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 240120089  775 CCLCSLRGGALQRANDDRWVHVSCAVAILEARFVNIAERSPVDVSKIPLPRFKLKCVFCKKRRKRNAGCCVQCSHGRCPT 854
Cdd:cd15713     1 CCLCSLRGGALQRANDDKWVHVMCAVAVLEARFVNIAERSPVDVSKIPLQRFKLKCIFCKKRRKRTAGCCVQCSHGRCPT 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 240120089  855 AFHVSCAQAAGVMMQPDDWPFVVFITCFRH 884
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 240120089   175 YLYFGMWKTSFAWHTEDMDLYSINYLHFGEPKSWYSVPPEHGKRLERLAKGFFPGSaqsCEAFLRHKMTLISPLMLKKYG 254
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLYSINYLHFGAPKVWYIIPPEYAEKFEKVLSDHFGGE---QPDDLLHLNTIISPKQLRENG 77

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 240120089   255 IPFDKVTQEAGEFMITFPYGYHAGFNHGFNCAESTNF 291
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 240120089  899 ITAGQKVISKHKNGRFYQCEVVRLTTETFYEVNFDDGSFSDNLYPEDIVSQDCLQ 953
Cdd:cd20463     1 ITAGQKVISKHKNGRFYQCEVVRLTKETFYEVNFDDGSFSDNLYPEDIVSQDCLQ 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 240120089  775 CCLCSLRGGALQRANDDRWVHVSCAVAILEARFVNIAERSPVDVSKIPLPRFKLKCVFCKKRRKRNAGCCVQCSHGRCPT 854
Cdd:cd15713     1 CCLCSLRGGALQRANDDKWVHVMCAVAVLEARFVNIAERSPVDVSKIPLQRFKLKCIFCKKRRKRTAGCCVQCSHGRCPT 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 240120089  855 AFHVSCAQAAGVMMQPDDWPFVVFITCFRH 884
Cdd:cd15713    81 SFHASCAQAAGVMMQPDDWPFVVFITCFRH 110

PHD-zinc-finger like domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240120089   774 DCCLCSLRGGALQRANDDRWVHVSCAVAILEARFVNIAERSPVDVSKIPLPRFKLKCVFCKKRRkrnaGCCVQCSHGRCP 853
Cdd:pfam13832    2 RCCLCPLRGGALKQTSDGRWVHVLCAIFVPEVRFGNVATMEPIDVSRIPPERWKLKCVFCKKRS----GACIQCSKGRCT 77

                           90       100       110
                   ....*....|....*....|....*....|..
gi 240120089   854 TAFHVSCAQAAGVMMQPDDWP-FVVFITCFRH 884
Cdd:pfam13832   78 TAFHVTCAQAAGVYMEPEDWPnVVVIAYCQKH 109

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 240120089  956 PPAEGEVVQVRWTDGQVYGAKFVASHPIQMYQVEFEDGSQLVVKRDDVYTLDEELP 1011
Cdd:cd20466     1 PPAEGEVVQVRWTDGQVYGAKFVASHPIQMYQVEFEDGSQLVVKRDDVYTLDEELP 56

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240120089  728 EEDGTSMLVSCKKCSVRVHASCYGVPPAkASEEWMCSRCSANALEEDCCL-CSLRGGALQRANDDRWVHVSCAVAILEAR 806
Cdd:COG5141   203 HNENSNAIVFCDGCEICVHQSCYGIQFL-PEGFWLCRKCIYGEYQIRCCSfCPSSDGAFKQTSDGRWGHVICAMFNPELS 281

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 240120089  807 FVNIAERSPVD-VSKIPLPRFKLKCVFCKKRrkrnAGCCVQCSHGRCPTAFHVSCAQAAGVMM 868
Cdd:COG5141   282 FGHLLSKDPIDnIASVSSSRWKLGCLICKEF----GGTCIQCSYFNCTRAYHVTCARRAGYFD 340

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 240120089   960 GEVVQVRWTDGQVYGAKFVASHPIQMYQVEFEDGS 994
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 240120089   902 GQKVISKHKNGRFYQCEVVRLTTETFYEVNFDDGS 936
Cdd:pfam18104    1 GQDVIARWTDGRYYLGKFIGIHTQTFYEVEFEDGS 35

jmjN domain;

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 240120089    15 MTFYPTMEEFRNFSRYIAYIESQGAhRAGLAKVVP 49
Cdd:pfam02375    1 PVFYPTEEEFKDPLKYIEKIRPLGE-KYGICKIVP 34

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 240120089    899 ITAGQKVISKHKNGRFYQCEVVRLTTETFYEVNFDDGSFSDNLYPEDIVSQDCLQ 953
Cdd:smart00333    3 FKVGDKVAARWEDGEWYRARIVKVDGEQLYEVFFIDYGNEEVVPPSDLRQLPEEL 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
                    ....*....|....*....|....*....|....
gi 240120089    735 LVSCKKCSVRVHASCYGVPPAKA--SEEWMCSRC 766
Cdd:smart00249   14 LLQCDGCDRWYHQTCLGPPLLEEepDGKWYCPKC 47

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 240120089  775 CCLCSLRGGALQRANDDRWVHVSCAVAILEARFVNIAERSPVDVSKIPLPRFKLKCVFCKKRRKRNAGCCVQCSHGRCPT 854
Cdd:cd15713     1 CCLCSLRGGALQRANDDKWVHVMCAVAVLEARFVNIAERSPVDVSKIPLQRFKLKCIFCKKRRKRTAGCCVQCSHGRCPT 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 240120089  855 AFHVSCAQAAGVMMQPDDWPFVVFITCFRH 884
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 240120089  775 CCLCSLRGGALQRANDDRWVHVSCAVAILEARFVNIAERSPVDVSKIPLPRFKLKCVFCKKRRKRNAGCCVQCSHGRCPT 854
Cdd:cd15715     1 CCLCNLRGGALKQTSDDKWAHVMCAVALPEVRFINVVERTPIDISRIPLQRLKLKCIFCRNRIKRVSGACIQCSYGRCPA 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 240120089  855 AFHVSCAQAAGVMMQPDDWPFVVFITCFRH 884
Cdd:cd15715    81 SFHVTCAHAAGVLMEPDDWPYVVFITCFRH 110

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 240120089  775 CCLCSLRGGALQRANDDRWVHVSCAVAILEARFVNIAERSPVDVSKIPLPRFKLKCVFCKKRRKRNAGCCVQCSHGRCPT 854
Cdd:cd15714     1 CCLCNLRGGALQMTTDERWVHVICAIAVPEARFLNVIERHPVDVSAIPEQRWKLKCVYCRKRMKKVSGACIQCSYDHCST 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 240120089  855 AFHVSCAQAAGVMMQPDDWPFVVFITCFRH 884
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 240120089   175 YLYFGMWKTSFAWHTEDMDLYSINYLHFGEPKSWYSVPPEHGKRLERLAKGFFPGSaqsCEAFLRHKMTLISPLMLKKYG 254
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLYSINYLHFGAPKVWYIIPPEYAEKFEKVLSDHFGGE---QPDDLLHLNTIISPKQLRENG 77

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 240120089   255 IPFDKVTQEAGEFMITFPYGYHAGFNHGFNCAESTNF 291
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 240120089  899 ITAGQKVISKHKNGRFYQCEVVRLTTETFYEVNFDDGSFSDNLYPEDIVSQDCLQ 953
Cdd:cd20463     1 ITAGQKVISKHKNGRFYQCEVVRLTKETFYEVNFDDGSFSDNLYPEDIVSQDCLQ 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 240120089  667 HCAVCMIFQTYHQvEFGAFSQSCGDASEPAAQTQRTKPLIPEMCFTTTGCSTDINLSTPYLEEDGTSMLVSCKKCSVRVH 746
Cdd:cd15576     1 YCAICTLFYPYTQ-SLQDPKEISDMSGLVSKVGQKTRPLIPEMCFTAGGENTEPLPSNSYIGDDGTSVLLSCAKCCLQVH 79

                          90       100
                  ....*....|....*....|
gi 240120089  747 ASCYGVPPAKASEEWMCSRC 766
Cdd:cd15576    80 ASCYGVNPDLVNEGWTCSRC 99

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 240120089  667 HCAVCMIFQTYHQVE-FGAFSQSCGDA---SEPAAQTQRTKPLIPEMCFTTTGCSTDINLSTPYLEEDGTSMLVSCKKCS 742
Cdd:cd15577     1 HCAICTLFMPYYKPDaLNEENSAQWEMelpAAPCISMRKTKPLIPEMCFIYREENCEPSPPNALLQEDGTSLLISCAKCC 80

                          90       100
                  ....*....|....*....|....
gi 240120089  743 VRVHASCYGVPPAKASEEWMCSRC 766
Cdd:cd15577    81 VQVHASCYGVPSHEIHDGWLCARC 104

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 240120089  956 PPAEGEVVQVRWTDGQVYGAKFVASHPIQMYQVEFEDGSQLVVKRDDVYTLDEELP 1011
Cdd:cd20392     1 PPEVGDPVKVKWTDGELYDAKFVGSSIVIMYTVEFEDGSVLTLKREDVYTLDEELP 56

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 240120089  775 CCLCSLRGGALQRANDDRWVHVSCAVAILEARFVNIAERSPVD-VSKIPLPRFKLKCVFCKKRrkrnAGCCVQCSHGRCP 853
Cdd:cd15670     1 CVLCPNKGGAFKQTDDGRWAHVVCALWIPEVSFANTVFLEPIDgIQNIPKARWKLTCYICKKR----MGACIQCHKKNCY 76

                          90
                  ....*....|....*
gi 240120089  854 TAFHVSCAQAAGVMM 868
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 240120089  899 ITAGQKVISKHKNGRFYQCEVVRLTTETFYEVNFDDGSFSDNLYPEDIVSQDCL 952
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 240120089  775 CCLCSLRGGALQRANDDRWVHVSCAVAILEARFVNIAERSPVD-VSKIPLPRFKLKCVFCKKRrkrNAGCCVQCSHGRCP 853
Cdd:cd15701     1 CALCPNKGGAFKQTDDGRWAHVVCALWIPEVCFANTVFLEPIDsIEHIPPARWKLTCYICKQR---GSGACIQCHKANCY 77

                          90
                  ....*....|....*.
gi 240120089  854 TAFHVSCAQAAGVMMQ 869
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 240120089  775 CCLCSLRGGALQRANDDRWVHVSCAVAILEARFVNIAERSPVD-VSKIPLPRFKLKCVFCKKRRKrnaGCCVQCSHGRCP 853
Cdd:cd15703     1 CVLCPNKGGAFKQTSDGRWAHVVCAIWIPEVCFANTVFLEPVEgVNNIPPARWKLTCYLCKQKGR---GAAIQCHKVNCY 77

                          90
                  ....*....|....*...
gi 240120089  854 TAFHVSCAQAAGVMMQPD 871
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 240120089  775 CCLCSLRGGALQRANDDRWVHVSCAVAILEARFVNIAERSPVD-VSKIPLPRFKLKCVFCKKRrkrnAGCCVQCSHGRCP 853
Cdd:cd15662     1 CCLCPVVGGALKPTTDGRWAHLACAIWIPETCLLDVKTMEPVDgINAISKERWELSCTICKQR----YGACIQCSNNSCR 76

                          90
                  ....*....|....*.
gi 240120089  854 TAFHVSCAQAAGVMMQ 869
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 240120089  775 CCLCSLRGGALQRANDDRWVHVSCAVAILEARFVNIAERSPVDVSKIPLPRFKLK-CVFCKKRRKRNAGCCVQCSHGRCP 853
Cdd:cd15674     1 CELCPNRGGIFKETDTGRWVHLVCALYTPGVAFGDVDKLSPVTLTEMNYSKWGAReCSLCEDPRFARTGVCISCDAGMCK 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 240120089  854 TAFHVSCAQAAGVMMQPDDW-----PFvvFITCFRH 884
Cdd:cd15674    81 SYFHVTCAQREGLLSEATDEediadPF--YAYCKQH 114

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 240120089  775 CCLCSLRGGALQRAN-DDRWVHVSCAVAILEARFVNIAERSP-VDVSKIPLPRFKLKCVFCKKRRkrnaGCCVQCShgRC 852
Cdd:cd15663     1 CCLCPVKGGALKPTDvEGLWVHVTCAWFRPEVCFKNEEKMEPaVGLLRIPLSTFLKACVICKQIH----GSCTQCC--KC 74

                          90
                  ....*....|....*..
gi 240120089  853 PTAFHVSCAQAAGVMMQ 869
Cdd:cd15663    75 ATYFHAMCASRAGYHME 91

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 240120089  775 CCLCSLRGGALQRAND-DRWVHVSCAVAILEARFVNIAERSPV-DVSKIPLPRFKLKCVFCKKrrkrNAGCCVQCSHGRC 852
Cdd:cd15705     1 CLLCPKRGGALKPTRSgTKWVHVSCALWIPEVSIGCPEKMEPItKISHIPASRWALSCSLCKE----CTGTCIQCSMPSC 76

                          90
                  ....*....|....*..
gi 240120089  853 PTAFHVSCAQAAGVMMQ 869
Cdd:cd15705    77 ITAFHVTCAFDHGLEMR 93

Small domain found in the jumonji family of transcription factors; To date, this domain always co-occurs with the JmjC domain (although the reverse is not true).

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|...
gi 240120089     13 RIMTFYPTMEEFRNFSRYIAYIESQgAHRAGLAKVVPPKEWKP 55
Cdd:smart00545    1 EIPVFYPTMEEFKDPLAYISKIRPQ-AEKYGICKVVPPKSWKP 42

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 240120089  775 CCLCSLRGGALQRAND-DRWVHVSCAVAILEARFVNIAERSPV-DVSKIPLPRFKLKCVFCKKRrkrnAGCCVQCSHGRC 852
Cdd:cd15706     1 CLLCPKTGGAMKATRTgTKWAHVSCALWIPEVSIACPERMEPItKVSHIPPSRWALVCSLCKLK----TGACIQCSVKSC 76

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 240120089  853 PTAFHVSCAQAAGVMMQP--DDWPFVVFIT-CFRH 884
Cdd:cd15706    77 ITAFHVTCAFEHSLEMKTilDEGDEVKFKSyCLKH 111

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 240120089    146 DEWNIGRLKTILDLVEKESGItIEGVNT-PYLYFGMWKTSFAWHTEDMDLysINYLHFGEP 205
Cdd:smart00558    1 QLWNLAKLPFKLNLLSDLPED-IPGPDVgPYLYMGMAGSTTPWHIDDYDL--VNYLHQGAG 58

Extended PHD finger found in protein Jade-1 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Jade-1. Jade-1, also termed PHD finger protein 17 (PHF17), is a novel binding partner of von Hippel-Lindau (VHL) tumor suppressor Pvhl, a key regulator of cellular oxygen sensing pathway. It is highly expressed in renal proximal tubules. Jade-1 functions as an essential regulator of multiple cell signaling pathways. It may be involved in the Serine/threonine kinase AKT/AKT1 pathway during renal cancer pathogenesis and normally prevents renal epithelial cell proliferation and transformation. It also acts as a pro-apoptotic and growth suppressive ubiquitin ligase to inhibit canonical Wnt downstream effector beta-catenin for proteasomal degradation and ASA transcription factor associated with histone acetyltransferase activity and with increased abundance of cyclin-dependent kinase inhibitor p21. Moreover, Jade-1 is required for ING4 and ING5 to associate with histone acetyltransferase (HAT) HBO1 and Eaf6 to form a HBO1 complex, and plays a role in epithelial cell regeneration. It has also been identified as a novel component of the nephrocystin protein (NPHP) complex and interacts with the ciliary protein nephrocystin-4 (NPHP4). Jade-1 contains a canonical plant homeodomain (PHD) finger followed by this non-canonical ePHD finger, both of which are zinc-binding motifs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240120089  775 CCLCSLRGGALQRAND-DRWVHVSCAVAILEARFVNIAERSPV-DVSKIPLPRFKLKCVFCKKRrkrnAGCCVQCSHGRC 852
Cdd:cd15704     4 CLLCPKKGGAMKPTRSgTKWVHVSCALWIPEVSIGSPEKMEPItKVSHIPSSRWALVCSLCNEK----VGASIQCSVKNC 79

                          90
                  ....*....|....*..
gi 240120089  853 PTAFHVSCAQAAGVMMQ 869
Cdd:cd15704    80 RTAFHVTCAFDRGLEMK 96

jmjN domain;

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 240120089    15 MTFYPTMEEFRNFSRYIAYIESQGAhRAGLAKVVP 49
Cdd:pfam02375    1 PVFYPTEEEFKDPLKYIEKIRPLGE-KYGICKIVP 34

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 240120089    899 ITAGQKVISKHKNGRFYQCEVVRLTTETFYEVNFDDGSFSDNLYPEDIVSQDCLQ 953
Cdd:smart00333    3 FKVGDKVAARWEDGEWYRARIVKVDGEQLYEVFFIDYGNEEVVPPSDLRQLPEEL 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 240120089  960 GEVVQVRWT-DGQVYGAKFVASHPIQMYQVEFEDGSQLVVKRDDVY 1004
Cdd:cd04508     1 GDRVEAKWSdDGQWYPATVVAVNDDGKYTVLFDDGNEEEVSEDDIR 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 240120089  775 CCLCSLRG-------GALQRANDDRWVHVSCAVAILEArFVNIAERSPVDVSKIPLPRfKLKCVFCKKrrkrnAGCCVQC 847
Cdd:cd15664     1 CALCGVYGddepndaGRLLYCGQDEWVHINCALWSAEV-FEEDDGSLQNVHSAVSRGR-MMKCELCGK-----PGATVGC 73

                          90       100
                  ....*....|....*....|....
gi 240120089  848 SHGRCPTAFHVSCAQAAGVMMQPD 871
Cdd:cd15664    74 CLKSCPANYHFMCARKAECVFQDD 97

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 240120089  775 CCLCSLRG-------GALQRANDDRWVHVSCAVAILE------ARFVNIAErspvdvskiPLPR-FKLKCVFCKKRrkrn 840
Cdd:cd15666     1 CVLCGGEGdgdtdgpGRLLNLDVDKWVHLNCALWSYEvyetqnGALMNVEE---------ALRRaLTTTCSHCGRT---- 67

                          90       100
                  ....*....|....*....|....*..
gi 240120089  841 aGCCVQCSHGRCPTAFHVSCAQAAGVM 867
Cdd:cd15666    68 -GATVPCFKPRCANVYHLPCAIKDGCM 93