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 1167803551 439 GDIVWAKIYGFPWWPARIL--------TITVSRKDNGLLVRqearisWFGSPTTSFLALSQLSPFLENFQSRF-----NK 505
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVVdpeelpenVLKPKKKDGEYLVR------FFGDSEFAWVKPKDLKPFDEGDEFEYlkkkkKK 74

                          90
                  ....*....|....*...
gi 1167803551 506 KRKGLYRKAITEAAKAAK 523
Cdd:pfam00855  75 KKKKAFKKALEEAEEALK 92

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1167803551 423 KNVSKCVTPDGRTICVGDIVWAKIYGFPWWPARILTITVSRKDNGLLVRQEARISWFGSPTTSFLALSQLSPFLENFQSR 502
Cdd:cd20153     1 KSVSKCVTEEGRTVSVGDIVWGKIHGFPWWPARVLSISLSQKEDGEPSWQEAKVSWFGSPTTSLLSVSKLSPFSEFFKLR 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1167803551 503 FNKKRKGLYRKAITEAAKAAKQLTPEVRALLTQFET 538
Cdd:cd20153    81 FNRKKKGMYRKAITEAAKAAEHLTPEIRELLTQFET 116

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 1167803551 438 VGDIVWAKIYGFPWWPARIltitVSRKDNGLLVRQE--ARISWFGSPTTSFLALSQLSPFLENFQSRF-NKKRKGLYRKA 514
Cdd:cd05835     2 IGDLVWAKLKGSPWWPGIV----VSHKDCGQKPPAEgsVWVFWFGDHKVSEVPLDKILPFAEFFNKFYiSKNSSKLYKKA 77

                          90
                  ....*....|..
gi 1167803551 515 ITEAAK-AAKQL 525
Cdd:cd05835    78 VYEALKeAAERS 89

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 1167803551 439 GDIVWAKIYGFPWWPARIL--------TITVSRKDNGLLVRqearisWFGSPTTSFLALSQLSPFLENFQSRF-----NK 505
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVVdpeelpenVLKPKKKDGEYLVR------FFGDSEFAWVKPKDLKPFDEGDEFEYlkkkkKK 74

                          90
                  ....*....|....*...
gi 1167803551 506 KRKGLYRKAITEAAKAAK 523
Cdd:pfam00855  75 KKKKAFKKALEEAEEALK 92

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 1167803551 439 GDIVWAKIYGFPWWPARILTI------TVSRKDNGLLVrqearISWFGSPTT---SFLALSQLSPFLENF-----QSRFN 504
Cdd:cd20143     3 GDLVWAKVGTHPFWPARVVEPaeqaeeVRRRCVPGSLC-----VYFFGPGGSrdyGWVRRSMIFPFTDDLarfqtQKIKN 77

                          90
                  ....*....|....*....
gi 1167803551 505 KKRKGLYRKAITEAAKAAK 523
Cdd:cd20143    78 KKRPQEFQEALEEAKLADA 96

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1167803551  439 GDIVWAKIYGFPWWPARILT--------ITVSRKDNGLLVRqearisWFGSPTTSFLALSQLSPFL 496
Cdd:smart00293   4 GDLVWAKMKGFPWWPALVISpkmtpdniMKRKSDENLYPVL------FFGDKDTAWIPSSKLFPLT 63

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 1167803551 438 VGDIVWAKIYGFPWWPARILTIT--------VSRKDNGLLVRqearisWFGSPTTSFLALSQLSPFLE-NFQSRFNKKRK 508
Cdd:cd05838     2 YGDIVWVKLGNYRWWPAEILHPRevpdniqsLPHPPGEFPVR------FFGSHDYYWVHRGRVFLFEEgDKGSKEKSKKS 75

                          90
                  ....*....|....*....
gi 1167803551 509 --GLYRKAITEAAKAAKQL 525
Cdd:cd05838    76 ldKSFKRALKEANEAFREL 94

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 1167803551 438 VGDIVWAKIYGFPWWPARILTITVSRKDNGLLVRQEAR----ISWFGSPTTSFLALSQLSPFLENFQSRFNKKRK-GLYR 512
Cdd:cd20142     2 PGDVVWAKVKGYPMWPALVIDEEHAERCGLEANRPGKKgtvpVQFFGTYEVARLNPKKVVGFSKGLDLKYHSKCKaPVFR 81

                  ....*..
gi 1167803551 513 KAITEAA 519
Cdd:cd20142    82 QALEEAE 88

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 1167803551 438 VGDIVWAKIYGFPWWPARILTITVSRKDNGLLVRQEARISWFGSPTT-SFLALSQLSPFLENFQSRFNKK-----RKGLY 511
Cdd:cd05837     3 PGDLVWAKLEGYPWWPSLVCNHPTTGFHKKFGKKGEVHVQFFDDPPSrAWVKAKNVKPFTGSDDKEFQKGgmffsKDPKW 82

                          90       100
                  ....*....|....*....|..
gi 1167803551 512 RKAITEAAKAAKqLTPEVRALL 533
Cdd:cd05837    83 KKAVKEADKALK-LSVEERLKL 103

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1167803551 438 VGDIVWAKIYGFPWWPArILTitvsrKD--NGLLVR-------QEARISWFGSPTTSFLALS------QLSPFLENFQSR 502
Cdd:cd20146    11 LGSLVWAKMTGYPRWPA-ILT-----PDpiCGEYVDydedgevEKYHVEFLGKPHSHAWISAksvepyNSNTKTPKCKTK 84

                          90       100
                  ....*....|....*....|....*...
gi 1167803551 503 FNKKRKGLYRKAITEAAKaAKQLTPEVR 530
Cdd:cd20146    85 KSKKRKKSYESALEEAER-LLKLTCEER 111

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 1167803551 438 VGDIVWAKIYGFPWWPARILT------ITVSRKDNGLLVRQ--------EARISWFGSpttsflalSQLSPF--LENFQS 501
Cdd:cd20144     1 VGDLVWAKVSGHPWWPCMVTYdpesglYTKIKGSGGRTYRQyhvqffgdNGERGWVSE--------KSLMPFegKEKFEE 72

                          90       100       110
                  ....*....|....*....|....*....|
gi 1167803551 502 RFNKKRKGLYRKaiTEAAKAAKQLTPEVRA 531
Cdd:cd20144    73 LVKELKKKAKKK--SKKAKLEKKVKPSRRK 100

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 1167803551 436 ICVGDIVWAKIYGFPWWPARILTITVSRKDNG------------------LLVR--QEARiSWfgspttSFLALSQLSPF 495
Cdd:cd05839     1 LEPGDLVWAKCRGYPWYPAEIVDPKDPKEGNGvpipvppdrvlkksneklYLVLffDAKR-TW------GWLPRNKLRPL 73

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1167803551 496 LENF---QSRFNKKRKGLYRKAITEAAKAAKQL 525
Cdd:cd05839    74 GVDEeldKLKLSEAKKSKRRKEVRKAYERACKH 106

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 1167803551 431 PDGRTICVGDIVWAKIYGFPWWPARILTITVSRkdngllVRQEAR---ISWFGSPTTSFLALSQLSPFLEnFQSRFNK-- 505
Cdd:cd20150     1 PRPREYKAGDLVFAKMKGYPHWPARIDELPEGA------VKPPANkypIFFFGTHETAFLGPKDLFPYKE-YKDKFGKsn 73

                  ....*
gi 1167803551 506 KRKGL 510
Cdd:cd20150    74 KRKGF 78

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 1167803551 441 IVWAKIYGFPWWPARILtitvsRKDNGLL-VRqearisWFGS------PTTSFLALSQLSPFLEnfqsrfnKKRKGLYRK 513
Cdd:cd20160     9 LVWAKLKGFPFWPAKAL-----RVNNGQVdVR------FFGAhdrawvPVKDCYLYSKEPPTSV-------KKKKSGLDE 70

                  ....*
gi 1167803551 514 AITEA 518
Cdd:cd20160    71 AMEEL 75

first 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, a 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 first PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1167803551 438 VGDIVWAKIYGFPWWPARI-----LTITVSRKDNGLLVRQeARISWFG-SPTTSFLALSQLSPFlenfqsrfnkKRKGLY 511
Cdd:cd20162     3 VGDLVWSKVSGYPWWPCMVsadplLHSHTKLKGQKKSARQ-YHVQFFGdAPERAWIFEKSLVPF----------EGEGQF 71

                          90
                  ....*....|.
gi 1167803551 512 RKAITEAAKAA 522
Cdd:cd20162    72 EQLCQESAKQA 82

second PWWP domain found in nuclear SET domain-containing protein 3 (NSD3) and similar proteins; NSD3, also called histone-lysine N-methyltransferase NSD3, protein whistle, WHSC1-like 1 isoform 9 with methyltransferase activity to lysine, or Wolf-Hirschhorn syndrome candidate 1-like protein 1 (WHSC1-like protein 1, or WHSC1L1), is a lysine methyltransferase encoded by gene NSD3, which is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD3 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, five plant-homeodomain (PHD) zinc finger motifs, 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1167803551 440 DIVWAKIYGFPWWPARI-------LTITVSRKDNGllvrqEARISWFGSPTTSFLALSQLSPFLENFQSRFNKKRKG--L 510
Cdd:cd20166     4 QIVWVKLGNYRWWPAEIcnprsvpLNIQGLKHDIG-----DFPVFFFGSHDYYWVHQGRVFPYVEGDKSFAEGQTSInkT 78

                          90
                  ....*....|....*
gi 1167803551 511 YRKAITEAAKAAKQL 525
Cdd:cd20166    79 FKKALEEAAKRFQEL 93

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 1167803551 438 VGDIVWAKIYGFPWWPARILTI 459
Cdd:cd20161     6 VGDLVWAKFSRRPWWPCRICAD 27