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 27369858    51 HENCLLYSSGLVECEAPDlpntvRNFDVKSVKKEIGRGRRLKCSFCKNK-GATMGYDLQSCTKNYHLSCAMEDHAILQVD 129
Cdd:pfam13771   1 HVVCALWSPELVQRGNDS-----MGFPIEDIEKIPKRRWKLKCYLCKKKgGACIQCSKKNCRRAFHVTCALEAGLLMQFD 75

                          90
                  ....*....|...
gi 27369858   130 EDHGTYKLFCQKH 142
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 27369858  28 CALCPEGHEWSQIYF--SPSANIVAHENCLLYSSGLVECEAPDlPNTVRNFDVKSVKKEIGRGRRLKCSFCKNKGATMGY 105
Cdd:cd15673   1 CGFCKSGEENKETGGklASGEKIAAHHNCMLFSSGLVQYVSPN-ENDFGGFDIEDVKKEIKRGRKLKCNLCKKTGATIGC 79

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 27369858 106 DLQSCTKNYHLSCAMEDHAILQVDEDHGTYKLFCQKH 142
Cdd:cd15673  80 DVKQCKKTYHYHCAKKDDAKIIERNSQGIYRVYCKNH 116

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 27369858  28 CALCPEGH--EWSQIYFSPSANIVAHENCLLYSSGLVECEAPDlpNTVRNFDVKSVKKEIGRGRRLKCSFCKNKGATMGY 105
Cdd:cd15710   1 CGFCRSNRekECGQLLISENQKVAAHHKCMLFSSALVSSHSDS--ENLGGFSIEDVQKEIKRGTKLMCSLCHCPGATIGC 78

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 27369858 106 DLQSCTKNYHLSCAMEDHAILQVDEDHGTYKLFCQKH 142
Cdd:cd15710  79 DVKTCHRTYHYYCALHDKAQIRENPSQGIYMIYCRKH 115

Extended PHD finger found in PHD finger protein 7 (PHF7) and G2/M phase-specific E3 ubiquitin-protein ligase (G2E3); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of PHF7 and G2E3. PHF7, also termed testis development protein NYD-SP6, is a testis-specific PHD finger-containing protein that associates with chromatin and binds histone H3 N-terminal tails with a preference for dimethyl lysine 4 (H3K4me2). It may play an important role in stimulating transcription involved in testicular development and/or spermatogenesis. PHF7 contains a PHD finger and a non-canonical ePHD finger, both of which may be involved in activating transcriptional regulation. G2E3 is a dual function ubiquitin ligase (E3) that may play a possible role in cell cycle regulation and the cellular response to DNA damage. It is essential for prevention of apoptosis in early embryogenesis. It is also a nucleo-cytoplasmic shuttling protein with DNA damage responsive localization. G2E3 contains two distinct RING-like ubiquitin ligase domains that catalyze lysine 48-linked polyubiquitination, and a C-terminal catalytic HECT domain that plays an important role in ubiquitin ligase activity and in the dynamic subcellular localization of the protein. The RING-like ubiquitin ligase domains consist of a PHD finger and an ePHD finger.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369858  47 NIVAHENCLLYSSGLveCEAPDLPNTVRNFDVKSVKKEIGRGRRLKCSFCKNKGATMGYDLQSCTKNYHLSCAMEDHAIL 126
Cdd:cd15669  22 GICAHYFCLLFSSGL--PQRGEDNEGIYGFLPEDIRKEVRRASRLRCFYCKKKGASIGCAVKGCRRSFHFPCGLENGCVT 99

                        90
                ....*....|....*.
gi 27369858 127 QVdedHGTYKLFCQKH 142
Cdd:cd15669 100 QF---FGEYRSFCWEH 112

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 27369858  51 HENCLLYSSGLVECEAPDLPNtvrnfdvksVKKEIGRGRRLKCSFCKNKGATMGYDLQSCTKNYHLSCAMEDHAILQVDE 130
Cdd:cd15664  28 HINCALWSAEVFEEDDGSLQN---------VHSAVSRGRMMKCELCGKPGATVGCCLKSCPANYHFMCARKAECVFQDDK 98

                        90
                ....*....|..
gi 27369858 131 dhgtyKLFCQKH 142
Cdd:cd15664  99 -----KVFCPAH 105

Extended PHD finger found in histone-lysine N-methyltransferase 2B (KMT2B); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This subfamily includes the ePHD finger of KMT2B. KMT2B is also called trithorax homolog 2 or WW domain-binding protein 7 (WBP-7). KMT2B is encoded by the gene that was first named myeloid/lymphoid or mixed-lineage leukemia 2 (MLL2), a second human homolog of Drosophila trithorax, located on chromosome 19. It belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2) and is vital for normal mammalian embryonic development. KMT2B functions as the catalytic subunit in the MLL2 complex, which contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex. The MLL2 complex is highly active and specific for histone 3 lysine 4 (H3K4) methylation, which stimulates chromatin transcription in a SAM- and H3K4-dependent manner. Moreover, KMT2B 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. KMT2B contains a CxxC (x for any residue) zinc finger domain, three PHD fingers, this 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 27369858  51 HENCLLYSSGLVECEAPDLpntvrnfdvKSVKKEIGRGRRLKCSFCKNKGATMGYDLQSCTKNYHLSCAMEDHAILQVDE 130
Cdd:cd15694  28 HVNCAIWSAEVFEENDGSL---------KNVHAAVARGRQMRCEHCQKIGATVGCCLSACLSNFHFMCARASRCCFQDDK 98

                        90
                ....*....|..
gi 27369858 131 dhgtyKLFCQKH 142
Cdd:cd15694  99 -----KVFCQKH 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369858  28 CALCPEGHEWsqiyfspsanivAHENCLLYSSGLVECEAPDLPNtvrnfdvksVKKEIGRGRRLKCSFCKNKGATMGYDL 107
Cdd:cd15665   1 CALCNLGEVY------------AHHCCAAWSEGVCQTEDGALEN---------VDKAVAKALSQKCSFCLRYGASISCRM 59

                        90       100       110
                ....*....|....*....|....*....|....*
gi 27369858 108 QSCTKNYHLSCAMEDHAILQVDedhgTYKLFCQKH 142
Cdd:cd15665  60 PSCSKSFHFPCAAAAGCFQDIK----TLTLFCPEH 90

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 27369858  51 HENCLLYSSGLVECEAPDLPNtvrnfdvksVKKEIGRGRRLKCSFCKNKGATMGYDLQSCTKNYHLSCAME 121
Cdd:cd15697  28 HLNCALWSTEVYETQAGALIN---------VELALRRGLQMKCVFCHKTGATSGCHRLRCTNVYHFTCAIK 89

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27369858  28 CALCPEGHEWsqiyfspsanivAHENCLLYSSGLVECEAPDLPNtvrnfdvksVKKEIGRGRRLKCSFCKNKGATMGYDL 107
Cdd:cd15696   1 CAFCYCGECW------------AHLRCAEWSLGVCQGEEQLLVN---------VDKAVVSGSTERCAFCKHLGATIKCCE 59

                        90
                ....*....|..
gi 27369858 108 QSCTKNYHLSCA 119
Cdd:cd15696  60 EKCTQMYHYPCA 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 27369858  28 CALCPEGHEWsqiyfspsanivAHENCLLYSSGLVECEAPDLpntvrnfdvKSVKKEIGRGRRLKCSFCKNKGATMGYDL 107
Cdd:cd15695   1 CALCNCGECW------------VHHWCAAWSAGVKQHEGDGL---------IGVDKAVFSGISQKCEHCKRLGATIQCHA 59

                        90       100       110
                ....*....|....*....|....*....|....*
gi 27369858 108 QSCTKNYHLSCAMEDHAILQVDedhgTYKLFCQKH 142
Cdd:cd15695  60 EGCPRFYHFPCAAASGSFQSMK----TLLLLCPEH 90

Extended PHD finger found in protein Jade-1, Jade-2, Jade-3 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Jade-1 (PHF17), Jade-2 (PHF15), and Jade-3 (PHF16); each of these proteins 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, has reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. This family also contains Drosophila melanogaster PHD finger protein rhinoceros (RNO). It is a novel plant homeodomain (PHD)-containing nuclear protein that may function as a transcription factor that antagonizes Ras signaling by regulating transcription of key EGFR/Ras pathway regulators in the Drosophila eye. All Jade proteins contain a canonical PHD finger followed by this non-canonical ePHD finger, both of which are zinc-binding motifs.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 27369858  91 LKCSFCKNK-GATMGYDLQSCTKNYHLSCA----MEDHAILQVDEDHGTYKLFCQKH 142
Cdd:cd15671  56 LVCVLCKEKtGACIQCSVKSCKTAFHVTCAfqhgLEMKTILEDEDDEVKFKSYCPKH 112

Extended PHD finger found in protein Jade-2 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Jade-2. 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 PHD finger followed by this non-canonical ePHD finger, both of which are zinc-binding motifs.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 27369858  91 LKCSFCKN-KGATMGYDLQSCTKNYHLSCA----MEDHAILQvDEDHGTYKLFCQKH 142
Cdd:cd15705  56 LSCSLCKEcTGTCIQCSMPSCITAFHVTCAfdhgLEMRTTLA-DNDEVKFKSFCLEH 111