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 1039753043  795 CCLCNLRGGALQRTTEHRWIHVICAIAVPEVRFLNVIERNPVDVSAIPEQRWKLKCIYCRKRMKRVSGACIQCSYEHCST 874
Cdd:cd15714      1 CCLCNLRGGALQMTTDERWVHVICAIAVPEARFLNVIERHPVDVSAIPEQRWKLKCVYCRKRMKKVSGACIQCSYDHCST 80

                           90       100       110
                   ....*....|....*....|....*....|
gi 1039753043  875 SFHVTCAHAAGVLMEPDDWPYVVSITCLKH 904
Cdd:cd15714     81 SFHVTCAHAAGVVMEPDDWPYVVSITCFKH 110

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 1039753043  652 YCAICTLFYPYSQvsclsglptlmapTVTCPTQPQCSLAycgpalsavtlqsvqterdsavqPPSKSGQRTRPLIPEMCF 731
Cdd:cd15576      1 YCAICTLFYPYTQ-------------SLQDPKEISDMSG-----------------------LVSKVGQKTRPLIPEMCF 44

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1039753043  732 TSSGENTEPLPANSYVGEDGTSPLISCAHCCLQVHASCYGVRPELAKEGWTCSRC 786
Cdd:cd15576     45 TAGGENTEPLPSNSYIGDDGTSVLLSCAKCCLQVHASCYGVNPDLVNEGWTCSRC 99

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        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1039753043  974 PPPEGELVELRWTDGNLYRARFISMATSLIYQVEFEDGSQLTVKRGDIFTLEEELP 1029
Cdd:cd20467      1 PPSEGELVELRWTDGNIYKAKFISAHLSHIYQVEFEDGSQLTVKRGEIFTLEEELP 56

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 1039753043  795 CCLCNLRGGALQRTTEHRWIHVICAIAVPEVRFLNVIERNPVDVSAIPEQRWKLKCIYCRKRMKRVSGACIQCSYEHCST 874
Cdd:cd15714      1 CCLCNLRGGALQMTTDERWVHVICAIAVPEARFLNVIERHPVDVSAIPEQRWKLKCVYCRKRMKKVSGACIQCSYDHCST 80

                           90       100       110
                   ....*....|....*....|....*....|
gi 1039753043  875 SFHVTCAHAAGVLMEPDDWPYVVSITCLKH 904
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 1039753043  176 YLYFGMWKTTFAWHTEDMDLYSINYLHFGEPKSWYAIPPEHGKRLERLAIGFFpgsSQGCDAFLRHKMTLISPIILKKYG 255
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLYSINYLHFGAPKVWYIIPPEYAEKFEKVLSDHF---GGEQPDDLLHLNTIISPKQLRENG 77

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1039753043  256 IPFSRITQEAGEFMITFPYGYHAGFNHGFNCAESTNF 292
Cdd:pfam02373   78 IPVYRFVQKPGEFVFTFPGWYHQVFNLGFNIAEAVNF 114

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 1039753043  917 VSLGQIVITKNRNGLYYRCRVIGTTAQTFYEVNFDDGSYSDNLYPESITSRDCL 970
Cdd:cd20464      1 VSLGQVVITKNRNGLYYRCRVIGTATQTFYEVNFDDGSYSDNVYPESITSRDCL 54

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 1039753043  974 PPPEGELVELRWTDGNLYRARFISMATSLIYQVEFEDGSQLTVKRGDIFTLEEELP 1029
Cdd:cd20467      1 PPSEGELVELRWTDGNIYKAKFISAHLSHIYQVEFEDGSQLTVKRGEIFTLEEELP 56

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 1039753043  752 TSPLISCAHCCLQVHASCYGVRPELAKEGWTCSRC 786
Cdd:pfam13831    1 TSPLVYCSKCSVQVHASCYGVPPIPDGDGWKCRRC 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 1039753043  978 GELVELRWTDGNLYRARFISMATSLIYQVEFEDGS 1012
Cdd:pfam18104    1 GQDVIARWTDGRYYLGKFIGIHTQTFYEVEFEDGS 35

jmjN domain;

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1039753043   16 MTFRPTMDEFRDFNRYVAYIESQGAhRAGLAKIIP 50
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 1039753043   973 GPPPEGELVELRWTDGNLYRARFISMATSLIYQVEFED-GSQLTVKRGDIFTLEEEL 1028
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 1039753043   850 CIYCRKRMKrvSGACIQCsyEHCSTSFHVTCAHAAGVLMEPDD 892
Cdd:smart00249    2 CSVCGKPDD--GGELLQC--DGCDRWYHQTCLGPPLLEEEPDG 40

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 1039753043  795 CCLCNLRGGALQRTTEHRWIHVICAIAVPEVRFLNVIERNPVDVSAIPEQRWKLKCIYCRKRMKRVSGACIQCSYEHCST 874
Cdd:cd15714      1 CCLCNLRGGALQMTTDERWVHVICAIAVPEARFLNVIERHPVDVSAIPEQRWKLKCVYCRKRMKKVSGACIQCSYDHCST 80

                           90       100       110
                   ....*....|....*....|....*....|
gi 1039753043  875 SFHVTCAHAAGVLMEPDDWPYVVSITCLKH 904
Cdd:cd15714     81 SFHVTCAHAAGVVMEPDDWPYVVSITCFKH 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 1039753043  795 CCLCNLRGGALQRTTEHRWIHVICAIAVPEVRFLNVIERNPVDVSAIPEQRWKLKCIYCRKRMKRVSGACIQCSYEHCST 874
Cdd:cd15715      1 CCLCNLRGGALKQTSDDKWAHVMCAVALPEVRFINVVERTPIDISRIPLQRLKLKCIFCRNRIKRVSGACIQCSYGRCPA 80

                           90       100       110
                   ....*....|....*....|....*....|
gi 1039753043  875 SFHVTCAHAAGVLMEPDDWPYVVSITCLKH 904
Cdd:cd15715     81 SFHVTCAHAAGVLMEPDDWPYVVFITCFRH 110

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 1039753043  795 CCLCNLRGGALQRTTEHRWIHVICAIAVPEVRFLNVIERNPVDVSAIPEQRWKLKCIYCRKRMKRVSGACIQCSYEHCST 874
Cdd:cd15713      1 CCLCSLRGGALQRANDDKWVHVMCAVAVLEARFVNIAERSPVDVSKIPLQRFKLKCIFCKKRRKRTAGCCVQCSHGRCPT 80

                           90       100       110
                   ....*....|....*....|....*....|
gi 1039753043  875 SFHVTCAHAAGVLMEPDDWPYVVSITCLKH 904
Cdd:cd15713     81 SFHASCAQAAGVMMQPDDWPFVVFITCFRH 110

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 1039753043  652 YCAICTLFYPYSQvsclsglptlmapTVTCPTQPQCSLAycgpalsavtlqsvqterdsavqPPSKSGQRTRPLIPEMCF 731
Cdd:cd15576      1 YCAICTLFYPYTQ-------------SLQDPKEISDMSG-----------------------LVSKVGQKTRPLIPEMCF 44

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1039753043  732 TSSGENTEPLPANSYVGEDGTSPLISCAHCCLQVHASCYGVRPELAKEGWTCSRC 786
Cdd:cd15576     45 TAGGENTEPLPSNSYIGDDGTSVLLSCAKCCLQVHASCYGVNPDLVNEGWTCSRC 99

Extended plant homeodomain (PHD) finger, characterized by Cys2HisCys5HisCys2His; PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. The extended PHD finger is characterized as Cys2HisCys5HisCys2His, which has 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753043  795 CCLCNLRGGAL------QRTTEHRWIHVICAIAVPEVRFLNVIERNPVDVSAIPEQRWKLKCIYCRKRmkrvSGACIQCS 868
Cdd:cd15571      1 CALCPRSGGALkgggalKTTSDGLWVHVVCALWSPEVYFDDGTLLEVEGVSKIPKRRKKLKCSICGKR----GGACIQCS 76

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1039753043  869 YEHCSTSFHVTCAHAAGVLMEPDDWPYVVSITCLKH 904
Cdd:cd15571     77 YPGCPRSFHVSCAIRAGCLFEFEDGPGNFVVYCPKH 112

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753043  750 DGTSPLISCAHCCLQVHASCYGVrPELAKEGWTCSRCAAHAWTAECCL-CNLRGGALQRTTEHRWIHVICAIAVPEVRFL 828
Cdd:COG5141    205 ENSNAIVFCDGCEICVHQSCYGI-QFLPEGFWLCRKCIYGEYQIRCCSfCPSSDGAFKQTSDGRWGHVICAMFNPELSFG 283

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1039753043  829 NVIERNPVD-VSAIPEQRWKLKCIYCRKRMkrvsGACIQCSYEHCSTSFHVTCAHAAGVLM 888
Cdd:COG5141    284 HLLSKDPIDnIASVSSSRWKLGCLICKEFG----GTCIQCSYFNCTRAYHVTCARRAGYFD 340

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 1039753043  652 YCAICTLFYPYSQVsclsglptlmaptvtcptqpqcslaycgPALSAVTlqSVQTERDsAVQPPSKSGQRTRPLIPEMCF 731
Cdd:cd15577      1 HCAICTLFMPYYKP----------------------------DALNEEN--SAQWEME-LPAAPCISMRKTKPLIPEMCF 49

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1039753043  732 TSSGENTEPLPANSYVGEDGTSPLISCAHCCLQVHASCYGVRPELAKEGWTCSRC 786
Cdd:cd15577     50 IYREENCEPSPPNALLQEDGTSLLISCAKCCVQVHASCYGVPSHEIHDGWLCARC 104

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 1039753043  795 CCLCNLRGGALQRTTEHRWIHVICAIAVPEVRFLNVIERNPVD-VSAIPEQRWKLKCIYCRKRMkrvSGACIQCSYEHCS 873
Cdd:cd15701      1 CALCPNKGGAFKQTDDGRWAHVVCALWIPEVCFANTVFLEPIDsIEHIPPARWKLTCYICKQRG---SGACIQCHKANCY 77

                           90
                   ....*....|....*.
gi 1039753043  874 TSFHVTCAHAAGVLME 889
Cdd:cd15701     78 TAFHVTCAQQAGLYMK 93

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 1039753043  795 CCLCNLRGGALQRTTEHR-WIHVICAIAVPEVRFLNVIERNPVD-VSAIPEQRWKLKCIYCRKRmkrvSGACIQCSYEHC 872
Cdd:cd15671      1 CVLCPKKGGAMKSTKSGTkWVHVSCALWIPEVSIGCPEKMEPITkISHIPMSRWALVCVLCKEK----TGACIQCSVKSC 76

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1039753043  873 STSFHVTCAHAAG-----VLMEPDDWPYVVSItCLKH 904
Cdd:cd15671     77 KTAFHVTCAFQHGlemktILEDEDDEVKFKSY-CPKH 112

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 1039753043  795 CCLCNLRGGALQRTTEHRWIHVICAIAVPEVRFLNVIERNPVD-VSAIPEQRWKLKCIYCRKRMkrvsGACIQCSYEHCS 873
Cdd:cd15662      1 CCLCPVVGGALKPTTDGRWAHLACAIWIPETCLLDVKTMEPVDgINAISKERWELSCTICKQRY----GACIQCSNNSCR 76

                           90
                   ....*....|....*.
gi 1039753043  874 TSFHVTCAHAAGVLME 889
Cdd:cd15662     77 VAYHPLCARAAGLCME 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 1039753043  795 CCLCNLRGGALQRTTEHRWIHVICAIAVPEVRFLNVIERNPVDVSAIPEQRWKLKCIYC---RKRMKRVSGACIQCSYEH 871
Cdd:cd15672      1 CELCPHKDGALKRTDNGGWAHVVCALYIPEVRFGNVATMEPIILQDVPQDRFNKTCYICeeqGRESKASTGACMQCNKSG 80

                           90
                   ....*....|....*...
gi 1039753043  872 CSTSFHVTCAHAAGVLME 889
Cdd:cd15672     81 CKQSFHVTCAQMAGLLCE 98

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 1039753043  917 VSLGQIVITKNRNGLYYRCRVIGTTAQTFYEVNFDDGSYSDNLYPESITSRDCL 970
Cdd:cd20465      1 ISVGQTVISKHRNTRYYSCRVTEVTSQTFYEVMFDDGSFSRDTFPEDIVSRDCL 54

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 1039753043  974 PPPEGELVELRWTDGNLYRARFISMATSLIYQVEFEDGSQLTVKRGDIFTLEEELP 1029
Cdd:cd20392      1 PPEVGDPVKVKWTDGELYDAKFVGSSIVIMYTVEFEDGSVLTLKREDVYTLDEELP 56

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 1039753043  795 CCLCNLRGGALQRT-TEHRWIHVICAIAVPEVRFLNVIERNPV-DVSAIPEQRWKLKCIYCRKRMkrvsGACIQCSYEHC 872
Cdd:cd15707      1 CILCPNKGGAMKSTrSGTKWAHVSCALWIPEVSIGCVEKMEPItKISSIPASRWALICVLCRERT----GACIQCSVKTC 76

                           90
                   ....*....|....*..
gi 1039753043  873 STSFHVTCAHAAGVLME 889
Cdd:cd15707     77 KTAYHVTCGFQHGLEMK 93

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 1039753043  795 CCLCNLRGGALQRTTEHRWIHVICAIAVPEVRFLNVIERNPVDVSAIPEQRWKLK-CIYCR-KRMKRVsGACIQCSYEHC 872
Cdd:cd15674      1 CELCPNRGGIFKETDTGRWVHLVCALYTPGVAFGDVDKLSPVTLTEMNYSKWGAReCSLCEdPRFART-GVCISCDAGMC 79

                           90       100
                   ....*....|....*....|
gi 1039753043  873 STSFHVTCAHAAGVLMEPDD 892
Cdd:cd15674     80 KSYFHVTCAQREGLLSEATD 99

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 1039753043  795 CCLCNLRGGALQRT-TEHRWIHVICAIAVPEVRFLNVIERNPV-DVSAIPEQRWKLKCIYCRKrmkrVSGACIQCSYEHC 872
Cdd:cd15705      1 CLLCPKRGGALKPTrSGTKWVHVSCALWIPEVSIGCPEKMEPItKISHIPASRWALSCSLCKE----CTGTCIQCSMPSC 76

                           90
                   ....*....|....*.
gi 1039753043  873 STSFHVTCAHAAGVLM 888
Cdd:cd15705     77 ITAFHVTCAFDHGLEM 92

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 1039753043  795 CCLCNLRGGALQRT-TEHRWIHVICAIAVPEVRFLNVIERNP-VDVSAIPEQRWKLKCIYCrkrmKRVSGACIQCSyeHC 872
Cdd:cd15663      1 CCLCPVKGGALKPTdVEGLWVHVTCAWFRPEVCFKNEEKMEPaVGLLRIPLSTFLKACVIC----KQIHGSCTQCC--KC 74

                           90
                   ....*....|....*..
gi 1039753043  873 STSFHVTCAHAAGVLME 889
Cdd:cd15663     75 ATYFHAMCASRAGYHME 91

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 1039753043  794 ECCLCNLRGGALQRT-TEHRWIHVICAIAVPEVRFLNVIERNPV-DVSAIPEQRWKLKCIYCRKRMkrvsGACIQCSYEH 871
Cdd:cd15704      3 KCLLCPKKGGAMKPTrSGTKWVHVSCALWIPEVSIGSPEKMEPItKVSHIPSSRWALVCSLCNEKV----GASIQCSVKN 78

                           90
                   ....*....|....*...
gi 1039753043  872 CSTSFHVTCAHAAGVLME 889
Cdd:cd15704     79 CRTAFHVTCAFDRGLEMK 96

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 1039753043  752 TSPLISCAHCCLQVHASCYGVRPELAKEGWTCSRC 786
Cdd:pfam13831    1 TSPLVYCSKCSVQVHASCYGVPPIPDGDGWKCRRC 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 1039753043  978 GELVELRWTDGNLYRARFISMATSLIYQVEFEDGS 1012
Cdd:pfam18104    1 GQDVIARWTDGRYYLGKFIGIHTQTFYEVEFEDGS 35

jmjN domain;

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1039753043   16 MTFRPTMDEFRDFNRYVAYIESQGAhRAGLAKIIP 50
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 1039753043   919 LGQIVITKNRNGLYYRCRVIGTTAQTFYEVNFDDGSYSDNLYPESITSRDC 969
Cdd:smart00333    5 VGDKVAARWEDGEWYRARIVKVDGEQLYEVFFIDYGNEEVVPPSDLRQLPE 55

Extended PHD finger found in Saccharomyces cerevisiae SANT domain-containing protein 2 (Snt2p) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Snt2p. Sntp2 is a yeast protein that may function in multiple stress pathways. It coordinates the transcriptional response to hydrogen peroxide-mediated oxidative stress through interaction with Ecm5 and the Rpd3 deacetylase. Snt2p contains a bromo adjacent homology (BAH) domain, two canonical PHD fingers, a non-canonical ePHD finger, and a SANT (SWI3, ADA2, N-CoR and TFIIIB) DNA-binding domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753043  795 CCLCNLRGG---------------ALQRTTEHRWIHVICAIAVPEVRFLNVIERNP-VDVSAIPEQRWKLKCIYCRKrmk 858
Cdd:cd15667      1 CSLCNAKESnyelakkqsprtrpdALKCTSNGTWCHVLCALFNEDIKFGNSKSLQPiLNTESVLLKGSRQKCEICKV--- 77

                           90       100
                   ....*....|....*....|...
gi 1039753043  859 rVSGACIQCsyEHCSTSFHVTCA 881
Cdd:cd15667     78 -SGGGLVKC--EVCDDRFHVSCA 97

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753043  795 CCLCNLrgGALqrttehrWIHVICAI------AVPEVRFLNVierNPVDVSAIPEqrwklKCIYCRKrmkrvSGACIQCS 868
Cdd:cd15665      1 CALCNL--GEV-------YAHHCCAAwsegvcQTEDGALENV---DKAVAKALSQ-----KCSFCLR-----YGASISCR 58

                           90
                   ....*....|....*..
gi 1039753043  869 YEHCSTSFHVTCAHAAG 885
Cdd:cd15665     59 MPSCSKSFHFPCAAAAG 75

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 1039753043  978 GELVELRWT-DGNLYRARFISMATSLIYQVEFEDGSQLTVKRGDI 1021
Cdd:cd04508      1 GDRVEAKWSdDGQWYPATVVAVNDDGKYTVLFDDGNEEEVSEDDI 45