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 679004203 676 CCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVDVGKIPLQRFRLKCIFCKKRRKRIAGCCVQCSHGRCPT 755
Cdd:cd15713    1 CCLCSLRGGALQRANDDKWVHVMCAVAVLEARFVNIAERSPVDVSKIPLQRFKLKCIFCKKRRKRTAGCCVQCSHGRCPT 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 679004203 756 SFHVSCAQAAGVMMQPDDWPFVVFITCFRH 785
Cdd:cd15713   81 SFHASCAQAAGVMMQPDDWPFVVFITCFRH 110

JmjC domain, hydroxylase; The JmjC domain belongs to the Cupin superfamily. JmjC-domain proteins may be protein hydroxylases that catalyze a novel histone modification. This is confirmed to be a hydroxylase: the human JmjC protein named Tyw5p unexpectedly acts in the biosynthesis of a hypermodified nucleoside, hydroxy-wybutosine, in tRNA-Phe by catalysing hydroxylation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 679004203   71 YLYFGMWKTSFAWHTEDMDLYSINYLHFGEPKSWYSIPPEHGKRLERLAKGFFPGSaqsCEAFLRHKMTLISPSILKKYG 150
Cdd:pfam02373   1 WLYLGMPFSTTPWHIEDQGLYSINYLHFGAPKVWYIIPPEYAEKFEKVLSDHFGGE---QPDDLLHLNTIISPKQLRENG 77

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 679004203  151 IPFDKVTQEAGEFMITFPYSYHAGFNHGFNCAESTNF 187
Cdd:pfam02373  78 IPVYRFVQKPGEFVFTFPGWYHQVFNLGFNIAEAVNF 114

first Tudor domain found in Jumonji domain-containing protein 2A (JMJD2A) and similar proteins; JMJD2A, also called 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 corepressor 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 plant homeodomain (PHD) domain, a noncanonical extended PHD domain, and tandem Tudor domains. The model corresponds to the first Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 679004203 804 GQIVISKHKNGRFYQCEVVSLAKETFYEVNFDDGSFSDNLYPEDIVSRDCLQ 855
Cdd:cd20463    4 GQKVISKHKNGRFYQCEVVRLTKETFYEVNFDDGSFSDNLYPEDIVSQDCLQ 55

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 679004203 676 CCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVDVGKIPLQRFRLKCIFCKKRRKRIAGCCVQCSHGRCPT 755
Cdd:cd15713    1 CCLCSLRGGALQRANDDKWVHVMCAVAVLEARFVNIAERSPVDVSKIPLQRFKLKCIFCKKRRKRTAGCCVQCSHGRCPT 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 679004203 756 SFHVSCAQAAGVMMQPDDWPFVVFITCFRH 785
Cdd:cd15713   81 SFHASCAQAAGVMMQPDDWPFVVFITCFRH 110

JmjC domain, hydroxylase; The JmjC domain belongs to the Cupin superfamily. JmjC-domain proteins may be protein hydroxylases that catalyze a novel histone modification. This is confirmed to be a hydroxylase: the human JmjC protein named Tyw5p unexpectedly acts in the biosynthesis of a hypermodified nucleoside, hydroxy-wybutosine, in tRNA-Phe by catalysing hydroxylation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 679004203   71 YLYFGMWKTSFAWHTEDMDLYSINYLHFGEPKSWYSIPPEHGKRLERLAKGFFPGSaqsCEAFLRHKMTLISPSILKKYG 150
Cdd:pfam02373   1 WLYLGMPFSTTPWHIEDQGLYSINYLHFGAPKVWYIIPPEYAEKFEKVLSDHFGGE---QPDDLLHLNTIISPKQLRENG 77

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 679004203  151 IPFDKVTQEAGEFMITFPYSYHAGFNHGFNCAESTNF 187
Cdd:pfam02373  78 IPVYRFVQKPGEFVFTFPGWYHQVFNLGFNIAEAVNF 114

second Tudor domain found in Jumonji domain-containing protein 2A (JMJD2A) and similar proteins; JMJD2A, also called 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 corepressor 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 plant homeodomain (PHD) domain, a noncanonical extended PHD domain, and tandem Tudor domains. The model corresponds to the second Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 679004203 858 PPAEGEVVQVRWTDGQVYGAKFVASHAIQMYQVEFEDGSQLMVKRDDVYTLEEELP 913
Cdd:cd20466    1 PPAEGEVVQVRWTDGQVYGAKFVASHPIQMYQVEFEDGSQLVVKRDDVYTLDEELP 56

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 679004203 629 EEDGTSVLITCKNCHVCVHASCYGVsPDKATEDWMCSRCTENALEEDCCL-CSLRGGALQRANDDKWVHVMCAVAVLEAK 707
Cdd:COG5141  203 HNENSNAIVFCDGCEICVHQSCYGI-QFLPEGFWLCRKCIYGEYQIRCCSfCPSSDGAFKQTSDGRWGHVICAMFNPELS 281

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 679004203 708 FVNIAERSPVD-VGKIPLQRFRLKCIFCKKRrkriAGCCVQCSHGRCPTSFHVSCAQAAGVMM 769
Cdd:COG5141  282 FGHLLSKDPIDnIASVSSSRWKLGCLICKEF----GGTCIQCSYFNCTRAYHVTCARRAGYFD 340

A domain family that is part of the cupin metalloenzyme superfamily; Probable enzymes, but of unknown functions, that regulate chromatin reorganisation processes (Clissold and Ponting, in press).

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 679004203    42 DAWNIGRLNTILDIVENESGItIEGVNT-PYLYFGMWKTSFAWHTEDMDLysINYLHFGEP 101
Cdd:smart00558   1 QLWNLAKLPFKLNLLSDLPED-IPGPDVgPYLYMGMAGSTTPWHIDDYDL--VNYLHQGAG 58

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
                  ....*....|....*....|....*....|....*
gi 679004203  633 TSVLITCKNCHVCVHASCYGVSPDKATEDWMCSRC 667
Cdd:pfam13831   1 TSPLVYCSKCSVQVHASCYGVPPIPDGDGWKCRRC 35

Tudor domain; Domain of unknown function present in several RNA-binding proteins. 10 copies in the Drosophila Tudor protein. Initial proposal that the survival motor neuron gene product contain a Tudor domain are corroborated by more recent database search techniques such as PSI-BLAST (unpublished).

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 679004203   799 QDLSPGQIVISKHKNGRFYQCEVVSLAKETFYEVNFDDGSFSDNLYPEDIVSRDCLQ 855
Cdd:smart00333   1 PTFKVGDKVAARWEDGEWYRARIVKVDGEQLYEVFFIDYGNEEVVPPSDLRQLPEEL 57

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
                   ....*....|....*....|....*....|....*....|...
gi 679004203   731 CIFCKKRRKriAGCCVQCSHgrCPTSFHVSCAQAAGVMMQPDD 773
Cdd:smart00249   2 CSVCGKPDD--GGELLQCDG--CDRWYHQTCLGPPLLEEEPDG 40

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 679004203 676 CCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVDVGKIPLQRFRLKCIFCKKRRKRIAGCCVQCSHGRCPT 755
Cdd:cd15713    1 CCLCSLRGGALQRANDDKWVHVMCAVAVLEARFVNIAERSPVDVSKIPLQRFKLKCIFCKKRRKRTAGCCVQCSHGRCPT 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 679004203 756 SFHVSCAQAAGVMMQPDDWPFVVFITCFRH 785
Cdd:cd15713   81 SFHASCAQAAGVMMQPDDWPFVVFITCFRH 110

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 679004203 676 CCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVDVGKIPLQRFRLKCIFCKKRRKRIAGCCVQCSHGRCPT 755
Cdd:cd15715    1 CCLCNLRGGALKQTSDDKWAHVMCAVALPEVRFINVVERTPIDISRIPLQRLKLKCIFCRNRIKRVSGACIQCSYGRCPA 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 679004203 756 SFHVSCAQAAGVMMQPDDWPFVVFITCFRH 785
Cdd:cd15715   81 SFHVTCAHAAGVLMEPDDWPYVVFITCFRH 110

PHD finger found in Jumonji domain-containing protein 2A (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 Cys4HisCys3 PHD finger, a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, and a Tudor domain. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 679004203 569 YCAVCMLFQTYQAEC-GGNSQNSGVTPAAVDGKIRTKPLIPEMCFTTTGCSTDLNLSTPYLEEDGTSVLITCKNCHVCVH 647
Cdd:cd15575    1 HCAVCMLFQTYQVDCwGGHNSSSGVAASEARIKKKTKPLIPEMCFTSTGCNTDLNLSTPYLEEDGTSILVTCKKCCVCVH 80

                         90       100
                 ....*....|....*....|
gi 679004203 648 ASCYGVSPDKATEDWMCSRC 667
Cdd:cd15575   81 ASCYGVSPEKAAEDWMCSRC 100

PHD-zinc-finger like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 679004203  675 DCCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVDVGKIPLQRFRLKCIFCKKRRkriaGCCVQCSHGRCP 754
Cdd:pfam13832   2 RCCLCPLRGGALKQTSDGRWVHVLCAIFVPEVRFGNVATMEPIDVSRIPPERWKLKCVFCKKRS----GACIQCSKGRCT 77

                          90       100       110
                  ....*....|....*....|....*....|..
gi 679004203  755 TSFHVSCAQAAGVMMQPDDWP-FVVFITCFRH 785
Cdd:pfam13832  78 TAFHVTCAQAAGVYMEPEDWPnVVVIAYCQKH 109

first Tudor domain found in Jumonji domain-containing protein 2A (JMJD2A) and similar proteins; JMJD2A, also called 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 corepressor 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 plant homeodomain (PHD) domain, a noncanonical extended PHD domain, and tandem Tudor domains. The model corresponds to the first Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 679004203 804 GQIVISKHKNGRFYQCEVVSLAKETFYEVNFDDGSFSDNLYPEDIVSRDCLQ 855
Cdd:cd20463    4 GQKVISKHKNGRFYQCEVVRLTKETFYEVNFDDGSFSDNLYPEDIVSQDCLQ 55

PHD finger found in Jumonji domain-containing protein 2B (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 Cys4HisCys3 PHD finger, a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, and a Tudor domain. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 679004203 569 YCAVCMLFQTYQAECGGNSQNSGVTPAAVDGKIRTKPLIPEMCFTTTGCSTDLNLSTPYLEEDGTSVLITCKNCHVCVHA 648
Cdd:cd15576    1 YCAICTLFYPYTQSLQDPKEISDMSGLVSKVGQKTRPLIPEMCFTAGGENTEPLPSNSYIGDDGTSVLLSCAKCCLQVHA 80

                         90
                 ....*....|....*....
gi 679004203 649 SCYGVSPDKATEDWMCSRC 667
Cdd:cd15576   81 SCYGVNPDLVNEGWTCSRC 99

first Tudor domain found in Jumonji domain-containing protein 2 (JMJD2) family of histone demethylases; JMJD2 proteins, also called 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 canonical PHD domain, a noncanonical extended PHD domain, and tandem Tudor domains. The model corresponds to the first Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions. JMJD2D is not included in this model, since it lacks both the PHD and Tudor domains and has a different substrate specificity. JMJD2A-C are required for efficient cancer cell growth.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 679004203 801 LSPGQIVISKHKNGRFYQCEVVSLAKETFYEVNFDDGSFSDNLYPEDIVSRDC 853
Cdd:cd20391    1 ISVGQRVIAKHKNGRYYEAEVVDLTTQTFYEVNFDDGSFSDDLPPEDIVSYNC 53

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 679004203 629 EEDGTSVLITCKNCHVCVHASCYGVsPDKATEDWMCSRCTENALEEDCCL-CSLRGGALQRANDDKWVHVMCAVAVLEAK 707
Cdd:COG5141  203 HNENSNAIVFCDGCEICVHQSCYGI-QFLPEGFWLCRKCIYGEYQIRCCSfCPSSDGAFKQTSDGRWGHVICAMFNPELS 281

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 679004203 708 FVNIAERSPVD-VGKIPLQRFRLKCIFCKKRrkriAGCCVQCSHGRCPTSFHVSCAQAAGVMM 769
Cdd:COG5141  282 FGHLLSKDPIDnIASVSSSRWKLGCLICKEF----GGTCIQCSYFNCTRAYHVTCARRAGYFD 340

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 679004203 676 CCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVD-VGKIPLQRFRLKCIFCKKRrkriAGCCVQCSHGRCP 754
Cdd:cd15670    1 CVLCPNKGGAFKQTDDGRWAHVVCALWIPEVSFANTVFLEPIDgIQNIPKARWKLTCYICKKR----MGACIQCHKKNCY 76

                         90
                 ....*....|....*
gi 679004203 755 TSFHVSCAQAAGVMM 769
Cdd:cd15670   77 TAFHVTCAQQAGLYM 91

first Tudor domain found in Jumonji domain-containing protein 2C (JMJD2C) and similar proteins; JMJD2C, also called lysine-specific demethylase 4C (KDM4C), 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) domain, a noncanonical extended PHD domain, and tandem Tudor domains. The model corresponds to the first Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 679004203 801 LSPGQIVISKHKNGRFYQCEVVSLAKETFYEVNFDDGSFSDNLYPEDIVSRDCL 854
Cdd:cd20465    1 ISVGQTVISKHRNTRYYSCRVTEVTSQTFYEVMFDDGSFSRDTFPEDIVSRDCL 54

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 679004203 676 CCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVD-VGKIPLQRFRLKCIFCKKRRkriAGCCVQCSHGRCP 754
Cdd:cd15701    1 CALCPNKGGAFKQTDDGRWAHVVCALWIPEVCFANTVFLEPIDsIEHIPPARWKLTCYICKQRG---SGACIQCHKANCY 77

                         90
                 ....*....|....*.
gi 679004203 755 TSFHVSCAQAAGVMMQ 770
Cdd:cd15701   78 TAFHVTCAQQAGLYMK 93

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 679004203 676 CCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVD-VGKIPLQRFRLKCIFCKKRRKriaGCCVQCSHGRCP 754
Cdd:cd15703    1 CVLCPNKGGAFKQTSDGRWAHVVCAIWIPEVCFANTVFLEPVEgVNNIPPARWKLTCYLCKQKGR---GAAIQCHKVNCY 77

                         90
                 ....*....|....*...
gi 679004203 755 TSFHVSCAQAAGVMMQPD 772
Cdd:cd15703   78 TAFHVTCAQRAGLFMKIE 95

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 679004203 676 CCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVD-VGKIPLQRFRLKCIFCKKRrkriAGCCVQCSHGRCP 754
Cdd:cd15662    1 CCLCPVVGGALKPTTDGRWAHLACAIWIPETCLLDVKTMEPVDgINAISKERWELSCTICKQR----YGACIQCSNNSCR 76

                         90
                 ....*....|....*.
gi 679004203 755 TSFHVSCAQAAGVMMQ 770
Cdd:cd15662   77 VAYHPLCARAAGLCME 92

Extended PHD finger found in PHD finger protein 14 (PHF14) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of PHF14. 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 this non-canonical ePHD finger. It can interact with histones through its PHD fingers.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 679004203 676 CCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVDVGKIPLQRFRLK-CIFCKKRRKRIAGCCVQCSHGRCP 754
Cdd:cd15674    1 CELCPNRGGIFKETDTGRWVHLVCALYTPGVAFGDVDKLSPVTLTEMNYSKWGAReCSLCEDPRFARTGVCISCDAGMCK 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 679004203 755 TSFHVSCAQAAGVMMQPDDW-----PFvvFITCFRH 785
Cdd:cd15674   81 SYFHVTCAQREGLLSEATDEediadPF--YAYCKQH 114

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 679004203 676 CCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVDVGKIPLQRFRLKCIFCK---KRRKRIAGCCVQCSHGR 752
Cdd:cd15708    5 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIVLQSVPHERYNKTCYICDeqgRESKAATGACMTCNKHG 84

                         90
                 ....*....|....*...
gi 679004203 753 CPTSFHVSCAQAAGVMMQ 770
Cdd:cd15708   85 CRQAFHVTCAQLAGLLCE 102

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 679004203 676 CCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVDVGKIPLQRFRLKCIFCK---KRRKRIAGCCVQCSHGR 752
Cdd:cd15709    5 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPIVLQYVPHDRFNKTCYICEeqgRESKAASGACMTCNRHG 84

                         90       100
                 ....*....|....*....|
gi 679004203 753 CPTSFHVSCAQAAGVMMQPD 772
Cdd:cd15709   85 CRQAFHVTCAQMAGLLCEEE 104

Jumonji domain-containing protein 2A Tudor domain; This is the tudor domain found in histone demethylase Jumonji domain-containing protein 2A (JMJD2A). Structure and function analysis indicate that this domain can recognize equally well two unrelated histone peptides, H3K4me3 and H4K20me3, by means of two very different binding mechanisms. JMJD2 also known as KDM4, is a conserved iron (II)-dependent jumonji-domain demethylase subfamily that is essential during development. Vertebrate KDM4A-C proteins contain a conserved double tudor domain (DTD).

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 679004203  862 GEVVQVRWTDGQVYGAKFVASHAIQMYQVEFEDGS 896
Cdd:pfam18104   1 GQDVIARWTDGRYYLGKFIGIHTQTFYEVEFEDGS 35

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 679004203 676 CCLCSLRGGALQRAND-DKWVHVMCAVAVLEAKFVNIAERSPV-DVGKIPLQRFRLKCIFCKKRrkriAGCCVQCSHGRC 753
Cdd:cd15706    1 CLLCPKTGGAMKATRTgTKWAHVSCALWIPEVSIACPERMEPItKVSHIPPSRWALVCSLCKLK----TGACIQCSVKSC 76

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 679004203 754 PTSFHVSCAQAAGVMMQP--DDWPFVVFIT-CFRH 785
Cdd:cd15706   77 ITAFHVTCAFEHSLEMKTilDEGDEVKFKSyCLKH 111

Jumonji domain-containing protein 2A Tudor domain; This is the tudor domain found in histone demethylase Jumonji domain-containing protein 2A (JMJD2A). Structure and function analysis indicate that this domain can recognize equally well two unrelated histone peptides, H3K4me3 and H4K20me3, by means of two very different binding mechanisms. JMJD2 also known as KDM4, is a conserved iron (II)-dependent jumonji-domain demethylase subfamily that is essential during development. Vertebrate KDM4A-C proteins contain a conserved double tudor domain (DTD).

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 679004203  804 GQIVISKHKNGRFYQCEVVSLAKETFYEVNFDDGS 838
Cdd:pfam18104   1 GQDVIARWTDGRYYLGKFIGIHTQTFYEVEFEDGS 35

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
                  ....*....|....*....|....*....|....*
gi 679004203  633 TSVLITCKNCHVCVHASCYGVSPDKATEDWMCSRC 667
Cdd:pfam13831   1 TSPLVYCSKCSVQVHASCYGVPPIPDGDGWKCRRC 35

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
                 ....*....|....*....|....*....|...
gi 679004203 636 LITCKNCHVCVHASCYGVSPDK-ATEDWMCSRC 667
Cdd:cd15493   10 LLVCSRCCVCVHASCYGVPDIPgDGEGWKCDRC 42

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 679004203 676 CCLCSLRGG---------------ALQRANDDKWVHVMCAVAVLEAKFVNIAERSP-VDVGKIPLQRFRLKCIFCKKrrk 739
Cdd:cd15667    1 CSLCNAKESnyelakkqsprtrpdALKCTSNGTWCHVLCALFNEDIKFGNSKSLQPiLNTESVLLKGSRQKCEICKV--- 77

                         90       100
                 ....*....|....*....|....
gi 679004203 740 rIAGCCVQCShgRCPTSFHVSCAQ 763
Cdd:cd15667   78 -SGGGLVKCE--VCDDRFHVSCAQ 98

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
                 ....*....|....*....|....*....|..
gi 679004203 636 LITCKNCHVCVHASCYGVsPDKATEDWMCSRC 667
Cdd:cd15492   16 IVFCDGCNVAVHQSCYGI-PLIPEGDWFCRKC 46

Extended PHD finger found in histone-lysine N-methyltransferase 2A (KMT2A) and 2B (KMT2B); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This subfamily includes the ePHD finger of histone-lysine N-methyltransferase trithorax (Trx) like proteins, KMT2A/MLL1 and KMT2B/MLL2. KMT2A and KMT2B comprise the mammalian Trx branch of COMPASS family, and are both essential for mammalian embryonic development. KMT2A 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. KMT2B is a second human homolog of Drosophila trithorax, located on chromosome 19 and functions as the catalytic subunit in the MLL2 complex. It 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. Both KMT2A and KMT2B contain a CxxC (x for any residue) zinc finger domain, three PHD fingers, this extended PHD (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 679004203 676 CCLCSLRG-------GALQRANDDKWVHVMCAVAVLEAkFVNIAER-----SPVDVGKiplqrfRLKCIFCKKrrkriAG 743
Cdd:cd15664    1 CALCGVYGddepndaGRLLYCGQDEWVHINCALWSAEV-FEEDDGSlqnvhSAVSRGR------MMKCELCGK-----PG 68

                         90       100
                 ....*....|....*....|....*....
gi 679004203 744 CCVQCSHGRCPTSFHVSCAQAAGVMMQPD 772
Cdd:cd15664   69 ATVGCCLKSCPANYHFMCARKAECVFQDD 97

Tudor domain found in PHD finger protein 20 (PHF20), PHF20-like protein 1 (PHF20L1), and similar proteins; PHF20, also called Glioma-expressed antigen 2, hepatocellular carcinoma-associated antigen 58, novel zinc finger protein, or transcription factor TZP (referring to Tudor and zinc finger domain containing protein), is a regulator of NF-kappaB activation by disrupting recruitment of PP2A to p65. It also functions as a transcription factor that binds to Akt and plays a role in Akt cell survival/growth signaling. Moreover, it transcriptionally regulates p53. The phosphorylation of PHF20 on Ser291 mediated by protein kinase B (PKB) is essential in tumorigenesis via the regulation of p53-mediated signaling. PHF20L1 is an active malignant brain tumor (MBT) domain-containing protein that binds to monomethylated lysine 142 on DNA (cytosine-5) Methyltransferase 1 (DNMT1) (DNMT1K142me1) and colocalizes at the perinucleolar space in a SET7-dependent manner. Both PHF20 and PHF20L1 contain an N-terminal malignant brain tumor (MBT) domain, a Tudor domain, a plant homeodomain (PHD) finger and putative DNA-binding domains AT hook and C2H2-type zinc finger. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 679004203 862 GEVVQVRWTDGQVYGAKFVASHAIQMYQVEFEDGSQLMVKRDDV 905
Cdd:cd20386    4 GEEVLARWSDCKFYPAKILKVLDNGTYEVLFYDGFKKTVKASNL 47

Tudor domain found in polycomb repressive complex 2 (PRC2)-associated polycomb-like (PCL) family proteins; The PCL family includes PHD finger protein1 (PHF1) and its homologs, metal-response element-binding transcription factor 2 (MTF2/PCL2) and PHF19/PCL3, which are accessory components of the Polycomb repressive complex 2 (PRC2) core complex. Members contain an N-terminal Tudor domain followed by two PHD domains, and a C-terminal MTF2 domain. PCL proteins 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 domain-containing proteins, the first PHD domains of PCL proteins do not display histone H3K4 binding affinity and they do not affect the binding of the Tudor domain to histones.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 679004203 860 AEGEVVQVRWTDGQVYGAKFV-ASHAIQMYQVEFEDGSQLMVKRDDVYTL 908
Cdd:cd20385    3 AEGQDVLARWTDGLFYLGTIKkVDSAKEKCLVIFEDDSTFWVLFKDIHKV 52

Extended PHD finger 1 found in histone-lysine N-methyltransferase 2C (KMT2C) and 2D (KMT2D); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the first ePHD finger of KMTC2C and KMTC2D. KMT2C, also termed myeloid/lymphoid or mixed-lineage leukemia protein 3 (MLL3), or homologous to ALR protein, is a histone H3 lysine 4 (H3K4) lysine methyltransferase that functions as a circadian factor contributing to genome-scale circadian transcription. It is a component of a large complex that acts as a coactivator of multiple transcription factors, including the bile acid (BA)-activated nuclear receptor, farnesoid X receptor (FXR), a critical player in BA homeostasis. The MLL3 complex is essential for p53 transactivation of small heterodimer partner (SHP). KMT2C is also a part of activating signal cointegrator-2 (ASC-2)-containing complex (ASCOM) that contains the transcriptional coactivator nuclear receptor coactivator 6 (NCOA6), KMT2C and its paralog MLL4. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named MLL4, a fourth human homolog of Drosophila trithorax, located on chromosome 12. It enzymatically generates trimethylated histone H3 Lysine 4 (H3K4me3). It plays an essential role in differentiating the human pluripotent embryonal carcinoma cell line NTERA-2 clone D1 (NT2/D1) stem cells by activating differentiation-specific genes, such as HOXA1-3 and NESTIN. KMT2D is also a part of ASCOM. Both KMT2C and KMT2D contain the catalytic domain SET, five plant PHD fingers, two ePHD fingers, a RING finger, an HMG (high-mobilitygroup)-binding motif, and two FY-rich regions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 679004203 676 CCLCSLrggalqranDDKWVHVMCA------VAVLEAKFVNiaerspvdVGKIPLQRFRLKCIFCKKrrkriAGCCVQCS 749
Cdd:cd15665    1 CALCNL---------GEVYAHHCCAawsegvCQTEDGALEN--------VDKAVAKALSQKCSFCLR-----YGASISCR 58