PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) finger typically characterized as Cys4HisCys3, and a non-canonical extended PHD finger, characterized as Cys2HisCys5HisCys2His. Variations include the RAG2 PHD finger characterized by Cys3His2Cys2His and the PHD finger 5 found in nuclear receptor-binding SET domain-containing proteins characterized by Cys4HisCys2His. The PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. Single or multiple copies of PHD fingers have been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors. The PHD finger domain SF is structurally similar to the RING and FYVE_like superfamilies.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678179234 595 YCAVCMLFQTYQVHR--PSLQNAGVTPTAVGGKIRTKPLIPEMCFTTTGCSTDLNLSTPYLEEDGTSVLITCKNCHVCVH 672
Cdd:cd15575    1 HCAVCMLFQTYQVDCwgGHNSSSGVAASEARIKKKTKPLIPEMCFTSTGCNTDLNLSTPYLEEDGTSILVTCKKCCVCVH 80

                         90       100
                 ....*....|....*....|
gi 678179234 673 ASCYGVSPDKATEDWMCSRC 692
Cdd:cd15575   81 ASCYGVSPEKAAEDWMCSRC 100

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 678179234 876 PPAEGEVVQVRWTDGQVYGAKFVASHAIQMYQVEFEDGSQLMVKRDDVYTLEEELP 931
Cdd:cd20466    1 PPAEGEVVQVRWTDGQVYGAKFVASHPIQMYQVEFEDGSQLVVKRDDVYTLDEELP 56

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 678179234 595 YCAVCMLFQTYQVHR--PSLQNAGVTPTAVGGKIRTKPLIPEMCFTTTGCSTDLNLSTPYLEEDGTSVLITCKNCHVCVH 672
Cdd:cd15575    1 HCAVCMLFQTYQVDCwgGHNSSSGVAASEARIKKKTKPLIPEMCFTSTGCNTDLNLSTPYLEEDGTSILVTCKKCCVCVH 80

                         90       100
                 ....*....|....*....|
gi 678179234 673 ASCYGVSPDKATEDWMCSRC 692
Cdd:cd15575   81 ASCYGVSPEKAAEDWMCSRC 100

PHD-zinc-finger like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678179234  700 DCCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVDVGKIPLQRFRLKCIFCKKRRkriaGCCVQCSHGRCP 779
Cdd:pfam13832   2 RCCLCPLRGGALKQTSDGRWVHVLCAIFVPEVRFGNVATMEPIDVSRIPPERWKLKCVFCKKRS----GACIQCSKGRCT 77

                          90       100       110
                  ....*....|....*....|....*....|..
gi 678179234  780 TSFHVSCAQAAGVMMQPDDWP-FVVFITCFRH 810
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 678179234 822 GQIVISKHKNGRFYQCEVVSLAKETFYEVNFDDGSFSDNLYPEDIVSRDCLQ 873
Cdd:cd20463    4 GQKVISKHKNGRFYQCEVVRLTKETFYEVNFDDGSFSDNLYPEDIVSQDCLQ 55

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 678179234  880 GEVVQVRWTDGQVYGAKFVASHAIQMYQVEFEDGS 914
Cdd:pfam18104   1 GQDVIARWTDGRYYLGKFIGIHTQTFYEVEFEDGS 35

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 678179234  822 GQIVISKHKNGRFYQCEVVSLAKETFYEVNFDDGS 856
Cdd:pfam18104   1 GQDVIARWTDGRYYLGKFIGIHTQTFYEVEFEDGS 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 678179234   875 GPPAEGEVVQVRWTDGQVYGAKFVASHAIQMYQVEFED-GSQLMVKRDDVYTLEEEL 930
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 678179234   654 EEDGTSVLITCKNCHVCVHASCYGVSPDKA--TEDWMCSRC 692
Cdd:smart00249   7 KPDDGGELLQCDGCDRWYHQTCLGPPLLEEepDGKWYCPKC 47

Extended PHD finger found in Jumonji domain-containing protein 2 (JMJD2) family of histone demethylases; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of JMJD2 proteins. JMJD2 proteins, also termed lysine-specific demethylase 4 histone demethylases (KDM4), have been implicated in various cellular processes including DNA damage response, transcription, cell cycle regulation, cellular differentiation, senescence, and carcinogenesis. They selectively catalyze the demethylation of di- and trimethylated H3K9 and H3K36. This model contains three JMJD2 proteins, JMJD2A-C, which all contain jmjN and jmjC domains in the N-terminal region, followed by a canonical PHD finger, this non-canonical ePHD finger, and a Tudor domain. JMJD2D is not included in this family, since it lacks both PHD and Tudor domains and has a different substrate specificity. JMJD2A-C are required for efficient cancer cell growth.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678179234 701 CCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVDVGKIPLQRFRLKCIFCKKRRK--RIAGCCVQCSHGRC 778
Cdd:cd15675    1 CCLCCLRGGALKPTTDGRWAHVVCAIAIPEVRFSNVPERGPIDISKIPPARLKLKCIYCSKITKsmSHMGACIQCSTGKC 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 678179234 779 PTSFHVSCAQAAGVMMQPDDWPFVVFITCFRH 810
Cdd:cd15675   81 TTSFHVTCAHAAGVQMEPDDWPYPVYVTCTKH 112

Extended PHD finger found in Jumonji domain-containing protein 2B (JMJD2B); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of JMJD2B. JMJD2B, also termed lysine-specific demethylase 4B (KDM4B), or JmjC domain-containing histone demethylation protein 3B (JHDM3B), specifically antagonizes the trimethyl group from H3K9 in pericentric heterochromatin and reduces H3K36 methylation in mammalian cells. It plays an essential role in the growth regulation of cancer cells by modulating the G1-S transition and promotes cell-cycle progression through the regulation of cyclin-dependent kinase 6 (CDK6). It interacts with heat shock protein 90 (Hsp90) and its stability can be regulated by Hsp90. JMJD2B also functions as a direct transcriptional target of p53, which induces its expression through promoter binding. Moreover, JMJD2B expression can be controlled by hypoxia-inducible factor 1alpha (HIF1alpha) in colorectal cancer and estrogen receptor alpha (ERalpha) in breast cancer. It is also involved in bladder, lung, and gastric cancer. JMJD2B contains jmjN and jmjC domains in the N-terminal region, followed by a canonical PHD finger, this non-canonical ePHD finger, and a Tudor domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678179234 701 CCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVDVGKIPLQRFRLKCIFCKKRRKRIAGCCVQCSHGRCPT 780
Cdd:cd15714    1 CCLCNLRGGALQMTTDERWVHVICAIAVPEARFLNVIERHPVDVSAIPEQRWKLKCVYCRKRMKKVSGACIQCSYDHCST 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 678179234 781 SFHVSCAQAAGVMMQPDDWPFVVFITCFRH 810
Cdd:cd15714   81 SFHVTCAHAAGVVMEPDDWPYVVSITCFKH 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 678179234  117 YLYFGMWKTSFAWHTEDMDLYSINYLHFGEPKSWYSIPPEHGKRLERLAKGFFPGSaqsCEAFLRHKMTLISPSILKKYG 196
Cdd:pfam02373   1 WLYLGMPFSTTPWHIEDQGLYSINYLHFGAPKVWYIIPPEYAEKFEKVLSDHFGGE---QPDDLLHLNTIISPKQLRENG 77

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 678179234  197 IPFDKVTQEAGEFMITFPYSYHAGFNHGFNCAESTNF 233
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 678179234 876 PPAEGEVVQVRWTDGQVYGAKFVASHAIQMYQVEFEDGSQLMVKRDDVYTLEEELP 931
Cdd:cd20466    1 PPAEGEVVQVRWTDGQVYGAKFVASHPIQMYQVEFEDGSQLVVKRDDVYTLDEELP 56

second Tudor domain found in Jumonji domain-containing protein 2B (JMJD2B) and similar proteins; JMJD2B, also called lysine-specific demethylase 4B (KDM4B), or JmjC domain-containing histone demethylation protein 3B (JHDM3B), specifically antagonizes the tri-methyl 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 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 678179234 876 PPAEGEVVQVRWTDGQVYGAKFVASHAIQMYQVEFEDGSQLMVKRDDVYTLEEELP 931
Cdd:cd20467    1 PPSEGELVELRWTDGNIYKAKFISAHLSHIYQVEFEDGSQLTVKRGEIFTLEEELP 56

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 678179234 595 YCAVCMLFQTYQ--VHRPSLQNAGVTPTAVGGKiRTKPLIPEMCFTTTGCSTDLNLSTPYLEEDGTSVLITCKNCHVCVH 672
Cdd:cd15576    1 YCAICTLFYPYTqsLQDPKEISDMSGLVSKVGQ-KTRPLIPEMCFTAGGENTEPLPSNSYIGDDGTSVLLSCAKCCLQVH 79

                         90       100
                 ....*....|....*....|
gi 678179234 673 ASCYGVSPDKATEDWMCSRC 692
Cdd:cd15576   80 ASCYGVNPDLVNEGWTCSRC 99

second 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 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 678179234 876 PPAEGEVVQVRWTDGQVYGAKFVASHAIQMYQVEFEDGSQLMVKRDDVYTLEEELPKRVK 935
Cdd:cd20468    1 PPAEGEVVQVKWPDGLLYGAKYLGSNIAHMYQVEFEDGSQIVMKREDIYTLDEELPKKVK 60

second 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 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. 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 678179234 876 PPAEGEVVQVRWTDGQVYGAKFVASHAIQMYQVEFEDGSQLMVKRDDVYTLEEELP 931
Cdd:cd20392    1 PPEVGDPVKVKWTDGELYDAKFVGSSIVIMYTVEFEDGSVLTLKREDVYTLDEELP 56

first Tudor domain found in Jumonji domain-containing protein 2B (JMJD2B) and similar proteins; JMJD2B, also called lysine-specific demethylase 4B (KDM4B), or JmjC domain-containing histone demethylation protein 3B (JHDM3B), specifically antagonizes the tri-methyl 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 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 678179234 819 LSPGQIVISKHKNGRFYQCEVVSLAKETFYEVNFDDGSFSDNLYPEDIVSRDCL 872
Cdd:cd20464    1 VSLGQVVITKNRNGLYYRCRVIGTATQTFYEVNFDDGSYSDNVYPESITSRDCL 54

Extended PHD finger found in bromodomain and PHD finger-containing protein 2 (BRPF2) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of BRPF2. BRPF2 also termed bromodomain-containing protein 1 (BRD1), or BR140-likeprotein, is encoded by BRL (BR140 Like gene). It is responsible for the bulk of the acetylation of H3K14 and forms a novel monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complex with HBO1 and ING4. The complex is required for full transcriptional activation of the erythroid-specific regulator genes essential for terminal differentiation and survival of erythroblasts in fetal liver. BRPF2 shows widespread expression and localizes to the nucleus within spermatocytes. It contains a cysteine rich region harboring a plant homeodomain (PHD) finger followed by a non-canonical ePHD finger, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678179234 701 CCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVD-VGKIPLQRFRLKCIFCKKRRkriAGCCVQCSHGRCP 779
Cdd:cd15702    1 CVLCPNKGGAFKKTDDDRWGHVVCALWIPEVGFANTVFIEPIDgVRNIPPARWKLTCYLCKQKG---VGACIQCHKANCY 77

                         90
                 ....*....|....*.
gi 678179234 780 TSFHVSCAQAAGVMMQ 795
Cdd:cd15702   78 TAFHVTCAQKAGLYMK 93

PHD finger found in Jumonji domain-containing protein 2C (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 through 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 Cys4HisCys3 plant homeodomain (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 678179234 595 YCAVCMLFQTYqvHRPSLQNAGVTP--------TAVGGKIRTKPLIPEMCFTTTGCSTDLNLSTPYLEEDGTSVLITCKN 666
Cdd:cd15577    1 HCAICTLFMPY--YKPDALNEENSAqwemelpaAPCISMRKTKPLIPEMCFIYREENCEPSPPNALLQEDGTSLLISCAK 78

                         90       100
                 ....*....|....*....|....*.
gi 678179234 667 CHVCVHASCYGVSPDKATEDWMCSRC 692
Cdd:cd15577   79 CCVQVHASCYGVPSHEIHDGWLCARC 104

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 678179234 701 CCLCSLRGGALQRAND-DKWVHVMCAVAVLEAKFVNIAERSPVD-VGKIPLQRFRLKCIFCKKRrkriAGCCVQCSHGRC 778
Cdd:cd15671    1 CVLCPKKGGAMKSTKSgTKWVHVSCALWIPEVSIGCPEKMEPITkISHIPMSRWALVCVLCKEK----TGACIQCSVKSC 76

                         90
                 ....*....|....*.
gi 678179234 779 PTSFHVSCAQAAGVMM 794
Cdd:cd15671   77 KTAFHVTCAFQHGLEM 92

Extended PHD finger found in protein AF-10 and AF-17; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of AF-10 and AF-17. AF-10, also termed ALL1 (acute lymphoblastic leukaemia)-fused gene from chromosome 10 protein, is a transcription factor encoded by gene AF10, a translocation partner of the MLL (mixed-lineage leukaemia) oncogene in leukaemia. AF-10 has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. It plays a key role in the survival of uncommitted hematopoietic cells. Moreover, AF-10 functions as a follistatin-related gene (FLRG)-interacting protein. The interaction with FLRG enhances AF10-dependent transcription. It interacts with the human counterpart of yeast Dot1, hDOT1L, and may act as a bridge for the recruitment of hDOT1L to the genes targeted by MLL-AF10. It also interacts with the synovial sarcoma associated protein SYT protein and may play a role in synovial sarcomas and acute leukemias. AF-17, also termed ALL1-fused gene from chromosome 17 protein, is encoded by gene AF17 that has been identified in hematological malignancies as translocation partners of the mixed lineage leukemia gene MLL. It is a putative transcription factor that may play a role in multiple signaling pathways. It is involved in chromatin-mediated gene regulation mechanisms. It functions as a component of the multi-subunit Dot1 complex (Dotcom) and plays a role in the Wnt/Wingless signaling pathway. It also seems to be a downstream target of the beta-catenin/T-cell factor pathway, and participates in G2-M progression. Moreover, it may function as an important regulator of ENaC-mediated Na+ transport and thus blood pressure. Both AF-10 and AF-17 contain an N-terminal plant homeodomain (PHD) finger followed by this non-canonical ePHD finger. The PHD finger is involved in their homo-oligomerization. In the C-terminal region, they possess a leucine zipper domain and a glutamine-rich region. This family also includes ZFP-1, the Caenorhabditis elegans AF10 homolog. It was originally identified as a factor promoting RNAi interference in C. elegans. It also acts as Dot1-interacting protein that opposes H2B ubiquitination to reduce polymerase II (Pol II) transcription.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678179234 701 CCLCSLRGGALQRANDDKWVHVMCAVAVLEAKFVNIAERSPVDVGKIPLQRFRLKCIFCKKRR---KRIAGCCVQCSHGR 777
Cdd:cd15672    1 CELCPHKDGALKRTDNGGWAHVVCALYIPEVRFGNVATMEPIILQDVPQDRFNKTCYICEEQGresKASTGACMQCNKSG 80

                         90
                 ....*....|....*.
gi 678179234 778 CPTSFHVSCAQAAGVM 793
Cdd:cd15672   81 CKQSFHVTCAQMAGLL 96

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 678179234 701 CCLCSLRGGALQRAN-DDKWVHVMCAVAVLEAKFVNIAERSP-VDVGKIPLQRFRLKCIFCKKrrkrIAGCCVQCShgRC 778
Cdd:cd15663    1 CCLCPVKGGALKPTDvEGLWVHVTCAWFRPEVCFKNEEKMEPaVGLLRIPLSTFLKACVICKQ----IHGSCTQCC--KC 74

                         90
                 ....*....|....*..
gi 678179234 779 PTSFHVSCAQAAGVMMQ 795
Cdd:cd15663   75 ATYFHAMCASRAGYHME 91

PHD-like zinc-binding domain; The members of this family are annotated as containing PHD domain, but the zinc-binding region here is not typical of PHD domains. The conformation here is a well-conserved cysteine-histidine rich region spanning 90 residues, where the Cys and His are arranged as HxxC(31)CxxC(6)CxxCxxxxCxxxxHxxC (21)CxxH.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678179234  721 HVMCAVAVLEAKFVNIAER--SPVDVGKIPLQRFRLKCIFCKKRRkriaGCCVQCSHGRCPTSFHVSCAQAAGVMMQ--P 796
Cdd:pfam13771   1 HVVCALWSPELVQRGNDSMgfPIEDIEKIPKRRWKLKCYLCKKKG----GACIQCSKKNCRRAFHVTCALEAGLLMQfdE 76

                          90
                  ....*....|....
gi 678179234  797 DDWPFVVFitCFRH 810
Cdd:pfam13771  77 DNGTFKSY--CKKH 88

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678179234 701 CCLCSLRGGALQRAND-DKWVHVMCAVAVLEAKFVNIAERSPV-DVGKIPLQRFRLKCIFCKKrrkrIAGCCVQCSHGRC 778
Cdd:cd15705    1 CLLCPKRGGALKPTRSgTKWVHVSCALWIPEVSIGCPEKMEPItKISHIPASRWALSCSLCKE----CTGTCIQCSMPSC 76

                         90
                 ....*....|....*..
gi 678179234 779 PTSFHVSCAQAAGVMMQ 795
Cdd:cd15705   77 ITAFHVTCAFDHGLEMR 93

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 678179234 701 CCLCSLRGGALQRAND-DKWVHVMCAVAVLEAKFVNIAERSPV-DVGKIPLQRFRLKCIFCKKRrkriAGCCVQCSHGRC 778
Cdd:cd15707    1 CILCPNKGGAMKSTRSgTKWAHVSCALWIPEVSIGCVEKMEPItKISSIPASRWALICVLCRER----TGACIQCSVKTC 76

                         90
                 ....*....|....*..
gi 678179234 779 PTSFHVSCAQAAGVMMQ 795
Cdd:cd15707   77 KTAYHVTCGFQHGLEMK 93

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 678179234    88 DAWNIGRLNTILDIVENESGItIEGVNT-PYLYFGMWKTSFAWHTEDMDLysINYLHFGEP 147
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 678179234  658 TSVLITCKNCHVCVHASCYGVSPDKATEDWMCSRC 692
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 678179234 661 LITCKNCHVCVHASCYGVSPDK-ATEDWMCSRC 692
Cdd:cd15493   10 LLVCSRCCVCVHASCYGVPDIPgDGEGWKCDRC 42

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 678179234   818 DLSPGQIVISKHKNGRFYQCEVVSLAKETFYEVNFDDGSFSDNLYPEDIVSRDCLQ 873
Cdd:smart00333   2 TFKVGDKVAARWEDGEWYRARIVKVDGEQLYEVFFIDYGNEEVVPPSDLRQLPEEL 57

Tudor domain superfamily; The Tudor domain is a conserved structural domain, originally identified in the Tudor protein of Drosophila, that adopts a beta-barrel-like core structure containing four short beta-strands followed by an alpha-helical region. It binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions. Tudor domain-containing proteins may mediate protein-protein interactions required for various DNA-templated biological processes, such as RNA metabolism, as well as histone modification and the DNA damage response. Members of this superfamily contain one or more copies of the Tudor domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 678179234 880 GEVVQVRWT-DGQVYGAKFVASHAIQMYQVEFEDGSQLMVKRDDVY 924
Cdd:cd04508    1 GDRVEAKWSdDGQWYPATVVAVNDDGKYTVLFDDGNEEEVSEDDIR 46

PHD finger found in Arabidopsis thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like protein ATX3, ATX4, ATX5, and similar proteins; The family includes A. thaliana 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. They show distinct phylogenetic origins from the ATX1 and ATX2 family. They are multi-domain containing proteins that consist of an N-terminal PWWP domain, a canonical Cys4HisCys3 plant homeodomain (PHD) finger, a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, and a C-terminal SET domain; this model corresponds to the Cys4HisCys3 canonical PHD finger.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 678179234 654 EEDGTSVLITCKNCHVCVHASCYGVSPDKATEDWMCSRC 692
Cdd:cd15495    9 EDDDNNPLITCNRCQISVHQKCYGIREVDPDGSWVCRAC 47

Extended PHD finger 2 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 second ePHD finger of KMT2C, and KMT2D. 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 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 678179234 701 CCLCSLRG-------GALQRANDDKWVHVMCAV---AVLEAK---FVNIAErspvdvgkiPLQRFR-LKCIFCKKRrkri 766
Cdd:cd15666    1 CVLCGGEGdgdtdgpGRLLNLDVDKWVHLNCALwsyEVYETQngaLMNVEE---------ALRRALtTTCSHCGRT---- 67

                         90       100
                 ....*....|....*....|....*..
gi 678179234 767 aGCCVQCSHGRCPTSFHVSCAQAAGVM 793
Cdd:cd15666   68 -GATVPCFKPRCANVYHLPCAIKDGCM 93

PHD finger 2 found in Saccharomyces cerevisiae SANT domain-containing protein 2 (Snt2p) and similar proteins; This group corresponds to Snt2p and similar proteins. Snt2p is a yeast protein that may function in multiple stress pathways. It coordinates the transcriptional response to hydrogen peroxide-mediated oxidative stress through interaction with Ecm5 and the Rpd3 deacetylase. Snt2p contains a bromo adjacent homology (BAH) domain, two canonical Cys4HisCys3 plant homeodomain (PHD) fingers, a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, and a SANT (SWI3, ADA2, N-CoR and TFIIIB) DNA-binding domain; this model corresponds to the second canonical Cys4HisCys3 PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 678179234 658 TSVLITCKNCHVCVHASCYGVS-PDKATED-------WMCSRC 692
Cdd:cd15498   13 FNTSLSCYNCGLNVHASCYGITvPGKMNKVknlksykWLCDPC 55

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 678179234 878 AEGEVVQVRWTDGQVYGAKFV-ASHAIQMYQVEFEDGSQLMVKRDDVYTL 926
Cdd:cd20385    3 AEGQDVLARWTDGLFYLGTIKkVDSAKEKCLVIFEDDSTFWVLFKDIHKV 52