Extended PHD finger found in protein AF-10 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of AF-10. AF-10, also termed ALL1 (acute lymphoblastic leukaemia)-fused gene from chromosome 10 protein, is a transcription factor encoded by gene AF10, a translocation partner of the MLL (mixed-lineage leukaemia) oncogene in leukaemia. AF-10 has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. It plays a key role in the survival of uncommitted hematopoietic cells. Moreover, AF-10 functions as a follistatin-related gene (FLRG)-interacting protein. The interaction with FLRG enhances AF10-dependent transcription. It interacts with human counterpart of the yeast Dot1, hDOT1L, and may act as a bridge for the recruitment of hDOT1L to the genes targeted by MLL-AF10. It also interacts with the synovial sarcoma associated protein SYT protein and may play a role in synovial sarcomas and acute leukemias. AF-10 contains an N-terminal plant homeodomain (PHD) finger followed by this non-canonical ePHD finger.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290   78 ARVRCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIVLQSVPHDRYNKTCYICDEQGRESKAATGACMTC 157
Cdd:cd15708      1 ARVRCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIVLQSVPHERYNKTCYICDEQGRESKAATGACMTC 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1958718290  158 NKHGCRQAFHVTCAQFAGLLCEEEGNGADNVQYCGYCKYHFSKLKKSKR 206
Cdd:cd15708     81 NKHGCRQAFHVTCAQLAGLLCEEEGNGADNVQYCGYCKYHYSKLKKSKR 129

coiled coil domain of ALL1-Fused gene from chromosome 10 protein (AF10) and similar proteins; This family includes AF10 (ALL1-Fused gene from chromosome 10 protein) which is one of mixed-lineage leukemia 1 (MLL1)-fusion partners that function in acute myeloid leukemia (ALL). Aberration of the mixed-lineage leukemia (MLL) gene is implicated in acute leukemia; chromosomal translocations of MLL1 generate oncogenic chimeric proteins, containing the non-catalytic N-terminal portion of MLL1 fused with many partners such as AF10. The MLL-AF10 fusion oncoprotein recruits DOT1L (disruptor of telomeric-silencing 1-like) to the homeobox A. The aberrant recruitment of DOT1L, a histone methyltransferase that methylates H3 lysine residues (H3K79), by MLL fusions and the resulting H3K79 methylation are thought to affect gene expression by altering chromatin accessibility. AF10 and DOT1L interact through their coiled coil domains.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958718290  717 SIEQLLERQWSEGQQFLLEQGTPSDILGMLKSLHQLQVENRRLEEQIKNLTAKKERLQLLNAQL 780
Cdd:cd20901      1 SIEQLLERQWSQGQQFLLEQASQFDVASLLSCLHQLRSENRRLESSISNLQSRRDHLLALNARL 64

Extended PHD finger found in protein AF-10 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of AF-10. AF-10, also termed ALL1 (acute lymphoblastic leukaemia)-fused gene from chromosome 10 protein, is a transcription factor encoded by gene AF10, a translocation partner of the MLL (mixed-lineage leukaemia) oncogene in leukaemia. AF-10 has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. It plays a key role in the survival of uncommitted hematopoietic cells. Moreover, AF-10 functions as a follistatin-related gene (FLRG)-interacting protein. The interaction with FLRG enhances AF10-dependent transcription. It interacts with human counterpart of the yeast Dot1, hDOT1L, and may act as a bridge for the recruitment of hDOT1L to the genes targeted by MLL-AF10. It also interacts with the synovial sarcoma associated protein SYT protein and may play a role in synovial sarcomas and acute leukemias. AF-10 contains an N-terminal plant homeodomain (PHD) finger followed by this non-canonical ePHD finger.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290   78 ARVRCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIVLQSVPHDRYNKTCYICDEQGRESKAATGACMTC 157
Cdd:cd15708      1 ARVRCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIVLQSVPHERYNKTCYICDEQGRESKAATGACMTC 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1958718290  158 NKHGCRQAFHVTCAQFAGLLCEEEGNGADNVQYCGYCKYHFSKLKKSKR 206
Cdd:cd15708     81 NKHGCRQAFHVTCAQLAGLLCEEEGNGADNVQYCGYCKYHYSKLKKSKR 129

PHD zinc finger-containing protein [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290   20 EMIGGCCVCSDERGWAENPLVYCDGhgCSVAVHQACYGIVQVPTGPWFCRKCESQERAARVrCELCPHKDGALKRTDNGG 99
Cdd:COG5141    191 EFDDICTKCTSTHNENSNAIVFCDG--CEICVHQSCYGIQFLPEGFWLCRKCIYGEYQIRC-CSFCPSSDGAFKQTSDGR 267

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290  100 WAHVVCALYIPEVQFANVSTMEPI-VLQSVPHDRYNKTCYICDEQGreskaatGACMTCNKHGCRQAFHVTCAQFAGL-- 176
Cdd:COG5141    268 WGHVICAMFNPELSFGHLLSKDPIdNIASVSSSRWKLGCLICKEFG-------GTCIQCSYFNCTRAYHVTCARRAGYfd 340

                          170       180
                   ....*....|....*....|...
gi 1958718290  177 LCEEEGNG-ADNVQYCGYCKYHF 198
Cdd:COG5141    341 LNIYSHNGiSYCIDHEPLCRKHY 363

coiled coil domain of ALL1-Fused gene from chromosome 10 protein (AF10) and similar proteins; This family includes AF10 (ALL1-Fused gene from chromosome 10 protein) which is one of mixed-lineage leukemia 1 (MLL1)-fusion partners that function in acute myeloid leukemia (ALL). Aberration of the mixed-lineage leukemia (MLL) gene is implicated in acute leukemia; chromosomal translocations of MLL1 generate oncogenic chimeric proteins, containing the non-catalytic N-terminal portion of MLL1 fused with many partners such as AF10. The MLL-AF10 fusion oncoprotein recruits DOT1L (disruptor of telomeric-silencing 1-like) to the homeobox A. The aberrant recruitment of DOT1L, a histone methyltransferase that methylates H3 lysine residues (H3K79), by MLL fusions and the resulting H3K79 methylation are thought to affect gene expression by altering chromatin accessibility. AF10 and DOT1L interact through their coiled coil domains.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958718290  717 SIEQLLERQWSEGQQFLLEQGTPSDILGMLKSLHQLQVENRRLEEQIKNLTAKKERLQLLNAQL 780
Cdd:cd20901      1 SIEQLLERQWSQGQQFLLEQASQFDVASLLSCLHQLRSENRRLESSISNLQSRRDHLLALNARL 64

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        50
                    ....*....|....*....|....*....|....*....|....*....|
gi 1958718290    25 CCVCSDERGWAEnpLVYCDGhgCSVAVHQACYGI---VQVPTGPWFCRKC 71
Cdd:smart00249    2 CSVCGKPDDGGE--LLQCDG--CDRWYHQTCLGPpllEEEPDGKWYCPKC 47

Extended PHD finger found in protein AF-10 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of AF-10. AF-10, also termed ALL1 (acute lymphoblastic leukaemia)-fused gene from chromosome 10 protein, is a transcription factor encoded by gene AF10, a translocation partner of the MLL (mixed-lineage leukaemia) oncogene in leukaemia. AF-10 has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. It plays a key role in the survival of uncommitted hematopoietic cells. Moreover, AF-10 functions as a follistatin-related gene (FLRG)-interacting protein. The interaction with FLRG enhances AF10-dependent transcription. It interacts with human counterpart of the yeast Dot1, hDOT1L, and may act as a bridge for the recruitment of hDOT1L to the genes targeted by MLL-AF10. It also interacts with the synovial sarcoma associated protein SYT protein and may play a role in synovial sarcomas and acute leukemias. AF-10 contains an N-terminal plant homeodomain (PHD) finger followed by this non-canonical ePHD finger.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290   78 ARVRCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIVLQSVPHDRYNKTCYICDEQGRESKAATGACMTC 157
Cdd:cd15708      1 ARVRCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIVLQSVPHERYNKTCYICDEQGRESKAATGACMTC 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1958718290  158 NKHGCRQAFHVTCAQFAGLLCEEEGNGADNVQYCGYCKYHFSKLKKSKR 206
Cdd:cd15708     81 NKHGCRQAFHVTCAQLAGLLCEEEGNGADNVQYCGYCKYHYSKLKKSKR 129

Extended PHD finger found in protein AF-17 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of AF-17. AF-17, also termed ALL1-fused gene from chromosome 17 protein, is encoded by gene AF17 that has been identified in hematological malignancies as a translocation partner of the mixed lineage leukemia gene MLL. It is a putative transcription factor that may play a role in multiple signaling pathways. It is involved in chromatin-mediated gene regulation mechanisms. It functions as a component of the multi-subunit Dot1 complex (Dotcom) and plays a role in the Wnt/Wingless signaling pathway. It also seems to be a downstream target of the beta-catenin/T-cell factor pathway, and participates in G2-M progression. Moreover, it may function as an important regulator of ENaC-mediated Na+ transport and thus blood pressure. AF-17 contains an N-terminal plant homeodomain (PHD) finger followed by a non-canonical ePHD finger.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290   78 ARVRCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIVLQSVPHDRYNKTCYICDEQGRESKAATGACMTC 157
Cdd:cd15709      1 ARVRCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPIVLQYVPHDRFNKTCYICEEQGRESKAASGACMTC 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1958718290  158 NKHGCRQAFHVTCAQFAGLLCEEEGNGADNVQYCGYCKYHFSKLK 202
Cdd:cd15709     81 NRHGCRQAFHVTCAQMAGLLCEEEVLEVDNVKYCGYCKYHFNKMK 125

PHD zinc finger-containing protein [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290   20 EMIGGCCVCSDERGWAENPLVYCDGhgCSVAVHQACYGIVQVPTGPWFCRKCESQERAARVrCELCPHKDGALKRTDNGG 99
Cdd:COG5141    191 EFDDICTKCTSTHNENSNAIVFCDG--CEICVHQSCYGIQFLPEGFWLCRKCIYGEYQIRC-CSFCPSSDGAFKQTSDGR 267

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290  100 WAHVVCALYIPEVQFANVSTMEPI-VLQSVPHDRYNKTCYICDEQGreskaatGACMTCNKHGCRQAFHVTCAQFAGL-- 176
Cdd:COG5141    268 WGHVICAMFNPELSFGHLLSKDPIdNIASVSSSRWKLGCLICKEFG-------GTCIQCSYFNCTRAYHVTCARRAGYfd 340

                          170       180
                   ....*....|....*....|...
gi 1958718290  177 LCEEEGNG-ADNVQYCGYCKYHF 198
Cdd:COG5141    341 LNIYSHNGiSYCIDHEPLCRKHY 363

Extended PHD finger found in BRPF proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the ePHD finger of the family of BRPF proteins, which includes BRPF1, BRD1/BRPF2, and BRPF3. These are scaffold proteins that form monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complexes with other regulatory subunits, such as inhibitor of growth 5 (ING5) and Esa1-associated factor 6 ortholog (EAF6). BRPF proteins have multiple domains, including a plant homeodomain (PHD) zinc finger followed by a non-canonical ePHD finger, a bromodomain and a proline-tryptophan-tryptophan-proline (PWWP) domain. This PHD finger binds to lysine 4 of histone H3 (K4H3), the bromodomain interacts with acetylated lysines on N-terminal tails of histones and other proteins, and the PWWP domain shows histone-binding and chromatin association properties.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290   82 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIV-LQSVPHDRYNKTCYICdeqgresKAATGACMTCNKH 160
Cdd:cd15670      1 CVLCPNKGGAFKQTDDGRWAHVVCALWIPEVSFANTVFLEPIDgIQNIPKARWKLTCYIC-------KKRMGACIQCHKK 73

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1958718290  161 GCRQAFHVTCAQFAGLL-----CEEEGNGADN-VQYCGYCKYH 197
Cdd:cd15670     74 NCYTAFHVTCAQQAGLYmkiepVKDPGNGTSDsVRKEAYCDKH 116

PHD finger found in protein AF-10 and AF-17; This family includes protein AF-10 and AF-17. AF-10, also termed ALL1 (acute lymphoblastic leukemia)-fused gene from chromosome 10 protein, is a transcription factor encoded by gene AF10, a translocation partner of the MLL (mixed-lineage leukemia) oncogene in leukemia. AF-10 has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. It plays a key role in the survival of uncommitted hematopoietic cells. Moreover, AF-10 functions as a follistatin-related gene (FLRG)-interacting protein. The interaction with FLRG enhances AF10-dependent transcription. It interacts with the human counterpart of the yeast Dot1, hDOT1L, and may act as a bridge for the recruitment of hDOT1L to the genes targeted by MLL-AF10. It also interacts with the synovial sarcoma associated SYT protein and may play a role in synovial sarcomas and acute leukemias. AF-17, also termed ALL1-fused gene from chromosome 17 protein, is encoded by gene AF17 that has been identified in hematological malignancies as translocation partners of the mixed lineage leukemia gene MLL. It is a putative transcription factor that may play a role in multiple signaling pathways. It is involved in chromatin-mediated gene regulation mechanisms. It functions as a component of the multi-subunit Dot1 complex (Dotcom) and plays a role in the Wnt/Wingless signaling pathway. It also seems to be a downstream target of the beta-catenin/T-cell factor pathway, and participates in G2-M progression. Moreover, it may function as an important regulator of ENaC-mediated Na+ transport and thus blood pressure. Both AF-10 and AF-17 contain an N-terminal canonical Cys4HisCys3 plant homeodomain (PHD) finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His. The PHD finger is involved in their homo-oligomerization. In the C-terminal region, they possess a leucine zipper domain and a glutamine-rich region. This family also includes ZFP-1, the Caenorhabditis elegans AF10 homolog. It was originally identified as a factor promoting RNAi interference in C. elegans. It also acts as a Dot1-interacting protein that opposes H2B ubiquitination to reduce polymerase II (Pol II) transcription. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1958718290   24 GCCVCSDERGWAENPLVYCDGHGCSVAVHQACYGIVQVPTGPWFCRKC 71
Cdd:cd15574      1 GCCVCSDERGWAENPLVYCDGHGCNVAVHQACYGIVQVPTGPWFCRKC 48

Extended PHD finger found in bromodomain and PHD finger-containing protein 3 (BRPF3) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of BRPF3. BRF3 is a homolog of BRPF1 and BRPF2. It is a scaffold protein that forms a novel monocytic leukemic zinc finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complex with other regulatory subunits. BRPF3 contains a plant homeodomain (PHD) finger followed by this non-canonical ePHD finger, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290   82 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIV-LQSVPHDRYNKTCYICDEQGReskaatGACMTCNKH 160
Cdd:cd15703      1 CVLCPNKGGAFKQTSDGRWAHVVCAIWIPEVCFANTVFLEPVEgVNNIPPARWKLTCYLCKQKGR------GAAIQCHKV 74

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1958718290  161 GCRQAFHVTCAQFAGLLC------EEEGNGAD-NVQYCGYCKYH 197
Cdd:cd15703     75 NCYTAFHVTCAQRAGLFMkiepvrETGLNGTTfTVRKTAYCENH 118

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        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290   82 CELCPHKDGALKRTDNG-GWAHVVCALYIPEVQFANVSTMEPIV-LQSVPHDRYNKTCYICDEQgreskaaTGACMTCNK 159
Cdd:cd15671      1 CVLCPKKGGAMKSTKSGtKWVHVSCALWIPEVSIGCPEKMEPITkISHIPMSRWALVCVLCKEK-------TGACIQCSV 73

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1958718290  160 HGCRQAFHVTCAQFAGL-LCEEEGNGADNVQYCGYCKYH 197
Cdd:cd15671     74 KSCKTAFHVTCAFQHGLeMKTILEDEDDEVKFKSYCPKH 112

coiled coil domain of ALL1-Fused gene from chromosome 10 protein (AF10) and similar proteins; This family includes AF10 (ALL1-Fused gene from chromosome 10 protein) which is one of mixed-lineage leukemia 1 (MLL1)-fusion partners that function in acute myeloid leukemia (ALL). Aberration of the mixed-lineage leukemia (MLL) gene is implicated in acute leukemia; chromosomal translocations of MLL1 generate oncogenic chimeric proteins, containing the non-catalytic N-terminal portion of MLL1 fused with many partners such as AF10. The MLL-AF10 fusion oncoprotein recruits DOT1L (disruptor of telomeric-silencing 1-like) to the homeobox A. The aberrant recruitment of DOT1L, a histone methyltransferase that methylates H3 lysine residues (H3K79), by MLL fusions and the resulting H3K79 methylation are thought to affect gene expression by altering chromatin accessibility. AF10 and DOT1L interact through their coiled coil domains.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958718290  717 SIEQLLERQWSEGQQFLLEQGTPSDILGMLKSLHQLQVENRRLEEQIKNLTAKKERLQLLNAQL 780
Cdd:cd20901      1 SIEQLLERQWSQGQQFLLEQASQFDVASLLSCLHQLRSENRRLESSISNLQSRRDHLLALNARL 64

Extended PHD finger found in Drosophila melanogaster PHD finger protein rhinoceros (RNO) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Drosophila melanogaster RNO. RNO is a novel plant homeodomain (PHD)-containing nuclear protein that may function as a transcription factor that antagonizes Ras signaling by regulating the transcription of key EGFR/Ras pathway regulators in the Drosophila eye. RNO contains a canonical PHD domain followed by this non-canonical ePHD domain, both of which are zinc-binding motifs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290   82 CELCPHKDGALKRTDNGG-WAHVVCALYIPEVQFANVSTMEPIV-LQSVPHDRYNKTCYICDEQgreskaaTGACMTCNK 159
Cdd:cd15707      1 CILCPNKGGAMKSTRSGTkWAHVSCALWIPEVSIGCVEKMEPITkISSIPASRWALICVLCRER-------TGACIQCSV 73

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1958718290  160 HGCRQAFHVTCAQFAGLLCEE--EGNGADNVQYCGYCKYH 197
Cdd:cd15707     74 KTCKTAYHVTCGFQHGLEMKTilDEESEDGVKLRSYCQKH 113

Extended PHD finger found in Arabidopsis thaliana ATX1, -2, and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This subfamily includes the ePHD finger of A. thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like proteins ATX1, -2, and similar proteins. ATX1 and -2 are sister paralogs originating from a segmental chromosomal duplication; they are plant counterparts of the Drosophila melanogaster trithorax (TRX) and mammalian mixed-lineage leukemia (MLL1) proteins. ATX1 (also known as protein SET domain group 27, or trithorax-homolog protein 1/TRX-homolog protein 1), is a methyltransferase that trimethylates histone H3 at lysine 4 (H3K4me3). It also acts as a histone modifier and as a positive effector of gene expression. ATX1 regulates transcription from diverse classes of genes implicated in biotic and abiotic stress responses. It is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways. ATX2 (also known as protein SET domain group 30, or trithorax-homolog protein 2/TRX-homolog protein 2), is involved in dimethylating histone H3 at lysine 4 (H3K4me2). ATX1 and ATX2 are multi-domain proteins that consist of an N-terminal PWWP domain, FYRN- and FYRC (DAST, domain associated with SET in trithorax) domains, a canonical PHD finger, this non-canonical ePHD finger, and a C-terminal SET domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290   82 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPI-VLQSVPHDRYNKTCYICdeqgresKAATGACMTCNKH 160
Cdd:cd15662      1 CCLCPVVGGALKPTTDGRWAHLACAIWIPETCLLDVKTMEPVdGINAISKERWELSCTIC-------KQRYGACIQCSNN 73

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1958718290  161 GCRQAFHVTCAQFAGLLCE-----EEGNGADNVQYCGYCKYH 197
Cdd:cd15662     74 SCRVAYHPLCARAAGLCMEvadegGEDPGDQGLRLLSYCPRH 115

Extended PHD finger found in protein Jade-3 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Jade-3. Jade-3, also termed PHD finger protein 16 (PHF16), is a plant homeodomain (PHD) zinc finger protein that is close related to Jade-1, which functions as an essential regulator of multiple cell signaling pathways. Like Jade-1, Jade-3 is required for ING4 and ING5 to associate with histone acetyl transferase (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-3 contains a canonical PHD domain followed by this non-canonical ePHD domain, both of which are zinc-binding motifs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290   82 CELCPHKDGALKRTDNG-GWAHVVCALYIPEVQFANVSTMEPIV-LQSVPHDRYNKTCYICdeqgresKAATGACMTCNK 159
Cdd:cd15706      1 CLLCPKTGGAMKATRTGtKWAHVSCALWIPEVSIACPERMEPITkVSHIPPSRWALVCSLC-------KLKTGACIQCSV 73

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1958718290  160 HGCRQAFHVTCAQFAGLLCEEEGNGADNVQYCGYCKYH 197
Cdd:cd15706     74 KSCITAFHVTCAFEHSLEMKTILDEGDEVKFKSYCLKH 111

Extended PHD finger found in Jumonji domain-containing protein 2B (JMJD2B); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of JMJD2B. JMJD2B, also termed lysine-specific demethylase 4B (KDM4B), or JmjC domain-containing histone demethylation protein 3B (JHDM3B), specifically antagonizes the trimethyl group from H3K9 in pericentric heterochromatin and reduces H3K36 methylation in mammalian cells. It plays an essential role in the growth regulation of cancer cells by modulating the G1-S transition and promotes cell-cycle progression through the regulation of cyclin-dependent kinase 6 (CDK6). It interacts with heat shock protein 90 (Hsp90) and its stability can be regulated by Hsp90. JMJD2B also functions as a direct transcriptional target of p53, which induces its expression through promoter binding. Moreover, JMJD2B expression can be controlled by hypoxia-inducible factor 1alpha (HIF1alpha) in colorectal cancer and estrogen receptor alpha (ERalpha) in breast cancer. It is also involved in bladder, lung, and gastric cancer. JMJD2B contains jmjN and jmjC domains in the N-terminal region, followed by a canonical PHD finger, this non-canonical ePHD finger, and a Tudor domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290   82 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIVLQSVPHDRYNKTCYICDeqgRESKAATGACMTCNKHG 161
Cdd:cd15714      1 CCLCNLRGGALQMTTDERWVHVICAIAVPEARFLNVIERHPVDVSAIPEQRWKLKCVYCR---KRMKKVSGACIQCSYDH 77

                           90
                   ....*....|....*...
gi 1958718290  162 CRQAFHVTCAQFAGLLCE 179
Cdd:cd15714     78 CSTSFHVTCAHAAGVVME 95

Extended PHD finger found in protein Jade-1 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Jade-1. 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 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 ASA 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 plant homeodomain (PHD) finger followed by this non-canonical ePHD finger, both of which are zinc-binding motifs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290   81 RCELCPHKDGALKRTDNG-GWAHVVCALYIPEVQFANVSTMEPIV-LQSVPHDRYNKTCYICDEQgreskaaTGACMTCN 158
Cdd:cd15704      3 KCLLCPKKGGAMKPTRSGtKWVHVSCALWIPEVSIGSPEKMEPITkVSHIPSSRWALVCSLCNEK-------VGASIQCS 75

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1958718290  159 KHGCRQAFHVTCAQFAGLLCEEEGNGADNVQYCGYCKYHFS 199
Cdd:cd15704     76 VKNCRTAFHVTCAFDRGLEMKTILAENDEVKFKSYCPKHSS 116

Extended PHD finger found in Saccharomyces cerevisiae SANT domain-containing protein 2 (Snt2p) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Snt2p. Sntp2 is a yeast protein that may function in multiple stress pathways. It coordinates the transcriptional response to hydrogen peroxide-mediated oxidative stress through interaction with Ecm5 and the Rpd3 deacetylase. Snt2p contains a bromo adjacent homology (BAH) domain, two canonical PHD fingers, a non-canonical ePHD finger, and a SANT (SWI3, ADA2, N-CoR and TFIIIB) DNA-binding domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958718290   82 CELCPHKDG---------------ALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIVL-QSVPHDRYNKTCYICDEQGr 145
Cdd:cd15667      1 CSLCNAKESnyelakkqsprtrpdALKCTSNGTWCHVLCALFNEDIKFGNSKSLQPILNtESVLLKGSRQKCEICKVSG- 79

                           90       100
                   ....*....|....*....|....*..
gi 1958718290  146 eskaatGACMTCNKhgCRQAFHVTCAQ 172
Cdd:cd15667     80 ------GGLVKCEV--CDDRFHVSCAQ 98

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 1958718290   25 CCVCSDERGWAENPLVYCDGhgCSVAVHQACYGIVQVPTGPWFCRKC 71
Cdd:cd15680      2 CDVCRSPEGEDGNEMVFCDK--CNVCVHQACYGILKVPTGSWLCRTC 46

PHD finger found in bromodomain and PHD finger-containing (BRPF) proteins; The family of BRPF proteins includes BRPF1, BRD1/BRPF2, and BRPF3. They are scaffold proteins that form monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complexes with other regulatory subunits, such as inhibitor of growth 5 (ING5) and Esa1-associated factor 6 ortholog (EAF6). BRPF proteins have multiple domains, including a canonical Cys4HisCys3 plant homeodomain (PHD) zinc finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, a bromodomain and a proline-tryptophan-tryptophan-proline (PWWP) domain. PHD and ePHD fingers both bind to lysine 4 of histone H3 (K4H3), bromodomains interact with acetylated lysines on N-terminal tails of histones and other proteins, and PWWP domains show histone-binding and chromatin association properties. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1958718290   25 CCVCSDERGWAENPLVYCDGhgCSVAVHQACYGIVQVPTGPWFCRKC 71
Cdd:cd15572      4 CCICLDGECQNSNVILFCDM--CNLAVHQECYGVPYIPEGQWLCRRC 48

PHD finger found in bromodomain and PHD finger-containing protein 2 (BRPF2) and similar proteins; BRPF2, also termed bromodomain-containing protein 1 (BRD1), or BR140-like protein, is encoded by BRL (BR140 Like gene). It is responsible for the bulk of the acetylation of H3K14 and forms a novel monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complex with HBO1 and ING4. The complex is required for full transcriptional activation of the erythroid-specific regulator genes essential for terminal differentiation and survival of erythroblasts in fetal liver. BRPF2 shows widespread expression and localizes to the nucleus within spermatocytes. It contains a cysteine rich region harboring a canonical Cys4HisCys3 plant homeodomain (PHD) finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1958718290   25 CCVCSDERGWAENPLVYCDGhgCSVAVHQACYGIVQVPTGPWFCRKC 71
Cdd:cd15677      4 CCICMDGECQNSNVILFCDM--CNLAVHQECYGVPYIPEGQWLCRHC 48

PHD-finger; PHD folds into an interleaved type of Zn-finger chelating 2 Zn ions in a similar manner to that of the RING and FYVE domains. Several PHD fingers have been identified as binding modules of methylated histone H3.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1958718290   25 CCVCSdeRGWAENPLVYCDGhgCSVAVHQACYGI----VQVPTGPWFCRKC 71
Cdd:pfam00628    2 CAVCG--KSDDGGELVQCDG--CDDWFHLACLGPpldpAEIPSGEWLCPEC 48

PHD finger found in bromodomain and PHD finger-containing protein 3 (BRPF3) and similar proteins; BRPF3 is a homolog of BRPF1 and BRPF2. It is a scaffold protein that forms a novel monocytic leukemic zinc finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complex with other regulatory subunits. BRPF3 contains a canonical Cys4HisCys3 plant homeodomain (PHD) finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1958718290   25 CCVCSDERGWAENPLVYCDGhgCSVAVHQACYGIVQVPTGPWFCRKC 71
Cdd:cd15678      4 CCVCLDDECHNSNVILFCDI--CNLAVHQECYGVPYIPEGQWLCRCC 48

PHD finger 1 found in PHD finger protein 14 (PHF14) and similar proteins; PHF14 is a novel nuclear transcription factor that controls the proliferation of mesenchymal cells by directly repressing platelet-derived growth factor receptor-alpha (PDGFRalpha) expression. It also acts as an epigenetic regulator and plays an important role in the development of multiple organs in mammals. PHF14 contains three canonical plant homeodomain (PHD) fingers and a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His. It can interact with histones through its PHD fingers. The model corresponds to the first PHD finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958718290   25 CCVCSDERGWAENPLVYCDghGCSVAVHQACYGIVQVP----------TGPWFCRKC 71
Cdd:cd15561      2 CCVCLGDRSNDADEIIECD--KCGISVHEGCYGVIDESdssssassssTEPWFCEPC 56

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
                   ....*....|....*....|....*....|....*....|....*....|
gi 1958718290   25 CCVCSDERGWaENPLVYCDGhgCSVAVHQACYGI---VQVPTGPWFCRKC 71
Cdd:cd15489      2 CIVCGKGGDL-GGELLQCDG--CGKWFHADCLGPplsSFVPNGKWICPVC 48

PHD finger 1 found in polycomb repressive complex 2 (PRC2)-associated polycomb-like (PCL) family proteins MTF2, PHF19, and similar proteins; The family includes two PCL family proteins, metal-response element-binding transcription factor 2 (MTF2/PCL2) and PHF19/PCL3, which are homologs of PHD finger protein1 (PHF1). PCL family proteins are accessory components of the polycomb repressive complex 2 (PRC2) core complex and all contain an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain. They specifically recognize tri-methylated H3K36 (H3K36me3) through their N-terminal Tudor domains. The interaction between their Tudor domains and H3K36me3 is critical for both the targeting and spreading of PRC2 into active chromatin regions and for the maintenance of optimal repression of poised developmental genes where PCL proteins, H3K36me3, and H3K27me3 coexist. Moreover, unlike other PHD finger-containing proteins, the first PHD fingers of PCL proteins do not display histone H3K4 binding affinity and they do not affect the Tudor domain binding to histones. This model corresponds to the first PHD finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1958718290   25 CCVCSDERGWAENPLVYCDGhgCSVAVHQACY-----GIVQVPTGPWFCRKCE 72
Cdd:cd15499      2 CSICGGAEARDGNEILICDK--CDKGYHQLCHspkvrTSPLEGDEKWFCSRCV 52

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 1958718290   25 CCVCSDErgwaeNPLVYCDGHGCSVAVHQACYGIVQVPTGPWFCR 69
Cdd:cd15568      2 CFRCGDG-----GDLVLCDFKGCPKVYHLSCLGLEKPPGGKWICP 41

PHD finger found in Arabidopsis thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like protein ATX1, ATX2, and similar proteins; The family includes A. thaliana ATX1 and ATX2, both of which are sister paralogs originating from a segmental chromosomal duplication. They are plant counterparts of the Drosophila melanogaster trithorax (TRX) and mammalian mixed-lineage leukemia (MLL1) proteins. ATX1, also termed protein SET domain group 27, or trithorax-homolog protein 1 (TRX-homolog protein 1), is a methyltransferase that trimethylates histone H3 at lysine 4 (H3K4me3). It also acts as a histone modifier and as a positive effector of gene expression. ATX1regulates transcription from diverse classes of genes implicated in biotic and abiotic stress responses. It is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways. ATX2, also termed protein SET domain group 30, or trithorax-homolog protein 2 (TRX-homolog protein 2), is involved in dimethylating histone H3 at lysine 4 (H3K4me2). Both ATX1 and ATX2 are multi-domain containing proteins that consist of an N-terminal PWWP domain, FYRN- and FYRC (DAST, domain associated with SET in trithorax) domains, a canonical Cys4HisCys3 plant homeodomain (PHD) finger, a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, and a C-terminal SET domain; this model corresponds to the Cys4HisCys3 canonical PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1958718290   25 CCVCSDERGWAENPLVYCDGhgCSVAVHQACYGIVQVPTGP-WFCRKC 71
Cdd:cd15494      2 CSVCGEDEEYEDNLLLQCDK--CRMMVHMRCYGVLEPPPGAlWLCNLC 47

PHD finger found in inhibitor of growth protein 3 (ING3) and similar proteins; ING3, also termed p47ING3, is one member of the inhibitor of growth (ING) family of type II tumor suppressors. It is ubiquitously expressed and has been implicated in transcription modulation, cell cycle control, and the induction of apoptosis. It is an important subunit of human NuA4 histone acetyltransferase complex, which regulates the acetylation of histones H2A and H4. Moreover, ING3 promotes ultraviolet (UV)-induced apoptosis through the Fas/caspase-8-dependent pathway in melanoma cells. It physically interacts with subunits of E3 ligase Skp1-Cullin-F-boxprotein complex (SCF complex) and is degraded by the SCF (F-box protein S-phase kinase-associated protein 2, Skp2)-mediated ubiquitin-proteasome system. It also acts as a suppression factor during tumorigenesis and progression of hepatocellular carcinoma (HCC). ING3 contains an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1958718290   26 CVCsDERGWAEnpLVYCDGHGCSVA-VHQACYGIVQVPTGPWFCRKC 71
Cdd:cd15585      2 CIC-NQVSYGE--MVGCDNDDCPIEwFHYGCVGLTEAPKGKWYCPQC 45

PHD finger found in Jumonji domain-containing protein 2 (JMJD2) family of histone demethylases; JMJD2 proteins, also termed lysine-specific demethylase 4 histone demethylases (KDM4), have been implicated in various cellular processes including DNA damage response, transcription, cell cycle regulation, cellular differentiation, senescence, and carcinogenesis. They selectively catalyze the demethylation of di- and trimethylated H3K9 and H3K36. This model contains only three JMJD2 proteins, JMJD2A-C, which all contain jmjN and jmjC domains in the N-terminal region, followed by a Cys4HisCys3 canonical PHD finger, a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, and a Tudor domain. JMJD2D is not included in this family, since it lacks both PHD and Tudor domains and has a different substrate specificity. JMJD2A-C are required for efficient cancer cell growth. This model corresponds to the Cys4HisCys3 canonical PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1958718290   25 CCVCSDERgwaenpLVYCDGhgCSVAVHQACYGIVQVP--TGPWFCRKC 71
Cdd:cd15493      2 CAICSLFR------LLVCSR--CCVCVHASCYGVPDIPgdGEGWKCDRC 42

PHD finger found in the inhibitor of growth (ING) protein family; The ING family includes a group of tumor suppressors, ING1-5, which act as readers and writers of the histone epigenetic code, affecting DNA damage response, chromatin remodeling, cellular senescence, differentiation, cell cycle regulation and apoptosis. They may have a general role in mediating the cellular response to genotoxic stress through binding to and regulating the activities of histone acetyltransferase (HAT) and histone deacetylase (HDAC) chromatin remodeling complexes. All ING proteins contain an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1958718290   26 CVCsdeRGWAENPLVYCDGHGCSVA-VHQACYGIVQVPTGPWFCRKC 71
Cdd:cd15505      2 CIC---NQVSYGEMVACDNPNCPIEwFHFECVGLTAKPKGKWYCPEC 45

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 1958718290   25 CCVCSdERGWAENpLVYCDGhgCSVAVHQACY--GIVQVPTGPWFCRKC 71
Cdd:cd15544      2 CKVCR-KKGDPDN-MILCDG--CDKAFHLYCLrpALREVPSGDWFCPAC 46

PHD finger 1 found in Schizosaccharomyces pombe Lid2 complex component Lid2p and similar proteins; Lid2p is a trimethyl H3K4 (H3K4me3) demethylase responsible for H3K4 hypomethylation in heterochromatin. It interacts with the histone lysine-9 methyltransferase, Clr4, through the Dos1/Clr8-Rik1 complex, and mediates H3K9 methylation and small RNA production. It also acts cooperatively with the histone modification enzymes Set1 and Lsd1 and plays an essential role in cross-talk between H3K4 and H3K9 methylation in euchromatin. Lid2p contains a JmjC domain, three PHD fingers and a JmjN domain. This model corresponds to the first PHD finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1958718290   24 GCCVCSdeRGWAENPLVYCDGhgCSVAVHQACYG--IVQVPTGPWFCRKC 71
Cdd:cd15519      1 GCEVCG--LDDNEGEVLLCDG--CDAEYHTSCLDppLGEIPPGTWFCPSC 46

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        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1958718290   26 CVCSdERGWAEnpLVYCDGHGCSVA-VHQACYGIVQVPTGPWFCRKC 71
Cdd:cd15586      2 CLCH-QVSYGE--MIGCDNPDCPIEwFHFACVGLTTKPKGKWFCPRC 45

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        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1958718290   24 GCCVCsdERGWAENPLVYCDGhgCSVAVHQACY--GIVQVPTGPWFCRKC 71
Cdd:cd15515      1 ICQVC--GRGDDEDKLLLCDG--CDDSYHTFCLipPLPDIPPGDWRCPKC 46