PHD finger found in PHD finger protein 23 (PHF23); PHF23, also termed PHD-containing protein JUNE-1, is a hypothetical protein with a plant homeodomain (PHD) finger. It is encoded by gene PHF23 that acts as a candidate fusion partner for the nucleoporin gene NUP98. The NUP98-PHF23 fusion results from a cryptic translocation t(11;17)(p15;p13) in acute myeloid leukemia (AML).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 116268091 341 TCYCRKPFAGRPMIECSLCGTWIHLSCAKIKKTNVPDFFYCQKC 384
Cdd:cd15631    1 TCYCGKPFAGRPMIECSQCGTWIHLSCAKIKKSNVPDFFYCQKC 44

PHD finger found in PHD finger protein 23 (PHF23); PHF23, also termed PHD-containing protein JUNE-1, is a hypothetical protein with a plant homeodomain (PHD) finger. It is encoded by gene PHF23 that acts as a candidate fusion partner for the nucleoporin gene NUP98. The NUP98-PHF23 fusion results from a cryptic translocation t(11;17)(p15;p13) in acute myeloid leukemia (AML).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 116268091 341 TCYCRKPFAGRPMIECSLCGTWIHLSCAKIKKTNVPDFFYCQKC 384
Cdd:cd15631    1 TCYCGKPFAGRPMIECSQCGTWIHLSCAKIKKSNVPDFFYCQKC 44

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 116268091  344 CRKPFAGRPMIECSLCGTWIHLSCAKIKKT--NVPDF-FYCQKCKE 386
Cdd:pfam00628   5 CGKSDDGGELVQCDGCDDWFHLACLGPPLDpaEIPSGeWLCPECKP 50

PHD finger found in PHD finger protein 23 (PHF23); PHF23, also termed PHD-containing protein JUNE-1, is a hypothetical protein with a plant homeodomain (PHD) finger. It is encoded by gene PHF23 that acts as a candidate fusion partner for the nucleoporin gene NUP98. The NUP98-PHF23 fusion results from a cryptic translocation t(11;17)(p15;p13) in acute myeloid leukemia (AML).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 116268091 341 TCYCRKPFAGRPMIECSLCGTWIHLSCAKIKKTNVPDFFYCQKC 384
Cdd:cd15631    1 TCYCGKPFAGRPMIECSQCGTWIHLSCAKIKKSNVPDFFYCQKC 44

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 116268091 339 LITCYCRKPFAGRPMIECSLCGTWIHLSCAKIKKTNVPDFFYCQKCK 385
Cdd:cd15632    1 LVTCFCMKPFAGRPMIECNECHTWIHLSCAKIRKSNVPEVYVCQKCR 47

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 116268091   342 CYCRKPFAGRPMIECSLCGTWIHLSCAKIKKT--NVPDFFYCQKC 384
Cdd:smart00249   3 SVCGKPDDGGELLQCDGCDRWYHQTCLGPPLLeeEPDGKWYCPKC 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
                 ....*....|....*....|....*....|....*....|....*....
gi 116268091 342 CYCRKPFAGRPMIECSLCGTWIHLSCAKIKKTNVPDF------FYCQKC 384
Cdd:cd15552    2 CICRKPHNNRFMICCDRCEEWFHGDCVGITEAQGKEMeenieeYVCPKC 50

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 116268091 341 TCY-CRKPF-AGRPMIECSLCGTWIHLSCAKIKKTNVPDF--FYCQKC 384
Cdd:cd15489    1 SCIvCGKGGdLGGELLQCDGCGKWFHADCLGPPLSSFVPNgkWICPVC 48

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 116268091  344 CRKPFAGRPMIECSLCGTWIHLSCAKIKKT--NVPDF-FYCQKCKE 386
Cdd:pfam00628   5 CGKSDDGGELVQCDGCDDWFHLACLGPPLDpaEIPSGeWLCPECKP 50

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 116268091 342 CYCRKPFAGRPMIECSLCGTWIHLSCAKIKKTNVP--DFFYCQKC 384
Cdd:cd16039    2 CICQKPDDGRWMIACDGCDEWYHFTCVNIPEADVElvDSFFCPPC 46

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
                 ....*....|....*....|....*....|....*.
gi 116268091 350 GRPMIECSLCGTWIHLSCAKIKKT-NVPDFFYCQKC 384
Cdd:cd15556   11 GERMIACDVCEVWQHTRCVGIADNeEPPDHFLCRRC 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 116268091 342 CYCRKPFAGRPMIECSLCGTWIHLSCAKIKKT------NVPDFFYCQKC 384
Cdd:cd15570    2 CPCGSSMEDGSMIQCEGCKTWQHMDCVLIPDKpadglpELPSKFYCELC 50

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 116268091 340 ITCYCRKPF-AGRPMIECSLCGTWIHLSCAKIKKTNVP--DFFYCQKCK 385
Cdd:cd15642    1 VYCLCRLPYdVTRFMIECDVCQDWFHGSCVGVEEEKAAeiDLYHCPNCQ 49

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 116268091 342 CYCRKPF-AGRPMIECSLCGTWIHLSCAKIKKTNVP--DFFYCQKCKE 386
Cdd:cd15641    2 CICRLPYdVTRFMIECDACKDWFHGSCVGVEEEEAPdiDIYHCPNCEK 49

PHD-like zinc-binding domain; The members of this family are annotated as containing PHD domain, but the zinc-binding region here is not typical of PHD domains. The conformation here is a well-conserved cysteine-histidine rich region spanning 90 residues, where the Cys and His are arranged as HxxC(31)CxxC(6)CxxCxxxxCxxxxHxxC (21)CxxH.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 116268091  305 STETSQDGDASSSEGEMRVMDEDImvesgdDSWDLITCYCRKPFaGrPMIECSL--CGTWIHLSCAK-------IKKTNV 375
Cdd:pfam13771   8 SPELVQRGNDSMGFPIEDIEKIPK------RRWKLKCYLCKKKG-G-ACIQCSKknCRRAFHVTCALeagllmqFDEDNG 79

                  ....*....
gi 116268091  376 PDFFYCQKC 384
Cdd:pfam13771  80 TFKSYCKKH 88

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 116268091 341 TCYCRKP-FAGRPMIECSLCGTWIHLSCAKIK-KTNVPDF----FYCQKC 384
Cdd:cd15583    1 YCYCGKDrNLGEVELQCSICLKWFHAKCVSIDnGSCLPFMtnyqFVCKRC 50

PHD finger 2 found in Lysine-specific demethylase KDM5A, KDM5B, KDM5C, KDM5D, and similar proteins; The JARID subfamily within the JmjC proteins includes Lysine-specific demethylase KDM5A, KDM5B, KDM5C, KDM5D and a Drosophila homolog protein, little imaginal discs (Lid). KDM5A was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation. It is involved in transcription through interacting with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK, and BMAL1. KDM5B has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of the pregnant female and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis. Both KDM5A and KDM5B function as trimethylated histone H3 lysine 4 (H3K4me3) demethylases. KDM5C is a H3K4 trimethyl-histone demethylase that catalyzes demethylation of H3K4me3 and H3K4me2 to H3K4me1. It plays a role in neuronal survival and dendrite development. KDM5C defects are associated with X-linked mental retardation (XLMR). KDM5D is a male-specific antigen that shows a demethylase activity specific for di- and tri-methylated histone H3K4 (H3K4me3 and H3K4me2), and has a male-specific function as a histone H3K4 demethylase by recruiting a meiosis-regulatory protein, MSH5, to condensed DNA. KDM5D directly interacts with a polycomb-like protein Ring6a/MBLR, and plays a role in regulation of transcriptional initiation through H3K4 demethylation. The family also includes Drosophila melanogaster protein little imaginal discs (Lid) that functions as a JmjC-dependent trimethyl histone H3K4 (H3K4me3) demethylase, which is required for dMyc-induced cell growth. It positively regulates Hox gene expression in S2 cells. Members in this family contain the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as two or three plant homeodomain (PHD) fingers. This model corresponds to the second PHD finger.

                         10        20        30
                 ....*....|....*....|....*....|.
gi 116268091 342 CYCRKPFAGrPMIECSLCGTWIHLSCAKIKK 372
Cdd:cd15516    2 CLCGKALAA-GMLQCELCQDWFHGSCVAVPR 31

PHD finger 2 and 3 found in bromodomain and PHD finger-containing transcription factor (BPTF); BPTF, also termed nucleosome-remodeling factor subunit BPTF, or fetal Alz-50 clone 1 protein (FAC1), or fetal Alzheimer antigen, functions as a transcriptional regulator that exhibits altered expression and subcellular localization during neuronal development and neurodegenerative diseases such as Alzheimer's disease. It interacts with the human orthologue of the Kelch-like Ech-associated protein (Keap1). Its function and subcellular localization can be regulated by Keap1. Moreover, BPTF is a novel DNA-binding protein that recognizes the DNA sequence CACAACAC and represses transcription through this site in a phosphorylation-dependent manner. Furthermore, BPTF interacts with the Myc-associated zinc finger protein (ZF87/MAZ) and alters its transcriptional activity, which has been implicated in gene regulation in neurodegeneration. Some family members contain two or three plant homeodomain (PHD) fingers, which may be involved in complex formation with histone H3 trimethylated at K4 (H3K4me3). This family corresponds to the second and third PHD fingers.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 116268091 342 CYCRKPFAG-RPMIECSLCGTWIHLSCAKIKKTNVP--DFFYCQKC 384
Cdd:cd15560    2 CICRTPYDEsQFYIGCDRCQDWFHGRCVGILQSEAEkiDEYVCPQC 47

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
                 ....*....|....*....|....*....|....*....|....*....
gi 116268091 342 CYCRKP--FAGRpMIECSLCGTWIHLSCakIKKTNVP----DFFYCQKC 384
Cdd:cd15503    2 CYCGGPgeWNLK-MLQCCKCRQWFHEAC--LQCLKKPllygDRFYNFCC 47