Tudor domain found in PHD finger protein 20 (PHF20) and similar proteins; PHF20, also called Glioma-expressed antigen 2, hepatocellular carcinoma-associated antigen 58, novel zinc finger protein, or transcription factor TZP (referring to Tudor and zinc finger domain containing protein), is a regulator of NF-kappaB activation by disrupting recruitment of PP2A to p65. It also functions as a transcription factor that binds to Akt and plays a role in Akt cell survival/growth signaling. Moreover, it transcriptionally regulates p53. The phosphorylation of PHF20 on Ser291 mediated by protein kinase B (PKB) is essential in tumorigenesis via the regulation of p53-mediated signaling. PHF20 contains an N-terminal malignant brain tumor (MBT) domain, a Tudor domain, a plant homeodomain (PHD) finger and putative DNA-binding domains AT hook and C2H2-type zinc finger. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 617436108   86 FHVNDKVLASWSDCRFYPAKVISVNKDASYTVKFYDGVIQTVKGMHVKPYIKE 138
Cdd:cd20453     1 FQVNEQVLACWSDCRFYPAKVTAVNKDGTYTVKFYDGVVQTVKHIHVKAFSKD 53

malignant brain tumor (MBT) repeat found in PHD finger protein 20-like protein 1 (PHF20L1) and similar domains; PHF20L1 associates with SOX2, antagonizes SOX2 ubiquitination and the sequential degradation induced by MLL1/WDR5 complexes. It binds both monomethylated Lys-42 and Lys-117 in SOX2 and thereby prevents SOX2 proteolysis. PHF20L1 also reads and controls enzyme levels of methylated DNMT1 in cells, thus representing a novel antagonist of DNMT1 degradation. PHF20L1 contains one MBT (malignant brain tumor) repeat. The MBT repeat is a protein module that recognizes methylated lysine residues on histones. MBT repeats contain a semi-aromatic cage to accommodate methyllysine and show specificity towards the lower methylation states of lysine. This model corresponds to the MBT repeat of PHF20L1 and similar domains that contains the semi-aromatic cage that may bind methylated lysine residues.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 617436108   13 FEVGAQLEARDSLKNWYAANIEKIDYDDEKVLIHYRQWSHRYDEWFDWTSPYLRPVER 70
Cdd:cd20104     1 FKVGDRVDALDGEGKWYEAKIVEVDEEENKVLVHYDGWSSRYDEWIDRDSERLRPLHT 58

Tudor domain found in PHD finger protein 20 (PHF20) and similar proteins; PHF20, also called Glioma-expressed antigen 2, hepatocellular carcinoma-associated antigen 58, novel zinc finger protein, or transcription factor TZP (referring to Tudor and zinc finger domain containing protein), is a regulator of NF-kappaB activation by disrupting recruitment of PP2A to p65. It also functions as a transcription factor that binds to Akt and plays a role in Akt cell survival/growth signaling. Moreover, it transcriptionally regulates p53. The phosphorylation of PHF20 on Ser291 mediated by protein kinase B (PKB) is essential in tumorigenesis via the regulation of p53-mediated signaling. PHF20 contains an N-terminal malignant brain tumor (MBT) domain, a Tudor domain, a plant homeodomain (PHD) finger and putative DNA-binding domains AT hook and C2H2-type zinc finger. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 617436108   86 FHVNDKVLASWSDCRFYPAKVISVNKDASYTVKFYDGVIQTVKGMHVKPYIKE 138
Cdd:cd20453     1 FQVNEQVLACWSDCRFYPAKVTAVNKDGTYTVKFYDGVVQTVKHIHVKAFSKD 53

malignant brain tumor (MBT) repeat found in PHD finger protein 20-like protein 1 (PHF20L1) and similar domains; PHF20L1 associates with SOX2, antagonizes SOX2 ubiquitination and the sequential degradation induced by MLL1/WDR5 complexes. It binds both monomethylated Lys-42 and Lys-117 in SOX2 and thereby prevents SOX2 proteolysis. PHF20L1 also reads and controls enzyme levels of methylated DNMT1 in cells, thus representing a novel antagonist of DNMT1 degradation. PHF20L1 contains one MBT (malignant brain tumor) repeat. The MBT repeat is a protein module that recognizes methylated lysine residues on histones. MBT repeats contain a semi-aromatic cage to accommodate methyllysine and show specificity towards the lower methylation states of lysine. This model corresponds to the MBT repeat of PHF20L1 and similar domains that contains the semi-aromatic cage that may bind methylated lysine residues.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 617436108   13 FEVGAQLEARDSLKNWYAANIEKIDYDDEKVLIHYRQWSHRYDEWFDWTSPYLRPVER 70
Cdd:cd20104     1 FKVGDRVDALDGEGKWYEAKIVEVDEEENKVLVHYDGWSSRYDEWIDRDSERLRPLHT 58

PHD-finger; PHD folds into an interleaved type of Zn-finger chelating 2 Zn ions in a similar manner to that of the RING and FYVE domains. Several PHD fingers have been identified as binding modules of methylated histone H3.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 617436108   635 RC-ICEVEEENDFMIQCEDCLCWQHGTCMGL---MEDNVPDRYTCYICR 679
Cdd:pfam00628    1 YCaVCGKSDDGGELVQCDGCDDWFHLACLGPpldPAEIPSGEWLCPECK 49

Present in Drosophila Scm, l(3)mbt, and vertebrate SCML2; Present in Drosophila Scm, l(3)mbt, and vertebrate SCML2. These proteins are involved in transcriptional regulation.

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 617436108      3 KTPPNRRGITFEVGAQLEARDsLKNWYA---ANIEKIDydDEKVLIHYRQWSHRYDEWFDWTSPYLRPV 68
Cdd:smart00561   18 KQPVDSPPNGFKVGMKLEAVD-PRNPSLicvATVVEVK--GYRLLLHFDGWDDKYDFWCHADSPDIFPV 83

mbt repeat; The function of this repeat is unknown, but is found in a number of nuclear proteins such as drosophila sex comb on midleg protein. The repeat is found in up to four copies as in Swiss:Q9UHJ3. The repeat contains a completely conserved glutamate at its amino terminus that may be important for function.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 617436108    19 LEARDSLKN---WyAANIEKIDydDEKVLIHYRQWSHRYDEWFDWTSPYLRPV 68
Cdd:pfam02820    3 LEAVDPLNPsliC-VATVVKVL--GGRLRLRFDGWDDSYDFWCHADSPDIHPV 52

Tudor domain found in PHD finger protein 20 (PHF20) and similar proteins; PHF20, also called Glioma-expressed antigen 2, hepatocellular carcinoma-associated antigen 58, novel zinc finger protein, or transcription factor TZP (referring to Tudor and zinc finger domain containing protein), is a regulator of NF-kappaB activation by disrupting recruitment of PP2A to p65. It also functions as a transcription factor that binds to Akt and plays a role in Akt cell survival/growth signaling. Moreover, it transcriptionally regulates p53. The phosphorylation of PHF20 on Ser291 mediated by protein kinase B (PKB) is essential in tumorigenesis via the regulation of p53-mediated signaling. PHF20 contains an N-terminal malignant brain tumor (MBT) domain, a Tudor domain, a plant homeodomain (PHD) finger and putative DNA-binding domains AT hook and C2H2-type zinc finger. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 617436108   86 FHVNDKVLASWSDCRFYPAKVISVNKDASYTVKFYDGVIQTVKGMHVKPYIKE 138
Cdd:cd20453     1 FQVNEQVLACWSDCRFYPAKVTAVNKDGTYTVKFYDGVVQTVKHIHVKAFSKD 53

PHD finger found in PHD finger protein 20-like protein 1 (P20L1); P20L1 is an active malignant brain tumor (MBT) domain-containing protein that binds to monomethylated lysine 142 on DNA (Cytosine-5) Methyltransferase 1 (DNMT1) (DNMT1K142me1) and colocalizes at the perinucleolar space in a SET7-dependent manner. Its MBT domain reads and controls enzyme levels of methylated DNMT1 in cells, thus representing a novel antagonist of DNMT1 proteasomal degradation. In addition to the MBT domain, PHF20L1 also contains two Tudor domains, a plant homeodomain (PHD) finger and the putative DNA-binding domains, AT hook and Cys2His2-type zinc finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 617436108  635 RCICEVEEENDFMIQCEDCLCWQHGTCMGLMEDNVPDRYTCYICRD 680
Cdd:cd15633     1 RCICEMDEENGFMIQCEECLCWQHSVCMGLLEESIPEQYICYICRD 46

PHD finger found in PHD finger protein 20 (PHF20) and PHD finger protein 20-like protein 1 (P20L1); PHF20, also termed Glioma-expressed antigen 2, or hepatocellular carcinoma-associated antigen 58, or novel zinc finger protein, or transcription factor TZP (referring to Tudor and zinc finger domain containing protein), is a regulator of NF-kappaB activation by disrupting recruitment of PP2A to p65. It also functions as a transcription factor that binds Akt and plays a role in Akt cell survival/growth signaling. Moreover, it transcriptionally regulates p53. The phosphorylation of PHF20 on Ser291 mediated by protein kinase B (PKB) is essential in tumorigenesis via the regulation of p53 mediated signaling. P20L1 is an active malignant brain tumor (MBT) domain-containing protein that binds to monomethylated lysine 142 on DNA (Cytosine-5) Methyltransferase 1 (DNMT1) (DNMT1K142me1) and colocalizes at the perinucleolar space in a SET7-dependent manner. Its MBT domain reads and controls enzyme levels of methylated DNMT1 in cells, thus representing a novel antagonist of DNMT1 proteasomal degradation. Both PHF20 and PHF20L1 contain an N-terminal MBT domain, two Tudor domains, a plant homeodomain (PHD) finger and the putative DNA-binding domains, AT hook and Cys2His2-type zinc finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 617436108  635 RCICEVEEENDFMIQCEDCLCWQHGTCMGLM-EDNVPDRYTCYIC 678
Cdd:cd15549     1 HCICGVNEENGLMIQCELCLCWQHGVCMGIEeEESVPERYVCYVC 45

Tudor domain found in PHD finger protein 20-like protein 1 (PHF20L1) and similar proteins; PHF20L1 is an active malignant brain tumor (MBT) domain-containing protein that binds to monomethylated lysine 142 on DNA (cytosine-5) Methyltransferase 1 (DNMT1) (DNMT1K142me1) and colocalizes at the perinucleolar space in a SET7-dependent manner. Its MBT domain reads and controls enzyme levels of methylated DNMT1 in cells, thus representing a novel antagonist of DNMT1 proteasomal degradation. In addition to the MBT domain, PHF20L1 also contains a Tudor domain, a plant homeodomain (PHD) finger and putative DNA-binding domains AT hook and C2H2-type zinc finger. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 617436108   86 FHVNDKVLASWSDCRFYPAKVISVNKDASYTVKFYDGVIQTVKGMHVK 133
Cdd:cd20454     2 FKAGEEVLARWTDCRYYPAKIEAINKEGTYTVQFYDGVIRCLKRMHIK 49

Tudor domain superfamily; The Tudor domain is a conserved structural domain, originally identified in the Tudor protein of Drosophila, that adopts a beta-barrel-like core structure containing four short beta-strands followed by an alpha-helical region. It binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions. Tudor domain-containing proteins may mediate protein-protein interactions required for various DNA-templated biological processes, such as RNA metabolism, as well as histone modification and the DNA damage response. Members of this superfamily contain one or more copies of the Tudor domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 617436108   89 NDKVLASWS-DCRFYPAKVISVNKDASYTVKFYDGVIQTVKGMHVKP 134
Cdd:cd04508     1 GDRVEAKWSdDGQWYPATVVAVNDDGKYTVLFDDGNEEEVSEDDIRP 47

PHD finger found in histone-lysine N-methyltransferase ASH1L; ASH1L, also termed ASH1-like protein, or absent small and homeotic disks protein 1 homolog, or lysine N-methyltransferase 2H, is a protein belonging to the Trithorax family. It methylates Lys36 of histone H3 independently of transcriptional elongation to promote the establishment of Hox gene expression by counteracting Polycomb silencing. It can suppress interleukin-6 (IL-6), and tumor necrosis factor (TNF) production in Toll-like receptor (TLR)-triggered macrophages, and inflammatory autoimmune diseases by inducing the ubiquitin-editing enzyme A20. ASH1L contains an associated with SET domain (AWS), a SET domain, a post-SET domain, a bromodomain, a bromo-adjacent homology domain (BAH), and a plant homeodomain (PHD) finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 617436108  634 VRCICEVEEENDFMIQCEDCLCWQHGTCMGLMEDnvPDRYTCYIC 678
Cdd:cd15548     1 IRCICGLYKDEGLMIQCEKCMVWQHCDCMGVNDD--VEHYLCEQC 43

malignant brain tumor (MBT) repeat; The MBT repeat is a protein module that recognizes methylated lysine residues on histones and are thought to affect a variety of chromatin processes, including transcription. It exists as tandem repeats and is found in a number of nuclear proteins such as Drosophila sex comb on midleg protein. In the human genome, there are at least 9 MBT repeat proteins, each containing two, three or four MBT repeats. MBT repeat proteins use a semi-aromatic cage to accommodate methyllysine and show specificity towards the lower methylation states of lysine (monomethyllysine and/or dimethyllysine).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 617436108   13 FEVGAQLEARDSLKN--WYAANIEKIDYDdeKVLIHYRQWSH-RYDEWFDWTSPYLRPV 68
Cdd:cd20088     1 FKVGMKLEAVDPLNPseICVATVVKVVGG--RLLLHFDGWDPsRYDFWCDVDSPDIHPV 57

PHD finger found in PHD finger protein 3 (PHF3), and death-inducer obliterator variants Dido1, Dido2, and Dido3; PHF3 is a human homolog of yeast protein bypass of Ess1 (Bye1), a nuclear protein with a domain resembling the central domain in the transcription elongation factor TFIIS. It is ubiquitously expressed in normal tissues including brain, but its expression is significantly reduced or lost in glioblastomas. PHF3 contains an N-terminal plant homeodomain (PHD) finger, a central RNA polymerase II (Pol II)-binding TFIIS-like domain (TLD) domain, and a C-terminal Spen paralogue and orthologue C-terminal (SPOC) domain. This family also includes Dido gene encoding three alternative splicing variants (Dido1, 2, and 3), which have been implicated in a number of cellular processes such as apoptosis and chromosomal segregation, particularly in the hematopoietic system. Dido1 is important for maintaining embryonic stem (ES) cells and directly regulates the expression of pluripotency factors. It is the shortest isoform that contains only a highly conserved PHD finger responsible for the binding of histone H3 with a higher affinity for trimethylated lysine4 (H3K4me3). Gene Dido1 is a Bone morphogenetic protein (BMP) target gene and promotes BMP-induced melanoma progression. It also triggers apoptosis after nuclear translocation and caspase upregulation. Dido3 is the largest isoform and is ubiquitously expressed in all human tissues. It is dispensable for ES cell self-renewal and pluripotency, but is involved in the maintenance of stem cell genomic stability and tumorigenesis. Dido3 contains a PHD finger, a transcription elongation factor S-II subunit M (TFSIIM) domain, a SPOC module, and a long C-terminal region (CT) of unknown homology.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 617436108  636 CICEVEEENDFMIQCEDCLCWQHGTCMGL-------MEDNVPDrYTCYIC 678
Cdd:cd15552     2 CICRKPHNNRFMICCDRCEEWFHGDCVGIteaqgkeMEENIEE-YVCPKC 50

PHD-finger; PHD folds into an interleaved type of Zn-finger chelating 2 Zn ions in a similar manner to that of the RING and FYVE domains. Several PHD fingers have been identified as binding modules of methylated histone H3.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 617436108   635 RC-ICEVEEENDFMIQCEDCLCWQHGTCMGL---MEDNVPDRYTCYICR 679
Cdd:pfam00628    1 YCaVCGKSDDGGELVQCDGCDDWFHLACLGPpldPAEIPSGEWLCPECK 49

second malignant brain tumor (MBT) repeat found in Lethal(3)malignant brain tumor-like protein 4 (L3MBTL4); L3MBTL4, also called L(3)mbt-like protein 4, or L3mbt-like 4, is a Polycomb group (PcG) protein that may act as a tumor suppressor. L3MBTL4 contains three MBT (malignant brain tumor) repeats. The MBT repeat is a protein module that recognizes methylated lysine residues on histones. MBT repeats contain a semi-aromatic cage to accommodate methyllysine and show specificity towards the lower methylation states of lysine. This model corresponds to the second MBT repeat that contains the semi-aromatic cage that binds methylated lysine residues.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 617436108   13 FEVGAQLEARDSlKNWYAANIEKI-DYDDEKVLIHYRQWSHRYDEWFDWTSPYLRPVERIQLRRQGLHddSSPGFHVNDK 91
Cdd:cd20136     5 FQVGMKLEAVDR-KNPSLVCVATIaDIVEDRLLVHFDNWDDSYDYWCDVNSPYIQPVGWCQENGRTLV--APQGYPNPEK 81

                  ....*..
gi 617436108   92 VlaSWSD 98
Cdd:cd20136    82 F--SWTE 86

PHD finger found in Schizosaccharomyces pombe meiosis-specific protein hop1 (Hop1p) and similar proteins; Fission yeast Hop1p, also termed linear element-associated protein hop1, is an S. pombe homolog of the synaptonemal complex (SC)-associated protein Hop1 in Saccharomyces cerevisiae. In contrast to S. cerevisiae, S. pombe forms thin threads, known as linear elements (LinEs), in meiotic nuclei, instead of a canonical synaptonemal complex. LinEs contain Rec10 protein and are evolutionary relics of SC axial elements. Fission yeast Hop1p is a linear element (LinE)-associated protein. It also associates with Rec10, which plays a role in recruiting the recombination machinery to chromatin. Hop1p contains an N-terminal HORMA (for Hop1p, Rev7p, and MAD2) domain and a C-terminal plant homeodomain (PHD) finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 617436108  635 RCICEVEEENDFMIQCEDCLCWQHGTCMGLMEDN---VPDRYTCYIC 678
Cdd:cd15558     1 RCECGDWGEDGAMIQCAFCDTWQHLLCYGFESAKdprIPDIHVCYRC 47

Tudor domain found in tumor suppressor TP53-binding protein 1 (53BP1) and similar proteins; 53BP1, also called p53-binding protein 1 (p53BP1), is a double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics, and class-switch recombination (CSR) during antibody genesis. It plays a key role in the repair of DSBs in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1. It is recruited to DSB sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSB sites. 53BP1 contains one Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 617436108   88 VNDKVLASW-SDCRFYPAKVISVNKDASYTVKFYDGVIQTVKGMHVK 133
Cdd:cd20383     1 VGTRVFAKWsSDGYYYPGIITRVLGDGKYKVLFDDGYERDVKGKDII 47

second malignant brain tumor (MBT) repeat found in Lethal(3)malignant brain tumor-like protein 1 (L3MBTL1); L3MBTL1, also called L(3)mbt-like, or L(3)mbt protein homolog, is a Polycomb group (PcG) protein that functions as a 'reader' of a network of post-translational modifications by specifically recognizing and binding mono- and dimethyllysine residues on target proteins. It acts as a chromatin compaction factor by binding mono- and dimethylated histone H1b/HIST1H1E at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condensed chromatin and repressed transcription. L3MBTL1 contains three MBT (malignant brain tumor) repeats. The MBT repeat is a protein module that recognizes methylated lysine residues on histones. MBT repeats contain a semi-aromatic cage to accommodate methyllysine and show specificity towards the lower methylation states of lysine. This model corresponds to the second MBT repeat that contains the semi-aromatic cage that binds methylated lysine residues.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 617436108   13 FEVGAQLEARDSLKNWYAANIEKIDYDDEKVLIHYRQWSHRYDEWFDWTSPYLRPV 68
Cdd:cd20134     6 FQVGMKLEAVDRMNPSLVCVASVTDVVDSRFLVHFDNWDDTYDYWCDPSSPYIHPV 61

Present in Drosophila Scm, l(3)mbt, and vertebrate SCML2; Present in Drosophila Scm, l(3)mbt, and vertebrate SCML2. These proteins are involved in transcriptional regulation.

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 617436108      3 KTPPNRRGITFEVGAQLEARDsLKNWYA---ANIEKIDydDEKVLIHYRQWSHRYDEWFDWTSPYLRPV 68
Cdd:smart00561   18 KQPVDSPPNGFKVGMKLEAVD-PRNPSLicvATVVEVK--GYRLLLHFDGWDDKYDFWCHADSPDIFPV 83

PHD finger found in Set1 complex component SPP1; Set1C component SPP1, also called COMPASS component Spp1, or Complex proteins associated with set1 protein Spp1, or Suppressor of PRP protein 1, is a component of the COMPASS complex that links histone methylation to initiation of meiotic recombination. It induces double-strand break (DSB) formation by tethering to recombinationally cold regions. SPP1 interacts with H3K4me3 and Mer2, a protein required for DSB formation, to promote recruitment of potential meiotic DSB sites to the chromosomal axis. SPP1 contains a PHD finger, a zinc binding motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 617436108  636 CICEVEEENDFMIQCEDCLCWQHGTCMGLMEDNVP--DRYTCYIC 678
Cdd:cd16039     2 CICQKPDDGRWMIACDGCDEWYHFTCVNIPEADVElvDSFFCPPC 46

Tudor domain found in Lamin-B receptor (LBR) and similar proteins; LBR, also called integral nuclear envelope inner membrane (INM) protein or LMN2R, is a nuclear envelope protein that anchors the lamina and the heterochromatin to the inner nuclear membrane, in cellular senescence induced by excess thymidine. It is also important for cholesterol biosynthesis. LBR can interact with chromodomain proteins and DNA. It contains one Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 617436108   86 FHVNDKVLASWSDCR-FYPAKVISVNKDASYTVKFYDGVIQTVKGMHVKP 134
Cdd:cd20381     2 FKVGETVMARWPGSRlYYEATVLNFDDSDEYTVKFKDGTELELKEKDVKA 51

PHD finger found in Saccharomyces cerevisiae extracellular matrix protein 5 (Ecm5p), Schizosaccharomyces pombe Lid2 complex component Lid2p, and similar proteins; The family includes Saccharomyces cerevisiae Ecm5p, Schizosaccharomyces pombe Lid2 complex component Lid2p, and similar proteins. Ecm5p is a JmjC domain-containing protein that directly removes histone lysine methylation via a hydroxylation reaction. It associates with the yeast Snt2p and Rpd3 deacetylase, which may play a role in regulating transcription in response to oxidative stress. Ecm5p promotes oxidative stress tolerance, while Snt2p ultimately decreases tolerance. Ecm5p contains an N-terminal ARID domain, a JmjC domain, and a C-terminal plant homeodomain (PHD) finger. Lid2p is a trimethyl H3K4 (H3K4me3) demethylase responsible for H3K4 hypomethylation in heterochromatin. It interacts with the histone lysine-9 methyltransferase, Clr4, through the Dos1/Clr8-Rik1 complex, and mediates H3K9 methylation and small RNA production. It also acts cooperatively with the histone modification enzymes Set1 and Lsd1 and plays an essential role in cross-talk between H3K4 and H3K9 methylation in euchromatin. Lid2p contains a JmjC domain, three PHD fingers and a JmjN domain. This model includes the second PHD finger of Lid2p.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 617436108  636 CICEvEEENDFMIQCEDCLCWQHGTCMGLMEDNVPDR--YTCYIC 678
Cdd:cd15518     2 CFCR-QGEGGTMIECEICKEWYHVKCIKNGRWKLDDDdkFVCPIC 45

PHD finger found in CXXC-type zinc finger protein 1 (Cfp1); Cfp1, also termed CpG-binding protein, or PHD finger and CXXC domain-containing protein 1 (PCCX1), is a specificity factor that binds to unmethylated CpGs and links H3K4me3 with CpG islands (CGIs). It integrates both promoter CpG content and gene activity for accurate trimethylation of histone H3 Lys 4 (H3K4me3) deposition in embryonic stem cells. Moreover, Cfp1 is an essential component of the SETD1 histone H3K4 methyltransferase complex and functions as a critical regulator of histone methylation, cytosine methylation, cellular differentiation, and vertebrate development. Cfp1 contains a plant homeodomain (PHD) finger, a CXXC domain, and a CpG binding protein zinc finger C-terminal domain. Its CXXC domain selectively binds to non-methylated CpG islands, following by a preference for a guanosine nucleotide.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 617436108  636 CICEVEEENDFMIQCEDCLCWQHGTCMGLME 666
Cdd:cd15553     2 CICRSSDISRFMIGCDNCEEWYHGDCINITE 32

third malignant brain tumor (MBT) repeat found in Lethal(3)malignant brain tumor-like protein 1 (L3MBTL1); L3MBTL1, also called L(3)mbt-like, or L(3)mbt protein homolog, is a Polycomb group (PcG) protein that functions as a 'reader' of a network of post-translational modifications by specifically recognizing and binding mono- and dimethyllysine residues on target proteins. It acts as a chromatin compaction factor by binding mono- and dimethylated histone H1b/HIST1H1E at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condensed chromatin and repressed transcription. L3MBTL1 contains three MBT (malignant brain tumor) repeats. The MBT repeat is a protein module that recognizes methylated lysine residues on histones. MBT repeats contain a semi-aromatic cage to accommodate methyllysine and show specificity towards the lower methylation states of lysine. This model corresponds to the third MBT repeat that contains the semi-aromatic cage that may bind methylated lysine residues.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 617436108   13 FEVGAQLEARDSLKNWYAANIEKIDYDDEKVLIHYRQWSHRYDEWFDWTSPYLRPV 68
Cdd:cd20137     5 FQVNMKLEAVDRRNPALIRVASVEDVEDHRIKIHFDGWSHGYDFWIDADHPDIHPA 60

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

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                    ....*....|....*....|....*....|....*....|....
gi 617436108    636 CICEVEEENDFMIQCEDCLCWQHGTCMGL-MEDNVPDRytCYIC 678
Cdd:smart00249    3 SVCGKPDDGGELLQCDGCDRWYHQTCLGPpLLEEEPDG--KWYC 44

PHD finger found in lysine-specific demethylase PHF2; PHF2, also termed GRC5, or PHD finger protein 2, is a histone lysine demethylase ubiquitously expressed in various tissues. It contains a plant homeodomain (PHD) finger and a JmjC domain and plays an important role in adipogenesis. The PHD finger domain can recognize trimethylated histone H3 lysine 4 (H3K4me3). PHF2 also has dimethylated histone H3 lysine 9(H3K9me2) demethylase activity and acts as a coactivator of several metabolism-related transcription factors. Moreover, it can demethylate ARID5B and further forms a complex with demethylated ARD5B to bind the promoter regions of target genes. The overexpression of PHF2 is involved in the progression of esophageal squamous cell carcinoma (ESCC).

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                  ....*....|....*....|....*....|....*....|....*.
gi 617436108  636 CICEVEEE-NDFMIQCEDCLCWQHGTCMGLMEDNVP--DRYTCYIC 678
Cdd:cd15641     2 CICRLPYDvTRFMIECDACKDWFHGSCVGVEEEEAPdiDIYHCPNC 47

PHD finger 3 found in histone-lysine N-methyltransferase 2A (KMT2A) and 2B (KMT2B); This family includes histone-lysine N-methyltransferase trithorax (Trx) like proteins, KMT2A (MLL1) and KMT2B (MLL2), which comprise the mammalian Trx branch of the COMPASS family, and are both essential for mammalian embryonic development. KMT2A regulates chromatin-mediated transcription through the catalysis of methylation of histone 3 lysine 4 (H3K4), and is frequently rearranged in acute leukemia. KMT2A functions as the catalytic subunit in the MLL1 complex. KMT2B is a second human homolog of Drosophila trithorax, located on chromosome 19 and functions as the catalytic subunit in the MLL2 complex. It plays a critical role in memory formation through mediating hippocampal H3K4 di- and trimethylation. It is also required for RNA polymerase II association and protection from DNA methylation at the MagohB CpG island promoter. Both KMT2A and KMT2B contain a CxxC (x for any residue) zinc finger domain, three plant homeodomain (PHD) fingers, an extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain. This model corresponds to the third PHD finger.

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                  ....*....|....*....|....*....|....*....|....*....|....
gi 617436108  637 ICEVE-EENDF---MIQCEDCLCWQHGTCMGLMED------NVPD--RYTCYIC 678
Cdd:cd15508     4 LCEKCyDDDDYdskMMQCSQCDHWVHAKCEGLSDEmyeilsYLPEsiEYTCSLC 57

fourth malignant brain tumor (MBT) repeat found in the Drosophila melanogaster Polycomb protein Sfmbt (dSfmbt)-like family; The dSfmbt-like family includes Drosophila melanogaster Scm-like with four MBT domain-containing protein 1 (dSfmbt), as well as its two vertebrate homologs, MBT domain-containing protein 1 (MBTD1) and Lethal(3)malignant brain tumor-like protein 2 (L3MBTL2). dSfmbt is a Polycomb group (PcG) repressor involved in epigenetic regulation of gene expression. MBTD1 and L3MBTL2, also called L(3)mbt-like protein 2, are putative PcG proteins that specifically bind to monomethylated and dimethylated 'Lys-20' on histone H4. L3MBTL2 also binds histone H3 peptides which are monomethylated or dimethylated on 'Lys-4', 'Lys-9' or 'Lys-27'. Members of this family contain four MBT (malignant brain tumor) repeats. The MBT repeat is a protein module that recognizes methylated lysine residues on histones. MBT repeats contain a semi-aromatic cage to accommodate methyllysine and show specificity towards the lower methylation states of lysine. This model corresponds to the fourth MBT repeat that contains the semi-aromatic cage that binds methylated lysine residues.

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                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 617436108   13 FEVGAQLEARDSLKNWY--AANIEKIDydDEKVLIHYRQWSHRYDEWFDWTSPYLRPV 68
Cdd:cd20100     3 FKVGMKLEAVDLMEPRLicVATVTRVV--GRLLRVHFDGWDDEFDQWVDCDSPDIYPV 58

mbt repeat; The function of this repeat is unknown, but is found in a number of nuclear proteins such as drosophila sex comb on midleg protein. The repeat is found in up to four copies as in Swiss:Q9UHJ3. The repeat contains a completely conserved glutamate at its amino terminus that may be important for function.

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                   ....*....|....*....|....*....|....*....|....*....|...
gi 617436108    19 LEARDSLKN---WyAANIEKIDydDEKVLIHYRQWSHRYDEWFDWTSPYLRPV 68
Cdd:pfam02820    3 LEAVDPLNPsliC-VATVVKVL--GGRLRLRFDGWDDSYDFWCHADSPDIHPV 52

PHD finger found in lysine-specific demethylase 7 (KDM7); KDM7, also termed JmjC domain-containing histone demethylation protein 1D (JHDM1D), or KIAA1718, is a dual histone demethylase that catalyzes demethylation of monomethylated and dimethylated H3K9 (H3K9me2/me1) and H3K27 (H3K27me2/me1), which functions as an eraser of silencing marks on chromatin during brain development. It also plays a tumor-suppressive role by regulating angiogenesis. KDM7 contains a plant homeodomain (PHD) that binds Lys4-trimethylated histone 3 (H3K4me3) and a jumonji domain that demethylates either H3K9me2 or H3K27me2.

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                  ....*....|....*....|....*....|....*....|....*.
gi 617436108  636 CIC-EVEEENDFMIQCEDCLCWQHGTCMGLMEDNVP--DRYTCYIC 678
Cdd:cd15640     2 CVCrQPYDVNRFMIECDICKDWFHGSCVQVEEHHAAdiDLYHCPNC 47

third malignant brain tumor (MBT) repeat found in Lethal(3)malignant brain tumor-like protein 3 (L3MBTL3); L3MBTL3, also called L(3)mbt-like protein 3, or MBT-1, is a Polycomb group (PcG) protein that recognizes mono- and dimethylated lysine residues on histone tails. It also acts as a methyl-binding protein that binds the K142-methylated DNMT1 and recruits a novel CRL4(DCAF5) ubiquitin ligase to degrade DNMT1. L3MBTL3 contains three MBT (malignant brain tumor) repeats. The MBT repeat is a protein module that recognizes methylated lysine residues on histones. MBT repeats contain a semi-aromatic cage to accommodate methyllysine and show specificity towards the lower methylation states of lysine. This model corresponds to the third MBT repeat that contains the semi-aromatic cage that may bind methylated lysine residues.

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                  ....*....|....*....|....*....|...
gi 617436108   36 IDYDDEKVLIHYRQWSHRYDEWFDWTSPYLRPV 68
Cdd:cd20138    32 ADTDDHRVKVHFDGWNNCYDYWIDADSPDIHPA 64

chromo barrel domain of retinoblastoma binding protein 1, and similar proteins; Retinoblastoma-binding protein 1 (RBP1), also termed AT-rich interaction domain 4A, is a ubiquitously expressed nuclear protein. RBP1 is a tumor and leukemia suppressor that binds both methylated histone tails and DNA, and is involved in epigenetic regulation in leukemia and Prader-Willi/Angelman syndromes. The chromo barrel domain of RBP1 has been reported to recognize histone H4K20me3 weakly, and this binding is enhanced by the simultaneous binding of DNA. RBP1 binds directly, with several other proteins, to retinoblastoma protein (pRB) which regulates cell proliferation; pRB represses transcription by recruiting RBP1. SH3-fold-beta-barrel domains of the chromo-like superfamily include chromodomains, chromo shadow domains, and chromo barrel domains, and are implicated in the recognition of lysine-methylated histone tails and nucleic acids. The chromodomain differs, in that it lacks the first strand of the SH3-fold-beta-barrel. This first strand is altered by insertion in the chromo shadow domains, and chromo barrel domains are typical SH3-fold-beta-barrel domains with sequence similarity to the canonical chromodomain.

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                  ....*....|....*....|....*....|....*....|
gi 617436108   20 EARDSLKNWYAANIEKIDYDDEKV--LIHYRQWSHRYDEW 57
Cdd:cd18641     7 YGRGKTQKIYEASIKSTEIDDGEVlyLVHYYGWNVRYDEW 46

SGF29 tudor-like domain; This domain is found in the yeast protein SAGA-associated factor 29. This domain is related to members of the Tudor domain superfamily such as pfam05641. The SAGA complex is involved in RNA polymerase II-dependent transcriptional regulation. The membership of the tudor domain superfamily suggests this domain may bind to RNA.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 617436108    71 IQLRRQGLHDDSSPGFHVNDKVLASWSD--CrFYPAKVISVNKDAS--YTVKF----YDGVIQTVKGMHVKPY 135
Cdd:pfam07039   59 IPLPKWKANPSTDPLFPKGTKVLALYPDttT-FYRAEVVSPPKKKDgtYRLKFeddeDADPLREVPRRYVVPF 130

Tudor domain found in Drosophila melanogaster maternal protein Tudor (dTUD) and similar proteins; dTUD is required during oogenesis for the formation of primordial germ cells and for normal abdominal segmentation. It contains 11 Tudor domains. The family also includes mitochondrial A-kinase anchor protein 1 (AKAP1) and Tudor domain-containing proteins (TDRDs). AKAP1, also called A-kinase anchor protein 149 kDa (AKAP 149), or dual specificity A-kinase-anchoring protein 1 (D-AKAP-1), or protein kinase A-anchoring protein 1 (PRKA1), or Spermatid A-kinase anchor protein 84 (S-AKAP84), is found in mitochondria and in the endoplasmic reticulum-nuclear envelope where it anchors protein kinases, phosphatases, and a phosphodiesterase. It regulates multiple cellular processes governing mitochondrial homeostasis and cell viability. AKAP1 binds to type I and II regulatory subunits of protein kinase A and anchors them to the cytoplasmic face of the mitochondrial outer membrane. TDRDs have diverse biological functions and may contain one or more copies of the Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

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                  ....*....|....*....|....*....|....*....|....*....
gi 617436108   88 VNDKVLASWS-DCRFYPAKVISVNKDASYTVKFYD-GVIQTVKGMHVKP 134
Cdd:cd20379     1 VGDLCAAKYEeDGKWYRARVLEVLSNDKVEVFFVDyGNTETVPLSDLRP 49

PHD finger found in transcription initiation factor TFIID subunit 3 (TAF3); TAF3 (also termed 140 kDa TATA box-binding protein-associated factor, TBP-associated factor 3, transcription initiation factor TFIID 140 kDa subunit (TAF140), or TAFII-140, is an integral component of TFIID) is a general initiation factor (GTF) that plays a key role in preinitiation complex (PIC) assembly through core promoter recognition. The interaction of H3K4me3 with TAF3 directs global TFIID recruitment to active genes, which regulates gene-selective functions of p53 in response to genotoxic stress. TAF3 is highly enriched in embryonic stem cells and is required for endoderm lineage differentiation and prevents premature specification of neuroectoderm and mesoderm. Moreover, TAF3, along with TRF3, forms a complex that is essential for myogenic differentiation. TAF3 contains a plant homeodomain (PHD) finger. This family also includes Drosophila melanogaster BIP2 (Bric-a-brac interacting protein 2) protein, which functions as an interacting partner of D. melanogaster p53 (Dmp53).

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                  ....*....|....*....|....*....|....*
gi 617436108  637 ICEVEEENDFMIQCEDCLCWQHGTCMGLMEDNVPD 671
Cdd:cd15522     4 ICKKPDDGSPMIGCDECDDWYHWECVGITDEPPEE 38

second malignant brain tumor (MBT) repeat found in the Polycomb protein sex comb on midleg family; The Sex comb on midleg (Scm) family of Polycomb proteins includes Drosophila melanogaster Scm protein, as well as two vertebrate homologs of Scm, Polycomb protein sex comb on midleg homolog 1 (SCMH1) and sex comb on midleg-like protein 2 (SCML2). Scm is a putative zinc finger protein that functions as a transcriptional regulator which represses multiple homeotic genes during embryonic stages. It coordinates Polycomb group (PcG) complexes, PRC1 (PcG-repressive complex 1) or PRC2 (PcG-repressive complex 2), and polymerizes to produce broad domains of PcG silencing. Both SCMH1 and SCML2 are components of PRC1, which acts as an E3 ubiquitin ligase both for histone H2A to silence transcription and for geminin to regulate its stability. SCMH1 provides the complex with an interaction domain for geminin. SCML2 is a germline-specific Polycomb protein that acts as a critical regulator of heterochromatin organization in spermatogenesis. Members of this family contain two MBT (malignant brain tumor) repeats. The MBT repeat is a protein module that recognizes methylated lysine residues on histones. MBT repeats contain a semi-aromatic cage to accommodate methyllysine and show specificity towards the lower methylation states of lysine. This model corresponds to the second MBT repeat that contains the semi-aromatic cage that binds methylated lysine residues.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 617436108   12 TFEVGAQLEARDSlKNWY---AANIEkiDYDDEKVLIHYRQWSHRYDEWFDWTSPYLRPV 68
Cdd:cd20092     5 MFKVGMKLEAVDR-KNPQlicPATVG--DVDGDEIHISFDGWRGAFDYWCRYDSRDIFPV 61