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 1907136025 584 SIEQLLERQWSEGQQFLLEQGTPGDILGMLKSLHQLQVENRRLEEQIKNLTAKKERLQLLNAQL 647
Cdd:cd20901     1 SIEQLLERQWSQGQQFLLEQASQFDVASLLSCLHQLRSENRRLESSISNLQSRRDHLLALNARL 64

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907136025 584 SIEQLLERQWSEGQQFLLEQGTPGDILGMLKSLHQLQVENRRLEEQIKNLTAKKERLQLLNAQL 647
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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907136025    3 TCYICDEqgresKAATGACMTCnkHGCRQAFHVTCAQFAGLLCEEEGNgadnvQYCGYC 61
Cdd:smart00249   1 YCSVCGK-----PDDGGELLQC--DGCDRWYHQTCLGPPLLEEEPDGK-----WYCPKC 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907136025   3 TCYICDEQGRESKAATGACMTCNKHGCRQAFHVTCAQFAGLLCEEEGNGADNVQYCGYCKYH 64
Cdd:cd15672    55 TCYICEEQGRESKASTGACMQCNKSGCKQSFHVTCAQMAGLLCEEAGNYSDNVKYCGYCSYH 116

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 1907136025 584 SIEQLLERQWSEGQQFLLEQGTPGDILGMLKSLHQLQVENRRLEEQIKNLTAKKERLQLLNAQL 647
Cdd:cd20901     1 SIEQLLERQWSQGQQFLLEQASQFDVASLLSCLHQLRSENRRLESSISNLQSRRDHLLALNARL 64

PHD-zinc-finger like domain;

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                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907136025   3 TCYICDEqgreskaATGACMTCNKHGCRQAFHVTCAQFAGLLCEEEGNgaDNVQYCGYCKYH 64
Cdd:pfam13832  57 KCVFCKK-------RSGACIQCSKGRCTTAFHVTCAQAAGVYMEPEDW--PNVVVIAYCQKH 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907136025   3 TCYICdeqgresKAATGACMTCNKHGCRQAFHVTCAQFAGLL-----CEEEGNGADN-VQYCGYCKYH 64
Cdd:cd15670    56 TCYIC-------KKRMGACIQCHKKNCYTAFHVTCAQQAGLYmkiepVKDPGNGTSDsVRKEAYCDKH 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907136025   3 TCYICDEQGreskaaTGACMTCNKHGCRQAFHVTCAQFAGLLCEEE------GNGAD-NVQYCGYCKYH 64
Cdd:cd15701    56 TCYICKQRG------SGACIQCHKANCYTAFHVTCAQQAGLYMKMEpvretgANGTSfSVRKTAYCDIH 118

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907136025   3 TCYICDEQGReskaatGACMTCNKHGCRQAFHVTCAQFAGLLC------EEEGNGAD-NVQYCGYCKYH 64
Cdd:cd15703    56 TCYLCKQKGR------GAAIQCHKVNCYTAFHVTCAQRAGLFMkiepvrETGLNGTTfTVRKTAYCENH 118

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907136025   3 TCYICdeqgresKAATGACMTCNKHGCRQAFHVTCAQFAGLLCE-----EEGNGADNVQYCGYCKYH 64
Cdd:cd15662    56 SCTIC-------KQRYGACIQCSNNSCRVAYHPLCARAAGLCMEvadegGEDPGDQGLRLLSYCPRH 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907136025   4 CYICdeqgresKAATGACMTCNKHGCRQAFHVTCAQFAGLLCEEEGNGADNVQYCGYCKYH 64
Cdd:cd15706    58 CSLC-------KLKTGACIQCSVKSCITAFHVTCAFEHSLEMKTILDEGDEVKFKSYCLKH 111

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.

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                  ....*....|....*....|....*....|....*....|...
gi 1907136025   4 CYICDEQgRESKAATGACMTCNKHGCRQAFHVTCAQFAGLLCE 46
Cdd:cd15675    56 CIYCSKI-TKSMSHMGACIQCSTGKCTTSFHVTCAHAAGVQME 97

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907136025   4 CYICDEQgreskaaTGACMTCNKHGCRQAFHVTCAQFAGLLCEEEGNGADNVQYCGYCKYHFS 66
Cdd:cd15704    61 CSLCNEK-------VGASIQCSVKNCRTAFHVTCAFDRGLEMKTILAENDEVKFKSYCPKHSS 116

Extended PHD finger found in Jumonji domain-containing protein 2C (JMJD2C); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of JMJD2C. JMJD2C, also termed lysine-specific demethylase 4C (KDM4C), or gene amplified in squamous cell carcinoma 1 protein (GASC-1 protein), or JmjC domain-containing histone demethylation protein 3C (JHDM3C), is an epigenetic factor that catalyzes the demethylation of di- and trimethylated H3K9 and H3K36, and may be involved in the development and/or progression of various types of cancer including esophageal squamous cell carcinoma (ESC) and breast cancer. It selectively interacts with hypoxia-inducible factor 1alpha (HIF1alpha) and plays a role in breast cancer progression. Moreover, JMJD2C may play an important role in the treatment of obesity and its complications by modulating the regulation of adipogenesis by nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma). JMJD2C contains jmjN and jmjC domains in the N-terminal region, followed by a canonical plant homeodomain (PHD) finger, this non-canonical ePHD finger, and a Tudor domain.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1907136025  15 KAATGACMTCNKHGCRQAFHVTCAQFAGLLCE 46
Cdd:cd15715    64 KRVSGACIQCSYGRCPASFHVTCAHAAGVLME 95

Extended PHD finger found in Arabidopsis thaliana ATX3, -4, -5, 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 ATX3 (also termed protein SET domain group 14, or trithorax-homolog protein 3), ATX4 (also termed protein SET domain group 16, or trithorax-homolog protein 4) and ATX5 (also termed protein SET domain group 29, or trithorax-homolog protein 5), which belong to the histone-lysine methyltransferase family. These proteins show distinct phylogenetic origins from the family of ATX1 and ATX2. They are multi-domain proteins that consist of an N-terminal PWWP domain, a canonical PHD finger, this non-canonical extended PHD finger, and a C-terminal SET domain.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907136025   4 CYICdeqgresKAATGACMTCNKhgCRQAFHVTCAQFAGLLCE---EEGNGADNVQYCGYCKYH 64
Cdd:cd15663    58 CVIC-------KQIHGSCTQCCK--CATYFHAMCASRAGYHMElhcLEKNGVQITRMVSYCSFH 112

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907136025   3 TCYICDEqgreskaaTGACMTCNKHGCRQAFHVTCAQFAGLLCEEEgngadnvQYCGYCKYH 64
Cdd:cd15668    57 VCSSCQQ--------TGATIGCLHKGCKAKYHYPCAVESGCQLDEE-------NFSLLCPKH 103