTPDNIMKRKsdENLYPVLFFGDKDTAWIPSSKLFPLT 63

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 756761804  378 EELEDEEPVKK----RSRKARGRGTPSSSDSEPEGELGKEGKKLAKKSQLPGSESARKPGQKEKRGRPDEKPRARPVKVE 453
Cdd:PTZ00121 1246 EEERNNEEIRKfeeaRMAHFARRQAAIKAEEARKADELKKAEEKKKADEAKKAEEKKKADEAKKKAEEAKKADEAKKKAE 1325

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 756761804  454 RTRKRSEGLSLERKGEKKKEPSVEERLQKLHSEIKFALKVDNPDVRKCLSALEELGTLQVTSQILQKNTDVVatlKKIRR 533
Cdd:PTZ00121 1326 EAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKKEEAKKKADAAKKKAEEKKKADEAK---KKAEE 1402

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 756761804  534 YKANKDVMAKAAEvyTRLKSRVLGPKVEALQKVN---KAGAEKERAD--NEKLEEQPGEQAPRELAEDEPSTDRSAPVNG 608
Cdd:PTZ00121 1403 DKKKADELKKAAA--AKKKADEAKKKAEEKKKADeakKKAEEAKKADeaKKKAEEAKKAEEAKKKAEEAKKADEAKKKAE 1480

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 756761804  609 EAtsQKGENMEDRAQEDGQDSEDGPRGGSSEELHDSPRdNSDPAKPGNERQDHERTRLASE 669
Cdd:PTZ00121 1481 EA--KKADEAKKKAEEAKKKADEAKKAAEAKKKADEAK-KAEEAKKADEAKKAEEAKKADE 1538

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 756761804   5 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKCKDKYGKPNKRKGFNEGLWEI 84
Cdd:cd20149    1 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKYKDKYGKPNKRKGFNEGLWEI 80

                 ....
gi 756761804  85 QNNP 88
Cdd:cd20149   81 QNNP 84

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 756761804   5 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKCKDKYGKPNKRKGFNEGLWEI 84
Cdd:cd20151    1 FKPGDLIFAKMKGYPHWPARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEI 80

                 ....*...
gi 756761804  85 QNNPHASY 92
Cdd:cd20151   81 DNNPKVKF 88

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 756761804   2 PHAFKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKCKDKYGKPNKRKGFNEGL 81
Cdd:cd20150    3 PREYKAGDLVFAKMKGYPHWPARIDELPEGAVKPPANKYPIFFFGTHETAFLGPKDLFPYKEYKDKFGKSNKRKGFNEGL 82

                         90
                 ....*....|.
gi 756761804  82 WEIQNNPHASY 92
Cdd:cd20150   83 WEIENNPGVKF 93

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 756761804   5 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNK--YPIFFFGTHETAFLGPKDLFPYDKCKDKYGKPNKRKGFNEGLW 82
Cdd:cd05836    1 FKIGDLVWAKMKGFPPWPGKIVNPPPDLKKPPRKKkmHCVYFFGSENYAWIEDENIKPYEEFKEEMLKSKKSAGFKDAVE 80

                 ..
gi 756761804  83 EI 84
Cdd:cd05836   81 AI 82

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 756761804    8 GDLVFAKMKGYPHWPARI---DDIADGAVKPP--PNKYPIFFFGTHETAFLGPKDLFPYD-----KCKDKYGKPNKRKGF 77
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVvdpEELPENVLKPKkkDGEYLVRFFGDSEFAWVKPKDLKPFDegdefEYLKKKKKKKKKKAF 80

                          90
                  ....*....|.
gi 756761804   78 NEGLWEIQNNP 88
Cdd:pfam00855  81 KKALEEAEEAL 91

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 756761804   8 GDLVFAKMKGYPHWPARI---DDIAD--GAVKPPPNKYPIFFFGTHETAFLGPKDLFPY---DKCKDKYGKPNKRKGFNE 79
Cdd:cd05838    3 GDIVWVKLGNYRWWPAEIlhpREVPDniQSLPHPPGEFPVRFFGSHDYYWVHRGRVFLFeegDKGSKEKSKKSLDKSFKR 82

                 ....
gi 756761804  80 GLWE 83
Cdd:cd05838   83 ALKE 86

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 756761804   7 PGDLVFAKMKGYPHWPAR-IDDIADGAVKPPPNK------YPIFFFGTHETAFLGPKDLFPYDK-CKDKYGKPNKRKGFN 78
Cdd:cd20142    2 PGDVVWAKVKGYPMWPALvIDEEHAERCGLEANRpgkkgtVPVQFFGTYEVARLNPKKVVGFSKgLDLKYHSKCKAPVFR 81

                 ....*
gi 756761804  79 EGLWE 83
Cdd:cd20142   82 QALEE 86

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 756761804   8 GDLVFAKMKGYPHWPA----------RIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDK--CKDKYGKPNKRK 75
Cdd:cd05840    1 GDLVLAKVKGYPPWPAmvlpeellpkNVLKAKKRKPKSKKTVYPVQFFPDNEYYWVSPSSLKPLTKeeIDKFLSKSKRKN 80

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 756761804   6 KPGDLVFAKMKGYPHWPARIDDIAD-GAVKPPPNKYPIFFFGTH------ETAFLGPKDLFpYDKCKDKYGKPNKRKGFN 78
Cdd:cd05835    1 KIGDLVWAKLKGSPWWPGIVVSHKDcGQKPPAEGSVWVFWFGDHkvsevpLDKILPFAEFF-NKFYISKNSSKLYKKAVY 79

                 ...
gi 756761804  79 EGL 81
Cdd:cd05835   80 EAL 82

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 756761804  10 LVFAKMKGYPHWPARIDDIADGAVKpppnkypIFFFGTHETAFL 53
Cdd:cd05841    9 LVWVKLDGFPFWPAKVMGTKDGQVD-------VRFFGDYDRAWL 45

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 756761804   5 FKPGDLVFAKMKGYPHWPARI---DDIADGAVKPPP------------NKYPIFFFGTHET-AFLGPKDLFP--YDKCKD 66
Cdd:cd05839    1 LEPGDLVWAKCRGYPWYPAEIvdpKDPKEGNGVPIPvppdrvlkksneKLYLVLFFDAKRTwGWLPRNKLRPlgVDEELD 80

                 .
gi 756761804  67 K 67
Cdd:cd05839   81 K 81

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 756761804   7 PGDLVFAKMKGYPHWPARI--DDIADGAVKPPPNKYPIF------FFG-THETAFLGPKDLFPY-------DKCKDKYGK 70
Cdd:cd20144    1 VGDLVWAKVSGHPWWPCMVtyDPESGLYTKIKGSGGRTYrqyhvqFFGdNGERGWVSEKSLMPFegkekfeELVKELKKK 80

                 ....*
gi 756761804  71 PNKRK 75
Cdd:cd20144   81 AKKKS 85

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
                 ....*....|....*....
gi 756761804   5 FKPGDLVFAKMKGYPHWPA 23
Cdd:cd05837    1 FSPGDLVWAKLEGYPWWPS 19

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 756761804   5 FKPGDLVFAKMKGYPHWPARIDDiadgaVKPPPNKYPIFFFGTHETAF---LGPKDLFPYDkCKDK 67
Cdd:cd06080    1 FSKGDIVWAKYRKYPYWPAVVKS-----VYKKPKKASVLFLELPPEKKgikVSLKKLKPFD-CKEK 60

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
                 ....*....|....*....|....*....|....*....|....*....|....
gi 756761804   5 FKPGDLVFAKMKGYPHWPARIDDIADGaVKPPPNKYPIFFFGTHETAFLGPKDL 58
Cdd:cd20141    1 FNVGDLVWGQIRGFPSWPGKLVSENDV-GKTNEGKVWVSWFGDHSFGQVEPDKL 53