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 19113240 336 NCECGDSTEDSEMFQCERCDGWVHCACYGFESDSDPRQPNQLLCYTC 382
Cdd:cd15558   1 RCECGDWGEDGAMIQCAFCDTWQHLLCYGFESAKDPRIPDIHVCYRC 47

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 19113240 336 NCECGDSTEDSEMFQCERCDGWVHCACYGFESDSDPRQPNQLLCYTC 382
Cdd:cd15558   1 RCECGDWGEDGAMIQCAFCDTWQHLLCYGFESAKDPRIPDIHVCYRC 47

HORMA domain; The HORMA (for Hop1p, Rev7p and MAD2) domain has been suggested to recognize chromatin states that result from DNA adducts, double stranded breaks or non-attachment to the spindle and acts as an adaptor that recruits other proteins. MAD2 is a spindle checkpoint protein which prevents progression of the cell cycle upon detection of a defect in mitotic spindle integrity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19113240    17 LKNLIFFAISTLCYKRALFNENCYKKVNFEIehfkgadfDCQLKptvvSLQAGVDKEADSFLEMMKTYIFSLVSMKVPFT 96
Cdd:pfam02301   5 VKTLLRVSISCILYLRGLFPEDAFEDRYLVS--------GLKLK----ILVRGKSPEADRLLDWLEKGVFDALEKGYLKA 72

                          90       100
                  ....*....|....*....|....*..
gi 19113240    97 VYLIISSQCKSilEDDAVEKEIFSFTI 123
Cdd:pfam02301  73 LVLVIYKDKDE--PENVLESYTFSFSY 97

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 19113240 336 NCECGDSTEDSEMFQCERCDGWVHCACYGFESDSDPRQPNQLLCYTC 382
Cdd:cd15558   1 RCECGDWGEDGAMIQCAFCDTWQHLLCYGFESAKDPRIPDIHVCYRC 47

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 19113240 337 CECGDSTEDSEMFQCERCDGWVHCACYGFESDsdpRQPNQLLCYTC 382
Cdd:cd15550   2 CICGFEHDDGFMICCDKCSVWQHGDCMGIDRE---NIPDSYLCEQC 44

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 19113240 337 CECGDSTEDSEMFQCERCDGWVHCACYGFESDSdprQPNQLLCYTC 382
Cdd:cd15633   2 CICEMDEENGFMIQCEECLCWQHSVCMGLLEES---IPEQYICYIC 44

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 19113240 337 CECGDSTEDSE-MFQCERCDGWVHCACYGFESDSDPrqPNQLLCYTC 382
Cdd:cd15556   2 CSCGTRDDDGErMIACDVCEVWQHTRCVGIADNEEP--PDHFLCRRC 46

PHD finger found in BRPF proteins, Jade proteins, protein AF-10, AF-17, and similar proteins; The family includes BRPF proteins, Jade proteins, protein AF-10 and AF-17. BRPF proteins are scaffold proteins that form monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complexes with other regulatory subunits, such as inhibitor of growth 5 (ING5) and Esa1-associated factor 6 ortholog (EAF6). BRPF proteins have multiple domains, including a canonical Cys4HisCys3 plant homeodomain (PHD) zinc finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, a bromodomain and a proline-tryptophan-tryptophan-proline (PWWP) domain. PHD and ePHD fingers both bind to lysine 4 of histone H3 (K4H3), bromodomains interact with acetylated lysines on N-terminal tails of histones and other proteins, and PWWP domains show histone-binding and chromatin association properties. Jade proteins are required for ING4 and ING5 to associate with histone acetyltransferase (HAT) HBO1 and EAF6, to form a HBO1 complex that has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. AF-10, also termed ALL1 (acute lymphoblastic leukemia)-fused gene from chromosome 10 protein, is a transcription factor that has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. AF-17, also termed ALL1-fused gene from chromosome 17 protein, is a putative transcription factor that may play a role in multiple signaling pathways. All Jade proteins, AF-10, and AF-17 contain a canonical PHD finger followed by a non-canonical ePHD finger. This model corresponds to the canonical PHD finger.

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                ....*....|....*....|....*....|....*....|....*.
gi 19113240 337 CECGDSTEDSEMFQCERCDGWVHCACYGFESDSDprqpNQLLCYTC 382
Cdd:cd15492   5 CLDGESEDDNEIVFCDGCNVAVHQSCYGIPLIPE----GDWFCRKC 46

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
                   ....*....|....*....|....*....|...
gi 19113240    339 CGDSTEDSEMFQCERCDGWVHCACYGFESDSDP 371
Cdd:smart00249   5 CGKPDDGGELLQCDGCDRWYHQTCLGPPLLEEE 37

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
                ....*....|....*....|....*....|....*....|...
gi 19113240 341 DSTEDSEMFQCERCDGWVHCACYGFESDS-DPRQPNQLLCYTC 382
Cdd:cd15542  12 EDEVEDEMIQCVLCEDWFHGRHLGLTPPEpDPDEFDEMICSGC 54

PHD finger 3 found in Histone-lysine N-methyltransferase 2B (KMT2B); KMT2B, also termed trithorax homolog 2 or WW domain-binding protein 7 (WBP-7), is encoded by the gene that was first named myeloid/lymphoid or mixed-lineage leukemia 2 (MLL2), a second human homolog of Drosophila trithorax, located on chromosome 19. It belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2) and is vital for normal mammalian embryonic development. KMT2B functions as the catalytic subunit in the MLL2 complex, which contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex. The MLL2 complex is highly active and specific for histone 3 lysine 4 (H3K4) methylation, which stimulates chromatin transcription in a SAM- and H3K4-dependent manner. Moreover, KMT2B 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. KMT2B contains 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
                ....*....|....*....|....*...
gi 19113240 341 DSTEDSEMFQCERCDGWVHCACYGFESD 368
Cdd:cd15593  11 DNDYESKMMQCAKCDHWVHAKCEGLSDE 38

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 19113240 337 CECGDSTEDSEMFQCERCDGWVHCACYGFESDSdprQPNQLLCYTC 382
Cdd:cd15634   2 CICEVQEENDFMIQCEECLCWQHGVCMGLLEDN---VPEKYTCYIC 44

PHD finger found in proteins Jade-1, Jade-2, Jade-3, and similar proteins; This family includes proteins Jade-1 (PHF17), Jade-2 (PHF15), and Jade-3 (PHF16), each of which is required for ING4 and ING5 to associate with histone acetyltransferase (HAT) HBO1 and EAF6 to form a HBO1 complex that has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. This family also contains Drosophila melanogaster PHD finger protein rhinoceros (RNO). It is a novel plant homeodomain (PHD)-containing nuclear protein that may function as a transcription factor that antagonizes Ras signaling by regulating transcription of key EGFR/Ras pathway regulators in the Drosophila eye. All Jade proteins contain a canonical Cys4HisCys3 PHD finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, both of which are zinc-binding motifs. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 19113240 337 CECGDSTEDSEMFQCERCDGWVHCACYGFESDSDprqpNQLLCYTC 382
Cdd:cd15573   5 CRSPDSEEGNEMVFCDKCNICVHQACYGIQKIPE----GSWLCRTC 46