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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958681681  50 HENCLLYSSGLVECEAHDPfniakNFDVSSVLEKIWNGSTSKCSFCN-NEGAIMGCDETSCAKNYHLLCAKEDRAILQV- 127
Cdd:pfam13771   1 HVVCALWSPELVQRGNDSM-----GFPIEDIEKIPKRRWKLKCYLCKkKGGACIQCSKKNCRRAFHVTCALEAGLLMQFd 75

                          90
                  ....*....|...
gi 1958681681 128 GVKRTYKIFCPEH 140
Cdd:pfam13771  76 EDNGTFKSYCKKH 88

Extended PHD finger found in PHD finger protein 6 (PHF6) and PHD finger protein 11 (PHF11); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the two ePHD fingers of PFH6 and the single ePHD finger of PFH11. 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. PHF6 contains two non-canonical ePHD fingers. 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 1958681681  27 CVLCPEGHDWSVIYF--SPSANIAAHENCLLYSSGLVECEAHDPFNIAkNFDVSSVLEKIWNGSTSKCSFCNNEGAIMGC 104
Cdd:cd15673     1 CGFCKSGEENKETGGklASGEKIAAHHNCMLFSSGLVQYVSPNENDFG-GFDIEDVKKEIKRGRKLKCNLCKKTGATIGC 79

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1958681681 105 DETSCAKNYHLLCAKEDRA-ILQVGVKRTYKIFCPEH 140
Cdd:cd15673    80 DVKQCKKTYHYHCAKKDDAkIIERNSQGIYRVYCKNH 116

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 1958681681  14 GFCQVTEKmekrtcvlcpEGHDWSVIYFSPSANIAAHENCLLYSSGLVECEAHDPFNIAkNFDVSSVLEKIWNGSTSKCS 93
Cdd:cd15711     2 GFCHAGEE----------ENETRGKLHIFNAKKAAAHYKCMLFSSGTVQLTTTSRAEFG-DFDIKTVIQEIKRGKRMKCT 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1958681681  94 FCNNEGAIMGCDETSCAKNYHLLCAKEDRAILQVGVKR-TYKIFCPEH 140
Cdd:cd15711    71 LCSQLGATIGCEIKACVKTYHYHCGVQDKAKYIENMSRgIYKLYCKNH 118

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 1958681681  42 SPSANIAAHENCLLYSSGLVECEAhDPFNIAkNFDVSSVLEKIWNGSTSKCSFCNNEGAIMGCDETSCAKNYHLLCAKED 121
Cdd:cd15710    18 SENQKVAAHHKCMLFSSALVSSHS-DSENLG-GFSIEDVQKEIKRGTKLMCSLCHCPGATIGCDVKTCHRTYHYYCALHD 95

                          90       100
                  ....*....|....*....|
gi 1958681681 122 RAILQVGVKR-TYKIFCPEH 140
Cdd:cd15710    96 KAQIRENPSQgIYMIYCRKH 115

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958681681  27 CVLCPEGHDWsviyfspsaniaAHENCLLYSSGLVeceahdpfnIAKNFDVSSVLEKIWNGSTSKCSFCNNEGAIMGCDE 106
Cdd:cd15665     1 CALCNLGEVY------------AHHCCAAWSEGVC---------QTEDGALENVDKAVAKALSQKCSFCLRYGASISCRM 59

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1958681681 107 TSCAKNYHLLCAKEDRAILqvgVKRTYKIFCPEH 140
Cdd:cd15665    60 PSCSKSFHFPCAAAAGCFQ---DIKTLTLFCPEH 90

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 1958681681  27 CVLCPEGHDWSVI----YFSPSANIAAHENCLLYSSGLVEceahdpfniAKNFDVSSVLEKIWNGSTSKCSFCNNEGAIM 102
Cdd:cd15666     1 CVLCGGEGDGDTDgpgrLLNLDVDKWVHLNCALWSYEVYE---------TQNGALMNVEEALRRALTTTCSHCGRTGATV 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1958681681 103 GCDETSCAKNYHLLCAKEDRAILqvgvkrtYK---IFCPEH 140
Cdd:cd15666    72 PCFKPRCANVYHLPCAIKDGCMF-------FKdktMLCPSH 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 1958681681  49 AHENCLLYSSGLVEceahDPFNIAKNFDVSSVlekiwNGSTSKCSFCNNEGAIMGCDETSCAKNYHLLCAKEDRAILQvg 128
Cdd:cd15693    29 THVNCALWSAEVFE----DDDGSLKNVHMAVI-----RGKQLRCEFCQKPGATVGCCLTSCTSNYHFMCSRAKNCVFL-- 97

                          90
                  ....*....|..
gi 1958681681 129 vkRTYKIFCPEH 140
Cdd:cd15693    98 --EDKKVYCQRH 107

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 1958681681  27 CVLCPEGHDWsviyfspsaniaAHENCLLYSSGLVECEAHDPFNIAKnfdvssvleKIWNGSTSKCSFCNNEGAIMGCDE 106
Cdd:cd15695     1 CALCNCGECW------------VHHWCAAWSAGVKQHEGDGLIGVDK---------AVFSGISQKCEHCKRLGATIQCHA 59

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1958681681 107 TSCAKNYHLLCAKEDRAILQVgvkRTYKIFCPEH 140
Cdd:cd15695    60 EGCPRFYHFPCAAASGSFQSM---KTLLLLCPEH 90

Extended PHD finger (ePHD) found in retinoic acid-induced protein 1 (RAI1); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the C-terminal ePHD/ADD (ATRX-DNMT3-DNMT3L) domain of RAI1. 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. It is strongly enriched on chromatin in interphase HeLa cells, and displays low nuclear mobility, and has been implicated in Smith-Magenis syndrome, Potocki-Lupski syndrome, and non-syndromic autism. RAI1 contains a region with homology to the novel nucleosome-binding region SPBP and an ePHD/ADD domain with ability to bind nucleosomes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958681681  49 AHENCLLYSSGLVeceahdpFNIAKNFDVSSVLEKiwnGSTSKCSFCNNEGAIMGCDETSCAKNYHLLCAKEDRAILqvg 128
Cdd:cd15700    26 VHEACAVWTTGVY-------LVAGKLFGLQEAVQK---AADAKCSSCQGAGATVGCCHKGCTQSYHYICAVEAGCLF--- 92

                          90
                  ....*....|..
gi 1958681681 129 VKRTYKIFCPEH 140
Cdd:cd15700    93 EEENFSLRCPKH 104

Extended PHD finger 2 found in histone-lysine N-methyltransferase 2C (KMT2C); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the second 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 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 1958681681  46 NIAAHENCLLYSSGLVECEAHDPFNIAKnfdvssvleKIWNGSTSKCSFCNNEGAIMGCDETSCAKNYHLLCA 118
Cdd:cd15697    24 DLWVHLNCALWSTEVYETQAGALINVEL---------ALRRGLQMKCVFCHKTGATSGCHRLRCTNVYHFTCA 87

PHD finger 5 found in nuclear receptor-binding SET domain-containing (NSD) proteins; The nuclear receptor binding SET domain (NSD) protein is a family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1, that are critical in maintaining chromatin integrity. Reducing NSD activity through specific lysine-HMTase inhibitors appears promising to help suppress cancer growth. NSD proteins have specific mono- and dimethylase activities for H3K36, and they play non-redundant roles during development. NSD1 plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. NSD2 is involved in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. NSD3 is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD proteins contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). This model corresponds to the fifth PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1958681681  92 CSFCNNEGAIMGCDETSCAKNYHLLCAKEDrailqVGVKRTYkiFCPEH 140
Cdd:cd15568     2 CFRCGDGGDLVLCDFKGCPKVYHLSCLGLE-----KPPGGKW--ICPWH 43