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 6325119      25 CICKRPDYGELMVGCDGCDDWFHFTCLHIPEQFKDLVFSFYCPYC 69
Cdd:smart00249   3 SVCGKPDDGGELLQCDGCDRWYHQTCLGPPLLEEEPDGKWYCPKC 47

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 6325119   20 GEDVYCICKRPDYGElMVGCDGCD---DWFHFTCLHIPEQFKDlvfSFYCPYCQ 70
Cdd:COG5034 219 GEELYCFCQQVSYGQ-MVACDNANckrEWFHLECVGLKEPPKG---KWYCPECK 268

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 6325119      25 CICKRPDYGELMVGCDGCDDWFHFTCLHIPEQFKDLVFSFYCPYC 69
Cdd:smart00249   3 SVCGKPDDGGELLQCDGCDRWYHQTCLGPPLLEEEPDGKWYCPKC 47

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 6325119     25 CICKRPDYGELMVGCDGCDDWFHFTCLHIPEQFKDLV-FSFYCPYCQ 70
Cdd:pfam00628   3 AVCGKSDDGGELVQCDGCDDWFHLACLGPPLDPAEIPsGEWLCPECK 49

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 6325119   20 GEDVYCICKRPDYGElMVGCDGCD---DWFHFTCLHIPEQFKDlvfSFYCPYCQ 70
Cdd:COG5034 219 GEELYCFCQQVSYGQ-MVACDNANckrEWFHLECVGLKEPPKG---KWYCPECK 268

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 6325119   24 YCICKRPDYGELMVGCDGCDDWFHFTCLHIPEQ----FKDLVFSFYCPYC 69
Cdd:cd15552   1 YCICRKPHNNRFMICCDRCEEWFHGDCVGITEAqgkeMEENIEEYVCPKC 50

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
                ....*....|....*....|....*....|....*....|....*....
gi 6325119   24 YCICKRPDYGElMVGCDGCD---DWFHFTCLHIPEQFKDlvfSFYCPYC 69
Cdd:cd15505   1 YCICNQVSYGE-MVACDNPNcpiEWFHFECVGLTAKPKG---KWYCPEC 45

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 6325119   25 CICKRP-DYGELMVGCDGCDDWFHFTCLHIPEQFKDLVFSFYCPYC 69
Cdd:cd15489   3 IVCGKGgDLGGELLQCDGCGKWFHADCLGPPLSSFVPNGKWICPVC 48

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        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 6325119   24 YCICKRPDYGeLMVGCDGCDDWFHFTCLHIP-------------EQFKDLvfSFYCPYC 69
Cdd:cd15606   1 YCICRKPFSG-FMLQCELCKDWFHSSCVPLPksssqkkggngsgQGAKEL--KFLCPLC 56

PHD finger found in lysine-specific demethylase PHF2; PHF2, also termed GRC5, or PHD finger protein 2, is a histone lysine demethylase ubiquitously expressed in various tissues. It contains a plant homeodomain (PHD) finger and a JmjC domain and plays an important role in adipogenesis. The PHD finger domain can recognize trimethylated histone H3 lysine 4 (H3K4me3). PHF2 also has dimethylated histone H3 lysine 9(H3K9me2) demethylase activity and acts as a coactivator of several metabolism-related transcription factors. Moreover, it can demethylate ARID5B and further forms a complex with demethylated ARD5B to bind the promoter regions of target genes. The overexpression of PHF2 is involved in the progression of esophageal squamous cell carcinoma (ESCC).

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 6325119   24 YCICKRP-DYGELMVGCDGCDDWFHFTCLHIPEQFKDLVFSFYCPYCQ 70
Cdd:cd15641   1 YCICRLPyDVTRFMIECDACKDWFHGSCVGVEEEEAPDIDIYHCPNCE 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
                ....*....|....*....|....*....|....*....|....*....
gi 6325119   23 VYCICKRP-DYGELMVGCDGCDDWFHFTCLHIPEQFKDLVFSFYCPYCQ 70
Cdd:cd15642   1 VYCLCRLPyDVTRFMIECDVCQDWFHGSCVGVEEEKAAEIDLYHCPNCQ 49

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 6325119   26 ICKRPDY--GELMVGCDGCDDWFHFTCLHIPEQFKDLVFSFYCPYC 69
Cdd:cd15517   4 ICNLETAavDELWVQCDGCDKWFHQFCLGLSNERYADEDKFKCPNC 49

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 6325119   25 CICKRPDYGELMVGCDGCDDWFHFTCLHIPEQ----FKDLVFSFYCPYC 69
Cdd:cd15570   2 CPCGSSMEDGSMIQCEGCKTWQHMDCVLIPDKpadgLPELPSKFYCELC 50

PHD finger found in inhibitor of growth protein 5 (ING5); ING5, also termed p28ING5, is one member of the inhibitor of growth (ING) family of type II tumor suppressors. It acts as 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. In addition, ING5 associates with histone acetyltransferase (HAT) complexes containing MOZ (monocytic leukemia zinc finger protein)/MORF (MOZ-related factor) and HBO1, and further directs the MOZ/MORF and HBO1 complexes to chromatin. ING5 contains an N-terminal ING histone-binding domain and a C-terminal plant homeodomain (PHD) finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 6325119   24 YCICKRPDYGElMVGCDGCD---DWFHFTCLHIPEQFKDlvfSFYCPYCQA 71
Cdd:cd15685   2 YCLCHQVSYGE-MIGCDNPDcpiEWFHFACVDLTTKPKG---KWFCPRCTQ 48

PHD finger found in inhibitor of growth protein 4 (ING4); ING4, also termed p29ING4, is one member of the inhibitor of growth (ING) family of type II tumor suppressors. It 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). In addition, ING4 associates with histone acetyltransferase (HAT) complexes containing MOZ (monocytic leukemia zinc finger protein)/MORF (MOZ-related factor) and HBO1, and further directs the MOZ/MORF and HBO1 complexes to chromatin. ING4 contains an N-terminal ING histone-binding domain and a C-terminal plant homeodomain (PHD) finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 6325119   24 YCICKRPDYGElMVGCDGCD---DWFHFTCLHIPEQFKDlvfSFYCPYC 69
Cdd:cd15684   2 YCLCHQVSYGE-MIGCDNPDcsiEWFHFACVGLTTKPRG---KWFCPRC 46

PHD finger found in inhibitor of growth protein 2 (ING2); ING2, also termed inhibitor of growth 1-like protein (ING1Lp), or p32, or p33ING2, is one member of 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. ING2 contains an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 6325119   24 YCICKRPDYGElMVGCDGCD---DWFHFTCLHIPEQFKDlvfSFYCPYCQA 71
Cdd:cd15683   2 YCLCNQVSYGE-MIGCDNEQcpiEWFHFSCVGLTYKPKG---KWYCPKCRG 48

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
                ....*....|....*....|....*....|....*....|....*....
gi 6325119   24 YCICKRPDYGElMVGCDG--CD-DWFHFTCLHIPEQFKDlvfSFYCPYC 69
Cdd:cd15584   1 YCLCNQVSYGE-MIGCDNdeCPiEWFHFSCVGLTHKPKG---KWYCPKC 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        40
                ....*....|....*....|....*....|....*....|....
gi 6325119   27 CKRPDYGEL-MVGCDGCDDWFHFTCLHIPEQFKDLVFSFYCPYC 69
Cdd:cd15610   7 CLKPTGDEVnWVQCDGCEEWFHLLCVGLSPEEVAEDEDYICPSC 50

PHD finger found in PHD and RING finger domain-containing protein 1 (PHRF1); PHRF1, also termed KIAA1542, or CTD-binding SR-like protein rA9, is a ubiquitin ligase that induces the ubiquitination of TGIF (TG-interacting factor) at lysine 130. It acts as a tumor suppressor that promotes the transforming growth factor (TGF)-beta cytostatic program through selective release of TGIF-driven promyelocytic leukemia protein (PML) inactivation. PHRF1 contains a plant homeodomain (PHD) finger and a RING finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 6325119   24 YC-ICKRPDYGELMVGCDGCDDWFHFTCLHIPEQFKDlVFSFYCPYC 69
Cdd:cd15536   1 YCeVCGRSDREDRLLLCDGCDAGYHMECLTPPLDEVP-IEEWFCPEC 46

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 6325119   23 VYCICKRPDYGELMVGCDGCDDWFHFTCL-----HIPEQF 57
Cdd:cd15632   2 VTCFCMKPFAGRPMIECNECHTWIHLSCAkirksNVPEVY 41

PHD finger 2 found in polycomb repressive complex 2 (PRC2)-associated polycomb-like (PCL) family proteins MTF2, PHF19, and similar proteins; The PCL family includes PHD finger protein1 (PHF1) and its homologs metal-response element-binding transcription factor 2 (MTF2/PCL2) and PHF19/PCL3, which are accessory components of the Polycomb repressive complex 2 (PRC2) core complex and all contain an N-terminal Tudor domain followed by two plant homeodomain (PHD) fingers, and a C-terminal MTF2 domain. PCL proteins specifically recognize tri-methylated H3K36 (H3K36me3) through their N-terminal Tudor domains. The interaction between their Tudor domains and H3K36me3 is critical for both the targeting and spreading of PRC2 into active chromatin regions and for the maintenance of optimal repression of poised developmental genes where PCL proteins, H3K36me3, and H3K27me3 coexist. Moreover, unlike other PHD finger-containing proteins, the first PHD finger of PCL proteins do not display histone H3K4 binding affinity and they do not affect the Tudor domain binding to histones. This model corresponds to the second PHD finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 6325119   24 YCICKRP-DYGELMVGCDGCDDWFHFTCLHI---PEQFKDLVFSFYCPYC 69
Cdd:cd15503   1 YCYCGGPgEWNLKMLQCCKCRQWFHEACLQClkkPLLYGDRFYNFCCSVC 50

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 6325119   24 YCICKRPDYGEL-MVGCDGCDDWFH---FTCLHIPEQFKDLVFSFYCPYC 69
Cdd:cd15581   1 YCYCGGPGEWYLkMLQCYRCRQWFHeacTQCLNDPMMFGDRFYLFFCAVC 50