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
                   ....*....|....*....|....*....|....*....|....*..
gi 1000864171  763 YCVCKTKYDeDRFMIACDRCDEWYHTTCVNMPDMEVELVDQFFCPPC 809
Cdd:cd16039      1 YCICQKPDD-GRWMIACDGCDEWYHFTCVNIPEADVELVDSFFCPPC 46

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
                   ....*....|....*....|....*....|....*....|....*..
gi 1000864171  763 YCVCKTKYDeDRFMIACDRCDEWYHTTCVNMPDMEVELVDQFFCPPC 809
Cdd:cd16039      1 YCICQKPDD-GRWMIACDGCDEWYHFTCVNIPEADVELVDSFFCPPC 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        40
                    ....*....|....*....|....*....|....*....|....*...
gi 1000864171   763 YC-VCKTKYDEDrFMIACDRCDEWYHTTCVNMPDMEVELVDQFFCPPC 809
Cdd:smart00249    1 YCsVCGKPDDGG-ELLQCDGCDRWYHQTCLGPPLLEEEPDGKWYCPKC 47

Chromatin remodeling protein, contains PhD zinc finger [Chromatin structure and dynamics];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1000864171  622 EDVTKKGESVG-ATSSQAAKKKKDAGNRTvNKKNKESATSVNSQPSTNNKpqKVKAAGSKKAKTADGTTIPIPNIAETKT 700
Cdd:COG5034    113 EKVAARIENCHdAVSRLERNSYSSAARRS-SGEHRSAASSQGSRHTKLKK--RKNIHNLKRRSPELSSKREVSFTLESPS 189

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1000864171  701 PGAKQAKSSASNKKPSTASHiaasrsrstsvipGGSVEPEPEPERkseekdeekdeaiddkLYCVC-KTKYDEdrfMIAC 779
Cdd:COG5034    190 VPDTATRVKEGNNGGSTKSR-------------GVSSEDNSEGEE----------------LYCFCqQVSYGQ---MVAC 237

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1000864171  780 DRCD---EWYHTTCVNM---PDMevelvdQFFCPPCIEQ 812
Cdd:COG5034    238 DNANckrEWFHLECVGLkepPKG------KWYCPECKKA 270

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
                   ....*....|....*....|....*....|....*....|....*..
gi 1000864171  763 YCVCKTKYDeDRFMIACDRCDEWYHTTCVNMPDMEVELVDQFFCPPC 809
Cdd:cd16039      1 YCICQKPDD-GRWMIACDGCDEWYHFTCVNIPEADVELVDSFFCPPC 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        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1000864171  763 YCVCKTKYDEDRFMIACDRCDEWYHTTCVNMPDMEVELVDQFFCPPC 809
Cdd:cd15554      1 YCICRQPYDVTRFMIECDVCKDWFHGSCVGVEEHQANDIERYHCPNC 47

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 1000864171  763 YCVCKtKYDEDRFMIACDRCDEWYHTTCV-----NMPDMEvELVDQFFCPPC 809
Cdd:cd15552      1 YCICR-KPHNNRFMICCDRCEEWFHGDCVgiteaQGKEME-ENIEEYVCPKC 50

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        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1000864171  763 YC-VCKtKYDEDRFMIACDRCDEWYHTTCVNMP-DMEVELVDQFFCPPCIE 811
Cdd:pfam00628    1 YCaVCG-KSDDGGELVQCDGCDDWFHLACLGPPlDPAEIPSGEWLCPECKP 50

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 1000864171   763 YC-VCKTKYDEDrFMIACDRCDEWYHTTCVNMPDMEVELVDQFFCPPC 809
Cdd:smart00249    1 YCsVCGKPDDGG-ELLQCDGCDRWYHQTCLGPPLLEEEPDGKWYCPKC 47

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 1000864171  764 CVCKTKYDEDRFMIACDRCDEWYHTTCVNMPDMEvELVDQFFCPPC 809
Cdd:cd15556      2 CSCGTRDDDGERMIACDVCEVWQHTRCVGIADNE-EPPDHFLCRRC 46

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
                   ....*....|....*....|....*....|....*....|....*...
gi 1000864171  762 LYCVCKTKYDEDRFMIACDRCDEWYHTTCVNMPDMEVELVDQFFCPPC 809
Cdd:cd15642      1 VYCLCRLPYDVTRFMIECDVCQDWFHGSCVGVEEEKAAEIDLYHCPNC 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 1000864171  763 YCVCKTkyDEDRFMIACDRCDEWYHTTCVNMPDMEVELVDQFFCPPC 809
Cdd:cd15518      1 YCFCRQ--GEGGTMIECEICKEWYHVKCIKNGRWKLDDDDKFVCPIC 45

PHD finger found in ubiquitin-like PHD and RING finger domain-containing protein UHRF1 and UHRF2; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumour suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of transcription factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) by interacting with the HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal RING finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1000864171  764 CVCKTKYDEDRfMIACDRCDEWYHTTCVNMPDMEVELVDQFFCPPC 809
Cdd:cd15525      3 HVCGGKQDPEK-QLLCDECDMAYHLYCLDPPLTSLPDDDEWYCPDC 47

PHD finger found in Transcription factor 19 (TCF-19), Lysine-specific demethylase KDM5A and KDM5B, and other similar proteins; TCF-19 was identified as a putative trans-activating factor with expression beginning at the late G1-S boundary in dividing cells. It functions as a novel islet factor necessary for proliferation and survival in the INS-1 beta cell line. It plays an important role in susceptibility to both Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM); it has been suggested that it may positively impact beta cell mass under conditions of beta cell stress and increased insulin demand. 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 interaction 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. This family also includes Caenorhabditis elegans Lysine-specific demethylase 7 homolog (ceKDM7A). ceKDM7A (also termed JmjC domain-containing protein 1.2, PHD finger protein 8 homolog, or PHF8 homolog) is a plant homeodomain (PHD)- and JmjC domain-containing protein that functions as a histone demethylase specific for H3K9me2 and H3K27me2. The binding of the PHD finger to H3K4me3 guides H3K9me2- and H3K27me2-specific demethylation by its catalytic JmjC domain in a trans-histone regulation mechanism. In addition, this family includes plant protein OBERON 1 and OBERON 2, Alfin1-like (AL) proteins, histone acetyltransferases (HATs) HAC, and AT-rich interactive domain-containing protein 4 (ARID4).

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1000864171  764 CVC--KTKYDEDRFMIACDRCDEWYHTTCVNMPDMEVELVDQFFCPPC 809
Cdd:cd15517      2 CGIcnLETAAVDELWVQCDGCDKWFHQFCLGLSNERYADEDKFKCPNC 49

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 1000864171  764 CVCKTKYDEDRFMIACDRCDEWYHTTCVNMPDMEVELVDQFFCPPC 809
Cdd:cd15520      2 CGCGEGFNIADRMIFCDRCERTVHLDCVGLSDRIVDSPSEFFCPEC 47

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 1000864171  763 YCVCKTKYDE-----DRFMIACDRCDEWYHTTCVNMPDMEVELVDQFF--CPPC 809
Cdd:cd15542      1 YCTCDRPYPDpedevEDEMIQCVLCEDWFHGRHLGLTPPEPDPDEFDEmiCSGC 54

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1000864171  366 PPSSRSSDSHRVVLDAQTLPKNSRDAKETQDAAARQPQHQQDPHEWLLDHYGQPSVHHHSPLEPPRSLSPSTSPVLSKAQ 445
Cdd:PHA03247  2556 PPAAPPAAPDRSVPPPRPAPRPSEPAVTSRARRPDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPSPAA 2635

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1000864171  446 TEKARTPPVEIPKPIIALRSPSPdADAALERELAELMAEEDELAPVRKHETDdmdidlavaeileeddkskvvpmdvdGA 525
Cdd:PHA03247  2636 NEPDPHPPPTVPPPERPRDDPAP-GRVSRPRRARRLGRAAQASSPPQRPRRR--------------------------AA 2688

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1000864171  526 DDVEDELLSLVDDRPPPSTTSA---VAGRKVATPTLPVAAFKPPPVLKADEVKRPSPPAPTL-STVSAATSPVVR--PPS 599
Cdd:PHA03247  2689 RPTVGSLTSLADPPPPPPTPEPaphALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATpGGPARPARPPTTagPPA 2768

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1000864171  600 TLPASERGSMPPPAvsrgkdrdedVTKKGESVGATSSQAAKKKKDAGNRTVNKKNKESATSVNSQPSTNN-KPQKVKAAG 678
Cdd:PHA03247  2769 PAPPAAPAAGPPRR----------LTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLpPPTSAQPTA 2838

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1000864171  679 SKKAKTADGTTIPIPNIAETKTPGAKQAKSSASNKKPSTASHIAASR------SRSTSVIPGGSVEPEPEPE 744
Cdd:PHA03247  2839 PPPPPGPPPPSLPLGGSVAPGGDVRRRPPSRSPAAKPAAPARPPVRRlarpavSRSTESFALPPDQPERPPQ 2910

PHD finger found in bromodomain adjacent to zinc finger domain protein 2A (BAZ2A) and 2B (BAZ2B); BAZ2A, also termed transcription termination factor I-interacting protein 5 (TTF-I-interacting protein 5, or Tip5), or WALp3, is an epigenetic regulator. It has been implicated in epigenetic rRNA gene silencing, as the large subunit of the SNF2h-containing chromatin-remodeling complex NoRC that induces nucleosome sliding in an ATP- and histone H4 tail-dependent fashion. BAZ2A has also been shown to be broadly overexpressed in prostate cancer, to regulate numerous protein-coding genes and to cooperate with EZH2 (enhancer of zeste homolog 2) to maintain epigenetic silencing at genes repressed in prostate cancer metastasis. Its overexpression is tightly associated with a prostate cancer subtype displaying CpG island methylator phenotype (CIMP) in tumors and with prostate cancer recurrence in patients. BAZ2B, also termed WALp4, is a bromodomain-containing protein whose biological role is still elusive. It shows high sequence similarly with BAZ2A. Both BAZ2A and BAZ2B contain a TAM (TIP5/ARBP/MBD) domain, a DDT domain, four AT-hooks, BAZ 1 and BAZ 2 motifs, a WAKZ (WSTF/Acf1/KIAA0314/ZK783.4) motif, a plant homeodomain (PHD) finger, and a bromodomain. BAZ2B also harbors an extra Apolipophorin-III like domain in its N-terminal region.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1000864171  763 YC-VCKTKYDEDRFMIaCDRCDEWYHTTCVNmPDMEVELVDQFFCPPC 809
Cdd:cd15545      1 SCqICRSGDNEDQLLL-CDGCDRGYHTYCFK-PKMTNVPEGDWFCPEC 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        30
                   ....*....|....*....|....*....|..
gi 1000864171  763 YCVCKTKYDEdrFMIACDRCDEWYHTTCVNMP 794
Cdd:cd15606      1 YCICRKPFSG--FMLQCELCKDWFHSSCVPLP 30

transcriptional regulator ICP4; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1000864171  536 VDDRPPPSTTSAVAG--RKVATPTLPVAAFKPPPVLKADEVKRPSPPAPTLSTVSAATSPVVRPPSTlPASERGSMPPPA 613
Cdd:PHA03307   122 PPASPPPSPAPDLSEmlRPVGSPGPPPAASPPAAGASPAAVASDAASSRQAALPLSSPEETARAPSS-PPAEPPPSTPPA 200

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1000864171  614 VSRGKDRDEDVTKKGESVGATSSQAAKKKKDAGNRTVNKKNKESATSVNSQPSTNNKPQkvkaAGSKKAKTADGTtiPIP 693
Cdd:PHA03307   201 AASPRPPRRSSPISASASSPAPAPGRSAADDAGASSSDSSSSESSGCGWGPENECPLPR----PAPITLPTRIWE--ASG 274

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1000864171  694 NIAETKTPGAKQAKSSASNKKPSTASHIAASRSRSTSVIPGGSVEPEPE 742
Cdd:PHA03307   275 WNGPSSRPGPASSSSSPRERSPSPSPSSPGSGPAPSSPRASSSSSSSRE 323

PHD finger 2 found in PHD finger protein 10 (PHF10) and similar proteins; PHF10, also termed BRG1-associated factor 45a (BAF45a), or XAP135, is a ubiquitously expressed transcriptional regulator that is required for maintaining the undifferentiated status of neuroblasts. It contains a SAY (supporter of activation of yellow) domain and two adjacent plant homeodomain (PHD) fingers. This model corresponds to the second PHD finger.

                           10        20        30
                   ....*....|....*....|....*....|
gi 1000864171  764 CVCKTKYDEDRfMIACDRCDEWYHTTCVNM 793
Cdd:cd15529      3 TKCGDPHDEDK-MMFCDQCDRGYHTFCVGL 31

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 1000864171  764 CVCKTKYDEDRfMIACDRCDEWYHTTCVNMPDMEV----ELVDQFFCPPC 809
Cdd:cd15570      2 CPCGSSMEDGS-MIQCEGCKTWQHMDCVLIPDKPAdglpELPSKFYCELC 50

DNA polymerase III subunit gamma/tau;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1000864171  532 LLSLVDDRPPPSTTSAVAGRkvATPTLPVAAFKPPPVLKADEVKRPSPPAPtlsTVSAATSPVVRPPSTLPA-SERGSMP 610
Cdd:PRK07003   352 LLRMLAFEPAVTGGGAPGGG--VPARVAGAVPAPGARAAAAVGASAVPAVT---AVTGAAGAALAPKAAAAAaATRAEAP 426

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1000864171  611 PPAVSRGKDRDEDVTKKGESVGATSSQAAKKKKDAgnrtvnkknkeSATSVNSQPSTNNKPQKVkAAGSKKAKTADGTTI 690
Cdd:PRK07003   427 PAAPAPPATADRGDDAADGDAPVPAKANARASADS-----------RCDERDAQPPADSGSASA-PASDAPPDAAFEPAP 494

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1000864171  691 PIPNIAETKTPGAKQAKSSASNKKPSTASHIAASRSRSTSVIPGGSVEP 739
Cdd:PRK07003   495 RAAAPSAATPAAVPDARAPAAASREDAPAAAAPPAPEARPPTPAAAAPA 543

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 1000864171  764 CVCKTKYdEDRFMIACDRCDEWYHTTCVNMPDM-EVELVDQFFCPPC 809
Cdd:cd15558      2 CECGDWG-EDGAMIQCAFCDTWQHLLCYGFESAkDPRIPDIHVCYRC 47

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 1000864171  764 CVCKTKyDEDRFMIACDRCDEWYHTTCVNMpdMEVELVDQFFCPPC 809
Cdd:cd15634      2 CICEVQ-EENDFMIQCEECLCWQHGVCMGL--LEDNVPEKYTCYIC 44

PHD finger found in ubiquitin-like PHD and RING finger domain-containing protein 2 (UHRF2); UHRF2 (also termed Np95/ICBP90-like RING finger protein (NIRF), Np95-like RING finger protein, nuclear protein 97, nuclear zinc finger protein Np97, RING finger protein 107, or E3 ubiquitin-protein ligase UHRF2) was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs,p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) by interacting with the HBV core protein and promoting its degradation. UHRF2 contains an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal RING finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1000864171  764 CVCKTKYDEDrFMIACDRCDEWYHTTCVNMPDMEVELVDQFFCPPC 809
Cdd:cd15617      3 YVCGGKQDAH-MQLLCDECNMAYHIYCLNPPLDKIPEDEDWYCPSC 47

PHD finger 6 found in Histone-lysine N-methyltransferase 2C (KMT2C); 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. KMT2C contains several plant homeodomain (PHD) fingers, two extended PHD (ePHD) fingers, Cys2HisCys5HisCys2His, an ATPase alpha beta signature, a high mobility group (HMG)-1 box, a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain and two FY (phenylalanine tyrosine)-rich domains. This model corresponds to the sixth PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1000864171  765 VCKTKYDEDRFMIACDRCDEWYHTTCVNM-PDMEVELVDQ--FFCPPC 809
Cdd:cd15600      4 ICYRNYREEELILQCRQCDRWMHASCQNLnTEEEVENAADngFDCTMC 51

PHD finger 2 found in Histone-lysine N-methyltransferase 2D (KMT2D); KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named myeloid/lymphoid or mixed-lineage leukemia 4 (MLL4), a fourth human homolog of Drosophila trithorax, located on chromosome 12. KMT2D enzymatically generates trimethylated histone H3 Lys 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 asHOXA1-3 and NESTIN. It 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 KMT2D. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2D contains the catalytic domain SET, five 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 second PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1000864171  765 VCKT--KYDEDRFMIACDRCDEWYHTTCVNmPDMEVELVDQFFCPPC 809
Cdd:cd15595      1 VCQTcrKPGEDSKMLVCEACDKGYHTFCLK-PAMESLPTDSWKCKAC 46

DNA translocase FtsK; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1000864171  366 PPSSRSSDSHRVVLDAQTLPKNSRDAKETQDAAARQPQHQQdphewlldhYGQPSVHHHSPLEPPrsLSPSTSPVLSKAQ 445
Cdd:PRK10263   345 PVASVDVPPAQPTVAWQPVPGPQTGEPVIAPAPEGYPQQSQ---------YAQPAVQYNEPLQQP--VQPQQPYYAPAAE 413

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1000864171  446 TEKARTPPVEIPKPIIALRSPSPDADAALERELAELMAEEDELAPVRKHETDDMDIDLAVAEILEEDDKSKVVPMDVDGA 525
Cdd:PRK10263   414 QPAQQPYYAPAPEQPAQQPYYAPAPEQPVAGNAWQAEEQQSTFAPQSTYQTEQTYQQPAAQEPLYQQPQPVEQQPVVEPE 493

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1000864171  526 DDVEDELLSlvddRPPPSTTSAVAGRKVATPTLPVAAFKPPPvlkaDEVKRPSPPAPTLSTVSAATSPVVRPPSTL 601
Cdd:PRK10263   494 PVVEETKPA----RPPLYYFEEVEEKRAREREQLAAWYQPIP----EPVKEPEPIKSSLKAPSVAAVPPVEAAAAV 561

PHD finger 1 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), PLU-1, or retinoblastoma-binding protein 2 homolog 1 (RBP2-H1 or RBBP2H1A)) 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 pregnant females 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 first PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1000864171  765 VCKTKYDEDRFMIaCDRCDEWYHTTCVNMPDMEVELVDqFFCPPC 809
Cdd:cd15603      4 VCGSGNDEDRLLL-CDGCDDSYHTFCLIPPLHDVPKGD-WRCPKC 46

PHD finger 3 found in histone-lysine N-methyltransferase 2A (KMT2A); KMT2A (also termed ALL-1, CXXC-type zinc finger protein 7, myeloid/lymphoid or mixed-lineage leukemia protein 1 (MLL1), trithorax-like protein (Htrx), or zinc finger protein HRX) is a histone methyltransferase that belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2). It 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, which also contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex. The MLL1 complex is highly active and specific for H3K4 methylation. KMT2A contains a CxxC (x for any residue) zinc finger domain, three plant homeodomain (PHD) fingers, a Bromodomain domain, 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 1000864171  763 YCV-CKTKYDEDRF---MIACDRCDEWYHTTCVNMPDMEVELVDQF 804
Cdd:cd15592      1 FCPlCDKCYDDDDYeskMMQCGKCDRWVHSKCENLSDEMYEILSNL 46

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
                   ....*....|....*....|....*....|....*....|....*....
gi 1000864171  764 CVCKTKYDEDRFMIACDRCDEWYHTTCVN-MPDMEVELVDQ--FFCPPC 809
Cdd:cd15514      3 PVCSRSYNEGELIIQCSQCERWLHGACDSlRTEEEAERAADngYRCLLC 51

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        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1000864171  763 YCVCKTKYDEdrFMIACDRCDEWYHTTCVNMPDMEV--------ELVDQFFCPPC 809
Cdd:cd15516      1 ICLCGKALAA--GMLQCELCQDWFHGSCVAVPRISSsprplawwEGDRKFLCPLC 53

PHD finger found in Transcription factor 19 (TCF-19) and similar proteins; TCF-19, also termed transcription factor SC1, was identified as a putative trans-activating factor with expression beginning at the late G1-S boundary in dividing cells. It also functions as a novel islet factor necessary for proliferation and survival in the INS-1 beta cell line. It plays an important role in susceptibility to both Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM); it has been suggested that it may positively impact beta cell mass under conditions of beta cell stress and increased insulin demand. TCF-19 contains an N-terminal fork head association domain (FHA), a proline rich region, and a C-terminal plant homeodomain (PHD) finger. The FHA domain may serve as a nuclear signaling domain or as a phosphoprotein binding domain. The proline rich region is a common characteristic of trans-activating factors. The PHD finger may allow TCF-19 to interact with chromatin via methylated histone H3.

                           10        20        30
                   ....*....|....*....|....*....|
gi 1000864171  779 CDRCDEWYHTTCVNMPDMEVELVD-QFFCP 807
Cdd:cd15609     20 CDDCDQWYHVACVGCDYNAVKDPDaDFHCG 49

PHD finger 2 found in Histone-lysine N-methyltransferase 2C (KMT2C) and 2D (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, five plant homeodomain (PHD) fingers, two extended PHD (ePHD) fingers, Cys2HisCys5HisCys2His, a RING finger, an HMG (high-mobilitygroup)-binding motif, and two FY-rich regions. This model corresponds to the second PHD finger.

                           10        20        30
                   ....*....|....*....|....*....|
gi 1000864171  765 VCKTKYDEDRfMIACDRCDEWYHTTCVNMP 794
Cdd:cd15510      4 ACRQPGDDTK-MLVCETCDKGYHTSCLRPV 32

PHD finger found in inhibitor of growth protein 4 (ING4) and 5 (ING5); ING4, also termed p29ING4, and ING5, also termed p28ING5, belong to the inhibitor of growth (ING) family of type II tumor suppressors. ING4 acts as an E3 ubiquitin ligase to induce ubiquitination of the p65 subunit of NF-kappaB and inhibit the transactivation of NF-kappaB target genes. It also induces apoptosis through a p53 dependent pathway, including increasing p53 acetylation, inhibiting Mdm2-mediated degradation of p53 and enhancing the expression of p53 responsive genes both at the transcriptional and post-translational levels. Moreover, ING4 can inhibit the translation of proto-oncogene MYC by interacting with AUF1. It also regulates other transcription factors, such as hypoxia-inducible factor (HIF). ING5 is a Tip60 cofactor that acetylates p53 at K120 and subsequently activates the expression of p53-dependent apoptotic genes in response to DNA damage. Aberrant ING5 expression may contribute to pathogenesis, growth, and invasion of gastric carcinomas and colorectal cancer. ING5 can physically interact with p300 and p53 in vivo, and its overexpression induces apoptosis in colorectal cancer cells. It also associates with cyclin A1 (INCA1) and functions as a growth suppressor with suppressed expression in Acute Myeloid Leukemia (AML). Moreover, ING5 translocation from the nucleus to the cytoplasm might be a critical event for carcinogenesis and tumor progression in human head and neck squamous cell carcinoma. Both ING4 and ING5 contain an N-terminal ING histone-binding domain and a C-terminal plant homeodomain (PHD) finger. They associate with histone acetyltransferase (HAT) complexes containing MOZ (monocytic leukemia zinc finger protein)/MORF (MOZ-related factor) and HBO1, and further direct the MOZ/MORF and HBO1 complexes to chromatin.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1000864171  763 YCVC-KTKYDEdrfMIACDRCD---EWYHTTCVnmpDMEVELVDQFFCPPC 809
Cdd:cd15586      1 YCLChQVSYGE---MIGCDNPDcpiEWFHFACV---GLTTKPKGKWFCPRC 45

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 1000864171  763 YCVCKTKYDEDRFMIACDRCDEWYHTTCVNMPDMEVELVDQFF---CPPC 809
Cdd:cd15580      1 YCYCGGPGDWYLKMLQCCKCKQWFHEACVQCLEKPMLFGDRFYtfiCSVC 50