histone-fold domain found in transcription initiation factor TFIID subunit 3 (TAF3) and similar proteins; TAF3, also called TATA Binding Protein (TBP) associated factor 3, 140 kDa TATA box-binding protein-associated factor, TBP-associated factor 3, or transcription initiation factor TFIID 140 kDa subunit (TAF(II)140, TAF140, TAFII-140,TAFII140), is a component of the TFIID complex that is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). TFIID is one of the general transcription factors required for accurate and regulated initiation by RNA polymerase II. It plays a central role in mediating promoter responses to various activators and repressors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1811052786   3 ESYSRSLLRVSVAQICQALGWDSVQLSACHLLTDVLQRYLQQLGRGCHRYSELYGRTDPILDDVSEAFQLMGVSLHELED 82
Cdd:cd22916     1 DEFSRSLLRVVVAQICQNVGWHSIQSSPLDLLTDVLQRYLLELARSAHRYAEQYGRTEPNLDDLGLAFKDMGISLNELED 80

                          90
                  ....*....|..
gi 1811052786  83 YIHNIEPVTFPH 94
Cdd:cd22916    81 YVLNVEPVPFPH 92

DNA topoisomerase 2-like protein; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1811052786  202 ETLDVVLLEAREPLSSINPQKIPPMLSPVHVQDSTDLAPPSPEPPMLAPVAKSQMP-TAKPLEAKSFTPKAKTKTGSPGQ 280
Cdd:PTZ00108  1145 EEVEEKEIAKEQRLKSKTKGKASKLRKPKLKKKEKKKKKSSADKSKKASVVGNSKRvDSDEKRKLDDKPDNKKSNSSGSD 1224

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1811052786  281 KTKSPKTAASPAVVGSPIRSPKTVSKEKKSPGRSKSPKSPKSPKVMTHIPQAPVRPE-------TPNRTPSATLSEKSSK 353
Cdd:PTZ00108  1225 QEDDEEQKTKPKKSSVKRLKSKKNNSSKSSEDNDEFSSDDLSKEGKPKNAPKRVSAVqysppppSKRPDGESNGGSKPSS 1304

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1811052786  354 ETLQVKQAQAPPDAGKLNSENPPKKAVVTDKTIDAS-IDAVIARAC-AEREPDPFEFSSGSESEGDIFTS 421
Cdd:PTZ00108  1305 PTKKKVKKRLEGSLAALKKKKKSEKKTARKKKSKTRvKQASASQSSrLLRRPRKKKSDSSSEDDDDSEVD 1374

histone-fold domain found in transcription initiation factor TFIID subunit 3 (TAF3) and similar proteins; TAF3, also called TATA Binding Protein (TBP) associated factor 3, 140 kDa TATA box-binding protein-associated factor, TBP-associated factor 3, or transcription initiation factor TFIID 140 kDa subunit (TAF(II)140, TAF140, TAFII-140,TAFII140), is a component of the TFIID complex that is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). TFIID is one of the general transcription factors required for accurate and regulated initiation by RNA polymerase II. It plays a central role in mediating promoter responses to various activators and repressors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1811052786   3 ESYSRSLLRVSVAQICQALGWDSVQLSACHLLTDVLQRYLQQLGRGCHRYSELYGRTDPILDDVSEAFQLMGVSLHELED 82
Cdd:cd22916     1 DEFSRSLLRVVVAQICQNVGWHSIQSSPLDLLTDVLQRYLLELARSAHRYAEQYGRTEPNLDDLGLAFKDMGISLNELED 80

                          90
                  ....*....|..
gi 1811052786  83 YIHNIEPVTFPH 94
Cdd:cd22916    81 YVLNVEPVPFPH 92

Bromodomain transcription factors and PHD domain containing proteins; subdomain of archael histone-like transcription factors

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1811052786    5 YSRSLLRVSVAQICQALGWDSVQLSACHLLTDVLQRYLQQLGRGCHRYSELYGRTDPILDDVSEAFQLMGVSLHE 79
Cdd:smart00576   3 LAFALLRIAVAQILESAGFDSFQESALETLTDILQSYIQELGRTAHSYAELAGRTEPNLGDVVLALENLGISVGE 77

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 1811052786  908 ICPGCNKPDDGSPMIGCDDCDDWYHWPCVGI-MAAPPEEMQWFCPKC 953
Cdd:smart00249   1 YCSVCGKPDDGGELLQCDGCDRWYHQTCLGPpLLEEEPDGKWYCPKC 47

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1811052786 912 CNKPDDGsPMIGCD--DCD-DWYHWPCVGIMAAPpeEMQWFCPKC 953
Cdd:COG5034   226 CQQVSYG-QMVACDnaNCKrEWFHLECVGLKEPP--KGKWYCPEC 267

histone-fold domain found in transcription initiation factor TFIID subunit 3 (TAF3) and similar proteins; TAF3, also called TATA Binding Protein (TBP) associated factor 3, 140 kDa TATA box-binding protein-associated factor, TBP-associated factor 3, or transcription initiation factor TFIID 140 kDa subunit (TAF(II)140, TAF140, TAFII-140,TAFII140), is a component of the TFIID complex that is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). TFIID is one of the general transcription factors required for accurate and regulated initiation by RNA polymerase II. It plays a central role in mediating promoter responses to various activators and repressors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1811052786   3 ESYSRSLLRVSVAQICQALGWDSVQLSACHLLTDVLQRYLQQLGRGCHRYSELYGRTDPILDDVSEAFQLMGVSLHELED 82
Cdd:cd22916     1 DEFSRSLLRVVVAQICQNVGWHSIQSSPLDLLTDVLQRYLLELARSAHRYAEQYGRTEPNLDDLGLAFKDMGISLNELED 80

                          90
                  ....*....|..
gi 1811052786  83 YIHNIEPVTFPH 94
Cdd:cd22916    81 YVLNVEPVPFPH 92

Bromodomain transcription factors and PHD domain containing proteins; subdomain of archael histone-like transcription factors

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1811052786    5 YSRSLLRVSVAQICQALGWDSVQLSACHLLTDVLQRYLQQLGRGCHRYSELYGRTDPILDDVSEAFQLMGVSLHE 79
Cdd:smart00576   3 LAFALLRIAVAQILESAGFDSFQESALETLTDILQSYIQELGRTAHSYAELAGRTEPNLGDVVLALENLGISVGE 77

histone fold domain (HFD) superfamily; The histone fold domain (HFD) is a structurally conserved interaction motif involved in heterodimerization of the core histones and their assembly into the nucleosome octamer. Histone fold heterodimers play crucial roles in gene regulation. The minimal HFD consists of three alpha helices connected by two short, unstructured loops. The HFD is found in core histones, TATA box-binding protein-associated factors (TAFs), and many other transcription factors. HFD plays a role in the nucleosomal core particle by conserving histone interactions; these contain more than one HFD. The structure of the nucleosome core particle has two modes that have the largest interaction surfaces, and these are the H3-H4 and H2A-H2B heterodimer interactions. Several TAFs interact via histone-fold (HF) motifs. Five HF-containing TAF pairs have been described in transcription factor II D (TFIID): TAF6-TAF9, TAF4-TAF12, TAF11-TAF13, TAF8-TAF10 and TAF3-TAF10.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1811052786   9 LLRVSVAQICQALGWDSVQLSACHLLTDVLQRYLQQLGRGCHRYSELYGRTDPILDDVSEAFQ 71
Cdd:cd00076     1 LLRSAVARILKSAGFDSVSKSALELLSDLLERYLEELARAAKAYAELAGRTTPNAEDVELALE 63

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 1811052786 912 CNKPDDGSPMIGCDDCDDWYHWPCVGIMAAPPEEM-QWFCPKC 953
Cdd:cd16039     4 CQKPDDGRWMIACDGCDEWYHFTCVNIPEADVELVdSFFCPPC 46

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 1811052786 908 ICPGCNKPDDGSPMIGCDDCDDWYHWPCVGI---MAAPPEEmQWFCPKC 953
Cdd:pfam00628   1 YCAVCGKSDDGGELVQCDGCDDWFHLACLGPpldPAEIPSG-EWLCPEC 48

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 1811052786 908 ICPGCNKP-DDGSPMIGCDDCDDWYHWPCVGI-MAAPPEEMQWFCPKC 953
Cdd:cd15489     1 SCIVCGKGgDLGGELLQCDGCGKWFHADCLGPpLSSFVPNGKWICPVC 48

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 1811052786 912 CNKPDDGSP-MIGCDDCDDWYHWPCVGIMAAPPEEM-QWFCPKC 953
Cdd:cd15560     4 CRTPYDESQfYIGCDRCQDWFHGRCVGILQSEAEKIdEYVCPQC 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        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1811052786 909 CPGCNKPDDGSPMIGCDDCDDWYHWPCVGIMAAPPEEM-----QWFCPKC 953
Cdd:cd15638     2 CGFCKKPHGNRFMVGCGRCDDWFHGDCVGLSLSQAQQMeeedkEYVCVKC 51

histone-fold domain found in Suppressor of Ty 7-like (SUPT7L) and similar proteins; SUPT7L, also called STAGA complex 65 subunit gamma, adenocarcinoma antigen ART1, SPTF-associated factor 65 gamma, or STAF65gamma, is the ortholog of yeast SPT7 in mammalian cells. It is highly similar to yeast SPT7 but lacks the N-terminal SPT7 bromodomain. SUPT7L is a protein component specific to STAGA (SPT3-TAF9-GCN5 Acetyltransferase)-type complexes. It plays an essential role for the integrity of the STAGA complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1811052786   7 RSLLRVSVAQICQALGWDSVQLSACHLLTDVLQRYLQQLGRGCHRYSE---LYGRTdPILDDVSEAFQLMGV-SLHELED 82
Cdd:cd06847     6 RQLLRKSVAAILAHAGFDSASESALEVLTDVLDEFLRKFTRLLRSAVDreaLSGET-GFPDILERVLHEMGIgGISSLHE 84

                  .
gi 1811052786  83 Y 83
Cdd:cd06847    85 Y 85

PHD finger found in Arabidopsis thaliana PHD finger protein MALE MEIOCYTE DEATH 1 (MMD1), PHD finger protein MALE STERILITY 1 (MS1), and similar proteins; MMD1 is a plant homeodomain (PHD) finger protein expressed in male meiocytes. It is encoded by the gene DUET, which is required for male meiotic chromosome organization and progression. MMD1 has been implicated in the regulation of gene expression during meiosis. The mmd1 mutation triggers cell death in male meiocytes. MS1 is a nuclear transcriptional activator that is important for tapetal development and pollen wall biosynthesis. It contains a Leu zipper-like domain and a PHD finger motif, both of which are essential for its function.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1811052786 909 CPGCNKPDDGSPMIGCDDCDDWYHWPCVGIMAAPPEEMQWFCPKC 953
Cdd:cd15556     2 CSCGTRDDDGERMIACDVCEVWQHTRCVGIADNEEPPDHFLCRRC 46

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 1811052786 912 CNKPDDGSPMIGCDDCDDWYHWPCVGIMA-APPEEmqWFCPKC 953
Cdd:cd15550     4 CGFEHDDGFMICCDKCSVWQHGDCMGIDReNIPDS--YLCEQC 44

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        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1811052786 909 CPGCNKPDDGSPM--IGCDDCDDWYHWPCVGImaaPPEE----MQWFCPKC 953
Cdd:cd15517     2 CGICNLETAAVDElwVQCDGCDKWFHQFCLGL---SNERyadeDKFKCPNC 49

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

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1811052786 921 MIGCDDCD---DWYHWPCVGIMAAPpeEMQWFCPKC 953
Cdd:cd15586    12 MIGCDNPDcpiEWFHFACVGLTTKP--KGKWFCPRC 45

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 1811052786 909 CPGCNKPDDGSPMIGCDDCDDWYHWPCVG--IMAAPPEemQWFCPKC 953
Cdd:cd15543     2 CRKCGLSDHPEWILLCDRCDAGYHTACLRppLMIIPDG--NWFCPPC 46

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1811052786 909 CPGCNKPDDGSPMIGCDDCDDWYHWPCVG-IMAAPPEEMQWFCPKC 953
Cdd:cd15525     2 CHVCGGKQDPEKQLLCDECDMAYHLYCLDpPLTSLPDDDEWYCPDC 47

PHD finger 1 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 (H3K4me2 and H3K4me3), 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. This family also includes Drosophila melanogaster protein little imaginal discs (Lid) that functions as a JmjC-dependent 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 first PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1811052786 908 ICPGCNKPDDGSPMIGCDDCDDWYHWPCV--GIMAAPPEEmqWFCPKC 953
Cdd:cd15515     1 ICQVCGRGDDEDKLLLCDGCDDSYHTFCLipPLPDIPPGD--WRCPKC 46

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1811052786 910 PGCNKP-DDGSPMIGCDDCDDWYHWPCVG--IMAAPPEEMQWFCP 951
Cdd:cd15609     5 PSCCLPqDETVSWVQCDDCDQWYHVACVGcdYNAVKDPDADFHCG 49

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1811052786 912 CNKPDDGSPMIGCDDCDDWYHWPCVGIMAAPPEEMQ-----WFCPKC 953
Cdd:cd15639     8 CRQPHNNRFMICCDRCEEWFHGDCVGITEARGRLLErngedYICPNC 54

PHD finger found in protein Jade-1 and similar proteins; Jade-1, also termed PHD finger protein 17 (PHF17), is a novel binding partner of von Hippel-Lindau (VHL) tumor suppressor Pvhl, a key regulator of the cellular oxygen sensing pathway. It is highly expressed in renal proximal tubules. Jade-1 functions as an essential regulator of multiple cell signaling pathways. It may be involved in the serine/threonine kinase AKT/AKT1 pathway during renal cancer pathogenesis and normally prevents renal epithelial cell proliferation and transformation. It also acts as a pro-apoptotic and growth suppressive ubiquitin ligase to inhibit canonical Wnt downstream effector beta-catenin for proteasomal degradation, and as a transcription factor associated with histone acetyltransferase activity and with increased abundance of cyclin-dependent kinase inhibitor p21. Moreover, Jade-1 is required for ING4 and ING5 to associate with histone acetyltransferase (HAT) HBO1 and Eaf6 to form a HBO1 complex, and plays a role in epithelial cell regeneration. It has also been identified as a novel component of the nephrocystin protein (NPHP) complex and interacts with the ciliary protein nephrocystin-4 (NPHP4). Jade-1 contains a canonical Cys4HisCys3 plant homeodomain (PHD) finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, both of which are zinc-binding motifs. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1811052786 908 ICPGCNKPD--DGSPMIGCDDCDDWYHWPCVGIMAAPpeEMQWFCPKC 953
Cdd:cd15679     1 VCDVCQSPDgeDGNEMVFCDKCNICVHQACYGILKVP--EGSWLCRTC 46

PHD finger 3 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 third PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1811052786 908 ICPGCNKPDD-GSPMIGCDDCDDWYHWPCVG-------IMAAPPEEMQWFCPKC 953
Cdd:cd15508     4 LCEKCYDDDDyDSKMMQCSQCDHWVHAKCEGlsdemyeILSYLPESIEYTCSLC 57

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 1811052786 910 PGCNKPD-DGSPMIGCDDCDDWYHWPCVGIMAAPPEEM-QWFCPKC 953
Cdd:cd15610     5 KQCLKPTgDEVNWVQCDGCEEWFHLLCVGLSPEEVAEDeDYICPSC 50

PHD finger 1 found in Drosophila melanogaster protein little imaginal discs (Lid) and similar proteins; Drosophila melanogaster Lid, also termed Retinoblastoma-binding protein 2 homolog, is identified genetically as a trithorax group (trxG) protein that is a Drosophila homolog of the human protein JARID1A/kdm5A, a member of the JARID subfamily within the JmjC proteins. Lid 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. Lid contains the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers. This model corresponds to the first PHD finger of Lid.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1811052786 908 ICPGCNKPDDGSPMIGCDDCDDWYHWPCvgiMAAPPEEM---QWFCPKC 953
Cdd:cd15605     1 VCHTCGRGDGEESMLLCDGCDDSYHTFC---LLPPLSEVpkgDWRCPKC 46

PHD finger 1 found in Lysine-specific demethylase 5C (KDM5C) and 5D (KDM5D); The family includes KDM5C and KDM5D, both of which belong to the JARID subfamily within the JmjC proteins. KDM5C (also termed Histone demethylase JARID1C, Jumonji/ARID domain-containing protein 1C, SmcX, or Xe169) 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 (also termed Histocompatibility Y antigen (H-Y), Histone demethylase JARID1D, Jumonji/ARID domain-containing protein 1D, or SmcY) is a male-specific antigen that shows a demethylase activity specific for di- and tri-methylated histone H3K4 (H3K4me3 andH3K4me2), 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. Both KDM5C and KDM5D 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 plant homeodomain (PHD) fingers. This model corresponds to the first PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1811052786 908 ICPGCNKPDDGSPMIGCDDCDDWYHWPCVGIMAAPPEEMQWFCPKC 953
Cdd:cd15604     1 VCRMCSRGDEDDKLLLCDGCDDNYHTFCLLPPLPEPPKGIWRCPKC 46

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
                  ....*....|....*....|....*....|....*..
gi 1811052786 921 MIGCDDCD---DWYHWPCVGIMAAPpeEMQWFCPKCA 954
Cdd:cd15685    13 MIGCDNPDcpiEWFHFACVDLTTKP--KGKWFCPRCT 47

PHD finger 2 found in Histone-lysine N-methyltransferase 2C (KMT2C); KMT2C, also termed myeloid/lymphoid or mixed-lineage leukemia protein 3 (MLL3) or homologous to ALR protein, is a histone H3 lysine 4 (H3K4) lysine methyltransferase that functions as a circadian factor contributing to genome-scale circadian transcription. It is a component of a large complex that acts as a coactivator of multiple transcription factors, including the bile acid (BA)-activated nuclear receptor, farnesoid X receptor (FXR), a critical player in BA homeostasis. The MLL3 complex is essential for p53 transactivation of small heterodimer partner (SHP). KMT2C is also a part of activating signal cointegrator-2 (ASC-2)-containing complex (ASCOM) that contains the transcriptional coactivator nuclear receptor coactivator 6 (NCOA6), KMT2C and its paralog MLL4. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2C contains several plant homeodomain (PHD) fingers, two extended PHD (ePHD) fingers, Cys2HisCys5HisCys2His, an ATPase alpha beta signature, a high mobility group (HMG)-1 box, a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain and two FY (phenylalanine tyrosine)-rich domains. This model corresponds to the second PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1811052786 908 ICPGCNKPDDGSPMIGCDDCDDWYHWPCVG-IMAAPPEEmQWFCPKC 953
Cdd:cd15594     1 VCQTCRQPGDDNKMLVCDTCDKGYHTFCLQpVMTTIPKN-GWKCKNC 46

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1811052786 909 CPGCNKPDDGSPMIGCDDCDDWYHWPCVGI-MAAPPEEmQWFCPKC 953
Cdd:cd15545     2 CQICRSGDNEDQLLLCDGCDRGYHTYCFKPkMTNVPEG-DWFCPEC 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
                  ....*....|....*....|....*....|....*....|....*
gi 1811052786 912 CNKPDDGSpMIGCDD--CD-DWYHWPCVGIMAAPpeEMQWFCPKC 953
Cdd:cd15683     5 CNQVSYGE-MIGCDNeqCPiEWFHFSCVGLTYKP--KGKWYCPKC 46

PHD finger found in protein Jade-2 and similar proteins; Jade-2, also termed PHD finger protein 15 (PHF15), is a plant homeodomain (PHD) zinc finger protein that is closely related to Jade-1, which functions as an essential regulator of multiple cell signaling pathways. Like Jade-1, Jade-2 is required for ING4 and ING5 to associate with histone acetyltransferase (HAT) HBO1 and Eaf6 to form a HBO1 complex that has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. Jade-2 contains a canonical Cys4HisCys3 PHD finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, both of which are zinc-binding motifs. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1811052786 908 ICPGCNKPD--DGSPMIGCDDCDDWYHWPCVGIMAAPpeEMQWFCPKC 953
Cdd:cd15680     1 VCDVCRSPEgeDGNEMVFCDKCNVCVHQACYGILKVP--TGSWLCRTC 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 1811052786 912 CNKPDDGSPMIGCDDCDDWYHWPCVGIMAAPPEEMqWFCPKC 953
Cdd:cd15632     6 CMKPFAGRPMIECNECHTWIHLSCAKIRKSNVPEV-YVCQKC 46

PHD finger found in bromodomain adjacent to zinc finger domain protein BAZ1A and BAZ1B; BAZ1A, also termed ATP-dependent chromatin-remodeling protein, or ATP-utilizing chromatin assembly and remodeling factor 1 (ACF1), or CHRAC subunit ACF1, or Williams syndrome transcription factor-related chromatin-remodeling factor 180 (WCRF180), or WALp1, is a subunit of the conserved imitation switch (ISWI)-family ATP-dependent chromatin assembly and remodeling factor (ACF)/chromatin accessibility complex (CHRAC) chromatin remodeling complex, which is required for DNA replication through heterochromatin. It alters the remodeling properties of the ATPase motor protein sucrose nonfermenting-2 homolog (SNF2H). Moreover, BAZ1A and its complexes play important roles in DNA double-strand break (DSB) repair. It is essential for averting improper gene expression during spermatogenesis. It also regulates transcriptional repression of vitamin D3 receptor-regulated genes. BAZ1B, also termed Tyrosine-protein kinase BAZ1B, or Williams syndrome transcription factor (WSTF), or Williams-Beuren syndrome chromosomal region 10 protein, Williams-Beuren syndrome chromosomal region 9 protein, or WALp2, is a multifunctional protein implicated in several nuclear processes, including replication, transcription, and the DNA damage response. BAZ1B/WSTF, together with the imitation switch (ISWI) ATPase, forms a WSTF-ISWI chromatin remodeling complex (WICH), which transiently associates with the human inactive X chromosome (Xi) during late S-phase prior to BRCA1 and gamma-H2AX. Moreover, BAZ1B/WSTF, SNF2h, and nuclear myosin 1 (NM1) forms the chromatin remodeling complex B-WICH that is involved in regulating rDNA transcription. Both BAZ1A and BAZ1B contain a WAC motif, a DDT domain, BAZ 1 and BAZ 2 motifs, a WAKZ (WSTF/Acf1/KIAA0314/ZK783.4) motif, a plant homeodomain (PHD) finger, and a bromodomain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1811052786 909 CPGCNKPDDGSPMIGCDDCDDWYHWPCVGIMAAPPEEMQWFCPKC 953
Cdd:cd15544     2 CKVCRKKGDPDNMILCDGCDKAFHLYCLRPALREVPSGDWFCPAC 46

DNA topoisomerase 2-like protein; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1811052786  202 ETLDVVLLEAREPLSSINPQKIPPMLSPVHVQDSTDLAPPSPEPPMLAPVAKSQMP-TAKPLEAKSFTPKAKTKTGSPGQ 280
Cdd:PTZ00108  1145 EEVEEKEIAKEQRLKSKTKGKASKLRKPKLKKKEKKKKKSSADKSKKASVVGNSKRvDSDEKRKLDDKPDNKKSNSSGSD 1224

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1811052786  281 KTKSPKTAASPAVVGSPIRSPKTVSKEKKSPGRSKSPKSPKSPKVMTHIPQAPVRPE-------TPNRTPSATLSEKSSK 353
Cdd:PTZ00108  1225 QEDDEEQKTKPKKSSVKRLKSKKNNSSKSSEDNDEFSSDDLSKEGKPKNAPKRVSAVqysppppSKRPDGESNGGSKPSS 1304

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1811052786  354 ETLQVKQAQAPPDAGKLNSENPPKKAVVTDKTIDAS-IDAVIARAC-AEREPDPFEFSSGSESEGDIFTS 421
Cdd:PTZ00108  1305 PTKKKVKKRLEGSLAALKKKKKSEKKTARKKKSKTRvKQASASQSSrLLRRPRKKKSDSSSEDDDDSEVD 1374

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 1811052786 912 CNKPDDGSP-MIGCDDCDDWYHWPCVGIMAAPPEEMQWF-CPKC 953
Cdd:cd15642     5 CRLPYDVTRfMIECDVCQDWFHGSCVGVEEEKAAEIDLYhCPNC 48

PHD finger found in protein kinase C-binding protein 1 (PRKCBP1); PRKCBP1, also termed cutaneous T-cell lymphoma-associated antigen se14-3 (CTCL-associated antigen se14-3), or Rack7, or zinc finger MYND domain-containing protein 8 (ZMYND8), is a novel receptor for activated C-kinase (RACK)-like protein that may play an important role in the activation and regulation of PKC-beta I, and the PKC signaling cascade. It also has been identified as a formin homology-2-domain containing protein 1 (FHOD1)-binding protein that may be involved in FHOD1-regulated actin polymerization and transcription. Moreover, PRKCBP1 may function as a REST co-repressor 2 (RCOR2) interacting factor; the RCOR2/ZMYND8 complex which might be involved in the regulation of neural differentiation. PRKCBP1 contains a plant homeodomain (PHD) finger, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1811052786 907 WICPGCNkpddgsPMIGCDDCDDWYHWPCVGIMAAPPEEmqWFCPKC 953
Cdd:cd15538     3 WRCHKEG------QVLCCSLCPRVYHKKCLKLTSEPDED--WVCPEC 41

PHD finger 3 found in lysine-specific demethylase 5B (KDM5B); 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), is a member of the JARID subfamily within the JmjC proteins. It has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of 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 as TIEG1/KLF10 (transforming growth factor-beta inducible early gene-1/Kruppel-like transcription factor 10), and possibly function as a transcriptional corepressor. KDM5B contains the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers. This model corresponds to the third PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1811052786 908 ICPG--CNKPD-DGSPMIGCD-DCDDWYHWPCVGIMAAPPEEMQWFCPKC 953
Cdd:cd15687     1 LCPAvsCLQPEgEEVDWVQCDgSCNRWFHQVCVGVSAEMAEKEDYICVSC 50

PHD finger 2 found in class II Chromodomain-Helicase-DNA binding (CHD) proteins; Class II CHD proteins includes chromodomain-helicase-DNA-binding protein CHD3, CHD4, and CHD5, which are nuclear and ubiquitously expressed chromatin remodelling ATPases generally associated with histone deacetylases (HDACs). They are involved in DNA Double Strand Break (DSB) signaling, DSB repair and/or p53-dependent pathways such as apoptosis and senescence, as well as in the maintenance of genomic stability, and/or cancer prevention. They function as subunits of the Nucleosome Remodelling and Deacetylase (NuRD) complex, which is generally associated with gene repression, heterochromatin formation, and overall chromatin compaction. In contrast to the class I CHD enzymes (CHD1 and CHD2), class II CHD proteins lack identifiable DNA-binding domains, but possess a C-terminal coiled-coil region. Moreover, in addition to the tandem chromodomains and a helicase domain, they all harbor tandem plant homeodomain (PHD) zinc fingers involved in the recognition of methylated histone tails. This model corresponds to the second PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1811052786 912 CNKPDDGSPMIGCDDCDDWYHWPCVGIMAAPPEEMQWFCPKC 953
Cdd:cd15532     2 CRVCKDGGELLCCDGCPSSYHLHCLNPPLAEIPDGDWFCPRC 43

PHD finger 2 found in Histone-lysine N-methyltransferase 2D (KMT2D); KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named myeloid/lymphoid or mixed-lineage leukemia 4 (MLL4), a fourth human homolog of Drosophila trithorax, located on chromosome 12. KMT2D enzymatically generates trimethylated histone H3 Lys 4 (H3K4me3). It plays an essential role in differentiating the human pluripotent embryonal carcinoma cell line NTERA-2 clone D1 (NT2/D1) stem cells by activating differentiation-specific genes, such asHOXA1-3 and NESTIN. It is also a part of activating signal cointegrator-2 (ASC-2)-containing complex (ASCOM) that contains the transcriptional coactivator nuclear receptor coactivator 6 (NCOA6), KMT2C and KMT2D. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2D contains the catalytic domain SET, five plant homeodomain (PHD) fingers, two extended PHD (ePHD) fingers, Cys2HisCys5HisCys2His, a RING finger, an HMG (high-mobility group)-binding motif, and two FY-rich regions. This model corresponds to the second PHD finger.

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gi 1811052786 908 ICPGCNKPDDGSPMIGCDDCDDWYHWPCvgiMAAPPEEM---QWFCPKC 953
Cdd:cd15595     1 VCQTCRKPGEDSKMLVCEACDKGYHTFC---LKPAMESLptdSWKCKAC 46

PHD finger 1 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 first PHD finger.

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gi 1811052786 908 ICPGCNKPDDGSPMIGCDDCDDWYHWPCVGIMAAPPEEMQWFCPKC 953
Cdd:cd15602     1 VCLFCGRGNNEDKLLLCDGCDDSYHTFCLIPPLPDVPKGDWRCPKC 46

PHD finger found in ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1); UHRF1 (also termed inverted CCAAT box-binding protein of 90 kDa, nuclear protein 95, nuclear zinc finger protein Np95 (Np95), RING finger protein 106, transcription factor ICBP90, or E3 ubiquitin-protein ligase UHRF1) is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumour suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of transcription factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF1 contains an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET and RING finger associated (SRA) domain, and a C-terminal RING-finger domain. It specifically binds to hemimethylated DNA, double-stranded CpG dinucleotides, and recruits the maintenance methyltransferase DNMT1 to its hemimethylated DNA substrate through its SRA domain. UHRF1-dependent H3K23 ubiquitylation has an essential role in maintaining DNA methylation and replication. The tandem Tudor domain directs UHRF1 binding to the heterochromatin mark histone H3K9me3 and the PHD finger targets UHRF1 to unmodified histone H3 in euchromatic regions. The RING-finger domain exhibit both autocatalytic E3 ubiquitin (Ub) ligase activity and activity against histone H3 and DNMT1.

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gi 1811052786 909 CPGCNKPDDGSPMIGCDDCDDWYHWPCVGI-MAAPPEEMQWFCPKC 953
Cdd:cd15616     2 CHVCGGKQDPDKQLMCDECDMAFHIYCLNPpLSSIPDDEDWYCPEC 47