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
                   ....*....|....*...
gi 1740127214    8 ACYGIVQVPTGPWFCRKC 25
Cdd:cd15574     31 ACYGIVQVPTGPWFCRKC 48

PHD-zinc-finger like domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1740127214   34 VRCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPIVLQYVPHDRFNKTCYICEEqgreskaASGACMTCNR 113
Cdd:pfam13832    1 VRCCLCPLRGGALKQTSDGRWVHVLCAIFVPEVRFGNVATMEPIDVSRIPPERWKLKCVFCKK-------RSGACIQCSK 73

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1740127214  114 HGCRQAFHVTCAQMAGLLCEEEvlEVDNVKYCGYCKYH 151
Cdd:pfam13832   74 GRCTTAFHVTCAQAAGVYMEPE--DWPNVVVIAYCQKH 109

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
                   ....*....|....*...
gi 1740127214    8 ACYGIVQVPTGPWFCRKC 25
Cdd:cd15574     31 ACYGIVQVPTGPWFCRKC 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        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1740127214    90 TCYICEEqgresKAASGACMTCnrHGCRQAFHVTCAQMAGLlceeevLEVDNVKYcgYCKYH 151
Cdd:smart00249    1 YCSVCGK-----PDDGGELLQC--DGCDRWYHQTCLGPPLL------EEEPDGKW--YCPKC 47

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 1740127214   36 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPIVLQYVPHDRFNKTCYICEEQGRESKAASGACMTCNRHG 115
Cdd:cd15672      1 CELCPHKDGALKRTDNGGWAHVVCALYIPEVRFGNVATMEPIILQDVPQDRFNKTCYICEEQGRESKASTGACMQCNKSG 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1740127214  116 CRQAFHVTCAQMAGLLCEEEVLEVDNVKYCGYCKYH 151
Cdd:cd15672     81 CKQSFHVTCAQMAGLLCEEAGNYSDNVKYCGYCSYH 116

PHD-zinc-finger like domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1740127214   34 VRCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPIVLQYVPHDRFNKTCYICEEqgreskaASGACMTCNR 113
Cdd:pfam13832    1 VRCCLCPLRGGALKQTSDGRWVHVLCAIFVPEVRFGNVATMEPIDVSRIPPERWKLKCVFCKK-------RSGACIQCSK 73

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1740127214  114 HGCRQAFHVTCAQMAGLLCEEEvlEVDNVKYCGYCKYH 151
Cdd:pfam13832   74 GRCTTAFHVTCAQAAGVYMEPE--DWPNVVVIAYCQKH 109

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 1740127214   36 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPIV-LQYVPHDRFNKTCYICeeqgresKAASGACMTCNRH 114
Cdd:cd15670      1 CVLCPNKGGAFKQTDDGRWAHVVCALWIPEVSFANTVFLEPIDgIQNIPKARWKLTCYIC-------KKRMGACIQCHKK 73

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1740127214  115 GCRQAFHVTCAQMAGL------LCEEEVLEVDNVKYCGYCKYH 151
Cdd:cd15670     74 NCYTAFHVTCAQQAGLymkiepVKDPGNGTSDSVRKEAYCDKH 116

Extended PHD finger found in bromodomain and PHD finger-containing protein 1 (BRPF1) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of BRPF1. BRPF1, also termed peregrin, or protein Br140, is a multi-domain protein that binds histones, mediates monocytic leukemic zinc-finger protein (MOZ) -dependent histone acetylation, and is required for Hox gene expression and segmental identity. It is a close partner of the MOZ histone acetyltransferase (HAT) complex and a novel Trithorax group (TrxG) member with a central role during development. BRPF1 is primarily a nuclear protein that has a broad tissue distribution and is abundant in testes and spermatogonia. It contains 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 methylated lysine 4 of histone H3 (H3K4me), 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. BRPF1 may be involved in chromatin remodeling.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1740127214   36 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPI-VLQYVPHDRFNKTCYICEEQGreskaaSGACMTCNRH 114
Cdd:cd15701      1 CALCPNKGGAFKQTDDGRWAHVVCALWIPEVCFANTVFLEPIdSIEHIPPARWKLTCYICKQRG------SGACIQCHKA 74

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1740127214  115 GCRQAFHVTCAQMAGLLCE-EEVLEVD------NVKYCGYCKYH 151
Cdd:cd15701     75 NCYTAFHVTCAQQAGLYMKmEPVRETGangtsfSVRKTAYCDIH 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 1740127214   36 CELCPHKDGALKRTDNG-GWAHVVCALYIPEVQFANVLTMEPIV-LQYVPHDRFNKTCYICEEQgreskaaSGACMTCNR 113
Cdd:cd15671      1 CVLCPKKGGAMKSTKSGtKWVHVSCALWIPEVSIGCPEKMEPITkISHIPMSRWALVCVLCKEK-------TGACIQCSV 73

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1740127214  114 HGCRQAFHVTCAQMAGL-LCEEEVLEVDNVKYCGYCKYH 151
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 1740127214   36 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPI-VLQYVPHDRFNKTCYICEEQGreskaaSGACMTCNRH 114
Cdd:cd15702      1 CVLCPNKGGAFKKTDDDRWGHVVCALWIPEVGFANTVFIEPIdGVRNIPPARWKLTCYLCKQKG------VGACIQCHKA 74

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1740127214  115 GCRQAFHVTCAQMAGLLCE-EEVLEVD------NVKYCGYCKYH 151
Cdd:cd15702     75 NCYTAFHVTCAQKAGLYMKmEPVKEVTgggttfSVRKTAYCDAH 118

Extended PHD finger found in Jumonji domain-containing protein 2 (JMJD2) family of histone demethylases; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of JMJD2 proteins. 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 three JMJD2 proteins, JMJD2A-C, which all contain jmjN and jmjC domains in the N-terminal region, followed by a canonical PHD finger, this non-canonical ePHD finger, 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1740127214   36 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPIVLQYVPHDRFNKTCYICEEQgRESKAASGACMTCNRHG 115
Cdd:cd15675      1 CCLCCLRGGALKPTTDGRWAHVVCAIAIPEVRFSNVPERGPIDISKIPPARLKLKCIYCSKI-TKSMSHMGACIQCSTGK 79

                           90
                   ....*....|....*...
gi 1740127214  116 CRQAFHVTCAQMAGLLCE 133
Cdd:cd15675     80 CTTSFHVTCAHAAGVQME 97

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 1740127214   36 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPI-VLQYVPHDRFNKTCYICeeqgresKAASGACMTCNRH 114
Cdd:cd15662      1 CCLCPVVGGALKPTTDGRWAHLACAIWIPETCLLDVKTMEPVdGINAISKERWELSCTIC-------KQRYGACIQCSNN 73

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1740127214  115 GCRQAFHVTCAQMAGLLCE--EEVLEV---DNVKYCGYCKYH 151
Cdd:cd15662     74 SCRVAYHPLCARAAGLCMEvaDEGGEDpgdQGLRLLSYCPRH 115

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 1740127214   36 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPIVLQYVPHDRFNKTCYICEeqgRESKAASGACMTCNRHG 115
Cdd:cd15714      1 CCLCNLRGGALQMTTDERWVHVICAIAVPEARFLNVIERHPVDVSAIPEQRWKLKCVYCR---KRMKKVSGACIQCSYDH 77

                           90
                   ....*....|....*...
gi 1740127214  116 CRQAFHVTCAQMAGLLCE 133
Cdd:cd15714     78 CSTSFHVTCAHAAGVVME 95

Extended PHD finger found in protein Jade-2 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Jade-2. Jade-2, also termed PHD finger protein 15 (PHF15), is a plant homeodomain (PHD) zinc finger protein that is closely related to Jade-1, which functions as an essential regulator of multiple cell signaling pathways. Like Jade-1, Jade-2 is required for ING4 and ING5 to associate with histone acetyltransferase (HAT) HBO1 and Eaf6 to form a HBO1 complex that has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. Jade-2 contains a canonical PHD finger followed by this non-canonical ePHD finger, both of which are zinc-binding motifs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1740127214   36 CELCPHKDGALKRTDNG-GWAHVVCALYIPEVQFANVLTMEPIV-LQYVPHDRFNKTCYICEEqgreskaASGACMTCNR 113
Cdd:cd15705      1 CLLCPKRGGALKPTRSGtKWVHVSCALWIPEVSIGCPEKMEPITkISHIPASRWALSCSLCKE-------CTGTCIQCSM 73

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1740127214  114 HGCRQAFHVTCAQMAGLLCEEEVLEVDNVKYCGYCKYH 151
Cdd:cd15705     74 PSCITAFHVTCAFDHGLEMRTTLADNDEVKFKSFCLEH 111

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 1740127214   35 RCELCPHKDGALKRTDNG-GWAHVVCALYIPEVQFANVLTMEPIV-LQYVPHDRFNKTCYICEEQgreskaaSGACMTCN 112
Cdd:cd15704      3 KCLLCPKKGGAMKPTRSGtKWVHVSCALWIPEVSIGSPEKMEPITkVSHIPSSRWALVCSLCNEK-------VGASIQCS 75

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1740127214  113 RHGCRQAFHVTCAQMAGLLCEEEVLEVDNVKYCGYCKYHFS 153
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 1740127214   36 CELCPHKDG---------------ALKRTDNGGWAHVVCALYIPEVQFANVLTMEPIVL-QYVPHDRFNKTCYICEEQGr 99
Cdd:cd15667      1 CSLCNAKESnyelakkqsprtrpdALKCTSNGTWCHVLCALFNEDIKFGNSKSLQPILNtESVLLKGSRQKCEICKVSG- 79

                           90       100
                   ....*....|....*....|....*..
gi 1740127214  100 eskaasGACMTCNRhgCRQAFHVTCAQ 126
Cdd:cd15667     80 ------GGLVKCEV--CDDRFHVSCAQ 98

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 1740127214  695 MEQLLEKQGDG--------EAGVNIVEMLKALHALQKENQRLQEQILSLTAKKERLQILNVQL 749
Cdd:cd20901      2 IEQLLERQWSQgqqflleqASQFDVASLLSCLHQLRSENRRLESSISNLQSRRDHLLALNARL 64

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1740127214   54 WAHVVCALYIPEVQFA--NVLTMEPIVLqyvphDRFNKTCYICEEqgreskaaSGACMTCNRHGCRQAFHVTCAQMAGLL 131
Cdd:cd15668     24 WVHEDCAVWAPGVYLVggKLYGLEEAVW-----VAKQSVCSSCQQ--------TGATIGCLHKGCKAKYHYPCAVESGCQ 90

                           90       100
                   ....*....|....*....|
gi 1740127214  132 CEEEvlevdnvKYCGYCKYH 151
Cdd:cd15668     91 LDEE-------NFSLLCPKH 103

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
                   ....*....|....*...
gi 1740127214    8 ACYGIVQVPTGPWFCRKC 25
Cdd:cd15573     29 ACYGIQKIPEGSWLCRTC 46

PHD finger found in protein Jade-3 and similar proteins; Jade-3, also termed PHD finger protein 16 (PHF16), 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-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 Cys4HisCys3 PHD domain followed by a non-canonical extended PHD (ePHD) domain, Cys2HisCys5HisCys2His, both of which are zinc-binding motifs. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                           10
                   ....*....|....*...
gi 1740127214    8 ACYGIVQVPTGPWFCRKC 25
Cdd:cd15681     29 ACYGILKVPEGSWLCRTC 46

Homeobox associated leucine zipper;

                           10        20
                   ....*....|....*....|....*...
gi 1740127214  713 EMLKALH-ALQKENQRLQEQILSLTAKK 739
Cdd:pfam02183   15 DALKSDFdSLKKENQKLQAELQELKEKL 42