PHD finger 2 found in PHD finger protein 19 (PHF19); PHF19, also termed Polycomb-like protein 3 (PCL3), is a component of the Polycomb repressive complex 2 (PRC2), which is the major H3K27 methyltransferase that regulates pluripotency, differentiation, and tumorigenesis through catalysis of histone H3 lysine 27 trimethylation (H3K27me3) on chromatin. PHF19 consists of an N-terminal Tudor domain followed by two plant homeodomain (PHD) fingers, and a C-terminal MTF2 domain. It binds H3K36me3 through its Tudor domain and recruits the PRC2 complex and the H3K36me3 demethylase NO66 to embryonic stem cell genes during differentiation. Moreover, PHF19 and its upstream regulator, Akt, play roles in the phenotype switch of melanoma cells from proliferative to invasive states. This model corresponds to the second PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370514258  24 YCYCGGPGEWYLRMLQCYRCRQWFHEACTQCLNEPMMFGDRFYLFFCSVCNQ 75
Cdd:cd15581     1 YCYCGGPGEWYLKMLQCYRCRQWFHEACTQCLNDPMMFGDRFYLFFCAVCNQ 52

PHD finger 2 found in PHD finger protein 19 (PHF19); PHF19, also termed Polycomb-like protein 3 (PCL3), is a component of the Polycomb repressive complex 2 (PRC2), which is the major H3K27 methyltransferase that regulates pluripotency, differentiation, and tumorigenesis through catalysis of histone H3 lysine 27 trimethylation (H3K27me3) on chromatin. PHF19 consists of an N-terminal Tudor domain followed by two plant homeodomain (PHD) fingers, and a C-terminal MTF2 domain. It binds H3K36me3 through its Tudor domain and recruits the PRC2 complex and the H3K36me3 demethylase NO66 to embryonic stem cell genes during differentiation. Moreover, PHF19 and its upstream regulator, Akt, play roles in the phenotype switch of melanoma cells from proliferative to invasive states. This model corresponds to the second PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370514258  24 YCYCGGPGEWYLRMLQCYRCRQWFHEACTQCLNEPMMFGDRFYLFFCSVCNQ 75
Cdd:cd15581     1 YCYCGGPGEWYLKMLQCYRCRQWFHEACTQCLNDPMMFGDRFYLFFCAVCNQ 52

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        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1370514258   24 YCY-CGGPGEWyLRMLQCYRCRQWFHEActqCLNEPMMFGDRFYLFFCSVC 73
Cdd:smart00249   1 YCSvCGKPDDG-GELLQCDGCDRWYHQT---CLGPPLLEEEPDGKWYCPKC 47

PHD finger 2 found in PHD finger protein 19 (PHF19); PHF19, also termed Polycomb-like protein 3 (PCL3), is a component of the Polycomb repressive complex 2 (PRC2), which is the major H3K27 methyltransferase that regulates pluripotency, differentiation, and tumorigenesis through catalysis of histone H3 lysine 27 trimethylation (H3K27me3) on chromatin. PHF19 consists of an N-terminal Tudor domain followed by two plant homeodomain (PHD) fingers, and a C-terminal MTF2 domain. It binds H3K36me3 through its Tudor domain and recruits the PRC2 complex and the H3K36me3 demethylase NO66 to embryonic stem cell genes during differentiation. Moreover, PHF19 and its upstream regulator, Akt, play roles in the phenotype switch of melanoma cells from proliferative to invasive states. This model corresponds to the second PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370514258  24 YCYCGGPGEWYLRMLQCYRCRQWFHEACTQCLNEPMMFGDRFYLFFCSVCNQ 75
Cdd:cd15581     1 YCYCGGPGEWYLKMLQCYRCRQWFHEACTQCLNDPMMFGDRFYLFFCAVCNQ 52

PHD finger 2 found in metal-response element-binding transcription factor 2 (MTF2); MTF2, also termed metal regulatory transcription factor 2, or metal-response element DNA-binding protein M96, or Polycomb-like protein 2 (PCL2), complexes with the Polycomb repressive complex-2 (PRC2) in embryonic stem cells and regulates the transcriptional networks during embryonic stem cell self-renewal and differentiation. It recruits the PRC2 complex to the inactive X chromosome and target loci in embryonic stem cells. Moreover, MTF2 is required for PRC2-mediated Hox cluster repression. It activates the Cdkn2a gene and promotes cellular senescence, thus suppressing the catalytic activity of PRC2 locally. MTF2 consists of an N-terminal Tudor domain followed by two plant homeodomain (PHD) fingers, and a C-terminal MTF2 domain. This model corresponds to the second PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370514258  24 YCYCGGPGEWYLRMLQCYRCRQWFHEACTQCLNEPMMFGDRFYLFFCSVCNQ 75
Cdd:cd15580     1 YCYCGGPGDWYLKMLQCCKCKQWFHEACVQCLEKPMLFGDRFYTFICSVCNS 52

Polycomb-like MTF2 factor 2; Mammalian Polycomb-like gene MTF2/PCL2 forms a complex with Polycomb repressive complex-2 (PRC2) and collaborates with PRC1 to achieve repression of Hox gene expression. The human MTF2 gene is expressed in three splicing variants, each of them contains the short C-terminal domain defined here. The domain is subject to structure determination by the Joint Center of Structural Genomics.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1370514258 358 SLSHLKSSITNYFGAAGRLACGEKYQVLARRVTPEGKVQYLVEWEGTT 405
Cdd:pfam14061   1 SMSDLKSSINSYFGAAGRIACGERYAVLAKRVTPNGKVQYLVEWEGTT 48

PHD finger found in Schizosaccharomyces pombe Set1 complex component ash2 (spAsh2p) and similar proteins; spAsh2p, also termed Set1C component ash2, or COMPASS component ash2, or complex proteins associated with set1 protein ash2, or Lid2 complex component ash2, or Lid2C component ash2, is orthologous to Drosophila melanogaster Ash2 protein. Both spAsh2p and D. melanogaster Ash2 contain a plant homeodomain (PHD) finger and a SPRY domain. In contrast, its counterpart in Saccharomyces cerevisiae, Bre2p, has no PHD finger and is not included in this family. spAsh2p shows histone H3 Lys4 (H3K4) methyltransferase activity through its PHD finger. It also interacts with Lid2p in S. pombe. Human Ash2L contains an atypical PHD finger that lacks part of the Cys4HisCys3 signature characteristic of PHD fingers, it binds to only one zinc ion through the second half of the motif and does not have histone tail binding activity.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370514258  24 YCYCGGPGEWYLRMLQCYRCRQWFHEACTQCLNEPMMFGDRFYLFFCSVC 73
Cdd:cd15583     1 YCYCGKDRNLGEVELQCSICLKWFHAKCVSIDNGSCLPFMTNYQFVCKRC 50

PHD finger found in Set1 complex component SPP1; Set1C component SPP1, also called COMPASS component Spp1, or Complex proteins associated with set1 protein Spp1, or Suppressor of PRP protein 1, is a component of the COMPASS complex that links histone methylation to initiation of meiotic recombination. It induces double-strand break (DSB) formation by tethering to recombinationally cold regions. SPP1 interacts with H3K4me3 and Mer2, a protein required for DSB formation, to promote recruitment of potential meiotic DSB sites to the chromosomal axis. SPP1 contains a PHD finger, a zinc binding motif.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370514258  24 YCYCGGP--GEWylrMLQCYRCRQWFHeacTQCLNEPMMFGDRFYLFFCSVC 73
Cdd:cd16039     1 YCICQKPddGRW---MIACDGCDEWYH---FTCVNIPEADVELVDSFFCPPC 46

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
                  ....*....|....*....|....*...
gi 1370514258  24 YCYCGGPGEWYLRMLQCYRCRQWFHEAC 51
Cdd:cd15554     1 YCICRQPYDVTRFMIECDVCKDWFHGSC 28

PHD finger found in lysine-specific demethylase 7 (KDM7); 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. KDM7 contains a plant homeodomain (PHD) that binds Lys4-trimethylated histone 3 (H3K4me3) and a jumonji domain that demethylates either H3K9me2 or H3K27me2.

                          10        20        30
                  ....*....|....*....|....*....|
gi 1370514258  24 YCYCGGPGEWYLRMLQCYRCRQWFHEACTQ 53
Cdd:cd15640     1 YCVCRQPYDVNRFMIECDICKDWFHGSCVQ 30