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        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 317373307   86 DFKAGEEVLARWTDCRYYPAKIEAINKEGTFTVQFYDGVIRCLKRMHIKAMPEDAKGQ 143
Cdd:cd20454     1 DFKAGEEVLARWTDCRYYPAKIEAINKEGTYTVQFYDGVIRCLKRMHIKSMPEDAKGQ 58

PHD finger protein 20-like protein 1; PHD20L1_u1 is a region of natively unstructured but highly conserved sequence on a set of higher eukaryotic PHD finger protein 20-like protein 1 like proteins. The function is not known.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 317373307   318 SQKKNEADISS--SANTQKPALLSSTLSSGKARSKKCKHESGDSSGCIKPPKSPLSPELIQVEDLTLV 383
Cdd:pfam16660    1 QEKKNEADIGSivPAESQKPALLSASASSGKARGKKCKHEPGDASGCIKNPKPPADLELHQEEDLTLV 68

Protein of unknown function (DUF3776); This domain family is found in eukaryotes, and is approximately 100 amino acids in length.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 317373307   197 SNKDKDKDERKWFKVPSKKEETS-TCIATPDVEKKEDLPTSSETFGlhvenvPKMVFPQPESTLSNKRKNNQGNSFQAKR 275
Cdd:pfam12618    1 GKKEEEEKTLKSEKICSEKGKKSeKSLPKNESEEKENISPNEEYSG------DTQVDKKPESDIVKSRSKPQGNLCEPKR 74

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 317373307   276 ARLNKITGLLASKAVGVDGAEKKEDYNETAPMLEQ 310
Cdd:pfam12618   75 KRLGKGAGCTELKAEGRPPSITPQQKVESSSQSLQ 109

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 317373307   86 DFKAGEEVLARWTDCRYYPAKIEAINKEGTFTVQFYDGVIRCLKRMHIKAMPEDAKGQ 143
Cdd:cd20454     1 DFKAGEEVLARWTDCRYYPAKIEAINKEGTYTVQFYDGVIRCLKRMHIKSMPEDAKGQ 58

PHD finger protein 20-like protein 1; PHD20L1_u1 is a region of natively unstructured but highly conserved sequence on a set of higher eukaryotic PHD finger protein 20-like protein 1 like proteins. The function is not known.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 317373307   318 SQKKNEADISS--SANTQKPALLSSTLSSGKARSKKCKHESGDSSGCIKPPKSPLSPELIQVEDLTLV 383
Cdd:pfam16660    1 QEKKNEADIGSivPAESQKPALLSASASSGKARGKKCKHEPGDASGCIKNPKPPADLELHQEEDLTLV 68

Protein of unknown function (DUF3776); This domain family is found in eukaryotes, and is approximately 100 amino acids in length.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 317373307   197 SNKDKDKDERKWFKVPSKKEETS-TCIATPDVEKKEDLPTSSETFGlhvenvPKMVFPQPESTLSNKRKNNQGNSFQAKR 275
Cdd:pfam12618    1 GKKEEEEKTLKSEKICSEKGKKSeKSLPKNESEEKENISPNEEYSG------DTQVDKKPESDIVKSRSKPQGNLCEPKR 74

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 317373307   276 ARLNKITGLLASKAVGVDGAEKKEDYNETAPMLEQ 310
Cdd:pfam12618   75 KRLGKGAGCTELKAEGRPPSITPQQKVESSSQSLQ 109

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 317373307      3 KKPPNRPGITFEIGARLEALDYL--QKWYPSRIEKIdyEEGKMLVHFERWSHRYDEWIYWDSNRLRPL 68
Cdd:smart00561   18 KQPVDSPPNGFKVGMKLEAVDPRnpSLICVATVVEV--KGYRLLLHFDGWDDKYDFWCHADSPDIFPV 83

Jumonji domain-containing protein 2A Tudor domain; This is the tudor domain found in histone demethylase Jumonji domain-containing protein 2A (JMJD2A). Structure and function analysis indicate that this domain can recognize equally well two unrelated histone peptides, H3K4me3 and H4K20me3, by means of two very different binding mechanisms. JMJD2 also known as KDM4, is a conserved iron (II)-dependent jumonji-domain demethylase subfamily that is essential during development. Vertebrate KDM4A-C proteins contain a conserved double tudor domain (DTD).

                           10        20        30
                   ....*....|....*....|....*....|....
gi 317373307    90 GEEVLARWTDCRYYPAKIEAINKEGTFTVQFYDG 123
Cdd:pfam18104    1 GQDVIARWTDGRYYLGKFIGIHTQTFYEVEFEDG 34

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 317373307    684 CICEMDEENGFMIQCEECLCWQHSVCMG--LLEESIPEQYICYIC 726
Cdd:smart00249    3 SVCGKPDDGGELLQCDGCDRWYHQTCLGppLLEEEPDGKWYCPKC 47

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 317373307   86 DFKAGEEVLARWTDCRYYPAKIEAINKEGTFTVQFYDGVIRCLKRMHIKAMPEDAKGQ 143
Cdd:cd20454     1 DFKAGEEVLARWTDCRYYPAKIEAINKEGTYTVQFYDGVIRCLKRMHIKSMPEDAKGQ 58

PHD finger protein 20-like protein 1; PHD20L1_u1 is a region of natively unstructured but highly conserved sequence on a set of higher eukaryotic PHD finger protein 20-like protein 1 like proteins. The function is not known.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 317373307   318 SQKKNEADISS--SANTQKPALLSSTLSSGKARSKKCKHESGDSSGCIKPPKSPLSPELIQVEDLTLV 383
Cdd:pfam16660    1 QEKKNEADIGSivPAESQKPALLSASASSGKARGKKCKHEPGDASGCIKNPKPPADLELHQEEDLTLV 68

PHD finger found in PHD finger protein 20 (PHF20); 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. PHF20 contains an N-terminal malignant brain tumor (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 317373307  683 RCICEMDEENGFMIQCEECLCWQHSVCMGLLEESIPEQYICYIC 726
Cdd:cd15634     1 RCICEVQEENDFMIQCEECLCWQHGVCMGLLEDNVPEKYTCYIC 44

Tudor domain found in PHD finger protein 20 (PHF20), PHF20-like protein 1 (PHF20L1), 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. 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. Both PHF20 and PHF20L1 contain 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 317373307   87 FKAGEEVLARWTDCRYYPAKIEAINKEGTFTVQFYDGVIRCLKRMHIKAM 136
Cdd:cd20386     1 FKVGEEVLARWSDCKFYPAKILKVLDNGTYEVLFYDGFKKTVKASNLKKM 50

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 317373307  683 RCICEMDEENGFMIQCEECLCWQHSVCMGLLEESIPEQYICYIC 726
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 317373307  682 VRCICEMDEENGFMIQCEECLCWQHSVCMGLLEEsiPEQYICYIC 726
Cdd:cd15548     1 IRCICGLYKDEGLMIQCEKCMVWQHCDCMGVNDD--VEHYLCEQC 43

PHD domain found in Saccharomyces cerevisiae bypass of ESS1 protein 1 (Bye1p), the E3 Sumo Ligase SIZ1, and similar proteins; Yeast Bye1p is a nuclear transcription factor with a domain resembling the central domain in the transcription elongation factor TFIIS and plays an inhibitory role during transcription elongation. It functions as a multicopy suppressor of Ess1, a peptidyl-prolyl cis-trans isomerase involved in proline isomerization of the C-terminal domain (CTD) of RNA polymerase II (Pol II). Bye1p contains an N-terminal plant homeodomain (PHD) finger, a central Pol II-binding TFIIS-like domain (TLD) domain, and a C-terminal Spen paralogue and orthologue C-terminal (SPOC) domain. The PHD domain binds to a histone H3 tail peptide containing trimethylated lysine 4 (H3K4me3). The TLD domain is responsible for the association with chromatin. Plant SIZ1 protein is a SUMO (small ubiquitin-related modifier) E3 ligase that facilitates conjugation of SUMO to substrate target proteins (sumoylation) and belongs to the protein inhibitor of activated STAT (PIAS) protein family. It negatively regulates abscisic acid (ABA) signaling, which is dependent on the bZIP transcripton factor ABI5. It also modulates plant growth and plays a role in drought stress response likely through the regulation of gene expression. SIZ1 functions as a floral repressor that not only represses the salicylic acid (SA)-dependent pathway, but also promotes FLOWERING LOCUS C (FLC) expression by repressing FLOWERING LOCUS D (FLD) activity through sumoylation. SIZ1 contains a PHD finger, which specifically binds methylated histone H3 at lysine 4 and arginine 2.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 317373307  683 RCICEMDEENGFMIQCEECLCWQHSVCMGLLEESI------PEQYICYIC 726
Cdd:cd15570     1 RCPCGSSMEDGSMIQCEGCKTWQHMDCVLIPDKPAdglpelPSKFYCELC 50

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 317373307  683 RCICEMDEENGFMIQCEECLCWQHSVCMGLL---EESIPEQYICYIC 726
Cdd:cd15558     1 RCECGDWGEDGAMIQCAFCDTWQHLLCYGFEsakDPRIPDIHVCYRC 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 317373307      3 KKPPNRPGITFEIGARLEALDYL--QKWYPSRIEKIdyEEGKMLVHFERWSHRYDEWIYWDSNRLRPL 68
Cdd:smart00561   18 KQPVDSPPNGFKVGMKLEAVDPRnpSLICVATVVEV--KGYRLLLHFDGWDDKYDFWCHADSPDIFPV 83

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 317373307  684 CICEMDEENGFMIQCEECLCWQHSVCMGL-------LEESIpEQYICYIC 726
Cdd:cd15552     2 CICRKPHNNRFMICCDRCEEWFHGDCVGIteaqgkeMEENI-EEYVCPKC 50

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 317373307   89 AGEEVLARW-TDCRYYPAKIEAINKEGTFTVQFYDGVIRCLKRMHIK 134
Cdd:cd20383     1 VGTRVFAKWsSDGYYYPGIITRVLGDGKYKVLFDDGYERDVKGKDII 47

PHD finger found in PHD finger protein 13 (PHF13); 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 317373307  681 IVRCICEMDEENGFMIQCEECLCWQHSVCMGLLEESIPEQYICYICR 727
Cdd:cd15632     1 LVTCFCMKPFAGRPMIECNECHTWIHLSCAKIRKSNVPEVYVCQKCR 47

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 317373307  684 CICEM-DEENGFMIQCEECLCWQHSVCMGLLEESI--PEQYICYIC 726
Cdd:cd15489     3 IVCGKgGDLGGELLQCDGCGKWFHADCLGPPLSSFvpNGKWICPVC 48

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 317373307    9 PGITFEIGARLEALDylqKWYPSRIEK---IDYEEGKMLVHFERWSHRYDEWIYWDSNRLRP 67
Cdd:cd20103     1 PPHGFEVGMKLEAVD---KRNPRLIRVatvADVEDYRVKLHFDGWPDIYDFWVDDDSPDIHP 59

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 317373307   13 FEIGARLEALDYLQKWY--PSRIEKIdyeEGKML-VHFERWSHRYDEWIYWDSNRLRP 67
Cdd:cd20100     3 FKVGMKLEAVDLMEPRLicVATVTRV---VGRLLrVHFDGWDDEFDQWVDCDSPDIYP 57

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 317373307  684 CIC-EMDE-ENGFMIQCEECLCWQHSVCMGLLEESIP-EQYICYIC 726
Cdd:cd15547     2 CICgELDEiDNKHRVQCLKCGLWQHAECVNYDEESDKrEPYLCPHC 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 317373307   12 TFEIGARLEALDylqKWYPSRI---EKIDYEEGKMLVHFERWSHRYDEWIYWDSNRLRP 67
Cdd:cd20102     3 GFRVGMKLEAVD---RKNPSLIcvaTVTDVIGNRFLVHFDGWDDSYDYWCDPDSPYIHP 58

second Tudor domain found in Jumonji domain-containing protein 2 (JMJD2) family of histone demethylases; JMJD2 proteins, also called lysine-specific demethylase 4 histone demethylases (KDM4), have been implicated in various cellular processes including DNA damage response, transcription, cell cycle regulation, cellular differentiation, senescence, and carcinogenesis. They selectively catalyze the demethylation of di- and trimethylated H3K9 and H3K36. This model contains only three JMJD2 proteins, JMJD2A-C, which all contain jmjN and jmjC domains in the N-terminal region, followed by a canonical PHD domain, a noncanonical extended PHD domain, and tandem Tudor domains. The model corresponds to the second 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. JMJD2D is not included in this model, since it lacks both the PHD and Tudor domains and has a different substrate specificity. JMJD2A-C are required for efficient cancer cell growth.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 317373307   88 KAGEEVLARWTDCRYYPAKIEAINKEGTFTVQFYDGVIRCLKRMHIKAMPED 139
Cdd:cd20392     3 EVGDPVKVKWTDGELYDAKFVGSSIVIMYTVEFEDGSVLTLKREDVYTLDEE 54

Tudor domain found in zinc finger CCCH-type with G patch domain-containing protein (ZGPAT) and similar proteins; ZGPAT, also called ZIP, G patch domain-containing protein 6 (GPATC6), GPATCH6, zinc finger CCCH domain-containing protein 9 (ZC3HDC9), ZC3H9, or zinc finger and G patch domain-containing protein, is a transcription repressor that specifically binds the 5'-GGAG[GA]A[GA]A-3' consensus sequence. It represses transcription by recruiting the chromatin multiprotein complex NuRD to target promoters. 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 317373307   83 DFFDFKAGEEVLARWTDCRYYPAKIEAINKEGTFTVQF 120
Cdd:cd20384     1 DFSSLKEGSRCLAKYDDGLWYPATVTDIDEDGKYTVKF 38

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.

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                  ....*....|....*....|....*....|....*....|....*....
gi 317373307  684 CICEMDEENGFMIQCEECLCWQHSVCMGLLE------ESIPEQYICYIC 726
Cdd:cd15639     6 CICRQPHNNRFMICCDRCEEWFHGDCVGITEargrllERNGEDYICPNC 54

Tudor domain found in polycomb repressive complex 2 (PRC2)-associated polycomb-like (PCL) family proteins; The PCL family includes PHD finger protein1 (PHF1) and its homologs, metal-response element-binding transcription factor 2 (MTF2/PCL2) and PHF19/PCL3, which are accessory components of the Polycomb repressive complex 2 (PRC2) core complex. Members contain an N-terminal Tudor domain followed by two PHD domains, and a C-terminal MTF2 domain. PCL proteins specifically recognize tri-methylated H3K36 (H3K36me3) through their N-terminal Tudor domains. The interaction between their Tudor domains and H3K36me3 is critical for both the targeting and spreading of PRC2 into active chromatin regions and for the maintenance of optimal repression of poised developmental genes where PCL proteins, H3K36me3, and H3K27me3 coexist. Moreover, unlike other PHD domain-containing proteins, the first PHD domains of PCL proteins do not display histone H3K4 binding affinity and they do not affect the binding of the Tudor domain to histones.

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                  ....*....|....*....|....*....|....*...
gi 317373307   86 DFKAGEEVLARWTDCRYYPAKIEAINKE-GTFTVQFYD 122
Cdd:cd20385     1 KFAEGQDVLARWTDGLFYLGTIKKVDSAkEKCLVIFED 38

Tudor domain found in Tudor domain-containing protein 3 (TDRD3) and similar proteins; TDRD3 is a scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. In the nucleus, it acts as a coactivator; it recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci. In the cytoplasm, it may play a role in the assembly and/or disassembly of mRNA stress granules and in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins. TDRD3 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 317373307   87 FKAGEEVLAR-WTDCRYYPAKIEAINKEG-TFTVQFYD 122
Cdd:cd20413     1 WKPGDECLAKyWEDNKFYRAEVTAVHPSGkTAVVKFME 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 317373307    8 RPGITFEIGARLEALDylqKWYPSRIE---KIDYEEGKMLVHFERWSHRYDEWIYWDSNRLRPL 68
Cdd:cd20139     4 RPPHGFQVNMKLEAVD---KRNPILIRvatIVDKDDHRIKLHFDGWDHNYDFWVDADSPDIHPV 64

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 317373307    9 PGITFEIGARLEALDYLQkwyPSRI---EKIDYEEGKMLVHFERWSHRYDEW----------IYWDSNRLRPLERPalrk 75
Cdd:cd20134     2 PPLGFQVGMKLEAVDRMN---PSLVcvaSVTDVVDSRFLVHFDNWDDTYDYWcdpsspyihpVGWCQKQGKPLTPP---- 74

                  ....*....
gi 317373307   76 EGLKDEEDF 84
Cdd:cd20134    75 QDYPDPDNF 83

PHD finger 3 found in Lysine-specific demethylase 5A (KDM5A), 5B (KDM5B), and similar proteins; The family includes KDM5A and KDM5B, both of which belong to the JARID subfamily within the JmjC proteins. KDM5A, also termed Histone demethylase JARID1A, or Jumonji/ARID domain-containing protein 1A, or Retinoblastoma-binding protein 2 (RBBP-2 or RBP2), 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 interacting with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK and BMAL1. KDM5A functions as the trimethylated histone H3 lysine 4 (H3K4me3) demethylase. It also displays DNA-binding activities that can recognize the specific DNA sequence CCGCCC. KDM5B, also termed Cancer/testis antigen 31 (CT31), or Histone demethylase JARID1B, or Jumonji/ARID domain-containing protein 1B (JARID1B), or PLU-1, or retinoblastoma-binding protein 2 homolog 1 (RBP2-H1 or RBBP2H1A), 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. KDM5B acts as a histone demethylase that catalyzes the removal of trimethylation of lysine 4 on histone H3 (H3K4me3), induced by polychlorinated biphenyls (PCBs). It also mediates demethylation of H3K4me2 and H3K4me1. Moreover, KDM5B functions as a negative regulator of hematopoietic stem cell (HSC) self-renewal and progenitor cell activity. KDM5B has also been shown to interact with the DNA binding transcription factors BF-1 and PAX9, as well asTIEG1/KLF10 (transforming growth factor-beta inducible early gene-1/Kruppel-like transcription factor 10), and possibly function as a transcriptional corepressor. The family also includes the Drosophila melanogaster protein little imaginal discs (Lid) that functions as a JmjC-dependent trimethyl histone H3K4 (H3K4me3) demethylase, which is required for dMyc-induced cell growth. It positively regulates Hox gene expression in S2 cells. Members in this family contain the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers. This model corresponds to the third PHD finger.

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                  ....*....|....*....|....*....|...
gi 317373307  696 IQCEECLCWQHSVCMGLLEESIP--EQYICYIC 726
Cdd:cd15610    18 VQCDGCEEWFHLLCVGLSPEEVAedEDYICPSC 50

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).

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                  ....*....|....*....|....*....|...
gi 317373307  696 IQCEECLCWQHSVCMGL--LEESIPEQYICYIC 726
Cdd:cd15517    17 VQCDGCDKWFHQFCLGLsnERYADEDKFKCPNC 49

second 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 second MBT repeat that contains the semi-aromatic cage that binds methylated lysine residues.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 317373307   13 FEIGARLEALDylqKWYPSRI---EKIDYEEGKMLVHFERWSHRYDEWIYWDSNRLRPL 68
Cdd:cd20135     6 FRVGMKLEAVD---KKNPSFIcvaTITDMVDNRLLIHFDNWDESYDYWCDASSPYIHPV 61

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 317373307  695 MIQCEECLCWQHSVCMGLLEE------SIPE--QYICYIC 726
Cdd:cd15508    18 MMQCSQCDHWVHAKCEGLSDEmyeilsYLPEsiEYTCSLC 57