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 1949705535   86 DFKAGEEVLARWTDCRYYPAKIEAVNKEGTFTVQFYDGVIRCLKRMHIKAMPEDAKGQ 143
Cdd:cd20454      1 DFKAGEEVLARWTDCRYYPAKIEAINKEGTYTVQFYDGVIRCLKRMHIKSMPEDAKGQ 58

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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1949705535   13 FEIGARLEALDYLQKWYPSRIEKIDYEEGKMLVHFERWSHRYDEWIYWDSNRLRPLERPA 72
Cdd:cd20104      1 FKVGDRVDALDGEGKWYEAKIVEVDEEENKVLVHYDGWSSRYDEWIDRDSERLRPLHTPT 60

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1949705535  223 ATIETEKKEELPTSSEPfglhidSVPKIVFPQPESTLTNKRKNNQGNSFQAKRARLNKITGLLASKAVGVDGAEK 297
Cdd:pfam12618   28 PKNESEEKENISPNEEY------SGDTQVDKKPESDIVKSRSKPQGNLCEPKRKRLGKGAGCTELKAEGRPPSIT 96

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 1949705535   86 DFKAGEEVLARWTDCRYYPAKIEAVNKEGTFTVQFYDGVIRCLKRMHIKAMPEDAKGQ 143
Cdd:cd20454      1 DFKAGEEVLARWTDCRYYPAKIEAINKEGTYTVQFYDGVIRCLKRMHIKSMPEDAKGQ 58

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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1949705535   13 FEIGARLEALDYLQKWYPSRIEKIDYEEGKMLVHFERWSHRYDEWIYWDSNRLRPLERPA 72
Cdd:cd20104      1 FKVGDRVDALDGEGKWYEAKIVEVDEEENKVLVHYDGWSSRYDEWIDRDSERLRPLHTPT 60

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        50
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1949705535    86 DFKAGEEVLARWTDCRYYPAKIEAVNKEGTFTVQFYD-GVIRCLKRMHIKAMPED 139
Cdd:smart00333    2 TFKVGDKVAARWEDGEWYRARIVKVDGEQLYEVFFIDyGNEEVVPPSDLRQLPEE 56

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 1949705535     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 1949705535   90 GEEVLARWTDCRYYPAKIEAVNKEGTFTVQFYDG 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 1949705535   684 CICEMDEENGFMIQCEECLCWQHSVCMG--LLEDSIPEQYICYIC 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 1949705535   86 DFKAGEEVLARWTDCRYYPAKIEAVNKEGTFTVQFYDGVIRCLKRMHIKAMPEDAKGQ 143
Cdd:cd20454      1 DFKAGEEVLARWTDCRYYPAKIEAINKEGTYTVQFYDGVIRCLKRMHIKSMPEDAKGQ 58

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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1949705535   13 FEIGARLEALDYLQKWYPSRIEKIDYEEGKMLVHFERWSHRYDEWIYWDSNRLRPLERPA 72
Cdd:cd20104      1 FKVGDRVDALDGEGKWYEAKIVEVDEEENKVLVHYDGWSSRYDEWIDRDSERLRPLHTPT 60

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 1949705535  683 RCICEMDEENGFMIQCEECLCWQHSVCMGLLEDSIPEQYICYIC 726
Cdd:cd15634      1 RCICEVQEENDFMIQCEECLCWQHGVCMGLLEDNVPEKYTCYIC 44

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 1949705535  683 RCICEMDEENGFMIQCEECLCWQHSVCMGLL-EDSIPEQYICYIC 726
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 1949705535  683 RCICEMDEENGFMIQCEECLCWQHSVCMGLLEDSIPEQYICYIC 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 1949705535  682 VRCICEMDEENGFMIQCEECLCWQHSVCMGLLEDsiPEQYICYIC 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 1949705535  683 RCICEMDEENGFMIQCEECLCWQHSVCMGLLEDSI------PEQYICYIC 726
Cdd:cd15570      1 RCPCGSSMEDGSMIQCEGCKTWQHMDCVLIPDKPAdglpelPSKFYCELC 50

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        50
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1949705535    86 DFKAGEEVLARWTDCRYYPAKIEAVNKEGTFTVQFYD-GVIRCLKRMHIKAMPED 139
Cdd:smart00333    2 TFKVGDKVAARWEDGEWYRARIVKVDGEQLYEVFFIDyGNEEVVPPSDLRQLPEE 56

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 1949705535     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 1949705535   90 GEEVLARWTDCRYYPAKIEAVNKEGTFTVQFYDG 123
Cdd:pfam18104    1 GQDVIARWTDGRYYLGKFIGIHTQTFYEVEFEDG 34

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 1949705535   87 FKAGEEVLARWTDCR-YYPAKIEAVNKEGTFTVQFYDGVIRCLKRMHIKA 135
Cdd:cd20381      2 FKVGETVMARWPGSRlYYEATVLNFDDSDEYTVKFKDGTELELKEKDVKA 51

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.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1949705535   87 FKAGEEVLARWT--DCRYYPAKIEAVNKEGT---FTVQFYD-GVIRCLKRMHIKAM 136
Cdd:cd20446      1 FKPGEVVMARWKsgDGKFYPARITSITGSSInpiYTVKFLDyGEIDTVYLKDIRPL 56

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 1949705535    9 PGITFEIGARLEALDylqKWYPSRIEK---IDYEEGKMLVHFERWSHRYDEWIYWDSNRLRP 67
Cdd:cd20103      1 PPHGFEVGMKLEAVD---KRNPRLIRVatvADVEDYRVKLHFDGWPDIYDFWVDDDSPDIHP 59

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 1949705535  684 CICEM-DEENGFMIQCEECLCWQHSVCMGLLEDSI--PEQYICYIC 726
Cdd:cd15489      3 IVCGKgGDLGGELLQCDGCGKWFHADCLGPPLSSFvpNGKWICPVC 48

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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1949705535    9 PGITFEIGARLEALDylqKWYPSRIEK---IDYEEGKMLVHFERWSHRYDEWIYWDSNRLRP 67
Cdd:cd20137      1 PPHGFQVNMKLEAVD---RRNPALIRVasvEDVEDHRIKIHFDGWSHGYDFWIDADHPDIHP 59

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 1949705535   93 VLARW--TDCRYYPAKIEAVNKEGT--FTVQFYDGVIRCLKRMHIKAM 136
Cdd:pfam18115    3 VFALWkgKDRAYYPATCLGTSGSGSqrYLVRFDDGTPTEVDSGQVRRL 50

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
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1949705535   12 TFEIGARLEALDylqKWYPSRI---EKIDYEEGKMLVHFERWSHRYDEWIYWDSNRLRP 67
Cdd:cd20102      3 GFRVGMKLEAVD---RKNPSLIcvaTVTDVIGNRFLVHFDGWDDSYDYWCDPDSPYIHP 58

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.

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1949705535   86 DFKAGEEVLARWTDCRYYPAKIEAVNKE-GTFTVQFYD 122
Cdd:cd20385      1 KFAEGQDVLARWTDGLFYLGTIKKVDSAkEKCLVIFED 38

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 1949705535  684 CIC-EMDE-ENGFMIQCEECLCWQHSVCMGLLEDSIP-EQYICYIC 726
Cdd:cd15547      2 CICgELDEiDNKHRVQCLKCGLWQHAECVNYDEESDKrEPYLCPHC 47

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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1949705535   88 KAGEEVLARWTDCRYYPAKIEAVNKEGTFTVQFYDGVIRCLKRMHI 133
Cdd:cd20392      3 EVGDPVKVKWTDGELYDAKFVGSSIVIMYTVEFEDGSVLTLKREDV 48

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 1949705535   684 CICEMDEENGFMIQCEECLCWQHSVCMG--LLEDSIPEQYICYIC 726
Cdd:smart00249    3 SVCGKPDDGGELLQCDGCDRWYHQTCLGppLLEEEPDGKWYCPKC 47

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|.
gi 1949705535    86 DFKAGEEVLARWTDCrYYPAKIEAVNKEGTFTVQFYDGVIR 126
Cdd:smart00743    2 DFKEGDRVEVFSEDS-WWEAVVTKVLGDGKYLVEYKGESEP 41

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 1949705535    9 PGITFEIGARLEALDYLQkwyPSRI---EKIDYEEGKMLVHFERWSHRYDEW----------IYWDSNRLRPLERPalrk 75
Cdd:cd20134      2 PPLGFQVGMKLEAVDRMN---PSLVcvaSVTDVVDSRFLVHFDNWDDTYDYWcdpsspyihpVGWCQKQGKPLTPP---- 74

                   ....*....
gi 1949705535   76 EGLKDEEEF 84
Cdd:cd20134     75 QDYPDPDNF 83

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 1949705535  684 CICEmDEENGFMIQCEECLCWQHSVCMG-----LLEDSIpeqYICYIC 726
Cdd:cd15518      2 CFCR-QGEGGTMIECEICKEWYHVKCIKngrwkLDDDDK---FVCPIC 45

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 1949705535   13 FEIGARLEALDylqKWYPSRI---EKIDYEEGKMLVHFERWSHRYDEWIYWDSNRLRPL 68
Cdd:cd20135      6 FRVGMKLEAVD---KKNPSFIcvaTITDMVDNRLLIHFDNWDESYDYWCDASSPYIHPV 61

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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1949705535    4 KPPNrpgiTFEIGARLEALDylqKWYPSRIEK---IDYEEGKMLVHFERWSHRYDEWIYWDSNRLRP 67
Cdd:cd20138      4 KPPH----GFQKNMKLEVVD---KRNPMLIRVatvADTDDHRVKVHFDGWNNCYDYWIDADSPDIHP 63

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
                   ....*....|....*....|....*....|...
gi 1949705535  696 IQCEECLCWQHSVCMGL--LEDSIPEQYICYIC 726
Cdd:cd15517     17 VQCDGCDKWFHQFCLGLsnERYADEDKFKCPNC 49

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.

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1949705535   86 DF---KAGEEVLARWTDCRYYPAKIEAVNKEGTFTVQF 120
Cdd:cd20384      1 DFsslKEGSRCLAKYDDGLWYPATVTDIDEDGKYTVKF 38