PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) finger typically characterized as Cys4HisCys3, and a non-canonical extended PHD finger, characterized as Cys2HisCys5HisCys2His. Variations include the RAG2 PHD finger characterized by Cys3His2Cys2His and the PHD finger 5 found in nuclear receptor-binding SET domain-containing proteins characterized by Cys4HisCys2His. The PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. Single or multiple copies of PHD fingers have been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors. The PHD finger domain SF is structurally similar to the RING and FYVE_like superfamilies.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94681069   6 CALCPKDVEYNVLYFAQSENIAAHENCLLYSSGLVECEDQDPLNPDRSFDVESVKKEIQRGRKLKCKFCHKRGATVGCDL 85
Cdd:cd15712   1 CAFCPKGEEYSIMYFAQEQNIAAHQNCLLYSSGFVESEEYNPLNLDRRFDVESVLNEIKRGKRLKCNFCRKKGATVGCEE 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 94681069  86 KNCNKNYHFFCAKKDDAVPQSDGVRGIYKLLCQQH 120
Cdd:cd15712  81 RACRRSYHYFCALCDDAAIETDEVRGIYRVFCQKH 115

Extended PHD finger found in PHD finger protein 11 (PHF11); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of PHF11. PHF11, also termed BRCA1 C-terminus-associated protein, or renal carcinoma antigen NY-REN-34, is a transcriptional co-activator of the Th1 effector cytokine genes, interleukin-2 (IL2) and interferon-gamma (IFNG), co-operating with nuclear factor kappa B (NF-kappaB). It is involved in T-cell activation and viability. Polymorphisms within PHF11 are associated with total IgE, allergic asthma and eczema.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94681069   6 CALCPKDVEYNVLYFAQSENIAAHENCLLYSSGLVECEDQDPLNPDRSFDVESVKKEIQRGRKLKCKFCHKRGATVGCDL 85
Cdd:cd15712   1 CAFCPKGEEYSIMYFAQEQNIAAHQNCLLYSSGFVESEEYNPLNLDRRFDVESVLNEIKRGKRLKCNFCRKKGATVGCEE 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 94681069  86 KNCNKNYHFFCAKKDDAVPQSDGVRGIYKLLCQQH 120
Cdd:cd15712  81 RACRRSYHYFCALCDDAAIETDEVRGIYRVFCQKH 115

Extended PHD finger found in PHD finger protein 11 (PHF11); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of PHF11. PHF11, also termed BRCA1 C-terminus-associated protein, or renal carcinoma antigen NY-REN-34, is a transcriptional co-activator of the Th1 effector cytokine genes, interleukin-2 (IL2) and interferon-gamma (IFNG), co-operating with nuclear factor kappa B (NF-kappaB). It is involved in T-cell activation and viability. Polymorphisms within PHF11 are associated with total IgE, allergic asthma and eczema.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94681069   6 CALCPKDVEYNVLYFAQSENIAAHENCLLYSSGLVECEDQDPLNPDRSFDVESVKKEIQRGRKLKCKFCHKRGATVGCDL 85
Cdd:cd15712   1 CAFCPKGEEYSIMYFAQEQNIAAHQNCLLYSSGFVESEEYNPLNLDRRFDVESVLNEIKRGKRLKCNFCRKKGATVGCEE 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 94681069  86 KNCNKNYHFFCAKKDDAVPQSDGVRGIYKLLCQQH 120
Cdd:cd15712  81 RACRRSYHYFCALCDDAAIETDEVRGIYRVFCQKH 115

Extended PHD finger 1 found in PHD finger protein 6 (PHF6); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. PHF6 contains two non-canonical ePHD fingers, this model corresponds to the first ePHD finger. PHF6, also termed the X-linked mental retardation disorder Borjeson-Forssman-Lehmann syndrome-associated protein, is a nucleolus, ribosomal RNA promoter-associated protein that regulates cell cycle progression by suppressing ribosomal RNA synthesis. It has been implicated in cell cycle control, genomic maintenance, and tumor suppression. PHF6 shows transcriptional repression activity through directly interacting with the nucleosome remodeling and deacetylation complex component RBBP4. .

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94681069   6 CALCP--KDVEYNVLYFAQSENIAAHENCLLYSSGLVECE-DQDPLNpdrSFDVESVKKEIQRGRKLKCKFCHKRGATVG 82
Cdd:cd15710   1 CGFCRsnREKECGQLLISENQKVAAHHKCMLFSSALVSSHsDSENLG---GFSIEDVQKEIKRGTKLMCSLCHCPGATIG 77

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 94681069  83 CDLKNCNKNYHFFCAKKDDAVPQSDGVRGIYKLLCQQH 120
Cdd:cd15710  78 CDVKTCHRTYHYYCALHDKAQIRENPSQGIYMIYCRKH 115

Extended PHD finger 2 found in PHD finger protein 6 (PHF6); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. PHF6 contains two non-canonical ePHD fingers, this model corresponds to the second ePHD finger. PHF6, also termed the X-linked mental retardation disorder Borjeson-Forssman-Lehmann syndrome-associated protein, is a nucleolus, ribosomal RNA promoter-associated protein that regulates cell cycle progression by suppressing ribosomal RNA synthesis. It has been implicated in cell cycle control, genomic maintenance, and tumor suppression. PHF6 shows transcriptional repression activity through directly interacting with the nucleosome remodeling and deacetylation complex component RBBP4.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94681069   6 CALCPKDVEYN----VLYFAQSENIAAHENCLLYSSGLVECEDQDPLNPDrSFDVESVKKEIQRGRKLKCKFCHKRGATV 81
Cdd:cd15711   1 CGFCHAGEEENetrgKLHIFNAKKAAAHYKCMLFSSGTVQLTTTSRAEFG-DFDIKTVIQEIKRGKRMKCTLCSQLGATI 79

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 94681069  82 GCDLKNCNKNYHFFCAKKDDAVPQSDGVRGIYKLLCQQH 120
Cdd:cd15711  80 GCEIKACVKTYHYHCGVQDKAKYIENMSRGIYKLYCKNH 118

Extended PHD finger found in histone-lysine N-methyltransferase 2A (KMT2A) and 2B (KMT2B); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This subfamily includes the ePHD finger of histone-lysine N-methyltransferase trithorax (Trx) like proteins, KMT2A/MLL1 and KMT2B/MLL2. KMT2A and KMT2B comprise the mammalian Trx branch of 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 by 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 PHD fingers, this extended PHD (ePHD) finger, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94681069   6 CALC-------PKDvEYNVLYFAQSENIaaHENCLLYSSGLVECEDQDPLNpdrsfdvesVKKEIQRGRKLKCKFCHKRG 78
Cdd:cd15664   1 CALCgvygddePND-AGRLLYCGQDEWV--HINCALWSAEVFEEDDGSLQN---------VHSAVSRGRMMKCELCGKPG 68

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 94681069  79 ATVGCDLKNCNKNYHFFCAKKDDAVPQSDGvrgiyKLLCQQH 120
Cdd:cd15664  69 ATVGCCLKSCPANYHFMCARKAECVFQDDK-----KVFCPAH 105

Extended PHD finger found in histone-lysine N-methyltransferase 2A (KMT2A); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This subfamily includes the ePHD finger of KMT2A. KMT2A also termed ALL-1, or CXXC-type zinc finger protein 7, or myeloid/lymphoid or mixed-lineage leukemia protein 1 (MLL1), or trithorax-like protein (Htrx), or zinc finger protein HRX, is a histone methyltransferase that belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2). It 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, which also contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex. The MLL1 complex is highly active and specific for H3K4methylation. KMT2A contains a CxxC (x for any residue) zinc finger domain, three PHD fingers, a Bromodomain domain, this extended PHD finger, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94681069   4 RTCALCPK--DVEYN----VLYFAQSEniAAHENCLLYSSGLVECEDQDplnpdrsfdVESVKKEIQRGRKLKCKFCHKR 77
Cdd:cd15693   1 RQCALCLKygDDSANdagrLLYIGQNE--WTHVNCALWSAEVFEDDDGS---------LKNVHMAVIRGKQLRCEFCQKP 69

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 94681069  78 GATVGCDLKNCNKNYHFFCAKKDDAVPQSDGvrgiyKLLCQQH 120
Cdd:cd15693  70 GATVGCCLTSCTSNYHFMCSRAKNCVFLEDK-----KVYCQRH 107

Extended PHD finger 2 found in histone-lysine N-methyltransferase 2C (KMT2C) and 2D (KMT2D); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the second ePHD finger of KMT2C, and KMT2D. 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. KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named MLL4, a fourth human homolog of Drosophila trithorax, located on chromosome 12. It enzymatically generates trimethylated histone H3 Lysine 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 as HOXA1-3 and NESTIN. KMT2D is also a part of ASCOM. Both KMT2C and KMT2D contain the catalytic domain SET, five PHD fingers, two ePHD fingers, a RING finger, an HMG (high-mobilitygroup)-binding motif, and two FY-rich regions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94681069  29 HENCLLYSSGLVECEDQDPLNPDRSfdvesvkkeIQRGRKLKCKFCHKRGATVGCDLKNCNKNYHFFCAKKDDAVPQSDg 108
Cdd:cd15666  28 HLNCALWSYEVYETQNGALMNVEEA---------LRRALTTTCSHCGRTGATVPCFKPRCANVYHLPCAIKDGCMFFKD- 97

                        90
                ....*....|..
gi 94681069 109 vRGIYkllCQQH 120
Cdd:cd15666  98 -KTML---CPSH 105

Extended PHD finger 1 found in histone-lysine N-methyltransferase 2C (KMT2C) and 2D (KMT2D); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the first ePHD finger of KMTC2C and KMTC2D. 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. KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named MLL4, a fourth human homolog of Drosophila trithorax, located on chromosome 12. It enzymatically generates trimethylated histone H3 Lysine 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 as HOXA1-3 and NESTIN. KMT2D is also a part of ASCOM. Both KMT2C and KMT2D contain the catalytic domain SET, five plant PHD fingers, two ePHD fingers, a RING finger, an HMG (high-mobilitygroup)-binding motif, and two FY-rich regions.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94681069  28 AHENCLLYSSGLVECEDQDplnpdrsfdVESVKKEIQRGRKLKCKFCHKRGATVGCDLKNCNKNYHFFCA 97
Cdd:cd15665  11 AHHCCAAWSEGVCQTEDGA---------LENVDKAVAKALSQKCSFCLRYGASISCRMPSCSKSFHFPCA 71

Extended PHD finger found in retinoic acid-induced protein 1 (RAI1), transcription factor 20 (TCF-20) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the C-terminal ePHD/ADD (ATRX-DNMT3-DNMT3L) domain of RAI1 and TCF-20. RAI1, a homolog of stromelysin-1 PDGF (platelet-derived growth factor)-responsive element-binding protein (SPBP, also termed TCF-20), is a chromatin-binding protein implicated in the regulation of gene expression. TCF-20 is involved in transcriptional activation of the MMP3 (matrix metalloprotease 3) promoter. It also functions as a transcriptional co-regulator that enhances or represses the transcriptional activity of certain transcription factors/cofactors, such as specificity protein 1 (Sp1), E twenty-six 1 (Ets1), paired box protein 6 (Pax6), small nuclear RING-finger (SNURF)/RNF4, c-Jun, androgen receptor (AR) and estrogen receptor alpha (ERalpha). Both RAI1 and TCF-20 are strongly enriched in chromatin in interphase HeLa cells, and display low nuclear mobility, and have been implicated in Smith-Magenis syndrome and Potocki-Lupski syndrome.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 94681069  67 RKLKCKFCHKRGATVGCDLKNCNKNYHFFCAKKDDAVPQSDGvrgiYKLLCQQH 120
Cdd:cd15668  54 KQSVCSSCQQTGATIGCLHKGCKAKYHYPCAVESGCQLDEEN----FSLLCPKH 103

Extended PHD finger 1 found in histone-lysine N-methyltransferase 2C (KMT2C); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the first ePHD finger of 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 PHD fingers, two ePHD fingers, 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94681069  28 AHENCLLYSSGLVECEDQDPLNpdrsfdvesVKKEIQRGRKLKCKFCHKRGATVGCDLKNCNKNYHFFCA 97
Cdd:cd15696  11 AHLRCAEWSLGVCQGEEQLLVN---------VDKAVVSGSTERCAFCKHLGATIKCCEEKCTQMYHYPCA 71

Extended PHD finger 1 found in histone-lysine N-methyltransferase 2D (KMT2D); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the first ePHD finger of 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 at 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 as HOXA1-3 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 PHD fingers, two ePHD fingers, a RING finger, an HMG (high-mobility group)-binding motif, and two FY-rich regions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94681069  28 AHENCLLYSSGLVECEDQDPLNPDRSfdvesvkkeIQRGRKLKCKFCHKRGATVGCDLKNCNKNYHFFCAkkddAVPQSD 107
Cdd:cd15695  11 VHHWCAAWSAGVKQHEGDGLIGVDKA---------VFSGISQKCEHCKRLGATIQCHAEGCPRFYHFPCA----AASGSF 77

                        90
                ....*....|...
gi 94681069 108 GVRGIYKLLCQQH 120
Cdd:cd15695  78 QSMKTLLLLCPEH 90