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 1958789574   86 DFKAGEEVLARWTDCRYYPAKIEAINKEGTFTVQFYDGVIRCLKRMHIKAMPEDAKGQ 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 1958789574   13 FEIGARLEALDYLQKWYPSRIEKIDYEEGKMLVHFERWSHRYDEWIYWDSNRLRPLERPS 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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958789574  201 SNKEKERDGGKWFKVPSKKAETS-TCIVTAEIEKKEELPTSSEPfvglhidSVPKIVFPQPESTLTNKRKNNQGNSFQAK 279
Cdd:pfam12618    1 GKKEEEEKTLKSEKICSEKGKKSeKSLPKNESEEKENISPNEEY-------SGDTQVDKKPESDIVKSRSKPQGNLCEPK 73

                           90       100
                   ....*....|....*....|....*.
gi 1958789574  280 RARLNKITGLLASKAVGVDGAEKKED 305
Cdd:pfam12618   74 RKRLGKGAGCTELKAEGRPPSITPQQ 99

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 1958789574   86 DFKAGEEVLARWTDCRYYPAKIEAINKEGTFTVQFYDGVIRCLKRMHIKAMPEDAKGQ 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 1958789574   13 FEIGARLEALDYLQKWYPSRIEKIDYEEGKMLVHFERWSHRYDEWIYWDSNRLRPLERPS 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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958789574  201 SNKEKERDGGKWFKVPSKKAETS-TCIVTAEIEKKEELPTSSEPfvglhidSVPKIVFPQPESTLTNKRKNNQGNSFQAK 279
Cdd:pfam12618    1 GKKEEEEKTLKSEKICSEKGKKSeKSLPKNESEEKENISPNEEY-------SGDTQVDKKPESDIVKSRSKPQGNLCEPK 73

                           90       100
                   ....*....|....*....|....*.
gi 1958789574  280 RARLNKITGLLASKAVGVDGAEKKED 305
Cdd:pfam12618   74 RKRLGKGAGCTELKAEGRPPSITPQQ 99

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 1958789574     3 KKPPNRPGITFEIGARLEALDYL--QKWYPSRIEKIdyEEGKMLVHFERWSHRYDEWIYWDSNRLRPL 68
Cdd:smart00561   18 KQPVDSPPNGFKVGMKLEAVDPRnpSLICVATVVEV--KGYRLLLHFDGWDDKYDFWCHADSPDIFPV 83

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 1958789574  689 CICELDEENGFMIQCEECLCWQHSVCMGLLEDSIP---EQYICYICR 732
Cdd:pfam00628    3 AVCGKSDDGGELVQCDGCDDWFHLACLGPPLDPAEipsGEWLCPECK 49

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 1958789574   689 CICELDEENGFMIQCEECLCWQHSVCMG--LLEDSIPEQYICYIC 731
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 1958789574   86 DFKAGEEVLARWTDCRYYPAKIEAINKEGTFTVQFYDGVIRCLKRMHIKAMPEDAKGQ 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 1958789574   13 FEIGARLEALDYLQKWYPSRIEKIDYEEGKMLVHFERWSHRYDEWIYWDSNRLRPLERPS 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 1958789574  688 RCICELDEENGFMIQCEECLCWQHSVCMGLLEDSIPEQYICYIC 731
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 1958789574  688 RCICELDEENGFMIQCEECLCWQHSVCMGLL-EDSIPEQYICYIC 731
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 1958789574  688 RCICELDEENGFMIQCEECLCWQHSVCMGLLEDSIPEQYICYIC 731
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 1958789574  687 VRCICELDEENGFMIQCEECLCWQHSVCMGLLEDsiPEQYICYIC 731
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 1958789574  688 RCICELDEENGFMIQCEECLCWQHSVCMGLLEDSI------PEQYICYIC 731
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 1958789574  688 RCICELDEENGFMIQCEECLCWQHSVCMGLLEDS---IPEQYICYIC 731
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 1958789574     3 KKPPNRPGITFEIGARLEALDYL--QKWYPSRIEKIdyEEGKMLVHFERWSHRYDEWIYWDSNRLRPL 68
Cdd:smart00561   18 KQPVDSPPNGFKVGMKLEAVDPRnpSLICVATVVEV--KGYRLLLHFDGWDDKYDFWCHADSPDIFPV 83

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 1958789574  689 CICELDEENGFMIQCEECLCWQHSVCMGLLEDSIP---EQYICYICR 732
Cdd:pfam00628    3 AVCGKSDDGGELVQCDGCDDWFHLACLGPPLDPAEipsGEWLCPECK 49

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 1958789574   89 AGEEVLARW-TDCRYYPAKIEAINKEGTFTVQFYDGVIRCLKRMHIK 134
Cdd:cd20383      1 VGTRVFAKWsSDGYYYPGIITRVLGDGKYKVLFDDGYERDVKGKDII 47

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 1958789574   87 FKAGEEVLARWTDCR-YYPAKIEAINKEGTFTVQFYDGVIRCLKRMHIKA 135
Cdd:cd20381      2 FKVGETVMARWPGSRlYYEATVLNFDDSDEYTVKFKDGTELELKEKDVKA 51

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 1958789574  686 IVRCICELDEENGFMIQCEECLCWQHSVCMGLLEDSIPEQYICYICR 732
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 1958789574  689 CICEL-DEENGFMIQCEECLCWQHSVCMGLLEDSI--PEQYICYIC 731
Cdd:cd15489      3 IVCGKgGDLGGELLQCDGCGKWFHADCLGPPLSSFvpNGKWICPVC 48

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 1958789574  689 CICELDEENG-FMIQCEECLCWQHSVCMGL-LEDSIPEQYICYIC 731
Cdd:cd15556      2 CSCGTRDDDGeRMIACDVCEVWQHTRCVGIaDNEEPPDHFLCRRC 46

PHD finger found in putative E3 ubiquitin-protein ligase UBR7; UBR7, also termed N-recognin-7, is a UBR box-containing protein that belongs to the E3 ubiquitin ligase family that recognizes N-degrons or structurally related molecules for ubiquitin-dependent proteolysis or related processes through the UBR box motif. In addition to the UBR box, UBR7 also harbors a plant homeodomain (PHD) finger. The biochemical properties of UBR7 remain unclear.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1958789574  689 CIC------ELDEENGFMIQCEECLCWQHSVCMGL-LEDSIPEQY---ICYIC 731
Cdd:cd15542      2 CTCdrpypdPEDEVEDEMIQCVLCEDWFHGRHLGLtPPEPDPDEFdemICSGC 54

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 1958789574   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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1958789574   88 KAGEEVLARWTDCRYYPAKIEAINKEGTFTVQFYDGVIRCLKRMHI 133
Cdd:cd20392      3 EVGDPVKVKWTDGELYDAKFVGSSIVIMYTVEFEDGSVLTLKREDV 48

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).

                           10        20        30
                   ....*....|....*....|....*....|..
gi 1958789574  700 MIQCEECLCWQHSVCMGLLEDSIPEQYICYIC 731
Cdd:cd15546     13 MIECSECLTWIHLSCAKIRKNNVPEVFICQKC 44

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 1958789574   689 CICELDEENGFMIQCEECLCWQHSVCMG--LLEDSIPEQYICYIC 731
Cdd:smart00249    3 SVCGKPDDGGELLQCDGCDRWYHQTCLGppLLEEEPDGKWYCPKC 47

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.

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1958789574   87 FKAGEEVLAR-WTDCRYYPAKIEAINKEG-TFTVQFYD 122
Cdd:cd20413      1 WKPGDECLAKyWEDNKFYRAEVTAVHPSGkTAVVKFME 38

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.

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1958789574   90 GEEVLARWT-DCRYYPAKIEAINKEGTFTVQFYDG 123
Cdd:cd21182      1 GDKCLAPYSdDGKYYEATIEEITEESDTATVVFDG 35

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 1958789574  689 CICELDEeNGFMIQCEECLCWQHSVCMG-----LLEDSIpeqYICYIC 731
Cdd:cd15518      2 CFCRQGE-GGTMIECEICKEWYHVKCIKngrwkLDDDDK---FVCPIC 45

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
                   ....*....|....*....|....*....|....*....|....*....
gi 1958789574  689 CICELDEENGFMIQCEECLCWQHSVCMGLLE------DSIPEQYICYIC 731
Cdd:cd15639      6 CICRQPHNNRFMICCDRCEEWFHGDCVGITEargrllERNGEDYICPNC 54

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|.
gi 1958789574    86 DFKAGEEVLARWTDCrYYPAKIEAINKEGTFTVQFYDGVIR 126
Cdd:smart00743    2 DFKEGDRVEVFSEDS-WWEAVVTKVLGDGKYLVEYKGESEP 41

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 1958789574   13 FEIGARLEALDylqKWYPSRI---EKIDYEEGKMLVHFERWSHRYDEWIYWDSNRLRPL 68
Cdd:cd20135      6 FRVGMKLEAVD---KKNPSFIcvaTITDMVDNRLLIHFDNWDESYDYWCDASSPYIHPV 61

PHD finger 2 found in Lysine-specific demethylase 5A (KDM5A); KDM5A (also termed Histone demethylase JARID1A, 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 a trimethylated histone H3 lysine 4 (H3K4me3) demethylase that belongs to the JARID subfamily within the JmjC proteins. It also displays DNA-binding activities that can recognize the specific DNA sequence CCGCCC. KDM5A contains 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 second PHD finger.

                           10        20
                   ....*....|....*....|....*....
gi 1958789574  689 CICElDEENGFMIQCEECLCWQHSVCMGL 717
Cdd:cd15606      2 CICR-KPFSGFMLQCELCKDWFHSSCVPL 29

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 1958789574    4 KPPNrpgiTFEIGARLEALDylqKWYPSRIEK---IDYEEGKMLVHFERWSHRYDEWIYWDSNRLRP 67
Cdd:cd20138      4 KPPH----GFQKNMKLEVVD---KRNPMLIRVatvADTDDHRVKVHFDGWNNCYDYWIDADSPDIHP 63

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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1958789574  700 MIQCEECLCWQHSVCMGL----------LEDSIPeqYICYIC 731
Cdd:cd15508     18 MMQCSQCDHWVHAKCEGLsdemyeilsyLPESIE--YTCSLC 57