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 2217335249   87 FQINEQVLACWSDCRFYPAKVTAVNKDGTYTVKFYDGVVQTVKHIHVKAFSKD 139
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 2217335249   13 FEVGAQLEARDRLKNWYPAHIEDIDYEEGKVLIHFKRWNHRYDEWFCWDSPYLRPLE 69
Cdd:cd20104      1 FKVGDRVDALDGEGKWYEAKIVEVDEEENKVLVHYDGWSSRYDEWIDRDSERLRPLH 57

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 2217335249   87 FQINEQVLACWSDCRFYPAKVTAVNKDGTYTVKFYDGVVQTVKHIHVKAFSKD 139
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 2217335249   13 FEVGAQLEARDRLKNWYPAHIEDIDYEEGKVLIHFKRWNHRYDEWFCWDSPYLRPLE 69
Cdd:cd20104      1 FKVGDRVDALDGEGKWYEAKIVEVDEEENKVLVHYDGWSSRYDEWIDRDSERLRPLH 57

DNA repair protein Crb2 Tudor domain; This is the tudor domain found in DNA repair protein crb2. Structural and functional studies of Crb2 and its mammalian homolog 53BP1 indicate that the conserved tandem-Tudor domain of 53BP1 and Crb2 preferentially interacts with H4K20me2, though it also binds to H4K20me1. Furthermore, despite low amino acid sequence similarity, Crb2 is structurally related to 53BP1 in having two tudor domains and a conserved dimethyllysine-binding pocket, and that, like 53BP1, it directly binds H4-K20me2.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2217335249   92 QVLACW--SDCRFYPAKVTAVNKDGT--YTVKFYDGVVQTVKHIHVKAF 136
Cdd:pfam18115    2 RVFALWkgKDRAYYPATCLGTSGSGSqrYLVRFDDGTPTEVDSGQVRRL 50

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.

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*
gi 2217335249   655 CICEVQEENDFMIQCEECQCWQHGVCMG--LLEENVPEKYTCYVC 697
Cdd:smart00249    3 SVCGKPDDGGELLQCDGCDRWYHQTCLGppLLEEEPDGKWYCPKC 47

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 2217335249     3 KHPPNRRGISFEVGAQLEARDRLkNWY---PAHIEDIdyEEGKVLIHFKRWNHRYDEWFCWDSPYLRPL 68
Cdd:smart00561   18 KQPVDSPPNGFKVGMKLEAVDPR-NPSlicVATVVEV--KGYRLLLHFDGWDDKYDFWCHADSPDIFPV 83

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 2217335249   87 FQINEQVLACWSDCRFYPAKVTAVNKDGTYTVKFYDGVVQTVKHIHVKAFSKD 139
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 2217335249   13 FEVGAQLEARDRLKNWYPAHIEDIDYEEGKVLIHFKRWNHRYDEWFCWDSPYLRPLE 69
Cdd:cd20104      1 FKVGDRVDALDGEGKWYEAKIVEVDEEENKVLVHYDGWSSRYDEWIDRDSERLRPLH 57

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 2217335249  654 RCICEVQEENDFMIQCEECQCWQHGVCMGLLEENVPEKYTCYVCQD 699
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 2217335249  654 RCICEVQEENDFMIQCEECQCWQHGVCMGLL-EENVPEKYTCYVC 697
Cdd:cd15549      1 HCICGVNEENGLMIQCELCLCWQHGVCMGIEeEESVPERYVCYVC 45

PHD finger found in mixed lineage leukemia 5 (MLL5); MLL5 is a histone methyltransferase that plays a key role in hematopoiesis, spermatogenesis and cell cycle progression. It contains a single plant homeodomain (PHD) finger followed by a catalytic SET domain. MLL5 can be recruited to E2F1-responsive promoters to stimulate H3K4 trimethylation and transcriptional activation by binding to the cell cycle regulator host cell factor (HCF-1), thereby facilitating the cell cycle G1 to S phase transition. It is also involved in mitotic fidelity and genomic integrity by modulating the stability of the chromosomal passenger complex (CPC) via the interaction with Borealin. Moreover, MLL5 is a component of a complex associated with retinoic acid receptor that requires GlcN Acylation of its SET domain in order to activate its histone lysine methyltransferase activity. It also participates in the camptothecin (CPT)-induced p53 activation. Furthermore, MLL5 indirectly regulates H3K4 methylation, represses cyclin A2 (CycA) expression, and promotes myogenic differentiation.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2217335249  654 RCICEVQEENDFMIQCEECQCWQHGVCMGLLEENVPEKYTCYVC 697
Cdd:cd15550      1 RCICGFEHDDGFMICCDKCSVWQHGDCMGIDRENIPDSYLCEQC 44

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 2217335249  653 VRCICEVQEENDFMIQCEECQCWQHGVCMGLleENVPEKYTCYVC 697
Cdd:cd15548      1 IRCICGLYKDEGLMIQCEKCMVWQHCDCMGV--NDDVEHYLCEQC 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 2217335249   13 FEVGAQLEARDRLKN--WYPAHIEDIDyeEGKVLIHFKRWNH-RYDEWFCWDSPYLRPL 68
Cdd:cd20088      1 FKVGMKLEAVDPLNPseICVATVVKVV--GGRLLLHFDGWDPsRYDFWCDVDSPDIHPV 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
                   ....*....|....*....|....*....|....*....|....*....
gi 2217335249  655 CICEVQEENDFMIQCEECQCWQHGVCMGLLE------ENVPEKYTCYVC 697
Cdd:cd15552      2 CICRKPHNNRFMICCDRCEEWFHGDCVGITEaqgkemEENIEEYVCPKC 50

PHD finger found in PHF2, PHF8 and KDM7; This family includes PHF2, PHF8, KDM7, and similar proteins. PHF2, also termed GRC5, or PHD finger protein 2, is a histone lysine demethylase ubiquitously expressed in various tissues. PHF8, also termed PHD finger protein 8, or KDM7B, is a monomethylated histone H4 lysine 20(H4K20me1) demethylase that transcriptionally regulates many cell cycle genes. It also preferentially acts on H3K9me2 and H3K9me1. PHF8 is modulated by CDC20-containing anaphase-promoting complex (APC (cdc20)) and plays an important role in the G2/M transition. It acts as a critical molecular sensor for mediating retinoic acid (RA) treatment response in RAR alpha-fusion-induced leukemia. Moreover, PHF8 is essential for cytoskeleton dynamics and is associated with X-linked mental retardation. 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. All family members contain a plant homeodomain (PHD) finger and a JmjC domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2217335249  655 CIC-EVQEENDFMIQCEECQCWQHGVCMGLLEENVP--EKYTCYVC 697
Cdd:cd15554      2 CICrQPYDVTRFMIECDVCKDWFHGSCVGVEEHQANdiERYHCPNC 47

second malignant brain tumor (MBT) repeat found in the Lethal(3)malignant brain tumor-like protein 1 (L3MBTL1)-like family; The L3MBTL1-like family includes L3MBTL1, L3MBTL3, and L3MBTL4. 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. L3MBTL3, also called L(3)mbt-like protein 3, or MBT-1, is a 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. L3MBTL4, also called L(3)mbt-like protein 4, or L3mbt-like 4, is a PcG protein that may act as a tumor suppressor. Members of this family contain 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217335249   13 FEVGAQLEARDRlKNwyP-----AHIEDIdyEEGKVLIHFKRWNHRYDEWFCWDSPYLRP 67
Cdd:cd20102      4 FRVGMKLEAVDR-KN--PslicvATVTDV--IGNRFLVHFDGWDDSYDYWCDPDSPYIHP 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 2217335249  655 CICEVQEENDFMIQCEECQCWQHGVCMG--LLEENVPE-KYTCYVCQ 698
Cdd:pfam00628    3 AVCGKSDDGGELVQCDGCDDWFHLACLGppLDPAEIPSgEWLCPECK 49

PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) finger typically characterized as Cys4HisCys3, and a non-canonical extended PHD finger, characterized as Cys2HisCys5HisCys2His. Variations include the RAG2 PHD finger characterized by Cys3His2Cys2His and the PHD finger 5 found in nuclear receptor-binding SET domain-containing proteins characterized by Cys4HisCys2His. The PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. Single or multiple copies of PHD fingers have been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors. The PHD finger domain SF is structurally similar to the RING and FYVE_like superfamilies.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2217335249  655 CIC-EVQEENDFMIQCEECQCWQHGVCMGLLEENV--PEKYTCYVC 697
Cdd:cd15489      3 IVCgKGGDLGGELLQCDGCGKWFHADCLGPPLSSFvpNGKWICPVC 48

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.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2217335249   13 FEVGAQLEARDRlKNWY---PAHIEDIDYEEgkVLIHFKRWNHRYDEWFCWDSPYLRP 67
Cdd:cd20092      6 FKVGMKLEAVDR-KNPQlicPATVGDVDGDE--IHISFDGWRGAFDYWCRYDSRDIFP 60

PHD finger found in Transcription factor 19 (TCF-19), Lysine-specific demethylase KDM5A and KDM5B, and other similar proteins; TCF-19 was identified as a putative trans-activating factor with expression beginning at the late G1-S boundary in dividing cells. It functions as a novel islet factor necessary for proliferation and survival in the INS-1 beta cell line. It plays an important role in susceptibility to both Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM); it has been suggested that it may positively impact beta cell mass under conditions of beta cell stress and increased insulin demand. KDM5A was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation. It is involved in transcription through interaction with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK, and BMAL1. KDM5B has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of the pregnant female and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis. Both KDM5A and KDM5B function as trimethylated histone H3 lysine 4 (H3K4me3) demethylases. This family also includes Caenorhabditis elegans Lysine-specific demethylase 7 homolog (ceKDM7A). ceKDM7A (also termed JmjC domain-containing protein 1.2, PHD finger protein 8 homolog, or PHF8 homolog) is a plant homeodomain (PHD)- and JmjC domain-containing protein that functions as a histone demethylase specific for H3K9me2 and H3K27me2. The binding of the PHD finger to H3K4me3 guides H3K9me2- and H3K27me2-specific demethylation by its catalytic JmjC domain in a trans-histone regulation mechanism. In addition, this family includes plant protein OBERON 1 and OBERON 2, Alfin1-like (AL) proteins, histone acetyltransferases (HATs) HAC, and AT-rich interactive domain-containing protein 4 (ARID4).

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2217335249  653 VRCICEVQEENDFMIQCEECQCWQHGVCMGL--LEENVPEKYTCYVC 697
Cdd:cd15517      3 GICNLETAAVDELWVQCDGCDKWFHQFCLGLsnERYADEDKFKCPNC 49

Tudor domain; Domain of unknown function present in several RNA-binding proteins. 10 copies in the Drosophila Tudor protein. Initial proposal that the survival motor neuron gene product contain a Tudor domain are corroborated by more recent database search techniques such as PSI-BLAST (unpublished).

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 2217335249    85 SEFQINEQVLACWSDCRFYPAKVTAVNKDGTYTVKFYD-GVVQTVK 129
Cdd:smart00333    1 PTFKVGDKVAARWEDGEWYRARIVKVDGEQLYEVFFIDyGNEEVVP 46

PHD finger found in death-inducer obliterator variants Dido1, Dido2, and Dido3; This family includes three alternative splicing variants (Dido1, 2, and 3) encoded by the Dido gene, which have been implicated in a number of cellular processes such as apoptosis and chromosomal segregation, particularly in the hematopoietic system. Dido1, also termed DIO-1, or death-associated transcription factor 1 (DATF-1), 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 plant homeodomain (PHD) finger responsible for the binding of histone H3 with a higher affinity for trimethylated lysine 4 (H3K4me3). Gene Dido is a Bonemorphogenetic protein (BMP) target gene, which promotes BMP-induced melanoma progression. It also triggers apoptosis after nuclear translocation and caspase upregulation. Dido3 is the largest isoform ubiquitously expressed in all human tissues. It is dispensable for ES cell self-renewal and pluripotency, but 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, aspen paralog and ortholog (SPOC) module, and a long C-terminal region (CT) of unknown homology. Its PHD finger interacts with H3K4me3.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2217335249  655 CICEVQEENDFMIQCEECQCWQHGVCMG-------LLEENvPEKYTCYVC 697
Cdd:cd15639      6 CICRQPHNNRFMICCDRCEEWFHGDCVGiteargrLLERN-GEDYICPNC 54

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        40
                   ....*....|....*....|....*....|....*....|....*
gi 2217335249  655 CICEVQEENDFMIQCEECQCWQHGVCMGLLEENVP--EKYTCYVC 697
Cdd:cd15553      2 CICRSSDISRFMIGCDNCEEWYHGDCINITEKEAKaiKEWYCQQC 46

PHD finger found in Arabidopsis thaliana PHD finger protein MALE MEIOCYTE DEATH 1 (MMD1), PHD finger protein MALE STERILITY 1 (MS1), and similar proteins; MMD1 is a plant homeodomain (PHD) finger protein expressed in male meiocytes. It is encoded by the gene DUET, which is required for male meiotic chromosome organization and progression. MMD1 has been implicated in the regulation of gene expression during meiosis. The mmd1 mutation triggers cell death in male meiocytes. MS1 is a nuclear transcriptional activator that is important for tapetal development and pollen wall biosynthesis. It contains a Leu zipper-like domain and a PHD finger motif, both of which are essential for its function.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2217335249  655 CICEVQEEN-DFMIQCEECQCWQHGVCMGL-LEENVPEKYTCYVC 697
Cdd:cd15556      2 CSCGTRDDDgERMIACDVCEVWQHTRCVGIaDNEEPPDHFLCRRC 46

PHD finger found in PHD finger proteins PHF13 and PHF23; PHF13, also termed survival time-associated PHD finger protein in ovarian cancer 1 (SPOC1), is a novel plant homeodomain (PHD) finger-containing protein that shows strong expression in spermatogonia and ovarian cancer cells, modulates chromatin structure and mitotic chromosome condensation, and is important for proper cell division. It is also required for spermatogonial stem cell differentiation and sustained spermatogenesis. The overexpression of PHF13 associates with unresectable carcinomas and shorter survival in ovarian cancer. PHF23, also termed PHD-containing protein JUNE-1, is a hypothetical protein with a PHD finger. It is encoded by gene PHF23 that acts as a candidate fusion partner for the nucleoporin gene NUP98. The NUP98-PHF23 fusion results from a cryptic translocation t(11;17)(p15;p13) in acute myeloid leukemia (AML).

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                   ....*....|....*....|....*....|..
gi 2217335249  666 MIQCEECQCWQHGVCMGLLEENVPEKYTCYVC 697
Cdd:cd15546     13 MIECSECLTWIHLSCAKIRKNNVPEVFICQKC 44

PHD finger found in E3 ubiquitin-protein ligase SHPRH; SHPRH, also termed SNF2, histone-linker, PHD and RING finger domain-containing helicase, belongs to the SWI2/SNF2 family of ATP-dependent chromatin remodeling enzymes, containing the Cys3HisCys4 RING-finger characteristic of E3 ubiquitin ligases. It plays a key role in the error-free branch of DNA damage tolerance. As functional homologs of Saccharomyces cerevisiae Rad5, SHPRH and its closely-related protein, helicase like transcription factor (HLTF), act as ubiquitin ligases that cooperatively mediate Ubc13-Mms2-dependent polyubiquitination of proliferating cell nuclear antigen (PCNA) and maintain genomic stability. SHPRH contains a SNF2 domain, a H1.5 (linker histone H1 and H5) domain, a plant homeodomain (PHD) finger, a Cys3HisCys4 RING-finger, and a C-terminal helicase domain.

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                   ....*....|....*....|....*....|....*....|....*.
gi 2217335249  655 CICEV--QEENDFMIQCEECQCWQHGVCMGLLEENVP-EKYTCYVC 697
Cdd:cd15547      2 CICGEldEIDNKHRVQCLKCGLWQHAECVNYDEESDKrEPYLCPHC 47

Tudor domain found in Schizosaccharomyces pombe splicing factor spf30 (SpSPF30) and similar proteins; SpSPF30, also called survival of motor neuron-related-splicing factor 30, is necessary for spliceosome assembly. 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.

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2217335249   87 FQINEQVLACW--SDCRFYPAKVTAVNKDGT---YTVKFYD-GVVQTVKHIHVKA 135
Cdd:cd20446      1 FKPGEVVMARWksGDGKFYPARITSITGSSInpiYTVKFLDyGEIDTVYLKDIRP 55

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2217335249   12 SFEVGAQLEARDRLKnwyPAHIED---IDYEEGKVLIHFKRWNHRYDEWFCWDSPYLRP 67
Cdd:cd20137      4 GFQVNMKLEAVDRRN---PALIRVasvEDVEDHRIKIHFDGWSHGYDFWIDADHPDIHP 59

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 2217335249  656 ICE-VQEENDF---MIQCEECQCWQHGVCMGLLEE------NVPE--KYTCYVC 697
Cdd:cd15508      4 LCEkCYDDDDYdskMMQCSQCDHWVHAKCEGLSDEmyeilsYLPEsiEYTCSLC 57

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 2217335249  655 CIC-EVQEENDFMIQCEECQCWQHGVCMGLLEENVP--EKYTCYVCQ 698
Cdd:cd15640      2 CVCrQPYDVNRFMIECDICKDWFHGSCVQVEEHHAAdiDLYHCPNCE 48

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 2217335249  656 ICEVQEENDFMIQCEECQCWQHGVCMGLLEENVPE 690
Cdd:cd15522      4 ICKKPDDGSPMIGCDECDDWYHWECVGITDEPPEE 38

fourth 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 third MBT repeat that contains the semi-aromatic cage that may bind methylated lysine residues.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2217335249   13 FEVGAQLEARDRLKNWYPAHIEDIDYEEGKVLIHFKRWNHRYDEWFCWDSPYLRPL 68
Cdd:cd20139      9 FQVNMKLEAVDKRNPILIRVATIVDKDDHRIKLHFDGWDHNYDFWVDADSPDIHPV 64

Tudor-like domain present in plant sequences; Domain in plant sequences with possible chromatin-associated functions.

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                    ....*....|....*....|....*....|....*....|
gi 2217335249    85 SEFQINEQVLACWSDCrFYPAKVTAVNKDGTYTVKFYDGV 124
Cdd:smart00743    1 SDFKEGDRVEVFSEDS-WWEAVVTKVLGDGKYLVEYKGES 39

second malignant brain tumor (MBT) repeat found in sex comb on midleg-like protein 2 (SCML2) and similar proteins; SCML2 is a homolog of Drosophila Sex comb on midleg (Scm). It is a component of PRC1 (Polycomb repressive complex 1), which acts as an E3 ubiquitin ligase, both for histone H2A to silence transcription and for geminin to regulate its stability. SCML2 is a germline-specific Polycomb protein that acts as a critical regulator of heterochromatin organization in spermatogenesis. SCML2 contains 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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217335249    5 PPNrrgiSFEVGAQLEARDRlKNWY---PAHIEDIDYEEgkVLIHFKRWNHRYDEWFCWDSPYLRPL 68
Cdd:cd20109      2 PLN----NFKVGMKLEAIDK-KNPYlicPATIGDVKGDE--VFITFDGWRGAFDYWCKYDSRDIFPV 61

Tudor domain found in survival motor neuron protein (SMN), motor neuron-related-splicing factor 30 (SPF30), and similar proteins; This group contains SMN, SPF30, Tudor domain-containing protein 3 (TDRD3), DNA excision repair protein ERCC-6-like 2 (ERCC6L2), and similar proteins. SMN, also called component of gems 1, or Gemin-1, is part of a multimeric SMN complex that includes spliceosomal Sm core proteins and plays a catalyst role in the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. SPF30, also called 30 kDa splicing factor SMNrp, SMN-related protein, or survival motor neuron domain-containing protein 1 (SMNDC1), is an essential pre-mRNA splicing factor required for assembly of the U4/U5/U6 tri-small nuclear ribonucleoprotein into the spliceosome. TDRD3 is a scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. ERCC6L2, also called DNA repair and recombination protein RAD26-like (RAD26L), may be involved in early DNA damage response. It regulates RNA Pol II-mediated transcription via its interaction with DNA-dependent protein kinase (DNA-PK) to resolve R loops and minimize transcription-associated genome instability. Members of this group contain a single 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 2217335249   91 EQVLACWS-DCRFYPAKVTAVNKD-GTYTVKF-YDGVVQTVKHIHVKAF 136
Cdd:cd21182      2 DKCLAPYSdDGKYYEATIEEITEEsDTATVVFdGYGNSEEVPLSDLKPL 50

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 2217335249   89 INEQVLACWS-DCRFYPAKVTAVNKDGTYTVKFYD-GVVQTVKHIHVK 134
Cdd:cd20379      1 VGDLCAAKYEeDGKWYRARVLEVLSNDKVEVFFVDyGNTETVPLSDLR 48

PHD finger found in Arabidopsis thaliana histone acetyltransferases (HATs) HAC and similar proteins; This family includes A. thaliana HACs (HAC1/2/4/5/12), which are histone acetyltransferases of the p300/CREB-binding protein (CBP) co-activator family. CBP-type HAT proteins are also found in animals, but absent in fungi. The domain architecture of CBP-type HAT proteins differs between plants and animals. Members in this family contain an N-terminal partially conserved KIX domain, a Zf-TAZ domain, a Cysteine rich CBP-type HAT domain that harbors a plant homeodomain (PHD) finger, a Zf-ZZ domain, and a Zf-TAZ domain. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins.

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                   ....*....|....*....|....*....|....*....|....
gi 2217335249  657 CEVQEEndFMIQCEECQCWQHGVCM---GLLEENVPEKYTCYVC 697
Cdd:cd15614     32 DEEFEE--AWVQCDKCERWQHQICGlynGRRNADETAEYVCPLC 73