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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375617 160 TLKELQNRLRRKREQEPTERPLKGIQSRLRKKRREEGPAETVGS------------EASDTVEGVLPSKQEPENDQGVVS 227
Cdd:COG5034  91 RAEKLLRRHRKLLDDRIAKRPHEKVAARIENCHDAVSRLERNSYssaarrssgehrSAASSQGSRHTKLKKRKNIHNLKR 170

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375617 228 QAGKD--------DRESKLEGKAAQDIKDEE-----PGDLGRPKPECEGydpNALYCICRQPHNNRfMICCD--RCE-EW 291
Cdd:COG5034 171 RSPELsskrevsfTLESPSVPDTATRVKEGNnggstKSRGVSSEDNSEG---EELYCFCQQVSYGQ-MVACDnaNCKrEW 246

                       170
                ....*....|.
gi 18375617 292 FHGDCVGISEA 302
Cdd:COG5034 247 FHLECVGLKEP 257

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 18375617   270 YC-ICRQPHNNRFMICCDRCEEWFHGDCVGISEARGRLLErngEDYICPNCT 320
Cdd:pfam00628   1 YCaVCGKSDDGGELVQCDGCDDWFHLACLGPPLDPAEIPS---GEWLCPECK 49

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375617 160 TLKELQNRLRRKREQEPTERPLKGIQSRLRKKRREEGPAETVGS------------EASDTVEGVLPSKQEPENDQGVVS 227
Cdd:COG5034  91 RAEKLLRRHRKLLDDRIAKRPHEKVAARIENCHDAVSRLERNSYssaarrssgehrSAASSQGSRHTKLKKRKNIHNLKR 170

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375617 228 QAGKD--------DRESKLEGKAAQDIKDEE-----PGDLGRPKPECEGydpNALYCICRQPHNNRfMICCD--RCE-EW 291
Cdd:COG5034 171 RSPELsskrevsfTLESPSVPDTATRVKEGNnggstKSRGVSSEDNSEG---EELYCFCQQVSYGQ-MVACDnaNCKrEW 246

                       170
                ....*....|.
gi 18375617 292 FHGDCVGISEA 302
Cdd:COG5034 247 FHLECVGLKEP 257

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 18375617 270 YCICRQPHNNRFMICCDRCEEWFHGDCVGISEARGRLLERNGEDYICPNC 319
Cdd:cd15552   1 YCICRKPHNNRFMICCDRCEEWFHGDCVGITEAQGKEMEENIEEYVCPKC 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        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 18375617 270 YCICRQPHN-NRFMICCDRCEEWFHGDCVGISEARGrlleRNGEDYICPNC 319
Cdd:cd15560   1 YCICRTPYDeSQFYIGCDRCQDWFHGRCVGILQSEA----EKIDEYVCPQC 47

PHD finger found in PHD finger protein 3 (PHF3); 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 18375617 272 ICRQPHNNRFMICCDRCEEWFHGDCVGISEARGRLLERNGEDYICPNC 319
Cdd:cd15638   4 FCKKPHGNRFMVGCGRCDDWFHGDCVGLSLSQAQQMEEEDKEYVCVKC 51

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 18375617 270 YCICRQPHNNRFMICCDRCEEWFHGDCVGISEARGRLLERngedYICPNC 319
Cdd:cd16039   1 YCICQKPDDGRWMIACDGCDEWYHFTCVNIPEADVELVDS----FFCPPC 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        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 18375617 269 LYCICRQPHN-NRFMICCDRCEEWFHGDCVGISEARGRLLERngedYICPNCTILQ 323
Cdd:cd15642   1 VYCLCRLPYDvTRFMIECDVCQDWFHGSCVGVEEEKAAEIDL----YHCPNCQVTH 52

PHD finger found in mixed lineage leukemia 5 (MLL5); MLL5 is a histone methyltransferase that plays a key role in hematopoiesis, spermatogenesis and cell cycle progression. It contains a single plant homeodomain (PHD) finger followed by a catalytic SET domain. MLL5 can be recruited to E2F1-responsive promoters to stimulate H3K4 trimethylation and transcriptional activation by binding to the cell cycle regulator host cell factor (HCF-1), thereby facilitating the cell cycle G1 to S phase transition. It is also involved in mitotic fidelity and genomic integrity by modulating the stability of the chromosomal passenger complex (CPC) via the interaction with Borealin. Moreover, MLL5 is a component of a complex associated with retinoic acid receptor that requires GlcN Acylation of its SET domain in order to activate its histone lysine methyltransferase activity. It also participates in the camptothecin (CPT)-induced p53 activation. Furthermore, MLL5 indirectly regulates H3K4 methylation, represses cyclin A2 (CycA) expression, and promotes myogenic differentiation.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 18375617 271 CICRQPHNNRFMICCDRCEEWFHGDCVGISEargrllERNGEDYICPNC 319
Cdd:cd15550   2 CICGFEHDDGFMICCDKCSVWQHGDCMGIDR------ENIPDSYLCEQC 44

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        50
                ....*....|....*....|....*....|....*....|....*....|
gi 18375617 271 CICRQPHN-NRFMICCDRCEEWFHGDCVGISEARGRLlernGEDYICPNC 319
Cdd:cd15489   3 IVCGKGGDlGGELLQCDGCGKWFHADCLGPPLSSFVP----NGKWICPVC 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        50
                ....*....|....*....|....*....|....*....|....*....|
gi 18375617 270 YCICRQPHNNrFMICCDRCEEWFHGDCVGISEARGrlleRNGEDYICPNC 319
Cdd:cd15518   1 YCFCRQGEGG-TMIECEICKEWYHVKCIKNGRWKL----DDDDKFVCPIC 45

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 18375617 285 CDRCEEWFHGDCVGISEargrLLERNGEDYICPNC 319
Cdd:cd15610  20 CDGCEEWFHLLCVGLSP----EEVAEDEDYICPSC 50

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375617 160 TLKELQNRLRRKREQEPTERPLKGIQSRLRKKRREEGPAETVGS------------EASDTVEGVLPSKQEPENDQGVVS 227
Cdd:COG5034  91 RAEKLLRRHRKLLDDRIAKRPHEKVAARIENCHDAVSRLERNSYssaarrssgehrSAASSQGSRHTKLKKRKNIHNLKR 170

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375617 228 QAGKD--------DRESKLEGKAAQDIKDEE-----PGDLGRPKPECEGydpNALYCICRQPHNNRfMICCD--RCE-EW 291
Cdd:COG5034 171 RSPELsskrevsfTLESPSVPDTATRVKEGNnggstKSRGVSSEDNSEG---EELYCFCQQVSYGQ-MVACDnaNCKrEW 246

                       170
                ....*....|.
gi 18375617 292 FHGDCVGISEA 302
Cdd:COG5034 247 FHLECVGLKEP 257

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 18375617 270 YCICRQPHN------NRFMICCDRCEEWFHGDCVGISEArgRLLERNGEDYICPNC 319
Cdd:cd15542   1 YCTCDRPYPdpedevEDEMIQCVLCEDWFHGRHLGLTPP--EPDPDEFDEMICSGC 54

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        50
                ....*....|....*....|....*....|....*....|....*....|
gi 18375617 271 CICRQPHNN-RFMICCDRCEEWFHGDCVGISEArgrllERNGEDYICPNC 319
Cdd:cd15556   2 CSCGTRDDDgERMIACDVCEVWQHTRCVGIADN-----EEPPDHFLCRRC 46

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
                ....*....|....*....|....*....|....*....|....*....
gi 18375617 271 CICRQPHNNRFMICCDRCEEWFHGDCVGISEARGRLLERNGEDYICPNC 319
Cdd:cd15570   2 CPCGSSMEDGSMIQCEGCKTWQHMDCVLIPDKPADGLPELPSKFYCELC 50

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        50
                ....*....|....*....|....*....|....*....|....*....|
gi 18375617 271 CICRQPHNNRFMICCDRCEEWFHGDCVGiseargrLLERN-GEDYICPNC 319
Cdd:cd15634   2 CICEVQEENDFMIQCEECLCWQHGVCMG-------LLEDNvPEKYTCYIC 44

PHD finger 1 found in histone-lysine N-methyltransferase 2A (KMT2A) and 2B (KMT2B); This family includes histone-lysine N-methyltransferase trithorax (Trx) like proteins, KMT2A (MLL1) and KMT2B (MLL2), which comprise the mammalian Trx branch of the COMPASS family, and are both essential for mammalian embryonic development. KMT2A regulates chromatin-mediated transcription through the catalysis of methylation of histone 3 lysine 4 (H3K4), and is frequently rearranged in acute leukemia. KMT2A functions as the catalytic subunit in the MLL1 complex. KMT2B is a second human homolog of Drosophila trithorax, located on chromosome 19 and functions as the catalytic subunit in the MLL2 complex. It plays a critical role in memory formation through mediating hippocampal H3K4 di- and trimethylation. It is also required for RNA polymerase II association and protection from DNA methylation at the MagohB CpG island promoter. Both KMT2A and KMT2B contain a CxxC (x for any residue) zinc finger domain, three plant homeodomain (PHD) fingers, an extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain. This model corresponds to the first PHD finger.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 18375617 282 MICCDRCEEWFHGDCVgisEARGRLLERNGEDYICPNC 319
Cdd:cd15506  13 LLYCSVCCEPYHTFCL---EEAERPLNINKDNWCCRRC 47

PHD finger found in PHD finger protein 20 (PHF20) and PHD finger protein 20-like protein 1 (P20L1); 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. P20L1 is an active malignant brain tumor (MBT) domain-containing protein that binds to monomethylated lysine 142 on DNA (Cytosine-5) Methyltransferase 1 (DNMT1) (DNMT1K142me1) and colocalizes at the perinucleolar space in a SET7-dependent manner. Its MBT domain reads and controls enzyme levels of methylated DNMT1 in cells, thus representing a novel antagonist of DNMT1 proteasomal degradation. Both PHF20 and PHF20L1 contain an N-terminal 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 18375617 271 CICRQPHNNRFMICCDRCEEWFHGDCVGISEArgrllERNGEDYICPNC 319
Cdd:cd15549   2 CICGVNEENGLMIQCELCLCWQHGVCMGIEEE-----ESVPERYVCYVC 45

PHD finger found in inhibitor of growth protein 1 (ING1) and 2 (ING2); ING1 is an epigenetic regulator and a type II tumor suppressor that impacts cell growth, aging, apoptosis, and DNA repair, by affecting chromatin conformation and gene expression. It acts as a reader of the active chromatin mark, the trimethylation of histone H3 lysine 4 (H3K4me3). It binds and directs Growth arrest and DNA damage inducible protein 45 a (Gadd45a) to target sites, thus linking the histone code with DNA demethylation. It interacts with the proliferating cell nuclear antigen (PCNA) via the PCNA-interacting protein (PIP) domain in a UV-inducible manner. It also interacts with a PCNA-interacting protein, p15 (PAF). Moreover, ING1 associates with members of the 14-3-3 family, which is necessary for cytoplasmic relocalization. Endogenous ING1 protein specifically interacts with the pro-apoptotic BCL2 family member BAX and colocalizes with BAX in a UV-inducible manner. It stabilizes the p53 tumor suppressor by inhibiting polyubiquitination of multi-monoubiquitinated forms via interaction with and colocalization of the herpesvirus-associated ubiquitin-specific protease (HAUSP)-deubiquitinase with p53. It is also involved in trichostatin A-induced apoptosis and caspase 3 signaling in p53-deficient glioblastoma cells. In addition, tyrosine kinase Src can bind and phosphorylate ING1 and further regulates its activity. ING2, also termed inhibitor of growth 1-like protein (ING1Lp), or p32, or p33ING2, belongs to the inhibitor of growth (ING) family of type II tumor suppressors. It is a core component of a multi-factor chromatin-modifying complex containing the transcriptional co-repressor SIN3A and histone deacetylase 1 (HDAC1). It has been implicated in the control of cell cycle, in genome stability, and in muscle differentiation. ING2 independently interacts with H3K4me3 (Histone H3 trimethylated on lysine 4) and PtdIns(5)P, and modulates crosstalk between lysine methylation and lysine acetylation on histone proteins through association with chromatin in the presence of DNA damage. It collaborates with SnoN to mediate transforming growth factor (TGF)-beta-induced Smad-dependent transcription and cellular responses. It is upregulated in colon cancer and increases invasion by enhanced MMP13 expression. It also acts as a cofactor of p300 for p53 acetylation and plays a positive regulatory role during p53-mediated replicative senescence. Both ING1 and ING2 contain an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 18375617 270 YCICRQPHNNRfMICCD--RCE-EWFHGDCVGIS-EARGRllerngedYICPNC 319
Cdd:cd15584   1 YCLCNQVSYGE-MIGCDndECPiEWFHFSCVGLThKPKGK--------WYCPKC 45

PHD finger found in histone-lysine N-methyltransferase ASH1L; ASH1L, also termed ASH1-like protein, or absent small and homeotic disks protein 1 homolog, or lysine N-methyltransferase 2H, is a protein belonging to the Trithorax family. It methylates Lys36 of histone H3 independently of transcriptional elongation to promote the establishment of Hox gene expression by counteracting Polycomb silencing. It can suppress interleukin-6 (IL-6), and tumor necrosis factor (TNF) production in Toll-like receptor (TLR)-triggered macrophages, and inflammatory autoimmune diseases by inducing the ubiquitin-editing enzyme A20. ASH1L contains an associated with SET domain (AWS), a SET domain, a post-SET domain, a bromodomain, a bromo-adjacent homology domain (BAH), and a plant homeodomain (PHD) finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 18375617 271 CICRQPHNNRFMICCDRCEEWFHGDCVGISEargrllerNGEDYICPNC 319
Cdd:cd15548   3 CICGLYKDEGLMIQCEKCMVWQHCDCMGVND--------DVEHYLCEQC 43

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 18375617 271 CICRQPHNNRFMICCDRCEEWFHGDCVGISEArgrlleRNGEDYICPNC 319
Cdd:cd15632   4 CFCMKPFAGRPMIECNECHTWIHLSCAKIRKS------NVPEVYVCQKC 46

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        50
                ....*....|....*....|....*....|....*....|....*....|
gi 18375617 273 CRQPHNNR--FMICCDRCEEWFHGDCVGISEARGRllernGEDYICPNCT 320
Cdd:cd15686   8 CQRPCKDKvdWVQCDGGCDEWFHQVCVGVSPEMAE-----NEDYICINCA 52

PHD finger found in Remodeling and spacing factor 1 (Rsf-1); Rsf-1, also termed HBV pX-associated protein 8, or Hepatitis B virus X-associated protein alpha (HBxAPalpha), or p325 subunit of RSF chromatin-remodeling complex, is a novel nuclear protein with histone chaperon function. It is a subunit of an ISWI chromatin remodeling complex, remodeling and spacing factor (RSF), and plays a role in mediating ATPase-dependent chromatin remodeling and conferring tumor aggressiveness in common carcinomas. As an ataxia-telangiectasia mutated (ATM)-dependent chromatin remodeler, Rsf-1 facilitates DNA damage checkpoints and homologous recombination repair. It regulates the mitotic spindle checkpoint and chromosome instability through the association with serine/threonine kinase BubR1 (BubR1) and Hepatitis B virus (HBV) X protein (HBx) in the chromatin fraction during mitosis. It also interacts with cyclin E1 and promotes tumor development. Rsf-1 contains a plant homeodomain (PHD) finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 18375617 271 CICRQPHNNRFMICCDRCEEWFHGDCVgiseaRGRLLERNGEDYICPNC 319
Cdd:cd15543   3 RKCGLSDHPEWILLCDRCDAGYHTACL-----RPPLMIIPDGNWFCPPC 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        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 18375617 271 CIC--RQPHNNRFMICCDRCEEWFHGDCVGI-SEARGRllerngEDYICPNC 319
Cdd:cd15547   2 CICgeLDEIDNKHRVQCLKCGLWQHAECVNYdEESDKR------EPYLCPHC 47