Extended PHD finger found in protein AF-10 and AF-17; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of AF-10 and AF-17. 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 the human counterpart of 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-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 plant homeodomain (PHD) finger followed by this non-canonical ePHD finger. 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 Dot1-interacting protein that opposes H2B ubiquitination to reduce polymerase II (Pol II) transcription.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617807  118 CELCPSRDGALKKTDNSGWAHVVCALYIPEVRFGNVTTMEPIILSLIPQERYSKTCYICQEIGKPNRANVGACMQCNKSN 197
Cdd:cd15672     1 CELCPHKDGALKRTDNGGWAHVVCALYIPEVRFGNVATMEPIILQDVPQDRFNKTCYICEEQGRESKASTGACMQCNKSG 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 442617807  198 CKQQFHVTCAQSLGLLCEEAGNYLDNVKYCGYCQHH 233
Cdd:cd15672    81 CKQSFHVTCAQMAGLLCEEAGNYSDNVKYCGYCSYH 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 442617807   60 GCCVCSDERGWPENPLVYCDGQNCTVAVHQACYGIVTVPTGPWYCRKC 107
Cdd:cd15574     1 GCCVCSDERGWAENPLVYCDGHGCNVAVHQACYGIVQVPTGPWFCRKC 48

Extended PHD finger found in protein AF-10 and AF-17; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of AF-10 and AF-17. 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 the human counterpart of 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-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 plant homeodomain (PHD) finger followed by this non-canonical ePHD finger. 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 Dot1-interacting protein that opposes H2B ubiquitination to reduce polymerase II (Pol II) transcription.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617807  118 CELCPSRDGALKKTDNSGWAHVVCALYIPEVRFGNVTTMEPIILSLIPQERYSKTCYICQEIGKPNRANVGACMQCNKSN 197
Cdd:cd15672     1 CELCPHKDGALKRTDNGGWAHVVCALYIPEVRFGNVATMEPIILQDVPQDRFNKTCYICEEQGRESKASTGACMQCNKSG 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 442617807  198 CKQQFHVTCAQSLGLLCEEAGNYLDNVKYCGYCQHH 233
Cdd:cd15672    81 CKQSFHVTCAQMAGLLCEEAGNYSDNVKYCGYCSYH 116

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617807   56 EMVGGCCVCSDERGWPENPLVYCDGqnCTVAVHQACYGIVTVPTGPWYCRKCESQERTSRVrCELCPSRDGALKKTDNSG 135
Cdd:COG5141   191 EFDDICTKCTSTHNENSNAIVFCDG--CEICVHQSCYGIQFLPEGFWLCRKCIYGEYQIRC-CSFCPSSDGAFKQTSDGR 267

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617807  136 WAHVVCALYIPEVRFGNVTTMEPI-ILSLIPQERYSKTCYICQEIGkpnranvGACMQCNKSNCKQQFHVTCAQSLGL-- 212
Cdd:COG5141   268 WGHVICAMFNPELSFGHLLSKDPIdNIASVSSSRWKLGCLICKEFG-------GTCIQCSYFNCTRAYHVTCARRAGYfd 340

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 442617807  213 LCEEAGN-YLDNVKYCGYCQHHYSKLKKGGNVKTIPPYK 250
Cdd:COG5141   341 LNIYSHNgISYCIDHEPLCRKHYPLGYGRMNGLRYFGYE 379

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 442617807   60 GCCVCSDERGWPENPLVYCDGQNCTVAVHQACYGIVTVPTGPWYCRKC 107
Cdd:cd15574     1 GCCVCSDERGWAENPLVYCDGHGCNVAVHQACYGIVQVPTGPWFCRKC 48

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 442617807     61 CCVCSDERGWpeNPLVYCDGqnCTVAVHQACYGI---VTVPTGPWYCRKC 107
Cdd:smart00249    2 CSVCGKPDDG--GELLQCDG--CDRWYHQTCLGPpllEEEPDGKWYCPKC 47

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

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 442617807   74 PLVYCDGQNCTVA-VHQACYGIVTVPTGPWYCRKCESQ 110
Cdd:COG5034   233 QMVACDNANCKREwFHLECVGLKEPPKGKWYCPECKKA 270

Extended PHD finger found in protein AF-10 and AF-17; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of AF-10 and AF-17. 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 the human counterpart of 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-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 plant homeodomain (PHD) finger followed by this non-canonical ePHD finger. 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 Dot1-interacting protein that opposes H2B ubiquitination to reduce polymerase II (Pol II) transcription.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617807  118 CELCPSRDGALKKTDNSGWAHVVCALYIPEVRFGNVTTMEPIILSLIPQERYSKTCYICQEIGKPNRANVGACMQCNKSN 197
Cdd:cd15672     1 CELCPHKDGALKRTDNGGWAHVVCALYIPEVRFGNVATMEPIILQDVPQDRFNKTCYICEEQGRESKASTGACMQCNKSG 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 442617807  198 CKQQFHVTCAQSLGLLCEEAGNYLDNVKYCGYCQHH 233
Cdd:cd15672    81 CKQSFHVTCAQMAGLLCEEAGNYSDNVKYCGYCSYH 116

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 442617807  114 SRVRCELCPSRDGALKKTDNSGWAHVVCALYIPEVRFGNVTTMEPIILSLIPQERYSKTCYICQEIGKPNRANVGACMQC 193
Cdd:cd15709     1 ARVRCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPIVLQYVPHDRFNKTCYICEEQGRESKAASGACMTC 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 442617807  194 NKSNCKQQFHVTCAQSLGLLCEEAGNYLDNVKYCGYCQHHYSKLK 238
Cdd:cd15709    81 NRHGCRQAFHVTCAQMAGLLCEEEVLEVDNVKYCGYCKYHFNKMK 125

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617807   56 EMVGGCCVCSDERGWPENPLVYCDGqnCTVAVHQACYGIVTVPTGPWYCRKCESQERTSRVrCELCPSRDGALKKTDNSG 135
Cdd:COG5141   191 EFDDICTKCTSTHNENSNAIVFCDG--CEICVHQSCYGIQFLPEGFWLCRKCIYGEYQIRC-CSFCPSSDGAFKQTSDGR 267

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617807  136 WAHVVCALYIPEVRFGNVTTMEPI-ILSLIPQERYSKTCYICQEIGkpnranvGACMQCNKSNCKQQFHVTCAQSLGL-- 212
Cdd:COG5141   268 WGHVICAMFNPELSFGHLLSKDPIdNIASVSSSRWKLGCLICKEFG-------GTCIQCSYFNCTRAYHVTCARRAGYfd 340

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 442617807  213 LCEEAGN-YLDNVKYCGYCQHHYSKLKKGGNVKTIPPYK 250
Cdd:COG5141   341 LNIYSHNgISYCIDHEPLCRKHYPLGYGRMNGLRYFGYE 379

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 442617807  118 CELCPSRDGALKKTDNSGWAHVVCALYIPEVRFGNVTTMEPII-LSLIPQERYSKTCYICQEIGkpnranvGACMQCNKS 196
Cdd:cd15670     1 CVLCPNKGGAFKQTDDGRWAHVVCALWIPEVSFANTVFLEPIDgIQNIPKARWKLTCYICKKRM-------GACIQCHKK 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 442617807  197 NCKQQFHVTCAQSLGLL-----CEEAGNYLDN-VKYCGYCQHH 233
Cdd:cd15670    74 NCYTAFHVTCAQQAGLYmkiepVKDPGNGTSDsVRKEAYCDKH 116

Extended plant homeodomain (PHD) finger, characterized by Cys2HisCys5HisCys2His; PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. The extended PHD finger is characterized as Cys2HisCys5HisCys2His, which has 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617807  118 CELCPSRDGALKK------TDNSGWAHVVCALYIPEVRFGNVTTMEPIILSLIPQERYSKTCYICQEigkpnraNVGACM 191
Cdd:cd15571     1 CALCPRSGGALKGggalktTSDGLWVHVVCALWSPEVYFDDGTLLEVEGVSKIPKRRKKLKCSICGK-------RGGACI 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 442617807  192 QCNKSNCKQQFHVTCAQSLGLLCEEAGnylDNVKYCGYCQHH 233
Cdd:cd15571    74 QCSYPGCPRSFHVSCAIRAGCLFEFED---GPGNFVVYCPKH 112

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 442617807  118 CELCPSRDGALKKT-DNSGWAHVVCALYIPEVRFGNVTTMEPII-LSLIPQERYSKTCYICQEigkpnraNVGACMQCNK 195
Cdd:cd15671     1 CVLCPKKGGAMKSTkSGTKWVHVSCALWIPEVSIGCPEKMEPITkISHIPMSRWALVCVLCKE-------KTGACIQCSV 73

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 442617807  196 SNCKQQFHVTCAQSLGL-LCEEAGNYLDNVKYCGYCQHH 233
Cdd:cd15671    74 KSCKTAFHVTCAFQHGLeMKTILEDEDDEVKFKSYCPKH 112

Extended PHD finger found in bromodomain and PHD finger-containing protein 2 (BRPF2) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of BRPF2. BRPF2 also termed bromodomain-containing protein 1 (BRD1), or BR140-likeprotein, 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 plant homeodomain (PHD) finger followed by a non-canonical ePHD finger, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442617807  118 CELCPSRDGALKKTDNSGWAHVVCALYIPEVRFGNVTTMEPII-LSLIPQERYSKTCYICQEIGkpnranVGACMQCNKS 196
Cdd:cd15702     1 CVLCPNKGGAFKKTDDDRWGHVVCALWIPEVGFANTVFIEPIDgVRNIPPARWKLTCYLCKQKG------VGACIQCHKA 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 442617807  197 NCKQQFHVTCAQSLGLLCE-------EAGNYLDNVKYCGYCQHH 233
Cdd:cd15702    75 NCYTAFHVTCAQKAGLYMKmepvkevTGGGTTFSVRKTAYCDAH 118

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 442617807   138 HVVCALYIPEVRF-GNVTTMEPII-LSLIPQERYSKTCYICQEigkpnraNVGACMQCNKSNCKQQFHVTCAQSLGLLCE 215
Cdd:pfam13771    1 HVVCALWSPELVQrGNDSMGFPIEdIEKIPKRRWKLKCYLCKK-------KGGACIQCSKKNCRRAFHVTCALEAGLLMQ 73

                           90
                   ....*....|....*...
gi 442617807   216 EAGnylDNVKYCGYCQHH 233
Cdd:pfam13771   74 FDE---DNGTFKSYCKKH 88

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 442617807  118 CELCPSRDGALKKT-DNSGWAHVVCALYIPEVRFGNVTTMEPII-LSLIPQERYSKTCYICQEigkpnraNVGACMQCNK 195
Cdd:cd15707     1 CILCPNKGGAMKSTrSGTKWAHVSCALWIPEVSIGCVEKMEPITkISSIPASRWALICVLCRE-------RTGACIQCSV 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 442617807  196 SNCKQQFHVTCAQSLGLlceEAGNYLD-----NVKYCGYCQHH 233
Cdd:cd15707    74 KTCKTAYHVTCGFQHGL---EMKTILDeesedGVKLRSYCQKH 113

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 442617807  118 CELCPSRDGALKKTDNSGWAHVVCALYIPEVRFGNVTTMEPIILSLIPQERYSKTCYICQeigKPNRANVGACMQCNKSN 197
Cdd:cd15714     1 CCLCNLRGGALQMTTDERWVHVICAIAVPEARFLNVIERHPVDVSAIPEQRWKLKCVYCR---KRMKKVSGACIQCSYDH 77

                          90       100
                  ....*....|....*....|
gi 442617807  198 CKQQFHVTCAQSLGLLCEEA 217
Cdd:cd15714    78 CSTSFHVTCAHAAGVVMEPD 97

PHD finger found in BRPF proteins, Jade proteins, protein AF-10, AF-17, and similar proteins; The family includes BRPF proteins, Jade proteins, protein AF-10 and AF-17. BRPF proteins 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. Jade proteins are 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. AF-10, also termed ALL1 (acute lymphoblastic leukemia)-fused gene from chromosome 10 protein, is a transcription factor that 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. AF-17, also termed ALL1-fused gene from chromosome 17 protein, is a putative transcription factor that may play a role in multiple signaling pathways. All Jade proteins, AF-10, and AF-17 contain a canonical PHD finger followed by a non-canonical ePHD finger. This model corresponds to the canonical PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 442617807   61 CCVCSDERGWPENPLVYCDGqnCTVAVHQACYGIVTVPTGPWYCRKC 107
Cdd:cd15492     2 CDVCLDGESEDDNEIVFCDG--CNVAVHQSCYGIPLIPEGDWFCRKC 46

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 442617807  117 RCELCPSRDGALKKT-DNSGWAHVVCALYIPEVRFGNVTTMEPII-LSLIPQERYSKTCYICQEigkpnraNVGACMQCN 194
Cdd:cd15704     3 KCLLCPKKGGAMKPTrSGTKWVHVSCALWIPEVSIGSPEKMEPITkVSHIPSSRWALVCSLCNE-------KVGASIQCS 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 442617807  195 KSNCKQQFHVTCAQSLGLLCEEAGNYLDNVKYCGYCQHHYS 235
Cdd:cd15704    76 VKNCRTAFHVTCAFDRGLEMKTILAENDEVKFKSYCPKHSS 116

Extended PHD finger (ePHD) found in Jumonji domain-containing protein 2A (JMJD2A); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of JMJD2A. JMJD2A, also termed lysine-specific demethylase 4A (KDM4A), or JmjC domain-containing histone demethylation protein 3A (JHDM3A), catalyzes the demethylation of di- and trimethylated H3K9 and H3K36. It is involved in carcinogenesis and functions as a transcription regulator that may either stimulate or repress gene transcription. It associates with nuclear receptor co-repressor complex or histone deacetylases. Moreover, JMJD2A forms complexes with both the androgen and estrogen receptor (ER) and plays an essential role in growth of both ER-positive and -negative breast tumors. It is also involved in prostate, colon, and lung cancer progression. JMJD2A 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 442617807  118 CELCPSRDGALKKTDNSGWAHVVCALYIPEVRFGNVTTMEPIILSLIPQERYSKTCYICQeigKPNRANVGACMQCNKSN 197
Cdd:cd15713     1 CCLCSLRGGALQRANDDKWVHVMCAVAVLEARFVNIAERSPVDVSKIPLQRFKLKCIFCK---KRRKRTAGCCVQCSHGR 77

                          90
                  ....*....|....*.
gi 442617807  198 CKQQFHVTCAQSLGLL 213
Cdd:cd15713    78 CPTSFHASCAQAAGVM 93

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 442617807  118 CELCPSRDG---------------ALKKTDNSGWAHVVCALYIPEVRFGNVTTMEPIIL---SLIPQERysKTCYICQEI 179
Cdd:cd15667     1 CSLCNAKESnyelakkqsprtrpdALKCTSNGTWCHVLCALFNEDIKFGNSKSLQPILNtesVLLKGSR--QKCEICKVS 78

                          90       100
                  ....*....|....*....|....*....
gi 442617807  180 GkpnranvGACMQCNKsnCKQQFHVTCAQ 208
Cdd:cd15667    79 G-------GGLVKCEV--CDDRFHVSCAQ 98

PHD finger found in proteins Jade-1, Jade-2, Jade-3, and similar proteins; This family includes proteins Jade-1 (PHF17), Jade-2 (PHF15), and Jade-3 (PHF16), each of which 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. 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 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 442617807   61 CCVCSDERGWPENPLVYCDGqnCTVAVHQACYGIVTVPTGPWYCRKC 107
Cdd:cd15573     2 CDVCRSPDSEEGNEMVFCDK--CNICVHQACYGIQKIPEGSWLCRTC 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 442617807   61 CCVCSDERGWPENPLVYCDgqNCTVAVHQACYGIVTVPTGPWYCRKC 107
Cdd:cd15572     4 CCICLDGECQNSNVILFCD--MCNLAVHQECYGVPYIPEGQWLCRRC 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 442617807   61 CCVCSDERGWPENPLVYCDgqNCTVAVHQACYGIVTVPTGPWYCRKC 107
Cdd:cd15677     4 CCICMDGECQNSNVILFCD--MCNLAVHQECYGVPYIPEGQWLCRHC 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 442617807    61 CCVCSdeRGWPENPLVYCDGqnCTVAVHQACYGI----VTVPTGPWYCRKC 107
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 442617807   61 CCVCSDERGWPENPLVYCDgqNCTVAVHQACYGIVTVPTGPWYCRKC 107
Cdd:cd15678     4 CCVCLDDECHNSNVILFCD--ICNLAVHQECYGVPYIPEGQWLCRCC 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 442617807   61 CCVCSDERGWPENPLVYCDgqNCTVAVHQACYGIV----------TVPTGPWYCRKC 107
Cdd:cd15561     2 CCVCLGDRSNDADEIIECD--KCGISVHEGCYGVIdesdssssasSSSTEPWFCEPC 56

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 442617807     61 CCVCSDERGWpeNPLVYCDGqnCTVAVHQACYGI---VTVPTGPWYCRKC 107
Cdd:smart00249    2 CSVCGKPDDG--GELLQCDG--CDRWYHQTCLGPpllEEEPDGKWYCPKC 47

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 442617807   61 CCVCSDERGWPENPLVYCDGqnCTVAVHQACYG--IVTVPT---GPWYCRKCE 108
Cdd:cd15499     2 CSICGGAEARDGNEILICDK--CDKGYHQLCHSpkVRTSPLegdEKWFCSRCV 52

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 442617807  136 WAHVVCALYIPEVRFGNVTTMEPIILSLIPQERYSktCYICQEIGkpnrANVGACMqcnkSNCKQQFHVTCAQSLGLLce 215
Cdd:cd15693    28 WTHVNCALWSAEVFEDDDGSLKNVHMAVIRGKQLR--CEFCQKPG----ATVGCCL----TSCTSNYHFMCSRAKNCV-- 95

                          90       100
                  ....*....|....*....|...
gi 442617807  216 eagnYLDNVKYcgYCQHHYSKLK 238
Cdd:cd15693    96 ----FLEDKKV--YCQRHKDLIK 112

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 442617807   61 CCVCSDERgwpenpLVYCdgQNCTVAVHQACYGIVTVP--TGPWYCRKC 107
Cdd:cd15493     2 CAICSLFR------LLVC--SRCCVCVHASCYGVPDIPgdGEGWKCDRC 42

PHD finger 2 found in PHD finger protein 10 (PHF10) and similar proteins; PHF10, also termed BRG1-associated factor 45a (BAF45a), or XAP135, is a ubiquitously expressed transcriptional regulator that is required for maintaining the undifferentiated status of neuroblasts. It contains a SAY (supporter of activation of yellow) domain and two adjacent plant homeodomain (PHD) fingers. This model corresponds to the second PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 442617807   61 CCVCSDERGwpENPLVYCDgqNCTVAVHQACYGIVTVPTGPWYCRKC 107
Cdd:cd15529     2 CTKCGDPHD--EDKMMFCD--QCDRGYHTFCVGLRSIPDGRWICPLC 44

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 442617807    172 TCYICQEIGKPnranvGACMQCNKsnCKQQFHVTCAQSLGLLCEEAGNYldnvkYCGYC 230
Cdd:smart00249    1 YCSVCGKPDDG-----GELLQCDG--CDRWYHQTCLGPPLLEEEPDGKW-----YCPKC 47

PHD finger found in Arabidopsis thaliana pathogenesis-related homeodomain protein (PRHA) and similar proteins; PRHA is a homeodomain protein encoded by a single-copy Arabidopsis thaliana homeobox gene, prha. It shows the capacity to bind to TAATTG core sequence elements but requires additional adjacent bases for high-affinity binding. PRHA contains a plant homeodomain (PHD) finger, a homeodomain, peptide repeats and a putative leucine zipper dimerization domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 442617807   61 CCVCSDERGWPENPLVYCDGqNCTVAVHQACYGIVTVPT------GPWYCRKC 107
Cdd:cd15504     2 CAKCQSGEASPDNDILLCDG-GCNRAYHQKCLEPPLLTEdippedEGWLCPLC 53

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 442617807  118 CELC------PSRD-GALKKTDNSGWAHVVCALYIPEVRFGNVTTMEPIILSLIPQERYSktCYICQEIGkpnrANVGAC 190
Cdd:cd15694     1 CALClkygdaDSKDaGRLLYIGQNEWTHVNCAIWSAEVFEENDGSLKNVHAAVARGRQMR--CEHCQKIG----ATVGCC 74

                          90
                  ....*....|....*....
gi 442617807  191 MqcnkSNCKQQFHVTCAQS 209
Cdd:cd15694    75 L----SACLSNFHFMCARA 89

PHD finger 2 found in Saccharomyces cerevisiae SANT domain-containing protein 2 (Snt2p) and similar proteins; This group corresponds to Snt2p and similar proteins. Snt2p 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 Cys4HisCys3 plant homeodomain (PHD) fingers, a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, and a SANT (SWI3, ADA2, N-CoR and TFIIIB) DNA-binding domain; this model corresponds to the second canonical Cys4HisCys3 PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 442617807   60 GCCVCSDERGWPENPLVYCdgQNCTVAVHQACYGIVT---------VPTGPWYCRKC 107
Cdd:cd15498     1 KCSVCSEQFASNFNTSLSC--YNCGLNVHASCYGITVpgkmnkvknLKSYKWLCDPC 55