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 922582220 219 YCVCQKPYDDTKFYVGCDSCQGWFHPECVGTTRAEAEQAADYNCPAC 265
Cdd:cd15560    1 YCICRTPYDESQFYIGCDRCQDWFHGRCVGILQSEAEKIDEYVCPQC 47

bromo domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922582220   307 HRMSTPFRNPVDLNEFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAETMQEVFD 386
Cdd:smart00297  22 HPLSWPFLKPVSRKEAPDYYDIIKKPMDLKTIKKKLENGKYSSVEEFVADFNLMFSNARTYNGPDSEVYKDAKKLEKFFE 101

                   ...
gi 922582220   387 KKL 389
Cdd:smart00297 102 KKL 104

Bromodomain; Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 922582220  307 HRMSTPFRNPVDLNEFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAET 380
Cdd:pfam00439  11 HPIAAPFLEPVDPDEYPDYYSVIKKPMDLSTIKKKLENGEYKSLAEFLADVKLIFSNARTYNGPGSVIYKAAEK 84

PHD finger found in lysine-specific demethylase 7 (KDM7); KDM7, also termed JmjC domain-containing histone demethylation protein 1D (JHDM1D), or KIAA1718, is a dual histone demethylase that catalyzes demethylation of monomethylated and dimethylated H3K9 (H3K9me2/me1) and H3K27 (H3K27me2/me1), which functions as an eraser of silencing marks on chromatin during brain development. It also plays a tumor-suppressive role by regulating angiogenesis. KDM7 contains a plant homeodomain (PHD) that binds Lys4-trimethylated histone 3 (H3K4me3) and a jumonji domain that demethylates either H3K9me2 or H3K27me2.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 922582220 159 HCTCQKIFDASKLYIQCELCARWYHGDCVGVAEQTILGLEHWSCEEC 205
Cdd:cd15640    1 YCVCRQPYDVNRFMIECDICKDWFHGSCVQVEEHHAADIDLYHCPNC 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 922582220   160 CTCQKIFDASKLyIQCELCARWYHGDCVGVAEQTILGLEHWSCEEC 205
Cdd:smart00249   3 SVCGKPDDGGEL-LQCDGCDRWYHQTCLGPPLLEEEPDGKWYCPKC 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        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 922582220  219 YC-VCQKPYDDTKFyVGCDSCQGWFHPECVGTTRAEAEQA-ADYNCPACTRE 268
Cdd:pfam00628   1 YCaVCGKSDDGGEL-VQCDGCDDWFHLACLGPPLDPAEIPsGEWLCPECKPK 51

bromo domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922582220   307 HRMSTPFRNPVDLNEFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAETMQEVFD 386
Cdd:smart00297  22 HPLSWPFLKPVSRKEAPDYYDIIKKPMDLKTIKKKLENGKYSSVEEFVADFNLMFSNARTYNGPDSEVYKDAKKLEKFFE 101

                   ...
gi 922582220   387 KKL 389
Cdd:smart00297 102 KKL 104

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 922582220 219 YCVCQKPYDDTKFYVGCDSCQGWFHPECVGTTRAEAEQAADYNCPAC 265
Cdd:cd15560    1 YCICRTPYDESQFYIGCDRCQDWFHGRCVGILQSEAEKIDEYVCPQC 47

Bromodomain; Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 922582220  307 HRMSTPFRNPVDLNEFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAET 380
Cdd:pfam00439  11 HPIAAPFLEPVDPDEYPDYYSVIKKPMDLSTIKKKLENGEYKSLAEFLADVKLIFSNARTYNGPGSVIYKAAEK 84

Bromodomain, uncharacterized subfamily specific to plants. Might function as a global transcription factor. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922582220 307 HRMSTPFRNPVD---LNeFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAETMQE 383
Cdd:cd05506   15 HKWGWVFNAPVDvvaLG-LPDYFDIIKKPMDLGTVKKKLEKGEYSSPEEFAADVRLTFANAMRYNPPGNDVHTMAKELLK 93

                 ....*
gi 922582220 384 VFDKK 388
Cdd:cd05506   94 IFETR 98

Bromodomain; Acf1_like or BAZ1A_like subfamily. Bromo adjacent to zinc finger 1A (BAZ1A) was identified as a novel human bromodomain gene by cDNA library screening. The Drosophila homologue, Acf1, is part of the CHRAC (chromatin accessibility complex) and regulates ISWI-induced nucleosome remodeling. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922582220 307 HRMSTPFRNPVDLNEFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAETMQEVFD 386
Cdd:cd05504   27 HKDSWPFLRPVSKIEVPDYYDIIKKPMDLGTIKEKLNMGEYKLAEEFLSDIQLVFSNCFLYNPEHTSVYKAGTRLQRFFI 106

                 ...
gi 922582220 387 KKL 389
Cdd:cd05504  107 KRC 109

Bromodomain, cbp_like subfamily. Cbp (CREB binding protein or CREBBP) is an acetyltransferase acting on histone, which gives a specific tag for transcriptional activation and also acetylates non-histone proteins. CREBBP binds specifically to phosphorylated CREB protein and augments the activity of phosphorylated CREB to activate transcription of cAMP-responsive genes. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922582220 310 STPFRNPVD--LNEFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAETMQEVFDK 387
Cdd:cd05495   22 SLPFRQPVDpkLLGIPDYFDIVKNPMDLSTIRRKLDTGQYQDPWQYVDDVWLMFDNAWLYNRKTSRVYKYCTKLAEVFEQ 101

                 ....*
gi 922582220 388 KLIDV 392
Cdd:cd05495  102 EIDPV 106

Bromodomain, BAZ2A/BAZ2B_like subfamily. Bromo adjacent to zinc finger 2A (BAZ2A) and 2B (BAZ2B) were identified as a novel human bromodomain gene by cDNA library screening. BAZ2A is also known as Tip5 (Transcription termination factor I-interacting protein 5) and hWALp3. The proteins may play roles in transcriptional regulation. Human Tip5 is part of a complex termed NoRC (nucleolar remodeling complex), which induces nucleosome sliding and may play a role in the regulation of the rDNA locus. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922582220 307 HRMSTPFRNPVDLNEFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAETMQEVFD 386
Cdd:cd05503   15 HEDAWPFLEPVNTKLVPGYRKIIKKPMDFSTIREKLESGQYKTLEEFAEDVRLVFDNCETFNEDDSEVGRAGHNMRKFFE 94

                 ..
gi 922582220 387 KK 388
Cdd:cd05503   95 KR 96

Bromodomain; brd1_like subfamily. BRD1 is a mammalian gene which encodes for a nuclear protein assumed to be a transcriptional regulator. BRD1 has been implicated with brain development and susceptibility to schizophrenia and bipolar affective disorder. Bromodomains are 110 amino acid long domains that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 922582220 313 FRNPVDLNEFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAETMQE 383
Cdd:cd05512   22 FSEPVDLSEVPDYLDHIKQPMDFSTMRKKLESQRYRTLEDFEADFNLIINNCLAYNAKDTIFYRAAVRLRD 92

Bromodomain; tif1_like subfamily. Tif1 (transcription intermediary factor 1) is a member of the tripartite motif (TRIM) protein family, which is characterized by a particular domain architecture. It functions by recruiting coactivators and/or corepressors to modulate transcription. Vertebrate Tif1-gamma, also labeled E3 ubiquitin-protein ligase TRIM33, plays a role in the control of hematopoiesis. Its homologue in Xenopus laevis, Ectodermin, has been shown to function in germ-layer specification and control of cell growth during embryogenesis. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922582220 307 HRMSTPFRNPVDlNEFPDYEKFIKKPMDLSTITKKVERTEYL-YLS--QFVNDVNQMFENAKTYNPKGNAVFKCAETMQE 383
Cdd:cd05502   19 HELSLPFHEPVS-PSVPNYYKIIKTPMDLSLIRKKLQPKSPQhYSSpeEFVADVRLMFKNCYKFNEEDSEVAQAGKELEL 97

                 ....*.
gi 922582220 384 VFDKKL 389
Cdd:cd05502   98 FFEEQL 103

Bromodomain; WDR9 repeat II_like subfamily. WDR9 is a human gene located in the Down Syndrome critical region-2 of chromosome 21. It encodes for a nuclear protein containing WD40 repeats and two bromodomains, which may function as a transcriptional regulator involved in chromatin remodeling and play a role in embryonic development. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 922582220 310 STPFRNPVDLNEFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNP 369
Cdd:cd05496   23 SEPFRQPVDLLKYPDYRDIIDTPMDLGTVKETLFGGNYDDPMEFAKDVRLIFSNSKSYTP 82

Bromodomain, SNF2-like subfamily, specific to fungi. SNF2 is a yeast protein involved in transcriptional activation, it is the catalytic component of the SWI/SNF ATP-dependent chromatin remodeling complex. The protein is essential for the regulation of gene expression (both positive and negative) of a large number of genes. The SWI/SNF complex changes chromatin structure by altering DNA-histone contacts within the nucleosome, which results in a re-positioning of the nucleosome and facilitates or represses the binding of gene-specific transcription factors. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 922582220 310 STPFRNPVDLNEFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAETMQEVFDKK 388
Cdd:cd05519   24 SELFLEKPSKKLYPDYYVIIKRPIALDQIKRRIEGRAYKSLEEFLEDFHLMFANARTYNQEGSIVYEDAVEMEKAFKKK 102

Bromodomain, polybromo repeat V. Polybromo is a nuclear protein of unknown function, which contains 6 bromodomains. The human ortholog BAF180 is part of a SWI/SNF chromatin-remodeling complex, and it may carry out the functions of Yeast Rsc-1 and Rsc-2. It was shown that polybromo bromodomains bind to histone H3 at specific acetyl-lysine positions. Bromodomains are found in many chromatin-associated proteins and in nuclear histone acetyltransferases. They interact specifically with acetylated lysine, but not all the bromodomains in polybromo may bind to acetyl-lysine.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 922582220 307 HRMSTPFRNPVDLNEFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAETMQEVF 385
Cdd:cd05515   21 RRLSLIFMRLPSKSEYPDYYDVIKKPIDMEKIRSKIEGNQYQSLDDMVSDFVLMFDNACKYNEPDSQIYKDALTLQKVL 99

Bromodomain, repeat II in Rsc1/2_like subfamily, specific to fungi. Rsc1 and Rsc2 are components of the RSC complex (remodeling the structure of chromatin), are essential for transcriptional control, and have a specific domain architecture including two bromodomains. The RSC complex has also been linked to homologous recombination and nonhomologous end-joining repair of DNA double strand breaks. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 922582220 307 HRMSTPFRNPVDLNEFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAETMQ 382
Cdd:cd05522   22 RLLTLHFEKLPDKAREPEYYQEISNPISLDDIKKKVKRRKYKSFDQFLNDLNLMFENAKLYNENDSQEYKDAVLLE 97

Bromodomain, SNF2L2-like subfamily, specific to animals. SNF2L2 (SNF2-alpha) or SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 is a global transcriptional activator, which cooperates with nuclear hormone receptors to boost transcriptional activation. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 922582220 308 RMSTPFRNPVDLNEFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAETMQEVFD 386
Cdd:cd05516   23 QLAEVFIQLPSRKELPEYYELIRKPVDFKKIKERIRNHKYRSLEDLEKDVMLLCQNAQTFNLEGSLIYEDSIVLQSVFK 101

Bromodomain, RACK7_like subfamily. RACK7 (also called human protein kinase C-binding protein) was identified as a potential tumor suppressor genes, it shares domain architecture with BS69/ZMYND11; both have been implicated in the regulation of cellular proliferation. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 922582220 310 STPFRNPVDLNEFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAETMQEV 384
Cdd:cd05508   20 AEPFLKPVDLEQFPDYAQYVFKPMDLSTLEKNVRKKAYGSTDAFLADAKWILHNAIIYNGGDHKLTQAAKAIVKI 94

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 922582220 219 YCVCQKPYDDTKFYVGCDSCQGWFHPECVGTTRAEAEQAADYNCPACTR 267
Cdd:cd15641    1 YCICRLPYDVTRFMIECDACKDWFHGSCVGVEEEEAPDIDIYHCPNCEK 49

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 922582220 218 LYCVCQKPYDDTKFYVGCDSCQGWFHPECVGTTRAEAEQAADYNCPAC 265
Cdd:cd15642    1 VYCLCRLPYDVTRFMIECDVCQDWFHGSCVGVEEEKAAEIDLYHCPNC 48

Bromodomain, repeat I in Rsc1/2_like subfamily, specific to fungi. Rsc1 and Rsc2 are components of the RSC complex (remodeling the structure of chromatin), are essential for transcriptional control, and have a specific domain architecture including two bromodomains. The RSC complex has also been linked to homologous recombination and nonhomologous end-joining repair of DNA double strand breaks. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922582220 321 EFPDYEKFIKKPMDLSTITKKVERteYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAETMQEVFDKKLI 390
Cdd:cd05521   36 DYPDYYKIIKNPLSLNTVKKRLPH--YTNAQEFVNDLAQIPWNARLYNTKGSVIYKYALILEKYINDVII 103

Bromodomain, polybromo repeat IV. Polybromo is a nuclear protein of unknown function, which contains 6 bromodomains. The human ortholog BAF180 is part of a SWI/SNF chromatin-remodeling complex, and it may carry out the functions of Yeast Rsc-1 and Rsc-2. It was shown that polybromo bromodomains bind to histone H3 at specific acetyl-lysine positions. Bromodomains are found in many chromatin-associated proteins and in nuclear histone acetyltransferases. They interact specifically with acetylated lysine, but not all the bromodomains in polybromo may bind to acetyl-lysine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922582220 314 RNPVDL-------NEFPDYEKFIKKPMDLSTITKKVERTEYLYLSQFVNDVNQMFENAKTYNPKGNAVFKCAETMQEVFD 386
Cdd:cd05518   21 RRLCDLfmekpskKDYPDYYKIILEPIDLKTIEHNIRNDKYATEEELMDDFKLMFRNARHYNEEGSQVYEDANILEKVLK 100

                 ...
gi 922582220 387 KKL 389
Cdd:cd05518  101 EKR 103

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 922582220 222 CQKPYDDTKFYVGCDSCQGWFHPECVGTTRAEAEQAADYNCPAC 265
Cdd:cd15610    7 CLKPTGDEVNWVQCDGCEEWFHLLCVGLSPEEVAEDEDYICPSC 50

PHD finger found in CXXC-type zinc finger protein 1 (Cfp1); Cfp1, also termed CpG-binding protein, or PHD finger and CXXC domain-containing protein 1 (PCCX1), is a specificity factor that binds to unmethylated CpGs and links H3K4me3 with CpG islands (CGIs). It integrates both promoter CpG content and gene activity for accurate trimethylation of histone H3 Lys 4 (H3K4me3) deposition in embryonic stem cells. Moreover, Cfp1 is an essential component of the SETD1 histone H3K4 methyltransferase complex and functions as a critical regulator of histone methylation, cytosine methylation, cellular differentiation, and vertebrate development. Cfp1 contains a plant homeodomain (PHD) finger, a CXXC domain, and a CpG binding protein zinc finger C-terminal domain. Its CXXC domain selectively binds to non-methylated CpG islands, following by a preference for a guanosine nucleotide.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 922582220 219 YCVCQKPyDDTKFYVGCDSCQGWFHPECVGTTRAEAEQAADYNCPAC 265
Cdd:cd15553    1 YCICRSS-DISRFMIGCDNCEEWYHGDCINITEKEAKAIKEWYCQQC 46

PHD finger found in death-inducer obliterator variants Dido1, Dido2, and Dido3; This family includes three alternative splicing variants (Dido1, 2, and 3) encoded by the Dido gene, which have been implicated in a number of cellular processes such as apoptosis and chromosomal segregation, particularly in the hematopoietic system. Dido1, also termed DIO-1, or death-associated transcription factor 1 (DATF-1), is important for maintaining embryonic stem (ES) cells and directly regulates the expression of pluripotency factors. It is the shortest isoform that contains only a highly conserved plant homeodomain (PHD) finger responsible for the binding of histone H3 with a higher affinity for trimethylated lysine 4 (H3K4me3). Gene Dido is a Bonemorphogenetic protein (BMP) target gene, which promotes BMP-induced melanoma progression. It also triggers apoptosis after nuclear translocation and caspase upregulation. Dido3 is the largest isoform ubiquitously expressed in all human tissues. It is dispensable for ES cell self-renewal and pluripotency, but involved in the maintenance of stem cell genomic stability and tumorigenesis. Dido3 contains a PHD finger, a transcription elongation factor S-II subunit M (TFSIIM) domain, aspen paralog and ortholog (SPOC) module, and a long C-terminal region (CT) of unknown homology. Its PHD finger interacts with H3K4me3.

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 922582220 217 ALYCVCQKPYDDtKFYVGCDSCQGWFHPECVGTTRAEA----EQAADYNCPAC 265
Cdd:cd15639    3 ALYCICRQPHNN-RFMICCDRCEEWFHGDCVGITEARGrlleRNGEDYICPNC 54

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.

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                 ....*....|....*....|....*....|....*....|....*..
gi 922582220 159 HCTCQKIFDASKLYIQCELCARWYHGDCVGVAEQTILGLEHWSCEEC 205
Cdd:cd15560    1 YCICRTPYDESQFYIGCDRCQDWFHGRCVGILQSEAEKIDEYVCPQC 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.

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                   ....*....|....*....|....*....|....*....|....*...
gi 922582220   219 YC-VCQKPYDDTKFyVGCDSCQGWFHPECVGTTRAEAEQAADYNCPAC 265
Cdd:smart00249   1 YCsVCGKPDDGGEL-LQCDGCDRWYHQTCLGPPLLEEEPDGKWYCPKC 47

PHD finger found in CXXC-type zinc finger protein 1 (Cfp1); Cfp1, also termed CpG-binding protein, or PHD finger and CXXC domain-containing protein 1 (PCCX1), is a specificity factor that binds to unmethylated CpGs and links H3K4me3 with CpG islands (CGIs). It integrates both promoter CpG content and gene activity for accurate trimethylation of histone H3 Lys 4 (H3K4me3) deposition in embryonic stem cells. Moreover, Cfp1 is an essential component of the SETD1 histone H3K4 methyltransferase complex and functions as a critical regulator of histone methylation, cytosine methylation, cellular differentiation, and vertebrate development. Cfp1 contains a plant homeodomain (PHD) finger, a CXXC domain, and a CpG binding protein zinc finger C-terminal domain. Its CXXC domain selectively binds to non-methylated CpG islands, following by a preference for a guanosine nucleotide.

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                 ....*....|....*....|....*....|....*....|....*..
gi 922582220 159 HCTCQKIfDASKLYIQCELCARWYHGDCVGVAEQTILGLEHWSCEEC 205
Cdd:cd15553    1 YCICRSS-DISRFMIGCDNCEEWYHGDCINITEKEAKAIKEWYCQQC 46

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.

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                 ....*....|....*....|....*....|....*....|....*.
gi 922582220 160 CTCQKIFDASKLYIQCELCARWYHGDCVGVAEQTILGLEHWSCEEC 205
Cdd:cd15489    3 IVCGKGGDLGGELLQCDGCGKWFHADCLGPPLSSFVPNGKWICPVC 48

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.

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                 ....*....|....*....|....*....|....*....|....*...
gi 922582220 222 CQKPYDDtKFYVGCDSCQGWFHPECVGTTRAEAEQAA----DYNCPAC 265
Cdd:cd15638    5 CKKPHGN-RFMVGCGRCDDWFHGDCVGLSLSQAQQMEeedkEYVCVKC 51

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 922582220 159 HCTCQKIFDASKLYIQCELCARWYHGDCVGVAEQTILGLEHWSCEEC 205
Cdd:cd15642    2 YCLCRLPYDVTRFMIECDVCQDWFHGSCVGVEEEKAAEIDLYHCPNC 48

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 922582220 160 CTCQKIFDaSKLYIQCELCARWYHGDCVGVAEQTILGLEH----WSCEEC 205
Cdd:cd15552    2 CICRKPHN-NRFMICCDRCEEWFHGDCVGITEAQGKEMEEnieeYVCPKC 50

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.

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                 ....*....|....*....|....*....|...
gi 922582220 173 IQCELCARWYHGDCVGVAEQTIlgLEHWSCEEC 205
Cdd:cd15550   14 ICCDKCSVWQHGDCMGIDRENI--PDSYLCEQC 44

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.

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                 ....*....|....*....|....*....|....*....|...
gi 922582220 222 CQKPYDDTKFYVGCDSCQGWFHPECVGTTRAEA-EQAADYNCP 263
Cdd:cd15609    7 CCLPQDETVSWVQCDDCDQWYHVACVGCDYNAVkDPDADFHCG 49

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.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 922582220  160 CTCQKIFDASKLyIQCELCARWYHGDCVGVA-EQTILGLEHWSCEECIEE 208
Cdd:pfam00628   3 AVCGKSDDGGEL-VQCDGCDDWFHLACLGPPlDPAEIPSGEWLCPECKPK 51