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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1958789586 558 RCICELDEENGFMIQCEECLCWQHSVCMGLLEDSIPEQYICYICRD 603
Cdd:cd15633     1 RCICEMDEENGFMIQCEECLCWQHSVCMGLLEESIPEQYICYICRD 46

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 1958789586  71 SNKEKERDGGKWFKVPSKKAETS-TCIVTAEIEKKEELPTSSEPfvglhidSVPKIVFPQPESTLTNKRKNNQGNSFQAK 149
Cdd:pfam12618   1 GKKEEEEKTLKSEKICSEKGKKSeKSLPKNESEEKENISPNEEY-------SGDTQVDKKPESDIVKSRSKPQGNLCEPK 73

                          90       100
                  ....*....|....*....|....*.
gi 1958789586 150 RARLNKITGLLASKAVGVDGAEKKED 175
Cdd:pfam12618  74 RKRLGKGAGCTELKAEGRPPSITPQQ 99

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1958789586 558 RCICELDEENGFMIQCEECLCWQHSVCMGLLEDSIPEQYICYICRD 603
Cdd:cd15633     1 RCICEMDEENGFMIQCEECLCWQHSVCMGLLEESIPEQYICYICRD 46

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 1958789586  71 SNKEKERDGGKWFKVPSKKAETS-TCIVTAEIEKKEELPTSSEPfvglhidSVPKIVFPQPESTLTNKRKNNQGNSFQAK 149
Cdd:pfam12618   1 GKKEEEEKTLKSEKICSEKGKKSeKSLPKNESEEKENISPNEEY-------SGDTQVDKKPESDIVKSRSKPQGNLCEPK 73

                          90       100
                  ....*....|....*....|....*.
gi 1958789586 150 RARLNKITGLLASKAVGVDGAEKKED 175
Cdd:pfam12618  74 RKRLGKGAGCTELKAEGRPPSITPQQ 99

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 1958789586  559 CICELDEENGFMIQCEECLCWQHSVCMG--LLEDSIPEQYICYIC 601
Cdd:smart00249   3 SVCGKPDDGGELLQCDGCDRWYHQTCLGppLLEEEPDGKWYCPKC 47

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1958789586 558 RCICELDEENGFMIQCEECLCWQHSVCMGLLEDSIPEQYICYICRD 603
Cdd:cd15633     1 RCICEMDEENGFMIQCEECLCWQHSVCMGLLEESIPEQYICYICRD 46

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 1958789586 193 SQKKNEAVISS--SANTQKPALLSSTLSSGKARSKKCKHESGESSGCIKAPKSPLAPELIQAKDLTLV 258
Cdd:pfam16660   1 QEKKNEADIGSivPAESQKPALLSASASSGKARGKKCKHEPGDASGCIKNPKPPADLELHQEEDLTLV 68

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 1958789586 558 RCICELDEENGFMIQCEECLCWQHSVCMGLLEDSIPEQYICYIC 601
Cdd:cd15550     1 RCICGFEHDDGFMICCDKCSVWQHGDCMGIDRENIPDSYLCEQC 44

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 1958789586 558 RCICELDEENGFMIQCEECLCWQHSVCMGLLEDSI------PEQYICYIC 601
Cdd:cd15570     1 RCPCGSSMEDGSMIQCEGCKTWQHMDCVLIPDKPAdglpelPSKFYCELC 50

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 1958789586  71 SNKEKERDGGKWFKVPSKKAETS-TCIVTAEIEKKEELPTSSEPfvglhidSVPKIVFPQPESTLTNKRKNNQGNSFQAK 149
Cdd:pfam12618   1 GKKEEEEKTLKSEKICSEKGKKSeKSLPKNESEEKENISPNEEY-------SGDTQVDKKPESDIVKSRSKPQGNLCEPK 73

                          90       100
                  ....*....|....*....|....*.
gi 1958789586 150 RARLNKITGLLASKAVGVDGAEKKED 175
Cdd:pfam12618  74 RKRLGKGAGCTELKAEGRPPSITPQQ 99

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 1958789586 559 CICELDEENGFMIQCEECLCWQHSVCMGL-------LEDSIpEQYICYIC 601
Cdd:cd15552     2 CICRKPHNNRFMICCDRCEEWFHGDCVGIteaqgkeMEENI-EEYVCPKC 50

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 1958789586 559 CICEL-DEENGFMIQCEECLCWQHSVCMGLLEDSI--PEQYICYIC 601
Cdd:cd15489     3 IVCGKgGDLGGELLQCDGCGKWFHADCLGPPLSSFvpNGKWICPVC 48

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 1958789586 559 CIC------ELDEENGFMIQCEECLCWQHSVCMGL-LEDSIPEQY---ICYIC 601
Cdd:cd15542     2 CTCdrpypdPEDEVEDEMIQCVLCEDWFHGRHLGLtPPEPDPDEFdemICSGC 54

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 1958789586 570 MIQCEECLCWQHSVCMGLLEDSIPEQYICYIC 601
Cdd:cd15546    13 MIECSECLTWIHLSCAKIRKNNVPEVFICQKC 44

PHD finger found in PHF2, PHF8 and KDM7; This family includes PHF2, PHF8, KDM7, and similar proteins. PHF2, also termed GRC5, or PHD finger protein 2, is a histone lysine demethylase ubiquitously expressed in various tissues. PHF8, also termed PHD finger protein 8, or KDM7B, is a monomethylated histone H4 lysine 20(H4K20me1) demethylase that transcriptionally regulates many cell cycle genes. It also preferentially acts on H3K9me2 and H3K9me1. PHF8 is modulated by CDC20-containing anaphase-promoting complex (APC (cdc20)) and plays an important role in the G2/M transition. It acts as a critical molecular sensor for mediating retinoic acid (RA) treatment response in RAR alpha-fusion-induced leukemia. Moreover, PHF8 is essential for cytoskeleton dynamics and is associated with X-linked mental retardation. KDM7, also termed JmjC domain-containing histone demethylation protein 1D (JHDM1D), or KIAA1718, is a dual histone demethylase that catalyzes demethylation of monomethylated and dimethylated H3K9 (H3K9me2/me1) and H3K27 (H3K27me2/me1), which functions as an eraser of silencing marks on chromatin during brain development. It also plays a tumor-suppressive role by regulating angiogenesis. All family members contain a plant homeodomain (PHD) finger and a JmjC domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1958789586 559 CICEL-DEENGFMIQCEECLCWQHSVCMGLLEDSIP--EQYICYIC 601
Cdd:cd15554     2 CICRQpYDVTRFMIECDVCKDWFHGSCVGVEEHQANdiERYHCPNC 47

PHD finger 2 and 3 found in bromodomain and PHD finger-containing transcription factor (BPTF); BPTF, also termed nucleosome-remodeling factor subunit BPTF, or fetal Alz-50 clone 1 protein (FAC1), or fetal Alzheimer antigen, functions as a transcriptional regulator that exhibits altered expression and subcellular localization during neuronal development and neurodegenerative diseases such as Alzheimer's disease. It interacts with the human orthologue of the Kelch-like Ech-associated protein (Keap1). Its function and subcellular localization can be regulated by Keap1. Moreover, BPTF is a novel DNA-binding protein that recognizes the DNA sequence CACAACAC and represses transcription through this site in a phosphorylation-dependent manner. Furthermore, BPTF interacts with the Myc-associated zinc finger protein (ZF87/MAZ) and alters its transcriptional activity, which has been implicated in gene regulation in neurodegeneration. Some family members contain two or three plant homeodomain (PHD) fingers, which may be involved in complex formation with histone H3 trimethylated at K4 (H3K4me3). This family corresponds to the second and third PHD fingers.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1958789586 559 CICELD-EENGFMIQCEECLCWQHSVCMGLLE---DSIpEQYICYIC 601
Cdd:cd15560     2 CICRTPyDESQFYIGCDRCQDWFHGRCVGILQseaEKI-DEYVCPQC 47

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 1958789586 559 CICELDEENGFMIQCEECLCWQHSVCMGLLE------DSIPEQYICYIC 601
Cdd:cd15639     6 CICRQPHNNRFMICCDRCEEWFHGDCVGITEargrllERNGEDYICPNC 54

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1958789586 559 CICELDEENGFMIQCEECLCWQHSVCMGLLED---SIPEQYiCYIC 601
Cdd:cd15553     2 CICRSSDISRFMIGCDNCEEWYHGDCINITEKeakAIKEWY-CQQC 46

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 1958789586 559 CICElDEENGFMIQCEECLCWQHSVCMGL 587
Cdd:cd15606     2 CICR-KPFSGFMLQCELCKDWFHSSCVPL 29

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 1958789586 570 MIQCEECLCWQHSVCMGL----------LEDSIPeqYICYIC 601
Cdd:cd15508    18 MMQCSQCDHWVHAKCEGLsdemyeilsyLPESIE--YTCSLC 57