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 1907136034 566 SIEQLLERQWSEGQQFLLEQGTPGDILGMLKSLHQLQVENRRLEEQIKNLTAKKERLQLLNAQL 629
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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907136034 566 SIEQLLERQWSEGQQFLLEQGTPGDILGMLKSLHQLQVENRRLEEQIKNLTAKKERLQLLNAQL 629
Cdd:cd20901     1 SIEQLLERQWSQGQQFLLEQASQFDVASLLSCLHQLRSENRRLESSISNLQSRRDHLLALNARL 64

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136034   1 MEPI-VLQSVPHDRYNKTCYICDEQGreskaatGACMTCNKHGCRQAFHVTCAQFAGL--LCEEEGNG-ADNVQYCGYCK 76
Cdd:COG5141   288 KDPIdNIASVSSSRWKLGCLICKEFG-------GTCIQCSYFNCTRAYHVTCARRAGYfdLNIYSHNGiSYCIDHEPLCR 360

                  ...
gi 1907136034  77 YHF 79
Cdd:COG5141   361 KHY 363

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907136034   1 MEPIVLQSVPHDRYNKTCYICDEQGRESKAATGACMTCNKHGCRQAFHVTCAQFAGLLCEEEGNGADNVQYCGYCKYH 78
Cdd:cd15672    39 MEPIILQDVPQDRFNKTCYICEEQGRESKASTGACMQCNKSGCKQSFHVTCAQMAGLLCEEAGNYSDNVKYCGYCSYH 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 1907136034 566 SIEQLLERQWSEGQQFLLEQGTPGDILGMLKSLHQLQVENRRLEEQIKNLTAKKERLQLLNAQL 629
Cdd:cd20901     1 SIEQLLERQWSQGQQFLLEQASQFDVASLLSCLHQLRSENRRLESSISNLQSRRDHLLALNARL 64

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907136034   1 MEPIV-LQSVPHDRYNKTCYICDEQgreskaaTGACMTCNKHGCRQAFHVTCAQFAGLLCEEEGngaDNVQYCGYCKYH 78
Cdd:pfam13771  20 GFPIEdIEKIPKRRWKLKCYLCKKK-------GGACIQCSKKNCRRAFHVTCALEAGLLMQFDE---DNGTFKSYCKKH 88

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 1907136034   1 MEPIV-LQSVPHDRYNKTCYICdeqgresKAATGACMTCNKHGCRQAFHVTCAQFAGLL-----CEEEGNGADN-VQYCG 73
Cdd:cd15670    39 LEPIDgIQNIPKARWKLTCYIC-------KKRMGACIQCHKKNCYTAFHVTCAQQAGLYmkiepVKDPGNGTSDsVRKEA 111

                  ....*
gi 1907136034  74 YCKYH 78
Cdd:cd15670   112 YCDKH 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 1907136034   1 MEPI-VLQSVPHDRYNKTCYICDEQGreskaaTGACMTCNKHGCRQAFHVTCAQFAGLLCEEE------GNGAD-NVQYC 72
Cdd:cd15701    39 LEPIdSIEHIPPARWKLTCYICKQRG------SGACIQCHKANCYTAFHVTCAQQAGLYMKMEpvretgANGTSfSVRKT 112

                  ....*.
gi 1907136034  73 GYCKYH 78
Cdd:cd15701   113 AYCDIH 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 1907136034   1 MEPIV-LQSVPHDRYNKTCYICDEQgreskaaTGACMTCNKHGCRQAFHVTCAQFAGL-LCEEEGNGADNVQYCGYCKYH 78
Cdd:cd15671    40 MEPITkISHIPMSRWALVCVLCKEK-------TGACIQCSVKSCKTAFHVTCAFQHGLeMKTILEDEDDEVKFKSYCPKH 112

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 1907136034   1 MEPIV-LQSVPHDRYNKTCYICDEQgreskaaTGACMTCNKHGCRQAFHVTCAQFAGLLCEE--EGNGADNVQYCGYCKY 77
Cdd:cd15707    40 MEPITkISSIPASRWALICVLCRER-------TGACIQCSVKTCKTAYHVTCGFQHGLEMKTilDEESEDGVKLRSYCQK 112

                  .
gi 1907136034  78 H 78
Cdd:cd15707   113 H 113

Extended PHD finger found in protein Jade-3 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Jade-3. Jade-3, also termed PHD finger protein 16 (PHF16), is a plant homeodomain (PHD) zinc finger protein that is close related to Jade-1, which functions as an essential regulator of multiple cell signaling pathways. Like Jade-1, Jade-3 is required for ING4 and ING5 to associate with histone acetyl transferase (HAT) HBO1 and Eaf6 to form a HBO1 complex that has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. Jade-3 contains a canonical PHD domain followed by this non-canonical ePHD domain, both of which are zinc-binding motifs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907136034   1 MEPIV-LQSVPHDRYNKTCYICdeqgresKAATGACMTCNKHGCRQAFHVTCAQFAGLLCEEEGNGADNVQYCGYCKYH 78
Cdd:cd15706    40 MEPITkVSHIPPSRWALVCSLC-------KLKTGACIQCSVKSCITAFHVTCAFEHSLEMKTILDEGDEVKFKSYCLKH 111

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907136034   1 MEPIV-LQSVPHDRYNKTCYICDEqgreskaATGACMTCNKHGCRQAFHVTCAQFAGLLCEEEGNGADNVQYCGYCKYH 78
Cdd:cd15705    40 MEPITkISHIPASRWALSCSLCKE-------CTGTCIQCSMPSCITAFHVTCAFDHGLEMRTTLADNDEVKFKSFCLEH 111

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136034   1 MEPIV-LQSVPHDRYNKTCYICdeqgresKAATGACMTCNKhgCRQAFHVTCAQFAGLLCE---EEGNGADNVQYCGYCK 76
Cdd:cd15663    40 MEPAVgLLRIPLSTFLKACVIC-------KQIHGSCTQCCK--CATYFHAMCASRAGYHMElhcLEKNGVQITRMVSYCS 110

                  ..
gi 1907136034  77 YH 78
Cdd:cd15663   111 FH 112

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        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907136034   3 PIVLQSVPHDRYNKTCYICDEQgreSKAATGACMTCNKHGCRQAFHVTCAQFAGLLCE 60
Cdd:cd15715    41 PIDISRIPLQRLKLKCIFCRNR---IKRVSGACIQCSYGRCPASFHVTCAHAAGVLME 95

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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907136034   3 PIVLQSVPHDRYNKTCYICDeqgRESKAATGACMTCNKHGCRQAFHVTCAQFAGLL 58
Cdd:cd15713    41 PVDVSKIPLQRFKLKCIFCK---KRRKRTAGCCVQCSHGRCPTSFHASCAQAAGVM 93

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 1907136034  15 NKTCYICDEqgreskaaTGACMTCNKHGCRQAFHVTCAQFAGLLCEEEgngadnvQYCGYCKYH 78
Cdd:cd15668    55 QSVCSSCQQ--------TGATIGCLHKGCKAKYHYPCAVESGCQLDEE-------NFSLLCPKH 103