PHD finger found in histone lysine demethylase PHF8; 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. PHF8 contains an N-terminal plant homeodomain (PHD) finger followed by a JmjC domain. The PHD finger mediates binding to nucleosomes at active gene promoters and the JmjC domain catalyzes the demethylation of mono- or dimethyl-lysines.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 569012054   6 VYCLCRLPYDVTRFMIECDMCQDWFHGSCVGVEEEKAADIDLYHCPNCEVLH 57
Cdd:cd15642    1 VYCLCRLPYDVTRFMIECDVCQDWFHGSCVGVEEEKAAEIDLYHCPNCQVTH 52

A domain family that is part of the cupin metalloenzyme superfamily; Probable enzymes, but of unknown functions, that regulate chromatin reorganisation processes (Clissold and Ponting, in press).

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569012054   199 RLSNLVETPRivrKLSWVENLWPEecvFERPNVQKYCLMSVRDSYTDFHIDFGGTSVWYHVLKG 262
Cdd:smart00558   1 QLWNLAKLPF---KLNLLSDLPED---IPGPDVGPYLYMGMAGSTTPWHIDDYDLVNYLHQGAG 58

PHD finger found in histone lysine demethylase PHF8; 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. PHF8 contains an N-terminal plant homeodomain (PHD) finger followed by a JmjC domain. The PHD finger mediates binding to nucleosomes at active gene promoters and the JmjC domain catalyzes the demethylation of mono- or dimethyl-lysines.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 569012054   6 VYCLCRLPYDVTRFMIECDMCQDWFHGSCVGVEEEKAADIDLYHCPNCEVLH 57
Cdd:cd15642    1 VYCLCRLPYDVTRFMIECDVCQDWFHGSCVGVEEEKAAEIDLYHCPNCQVTH 52

A domain family that is part of the cupin metalloenzyme superfamily; Probable enzymes, but of unknown functions, that regulate chromatin reorganisation processes (Clissold and Ponting, in press).

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569012054   199 RLSNLVETPRivrKLSWVENLWPEecvFERPNVQKYCLMSVRDSYTDFHIDFGGTSVWYHVLKG 262
Cdd:smart00558   1 QLWNLAKLPF---KLNLLSDLPED---IPGPDVGPYLYMGMAGSTTPWHIDDYDLVNYLHQGAG 58

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 569012054    7 YC-LCRLPyDVTRFMIECDMCQDWFHGSCVGVEEEKAADID-LYHCPNC 53
Cdd:pfam00628   1 YCaVCGKS-DDGGELVQCDGCDDWFHLACLGPPLDPAEIPSgEWLCPEC 48

PHD finger found in histone lysine demethylase PHF8; 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. PHF8 contains an N-terminal plant homeodomain (PHD) finger followed by a JmjC domain. The PHD finger mediates binding to nucleosomes at active gene promoters and the JmjC domain catalyzes the demethylation of mono- or dimethyl-lysines.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 569012054   6 VYCLCRLPYDVTRFMIECDMCQDWFHGSCVGVEEEKAADIDLYHCPNCEVLH 57
Cdd:cd15642    1 VYCLCRLPYDVTRFMIECDVCQDWFHGSCVGVEEEKAAEIDLYHCPNCQVTH 52

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        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 569012054   7 YCLCRLPYDVTRFMIECDMCQDWFHGSCVGVEEEKAADIDLYHCPNCEVL 56
Cdd:cd15640    1 YCVCRQPYDVNRFMIECDICKDWFHGSCVQVEEHHAADIDLYHCPNCEVL 50

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 569012054   7 YCLCRLPYDVTRFMIECDMCQDWFHGSCVGVEEEKAADIDLYHCPNC 53
Cdd:cd15560    1 YCICRTPYDESQFYIGCDRCQDWFHGRCVGILQSEAEKIDEYVCPQC 47

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 569012054   7 YCLCRLPyDVTRFMIECDMCQDWFHGSCVGVEEEKAADIDLYHCPNC 53
Cdd:cd15553    1 YCICRSS-DISRFMIGCDNCEEWYHGDCINITEKEAKAIKEWYCQQC 46

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        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 569012054   6 VYCLCRLPYDvTRFMIECDMCQDWFHGSCVGVEEEKAADIDL----YHCPNC 53
Cdd:cd15639    4 LYCICRQPHN-NRFMICCDRCEEWFHGDCVGITEARGRLLERngedYICPNC 54

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 569012054   7 YC-LCRLPYDVTRFMIECDMCQDWFHGSCVGVEEEKAADIDLYHCPNC 53
Cdd:cd15489    1 SCiVCGKGGDLGGELLQCDGCGKWFHADCLGPPLSSFVPNGKWICPVC 48

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 569012054   7 YCLCRLPYDVTrfMIECDMCQDWFHGSCVGVEEEKAADIDLYHCPNC 53
Cdd:cd15518    1 YCFCRQGEGGT--MIECEICKEWYHVKCIKNGRWKLDDDDKFVCPIC 45

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 569012054     7 YC-LCRLPYDvTRFMIECDMCQDWFHGSCVGVEEEKAADIDLYHCPNC 53
Cdd:smart00249   1 YCsVCGKPDD-GGELLQCDGCDRWYHQTCLGPPLLEEEPDGKWYCPKC 47

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        30
                 ....*....|....*....|....*....|
gi 569012054   7 YCLCRLPydVTRFMIECDMCQDWFHGSCVG 36
Cdd:cd15606    1 YCICRKP--FSGFMLQCELCKDWFHSSCVP 28

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 569012054   7 YCLCRLPY-----DVTRFMIECDMCQDWFHGSCVGV------EEEKAADIdlyhCPNC 53
Cdd:cd15542    1 YCTCDRPYpdpedEVEDEMIQCVLCEDWFHGRHLGLtppepdPDEFDEMI----CSGC 54

PHD finger 3 found in Lysine-specific demethylase 5A (KDM5A), 5B (KDM5B), and similar proteins; The family includes KDM5A and KDM5B, both of which belong to the JARID subfamily within the JmjC proteins. KDM5A, also termed Histone demethylase JARID1A, or 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 the trimethylated histone H3 lysine 4 (H3K4me3) demethylase. It also displays DNA-binding activities that can recognize the specific DNA sequence CCGCCC. KDM5B, also termed Cancer/testis antigen 31 (CT31), or Histone demethylase JARID1B, or Jumonji/ARID domain-containing protein 1B (JARID1B), or PLU-1, or retinoblastoma-binding protein 2 homolog 1 (RBP2-H1 or RBBP2H1A), 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. KDM5B acts as a histone demethylase that catalyzes the removal of trimethylation of lysine 4 on histone H3 (H3K4me3), induced by polychlorinated biphenyls (PCBs). It also mediates demethylation of H3K4me2 and H3K4me1. Moreover, KDM5B functions as a negative regulator of hematopoietic stem cell (HSC) self-renewal and progenitor cell activity. KDM5B has also been shown to interact with the DNA binding transcription factors BF-1 and PAX9, as well asTIEG1/KLF10 (transforming growth factor-beta inducible early gene-1/Kruppel-like transcription factor 10), and possibly function as a transcriptional corepressor. The family also includes the Drosophila melanogaster protein little imaginal discs (Lid) that functions as a JmjC-dependent trimethyl histone H3K4 (H3K4me3) demethylase, which is required for dMyc-induced cell growth. It positively regulates Hox gene expression in S2 cells. Members in this family contain 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 third PHD finger.

                         10        20        30
                 ....*....|....*....|....*....|.
gi 569012054  23 CDMCQDWFHGSCVGVEEEKAADIDLYHCPNC 53
Cdd:cd15610   20 CDGCEEWFHLLCVGLSPEEVAEDEDYICPSC 50

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 569012054   8 CLCRLPYDVTRFMIECDMCQDWFHGSCVGVEEEKAADiDLYHCPNC 53
Cdd:cd15556    2 CSCGTRDDDGERMIACDVCEVWQHTRCVGIADNEEPP-DHFLCRRC 46

PHD finger 2 found in Lysine-specific demethylase KDM5A, KDM5B, KDM5C, KDM5D, and similar proteins; The JARID subfamily within the JmjC proteins includes Lysine-specific demethylase KDM5A, KDM5B, KDM5C, KDM5D and a Drosophila homolog protein, little imaginal discs (Lid). 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 interacting 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. KDM5C is a H3K4 trimethyl-histone demethylase that catalyzes demethylation of H3K4me3 and H3K4me2 to H3K4me1. It plays a role in neuronal survival and dendrite development. KDM5C defects are associated with X-linked mental retardation (XLMR). KDM5D is a male-specific antigen that shows a demethylase activity specific for di- and tri-methylated histone H3K4 (H3K4me3 and H3K4me2), and has a male-specific function as a histone H3K4 demethylase by recruiting a meiosis-regulatory protein, MSH5, to condensed DNA. KDM5D directly interacts with a polycomb-like protein Ring6a/MBLR, and plays a role in regulation of transcriptional initiation through H3K4 demethylation. The family also includes Drosophila melanogaster protein little imaginal discs (Lid) that functions as a JmjC-dependent trimethyl histone H3K4 (H3K4me3) demethylase, which is required for dMyc-induced cell growth. It positively regulates Hox gene expression in S2 cells. Members in this family contain the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as two or three plant homeodomain (PHD) fingers. This model corresponds to the second PHD finger.

                         10        20        30
                 ....*....|....*....|....*....|.
gi 569012054   7 YCLCRlpYDVTRFMIECDMCQDWFHGSCVGV 37
Cdd:cd15516    1 ICLCG--KALAAGMLQCELCQDWFHGSCVAV 29

PHD finger found in PHD finger protein 23 (PHF23); PHF23, also termed PHD-containing protein JUNE-1, is a hypothetical protein with a plant homeodomain (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        40
                 ....*....|....*....|....*....|....*....|....*.
gi 569012054   8 CLCRLPYdVTRFMIECDMCQDWFHGSCVGVEEEKAADIdlYHCPNC 53
Cdd:cd15631    2 CYCGKPF-AGRPMIECSQCGTWIHLSCAKIKKSNVPDF--FYCQKC 44

PHD finger 3 found in Schizosaccharomyces pombe Lid2 complex component Lid2p and similar proteins; 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. The family corresponds to the third PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 569012054   8 CLCRLPYDVTRFMIECDMCQDWFHGSCVGVEEEKAADIDLYHCPNC 53
Cdd:cd15520    2 CGCGEGFNIADRMIFCDRCERTVHLDCVGLSDRIVDSPSEFFCPEC 47

PHD finger found in the inhibitor of growth (ING) protein family; The ING family includes a group of tumor suppressors, ING1-5, which act as readers and writers of the histone epigenetic code, affecting DNA damage response, chromatin remodeling, cellular senescence, differentiation, cell cycle regulation and apoptosis. They may have a general role in mediating the cellular response to genotoxic stress through binding to and regulating the activities of histone acetyltransferase (HAT) and histone deacetylase (HDAC) chromatin remodeling complexes. All ING proteins contain an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 569012054   7 YCLCRLPYDVTrfMIECD--MCQ-DWFHGSCVGVeeeKAADIDLYHCPNC 53
Cdd:cd15505    1 YCICNQVSYGE--MVACDnpNCPiEWFHFECVGL---TAKPKGKWYCPEC 45

PHD finger 6 found in Histone-lysine N-methyltransferase 2C (KMT2C) and PHD finger 5 found in KMT2D; KMT2C, also termed myeloid/lymphoid or mixed-lineage leukemia protein 3 (MLL3), or homologous to ALR protein, is a histone H3 lysine 4 (H3K4) lysine methyltransferase that functions as a circadian factor contributing to genome-scale circadian transcription. It is a component of a large complex that acts as a coactivator of multiple transcription factors, including the bile acid (BA)-activated nuclear receptor, farnesoid X receptor (FXR), a critical player in BA homeostasis. The MLL3 complex is essential for p53 transactivation of small heterodimer partner (SHP). KMT2C is also a part of activating signal cointegrator-2 (ASC-2)-containing complex (ASCOM) that contains the transcriptional coactivator nuclear receptor coactivator 6 (NCOA6), KMT2C and its paralog MLL4. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named MLL4, a fourth human homolog of Drosophila trithorax, located on chromosome 12. It enzymatically generates trimethylated histone H3 Lysine 4 (H3K4me3). It plays an essential role in differentiating the human pluripotent embryonal carcinoma cell line NTERA-2 clone D1 (NT2/D1) stem cells by activating differentiation-specific genes, such as HOXA1-3 and NESTIN. KMT2D is also a part of ASCOM. Both KMT2C and KMT2D contain the catalytic domain SET, several plant homeodomain (PHD) fingers, two extended PHD (ePHD) fingers, Cys2HisCys5HisCys2His, a RING finger, an HMG (high-mobility group)-binding motif, and two FY-rich regions. This model corresponds to the sixth PHD finger of KMT2C and the fifth PHD finger of KMT2D.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 569012054   8 CLCRLPYDVTRFMIECDMCQDWFHGSCVGV--EE--EKAADIDlYHCPNC 53
Cdd:cd15514    3 PVCSRSYNEGELIIQCSQCERWLHGACDSLrtEEeaERAADNG-YRCLLC 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 569012054   6 VYCLCRLPYdVTRFMIECDMCQDWFHGSCVGVEEEKAADIdlYHCPNC 53
Cdd:cd15632    2 VTCFCMKPF-AGRPMIECNECHTWIHLSCAKIRKSNVPEV--YVCQKC 46

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
                 ....*....|....*....|....*....|...
gi 569012054  21 IECDMCQDWFHGSCVGVEEEkAADIDLYHCPNC 53
Cdd:cd15547   16 VQCLKCGLWQHAECVNYDEE-SDKREPYLCPHC 47

Cupin-like domain; This cupin like domain shares similarity to the JmjC domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012054  169 KMKLGDFVKYYYSGKREKVLNVISLEFSDTR--LSNLVETPRIVrklswvenlWPEECvFERPNVQKYCLMSVRDSYTDF 246
Cdd:pfam13621  76 RMPFGEFLDRLEAGEDTDTAPYAYLQSDNLRseFPELLEDNDLP---------FATEA-FGGEPDAVNLWMGNGRSVTSL 145

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012054  247 HIDfggtsvWYH----VLKGEKIFYLIRPT-NANLTLFECWSSSSNQN-----------EMF--FGDqVEKCYKCSVKQG 308
Cdd:pfam13621 146 HYD------HYEnlycVVRGRKRFTLFPPSdVPNLYPGPLEPTPEGQVfslvdplapdfERFprFRD-AARPLVVTLNPG 218

                         170
                  ....*....|...
gi 569012054  309 QTLFIPTGWIHAV 321
Cdd:pfam13621 219 DVLYLPALWWHHV 231

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
                 ....*....|....*....|....*....
gi 569012054   7 YCLCRLPYDVTRFMIECDMCQDWFHGSCV 35
Cdd:cd15580    1 YCYCGGPGDWYLKMLQCCKCKQWFHEACV 29

PHD finger 2 found in lysine-specific demethylase 5B (KDM5B); KDM5B (also termed Cancer/testis antigen 31 (CT31), Histone demethylase JARID1B, Jumonji/ARID domain-containing protein 1B (JARID1B), retinoblastoma-binding protein 2 homolog 1 (RBP2-H1 or RBBP2H1A), or PLU-1) is a member of the JARID subfamily within the JmjC proteins. It 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. KDM5B acts as a histone demethylase that catalyzes the removal of trimethylation of lysine 4 on histone H3 (H3K4me3), induced by polychlorinated biphenyls (PCBs). It also mediates demethylation of H3K4me2 and H3K4me1. Moreover, KDM5B functions as a negative regulator of hematopoietic stem cell (HSC) self-renewal and progenitor cell activity. KDM5B has also been shown to interact with the DNA binding transcription factors BF-1 and PAX9, as well as TIEG1/KLF10 (transforming growth factor-beta inducible early gene-1/Kruppel-like transcription factor 10), and possibly function as a transcriptional corepressor. KDM5B 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        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 569012054   8 CLCRLPYDVTrfMIECDMCQDWFHGSCVGVEEEkAADIDLYHCPNC 53
Cdd:cd15607    2 CVCQKAPMAP--MIQCELCRDAFHSGCVTAPSD-PQGPQAWLCPQC 44

PHD finger 3 found in Lysine-specific demethylase 5A (KDM5A); KDM5A, also termed Histone demethylase JARID1A, or 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 third PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 569012054  10 CRLPYDVTRFMIECDM-CQDWFHGSCVGVEEEKAADIDlYHCPNC 53
Cdd:cd15686    8 CQRPCKDKVDWVQCDGgCDEWFHQVCVGVSPEMAENED-YICINC 51

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 569012054   7 YCLCRLPYDVTRFMIECDMCQDWFHGSCVGVEEEKAADIDL---YHCPNC 53
Cdd:cd15583    1 YCYCGKDRNLGEVELQCSICLKWFHAKCVSIDNGSCLPFMTnyqFVCKRC 50