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 2217351952 220 YNVGDLVWSKVSGYPWWPCMVSADPLLHSYTKLKGQKKSARQYHVQFFGDAPERAWIFEKSLVAFEGEGQFEKLCQESAK 299
Cdd:cd20162     1 YNVGDLVWSKVSGYPWWPCMVSADPLLHSHTKLKGQKKSARQYHVQFFGDAPERAWIFEKSLVPFEGEGQFEQLCQESAK 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2217351952 300 QAPTKAEKIKLLKPISGKLRAQWEMGIVQAEEAASMSVEERKAKFTFL 347
Cdd:cd20162    81 QAPTKAEKIKLLKPISGKLRAQWDMGIVQAEEAASMTVEERKAKFTFL 128

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 2217351952 220 YNVGDLVWSKVSGYPWWPCMVSADPLLHSYTKLKGQKKSARQYHVQFFGDAPERAWIFEKSLVAFEGEGQFEKLCQESAK 299
Cdd:cd20162     1 YNVGDLVWSKVSGYPWWPCMVSADPLLHSHTKLKGQKKSARQYHVQFFGDAPERAWIFEKSLVPFEGEGQFEQLCQESAK 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2217351952 300 QAPTKAEKIKLLKPISGKLRAQWEMGIVQAEEAASMSVEERKAKFTFL 347
Cdd:cd20162    81 QAPTKAEKIKLLKPISGKLRAQWDMGIVQAEEAASMTVEERKAKFTFL 128

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 2217351952 223 GDLVWSKVSGYPWWPCMVSADPLLHSYTKLKgqKKSARQYHVQFFGDaPERAWIFEKSLVAFEGEGQFEKLCQESAKQAP 302
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVVDPEELPENVLKP--KKKDGEYLVRFFGD-SEFAWVKPKDLKPFDEGDEFEYLKKKKKKKKK 77

                  ....*
gi 2217351952 303 TKAEK 307
Cdd:pfam00855  78 KAFKK 82

high mobility group;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2217351952  458 SQFLVFCQKHRDEVVAEHPDASGEEIEELLRSQWSLLSEKQRARYNTKFALVAPVQAEEDS 518
Cdd:smart00398   7 SAFMLFSQENRAKIKAENPDLSNAEISKKLGERWKLLSEEEKAPYEEKAKKDKERYEEEMP 67

Chromatin-associated proteins containing the HMG domain [Chromatin structure and dynamics];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217351952 441 RKKTTVSMPRSRKGD------AASQFLVFCQKHRDEVVAEHPDASGEEIEELLRSQWSLLSEKQRARYNTKF 506
Cdd:COG5648    53 RKKTKSKRLVRKKKDpngpkrPLSAYFLYSAENRDEIRKENPKLTFGEVGKLLSEKWKELTDEEKEPYYKEA 124

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 2217351952 220 YNVGDLVWSKVSGYPWWPCMVSADPLLHSYTKLKGQKKSARQYHVQFFGDAPERAWIFEKSLVAFEGEGQFEKLCQESAK 299
Cdd:cd20162     1 YNVGDLVWSKVSGYPWWPCMVSADPLLHSHTKLKGQKKSARQYHVQFFGDAPERAWIFEKSLVPFEGEGQFEQLCQESAK 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2217351952 300 QAPTKAEKIKLLKPISGKLRAQWEMGIVQAEEAASMSVEERKAKFTFL 347
Cdd:cd20162    81 QAPTKAEKIKLLKPISGKLRAQWDMGIVQAEEAASMTVEERKAKFTFL 128

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217351952 220 YNVGDLVWSKVSGYPWWPCMVSADPLLHSYTKLkgQKKSARQYHVQFFGDAPERAWIFEKSLVAFEGEGQFEKLCQESAK 299
Cdd:cd20163     1 FQVGDLVWSKVGTYPWWPCMVSSDPQLEVHTKI--NTRGAREYHVQFFSSQPERAWVHEKRVREYKGHKQYEELLAEATK 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2217351952 300 QAPTKAEKIKLLKPISGKLRAQWEMGIVQAEEAASMSVEERKAKFTFLYV 349
Cdd:cd20163    79 QASNHSEKQKIRKPRPQRERAQWDIGIAHAEKALKMTREERIEQYTFIYI 128

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 2217351952 219 KYNVGDLVWSKVSGYPWWPCMVSADPLLHSYTKLKGQKKSARQYHVQFFGDAPERAWIFEKSLVAFEGegqfeklcqesa 298
Cdd:cd20145     5 KYTPGSLVWAKMPGYPWWPAMVEDDPDTEEFFWLDEESDIPTKYHVTFFDKPVSRAWVRASSIKPFTD------------ 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2217351952 299 kqaptKAEKIKLLKPISGKLRAQWEMGIVQAEEAASMSVEERKAKFTF 346
Cdd:cd20145    73 -----NSNEPNLTKKKGKKYKKRLNEAVEMAREALKLSIKERLKKFGF 115

high mobility group (HMG)-box found in nuclear SET domain-containing protein 2 (NSD2) and similar proteins; NSD2, also called multiple myeloma SET domain-containing protein (MMSET), protein trithorax-5 (TRX5), or wolf-Hirschhorn syndrome candidate 1 protein (WHSC1), acts as a histone-lysine N-methyltransferase with histone H3 'Lys-36' (H3K36me) methyltransferase activity. NSD2 has been shown to mediate di- and trimethylation of H3K36 and dimethylation of H4K20 in different systems and has been characterized as a transcriptional repressor interacting with histone deacetylase HDAC1 and histone demethylase LSD1. NSD2 mediates constitutive NF-kappaB signaling for cancer cell proliferation, survival and tumor growth. It is highly overexpressed in several types of human cancers, including small-cell lung cancers, neuroblastoma, carcinomas of stomach and colon, and bladder cancers, and its overexpression tends to be associated with tumor aggressiveness.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2217351952 452 RKGDAASQFLVFCQKHRDEVVAEHPDASGEEIEELLRSQWSLLSEKQRARYNTKFALVAPV 512
Cdd:cd21991     1 KKKVKKGQFEVFCQKHREEVAQEHPDLSEEEIEEYLKKQWNNMSEKQRARYKSKFASDTSR 61

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 2217351952 223 GDLVWSKVSGYPWWPCMVSADPLLHSYTKLKGQKKsarQYHVQFFGDApERAWIFEKSLVAFEGEGQFEKLCQESAKQAP 302
Cdd:cd05162     1 GDLVWAKLKGYPWWPARVVDPEELPEEVGKKKKKG---GVLVQFFGDN-DYAWVKSKNIKPFEEGFKKEFKKKKKKSKKF 76

                  ...
gi 2217351952 303 TKA 305
Cdd:cd05162    77 KKA 79

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217351952  220 YNVGDLVWSKVSGYPWWPCMV---SADPLLHSYtklkgQKKSARQYHVQFFGDaPERAWIFEKSLV 282
Cdd:smart00293   1 FKPGDLVWAKMKGFPWWPALVispKMTPDNIMK-----RKSDENLYPVLFFGD-KDTAWIPSSKLF 60

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217351952 220 YNVGDLVWSKVSGYPWWPCMVSADPllhsytklKGQKKSARQYHVQFFGdAPERAWIFEKSLVAFE 285
Cdd:cd05834     1 FKPGDLVFAKVKGYPPWPARIDEIP--------EGAKIPKNKYPVFFYG-THETAFLKPKDLFPYE 57

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2217351952 221 NVGDLVWSKVSGYPWWPCMVsadpLLHSYTKLKG----QKKSARQYHVQFFGDApERAWIFEKSLVAFE 285
Cdd:cd20142     1 SPGDVVWAKVKGYPMWPALV----IDEEHAERCGleanRPGKKGTVPVQFFGTY-EVARLNPKKVVGFS 64

high mobility group;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2217351952  458 SQFLVFCQKHRDEVVAEHPDASGEEIEELLRSQWSLLSEKQRARYNTKFALVAPVQAEEDS 518
Cdd:smart00398   7 SAFMLFSQENRAKIKAENPDLSNAEISKKLGERWKLLSEEEKAPYEEKAKKDKERYEEEMP 67

PWWP domain found in the PWWP domain-containing protein 2 (PWWP2) family; The PWWP2 family includes PWWP2A and its paralog PWWP2B. PWWP2A is a H2A.Z-specific chromatin binding protein which may play an important role in the neural crest stem cell migration and differentiation during early development. It is also required for proper mitosis progression. PWWP2A and PWWP2B form a stable complex with NuRD subunits MTA1/2/3:HDAC1/2:RBBP4/7, but not with MBD2/3, p66alpha/beta, and CHD3/4. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20
                  ....*....|....*....|...
gi 2217351952 220 YNVGDLVWSKVSGYPWWPCMVSA 242
Cdd:cd20140     4 LRVGDIVWGKIHGFPWWPGRILS 26

HMG (high mobility group) box;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2217351952 458 SQFLVFCQKHRDEVVAEHPDASGEEIEELLRSQWSLLSEKQRARYNTKFA 507
Cdd:pfam00505   6 SAFFLFSKEQRAKLKAENPGLKNAEISKILGEKWKALSEEEKKPYEEKAE 55

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
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2217351952 224 DLVWSKVSGYPWWPCMVsadpllhsytklkgQKKSARQYHVQFFGDAPERAWIFEKS 280
Cdd:cd20159     8 ELVWAKQKGFPYWPAKV--------------IQKEDNQYDVRFFGGHHQRAWIPKEN 50

second high mobility group (HMG)-box found in the high mobility group protein B (HMGB) family; HMGB proteins are chromatin-associated nuclear proteins that act as architectural factors in nucleoprotein structures, which regulate DNA-dependent processes including transcription. In mammals, four family members are present: HMGB1, HMGB2, HMGB3 and HMGB4. They regulate the expression of a wide range of genes through architectural remodeling of the chromatin structure. HMGB1, also called high mobility group protein 1 (HMG-1), is a prototypical alarmin or damage-associated molecular pattern (DAMP) molecule when released from cells. It plays important roles in the regulation of a wide range of processes, including transcription, replication, DNA repair, and nucleosome formation, in the nucleus. It also plays multiple roles in regulating inflammation and responses to cell and tissue stress. HMGB2, also called high mobility group protein 2 (HMG-2), has been implicated in numerous cellular processes, including proliferation, differentiation, apoptosis, and tumor growth. It acts as a chromatin-associated nonhistone protein involved in transcriptional regulation and nucleic-acid-mediated innate immune responses in mammalian. It binds DNA to stabilize nucleosomes and promote transcription. HMGB3, also called high mobility group protein 2a (HMG-2a), or high mobility group protein 4 (HMG-4), is an X-linked member of HMGB family and functions as a universal sentinel for nucleic acid-mediated innate immune responses. HMGB3 has been implicated in the regulation of cellular proliferation and differentiation, as well as inflammatory response. HMGB4 is expressed by neuronal cells and affects the expression of genes involved in neural differentiation. It is a factor that regulates chromatin and expression of neuronal differentiation markers. The family also includes high mobility group protein B1 pseudogene 1 (HMGB1P1) and nuclear auto-antigen Sp-100. HMGB1P1, also called putative high mobility group protein B1-like 1 (HMGB1L1), or putative high mobility group protein 1-like 1 (HMG-1L1), is an HMG-box containing protein that binds preferentially single-stranded DNA and unwinds double-stranded DNA. Sp-100, also called nuclear dot-associated Sp100 protein, or speckled 100 kDa. It is a tumor suppressor that is a major constituent of the promyelocytic leukemia (PML) bodies, a subnuclear organelle involved in many physiological processes including cell growth, differentiation and apoptosis. Through the regulation of ETS1, Sp-100 may play a role in angiogenesis, controlling endothelial cell motility and invasion. It may also play roles in the regulation of telomeres lengthening, TP53-mediated transcription, FAS-mediated apoptosis, etc. In addition, the family includes Drosophila melanogaster high mobility group protein DSP1 (dDSP1) and similar proteins. dDSP1, also called protein dorsal switch 1, is a Drosophila HMG1 protein that binds preferentially single-stranded DNA and unwinds double-stranded DNA. It converts Dorsal and nuclear factor (NF)-kappa B from transcriptional activators to repressors. Members of the HMGB family contain two HMG-box domains. This model corresponds to the second one.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2217351952 458 SQFLVFCQKHRDEVVAEHPDASGEEIEELLRSQWSLLSEKQRARYNTKFA 507
Cdd:cd21979     8 SAFFLFCSEHRPKIKGEHPGLSIGDVAKKLGEMWNNTSAKDKQPYEKKAA 57

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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2217351952 225 LVWSKVSGYPWWPCmvsadpllhsytklKGQKKSARQYHVQFFGDApERAWI 276
Cdd:cd20160     9 LVWAKLKGFPFWPA--------------KALRVNNGQVDVRFFGAH-DRAWV 45

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
                  ....*....|....*....|.
gi 2217351952 222 VGDLVWSKVSGYPWWPCMVSA 242
Cdd:cd20152    22 VGDIVWAKIYGFPWWPARILA 42

PWWP domain found in DNA (cytosine-5)-methyltransferase 3B (DNMT3B); DNMT3B, also called DNA methyltransferase HsaIIIB, DNA MTase HsaIIIB, or M.HsaIIIB, is required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. It 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. 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 anomalies) syndrome, a rare autosomal recessive disorder characterized by hypomethylation of classical satellite DNA.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 2217351952 222 VGDLVWSKVSGYPWWPCMVSadpllhSYTKLKGQKKSARQYHVQFFGD 269
Cdd:cd20155     2 IGELVWGKIKGFSWWPAMVV------SWRATGKRQASSGMRWLQWFGD 43

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.

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                  ....*....|....*....|....*....|....*....|....*....
gi 2217351952 222 VGDLVWSKVSGYPWWPCMVsadpLLHSYTKLKGQKKSAR--QYHVQFFG 268
Cdd:cd05838     2 YGDIVWVKLGNYRWWPAEI----LHPREVPDNIQSLPHPpgEFPVRFFG 46

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217351952 220 YNVGDLVWSKVSGYPWWPCMV---SADPLLHSYTK-----LKGQKKSARQYHVQFFgDAPeRAW 275
Cdd:cd05839     1 LEPGDLVWAKCRGYPWYPAEIvdpKDPKEGNGVPIpvppdRVLKKSNEKLYLVLFF-DAK-RTW 62

third high mobility group (HMG)-box found in Arabidopsis thaliana high mobility group B protein 6 (HMGB6) and similar proteins; HMGB6, also called nucleosome/chromatin assembly factor group D 06 (or D 6), WRKY transcription factor 53 (WRKY53), or WRKY DNA-binding protein 53, is a master regulator of age-induced leaf senescence. It acts in a complex transcription factor signaling network regulating senescence specific gene expression; hydrogen peroxide might be involved in signal transduction. The subfamily also includes Arabidopsis thaliana HMGB13 (also known as nucleosome/chromatin assembly factor group D 13). Both HMGB6 and HMGB13 contain three HMG-box domains. This model corresponds to the third one.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217351952 442 KKTTVSMPRSRKgdAASQFLVFCQKHRDEVVAEHPDASGEEIEELLRSQWSLLSEKQRARYNTKFA 507
Cdd:cd22008     1 KNKNVDPNKPKK--PASSYLLFGKEYRKKLQEERPGANNATVTALISLKWKELGEEEKQVYNDKAA 64

fourth high mobility group (HMG)-box found in upstream-binding factor 1 (UBF1) and similar proteins; UBF1, also called UBTF, nucleolar transcription factor 1, or auto-antigen NOR-90, is a nucleolar transcription factor that recognizes the ribosomal RNA gene promoter and activates transcription mediated by RNA polymerase I through cooperative interactions with the transcription factor SL1/TIF-IB complex. It binds specifically to the upstream control element. UBF1 contains six HMG-box domains. This model corresponds to the fourth one.

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                  ....*....|....*....|....*....|....*....|....*.
gi 2217351952 463 FCQKHRDEVVAEHPDASGEEIEELLRSQWSLLSEKQRARYNTKFAL 508
Cdd:cd22001    13 YSKEKRSKLKKKHPELSEQELTRLLAKKYNELPDKKKAKYKKKEAL 58

high mobility group (HMG)-box found in the high mobility group protein 20 (HMG20) subfamily; The HMG20 subfamily includes HMG20A and HMG20B. HMG20A, also called HMG box-containing protein 20A, HMG domain-containing protein 1, HMG domain-containing protein HMGX1, HMGXB1, or iBRAF, is a chromatin-associated protein involved in neuronal differentiation and maturation. It is required for SNAI1-mediated epithelial to mesenchymal transition. HMG20A acts as an inhibitor of HMG20B. HMG20B, also called SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related, SMARCE1-related protein (SMARCE1R), BRCA2-associated factor 35 (BRAF35), HMG box-containing protein 20B, HMG domain-containing protein 2, HMG domain-containing protein HMGX2, Sox-like transcriptional factor, or structural DNA-binding protein BRAF35, is a DNA binding factor that acts as a repressor of erythroid differentiation. It is required for correct progression through the G2 phase of the cell cycle and entry into mitosis. It is also required for RCOR1/CoREST mediated repression of neuronal specific gene promoters. HMG20B is a core subunit of the Lys-specific demethylase 1/REST co-repressor 1 (LSD1-CoREST) histone demethylase complex. Both HMG20A and HMG20B contain one HMG-box.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217351952 460 FLVFCQKHRDEVVAEHPDASGEEIEELLRSQWSLLSEKQRARYNTkfalvapvQAEEDsgnvngKKR 526
Cdd:cd21980     9 YVRFLNERREKLRAENPDLSFPEITKILGAEWSSLSAEEKQKYLD--------EAEKD------KER 61

Chromatin-associated proteins containing the HMG domain [Chromatin structure and dynamics];

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217351952 441 RKKTTVSMPRSRKGD------AASQFLVFCQKHRDEVVAEHPDASGEEIEELLRSQWSLLSEKQRARYNTKF 506
Cdd:COG5648    53 RKKTKSKRLVRKKKDpngpkrPLSAYFLYSAENRDEIRKENPKLTFGEVGKLLSEKWKELTDEEKEPYYKEA 124

high mobility group (HMG)-box found in high mobility group protein 20A (HMG20A) and similar proteins; HMG20A, also called HMG box-containing protein 20A, HMG domain-containing protein 1 (HMGXB1), HMG domain-containing protein HMGX1, HMGXB1, or iBRAF, is a chromatin-associated protein involved in neuronal differentiation and maturation. It is required for SNAI1-mediated epithelial to mesenchymal transition. HMG20A acts as an inhibitor of HMG20B.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2217351952 432 RRGvGSPPGRKKTTVSMPRSRKGDAASQFLVFCQKHRDEVVAEHPDASGEEIEELLRSQWSLLSEKQRARY 502
Cdd:cd22017     1 KRG-GWSKGRKRKKPLRDSNAPKAPLTGYVRFMNERREQLRAERPDVPFPEITRMLGNEWSKLPAEEKQRY 70