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 1237937754 318 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFCRHRVKRVSGACIQCSYGRCPA 397
Cdd:cd15715     1 CCLCNLRGGALKQTSDDKWAHVMCAVALPEVRFINVVERTPIDISRIPLQRLKLKCIFCRNRIKRVSGACIQCSYGRCPA 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1237937754 398 SFHVTCAHAAGVLMEPDDWPYVVNITCFRH 427
Cdd:cd15715    81 SFHVTCAHAAGVLMEPDDWPYVVFITCFRH 110

second Tudor domain found in Jumonji domain-containing protein 2C (JMJD2C) and similar proteins; JMJD2C, also called lysine-specific demethylase 4C (KDM4C), gene amplified in squamous cell carcinoma 1 protein (GASC-1 protein), or JmjC domain-containing histone demethylation protein 3C (JHDM3C), is an epigenetic factor that catalyzes the demethylation of di- and trimethylated H3K9 and H3K36, and may be involved in the development and/or progression of various types of cancer including esophageal squamous cell carcinoma (ESC) and breast cancer. It selectively interacts with hypoxia-inducible factor 1alpha (HIF1alpha) and plays a role in breast cancer progression. Moreover, JMJD2C may play an important role in the treatment of obesity and its complications by modulating the regulation of adipogenesis by nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma). JMJD2C contains jmjN and jmjC domains in the N-terminal region, followed by a canonical plant homeodomain (PHD) domain, a noncanonical extended PHD domain, and tandem Tudor domains. The model corresponds to the second Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937754 532 PPAEGEVVQVKWPDGKLYGAKYFGSNIAHMYQVEFEDGSQIAMKREDIYTLDEELPKRVK 591
Cdd:cd20468     1 PPAEGEVVQVKWPDGLLYGAKYLGSNIAHMYQVEFEDGSQIVMKREDIYTLDEELPKKVK 60

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 1237937754 318 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFCRHRVKRVSGACIQCSYGRCPA 397
Cdd:cd15715     1 CCLCNLRGGALKQTSDDKWAHVMCAVALPEVRFINVVERTPIDISRIPLQRLKLKCIFCRNRIKRVSGACIQCSYGRCPA 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1237937754 398 SFHVTCAHAAGVLMEPDDWPYVVNITCFRH 427
Cdd:cd15715    81 SFHVTCAHAAGVLMEPDDWPYVVFITCFRH 110

PHD-zinc-finger like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937754 316 AECCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFCRHRvkrvSGACIQCSYGRC 395
Cdd:pfam13832   1 VRCCLCPLRGGALKQTSDGRWVHVLCAIFVPEVRFGNVATMEPIDVSRIPPERWKLKCVFCKKR----SGACIQCSKGRC 76

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1237937754 396 PASFHVTCAHAAGVLMEPDDWP-YVVNITCFRH 427
Cdd:pfam13832  77 TTAFHVTCAQAAGVYMEPEDWPnVVVIAYCQKH 109

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 1237937754 475 ISVGQTVITKHRNTRYYSCRVMAVTSQTFYEVMFDDGSFSRDTFPEDIVSRDCL 528
Cdd:cd20465     1 ISVGQTVISKHRNTRYYSCRVTEVTSQTFYEVMFDDGSFSRDTFPEDIVSRDCL 54

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 1237937754 536 GEVVQVKWPDGKLYGAKYFGSNIAHMYQVEFEDGS 570
Cdd:pfam18104   1 GQDVIARWTDGRYYLGKFIGIHTQTFYEVEFEDGS 35

PHD-finger; PHD folds into an interleaved type of Zn-finger chelating 2 Zn ions in a similar manner to that of the RING and FYVE domains. Several PHD fingers have been identified as binding modules of methylated histone H3.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1237937754 275 TSLLISCAKCCVRVHASCYGIPSHEICDGWLCARC 309
Cdd:pfam13831   1 TSPLVYCSKCSVQVHASCYGVPPIPDGDGWKCRRC 35

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1237937754  531 GPPAEGEVVQVKWPDGKLYGAKYFGSNIAHMYQVEFED-GSQIAMKREDIYTLDEEL 586
Cdd:smart00333   1 PTFKVGDKVAARWEDGEWYRARIVKVDGEQLYEVFFIDyGNEEVVPPSDLRQLPEEL 57

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 1237937754 318 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFCRHRVKRVSGACIQCSYGRCPA 397
Cdd:cd15715     1 CCLCNLRGGALKQTSDDKWAHVMCAVALPEVRFINVVERTPIDISRIPLQRLKLKCIFCRNRIKRVSGACIQCSYGRCPA 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1237937754 398 SFHVTCAHAAGVLMEPDDWPYVVNITCFRH 427
Cdd:cd15715    81 SFHVTCAHAAGVLMEPDDWPYVVFITCFRH 110

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 1237937754 207 HCAICTLLMPYHKPDSSNEENDARWET-KLDEVVTSEGKTKPLIPEMCFIYSEENIEYSPPNAFLEEDGTSLLISCAKCC 285
Cdd:cd15577     1 HCAICTLFMPYYKPDALNEENSAQWEMeLPAAPCISMRKTKPLIPEMCFIYREENCEPSPPNALLQEDGTSLLISCAKCC 80

                          90       100
                  ....*....|....*....|....
gi 1237937754 286 VRVHASCYGIPSHEICDGWLCARC 309
Cdd:cd15577    81 VQVHASCYGVPSHEIHDGWLCARC 104

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 1237937754 318 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFCRHRVKRVSGACIQCSYGRCPA 397
Cdd:cd15714     1 CCLCNLRGGALQMTTDERWVHVICAIAVPEARFLNVIERHPVDVSAIPEQRWKLKCVYCRKRMKKVSGACIQCSYDHCST 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1237937754 398 SFHVTCAHAAGVLMEPDDWPYVVNITCFRH 427
Cdd:cd15714    81 SFHVTCAHAAGVVMEPDDWPYVVSITCFKH 110

second Tudor domain found in Jumonji domain-containing protein 2C (JMJD2C) and similar proteins; JMJD2C, also called lysine-specific demethylase 4C (KDM4C), gene amplified in squamous cell carcinoma 1 protein (GASC-1 protein), or JmjC domain-containing histone demethylation protein 3C (JHDM3C), is an epigenetic factor that catalyzes the demethylation of di- and trimethylated H3K9 and H3K36, and may be involved in the development and/or progression of various types of cancer including esophageal squamous cell carcinoma (ESC) and breast cancer. It selectively interacts with hypoxia-inducible factor 1alpha (HIF1alpha) and plays a role in breast cancer progression. Moreover, JMJD2C may play an important role in the treatment of obesity and its complications by modulating the regulation of adipogenesis by nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma). JMJD2C contains jmjN and jmjC domains in the N-terminal region, followed by a canonical plant homeodomain (PHD) domain, a noncanonical extended PHD domain, and tandem Tudor domains. The model corresponds to the second Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937754 532 PPAEGEVVQVKWPDGKLYGAKYFGSNIAHMYQVEFEDGSQIAMKREDIYTLDEELPKRVK 591
Cdd:cd20468     1 PPAEGEVVQVKWPDGLLYGAKYLGSNIAHMYQVEFEDGSQIVMKREDIYTLDEELPKKVK 60

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 1237937754 318 CCLCNLRGGALKQ------TKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFCRHRvkrvSGACIQCS 391
Cdd:cd15571     1 CALCPRSGGALKGggalktTSDGLWVHVVCALWSPEVYFDDGTLLEVEGVSKIPKRRKKLKCSICGKR----GGACIQCS 76

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1237937754 392 YGRCPASFHVTCAHAAGVLMEPDDWPYVVNITCFRH 427
Cdd:cd15571    77 YPGCPRSFHVSCAIRAGCLFEFEDGPGNFVVYCPKH 112

PHD finger found in Jumonji domain-containing protein 2A (JMJD2A); JMJD2A, also termed lysine-specific demethylase 4A (KDM4A), or JmjC domain-containing histone demethylation protein 3A (JHDM3A), catalyzes the demethylation of di- and trimethylated H3K9 and H3K36. It is involved in carcinogenesis and functions as a transcription regulator that may either stimulate or repress gene transcription. It associates with nuclear receptor co-repressor complex or histone deacetylases. Moreover, JMJD2A forms complexes with both the androgen and estrogen receptor (ER) and plays an essential role in growth of both ER-positive and -negative breast tumors. It is also involved in prostate, colon, and lung cancer progression. JMJD2A contains jmjN and jmjC domains in the N-terminal region, followed by a canonical Cys4HisCys3 PHD finger, a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, and a Tudor domain. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937754 207 HCAICTLLMPYHKPDSSNEENDARWETKLdevVTSEGKTKPLIPEMCFIYSEENIEYSPPNAFLEEDGTSLLISCAKCCV 286
Cdd:cd15575     1 HCAVCMLFQTYQVDCWGGHNSSSGVAASE---ARIKKKTKPLIPEMCFTSTGCNTDLNLSTPYLEEDGTSILVTCKKCCV 77

                          90       100
                  ....*....|....*....|...
gi 1237937754 287 RVHASCYGIPSHEICDGWLCARC 309
Cdd:cd15575    78 CVHASCYGVSPEKAAEDWMCSRC 100

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 1237937754 318 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQID-VGRIPLQRLKLKCIFCRHRVkrvsGACIQCSYGRCP 396
Cdd:cd15670     1 CVLCPNKGGAFKQTDDGRWAHVVCALWIPEVSFANTVFLEPIDgIQNIPKARWKLTCYICKKRM----GACIQCHKKNCY 76

                          90
                  ....*....|....*.
gi 1237937754 397 ASFHVTCAHAAGVLME 412
Cdd:cd15670    77 TAFHVTCAQQAGLYMK 92

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937754 271 EEDGTSLLISCAKCCVRVHASCYGIPshEICDG-WLCARCKRNAWTAECCL-CNLRGGALKQTKNNKWAHVMCAVAVPEV 348
Cdd:COG5141   203 HNENSNAIVFCDGCEICVHQSCYGIQ--FLPEGfWLCRKCIYGEYQIRCCSfCPSSDGAFKQTSDGRWGHVICAMFNPEL 280

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1237937754 349 RFTNVPERTQID-VGRIPLQRLKLKCIFCRHRVkrvsGACIQCSYGRCPASFHVTCAHAAGVLM 411
Cdd:COG5141   281 SFGHLLSKDPIDnIASVSSSRWKLGCLICKEFG----GTCIQCSYFNCTRAYHVTCARRAGYFD 340

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 1237937754 532 PPAEGEVVQVKWPDGKLYGAKYFGSNIAHMYQVEFEDGSQIAMKREDIYTLDEELP 587
Cdd:cd20467     1 PPSEGELVELRWTDGNIYKAKFISAHLSHIYQVEFEDGSQLTVKRGEIFTLEEELP 56

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 1237937754 318 CCLCNLRGGALKQTKN-NKWAHVMCAVAVPEVRFTNvPERTQ--IDVGRIPLQRLKLKCIFCRHRVkrvsGACIQCSYGR 394
Cdd:cd15671     1 CVLCPKKGGAMKSTKSgTKWVHVSCALWIPEVSIGC-PEKMEpiTKISHIPMSRWALVCVLCKEKT----GACIQCSVKS 75

                          90
                  ....*....|....*..
gi 1237937754 395 CPASFHVTCAHAAGVLM 411
Cdd:cd15671    76 CKTAFHVTCAFQHGLEM 92

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937754 318 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQID-VGRIPLQRLKLKCIFCRhrvKRVSGACIQCSYGRCP 396
Cdd:cd15702     1 CVLCPNKGGAFKKTDDDRWGHVVCALWIPEVGFANTVFIEPIDgVRNIPPARWKLTCYLCK---QKGVGACIQCHKANCY 77

                          90
                  ....*....|....*.
gi 1237937754 397 ASFHVTCAHAAGVLME 412
Cdd:cd15702    78 TAFHVTCAQKAGLYMK 93

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 1237937754 475 ISVGQTVITKHRNTRYYSCRVMAVTSQTFYEVMFDDGSFSRDTFPEDIVSRDCL 528
Cdd:cd20464     1 VSLGQVVITKNRNGLYYRCRVIGTATQTFYEVNFDDGSYSDNVYPESITSRDCL 54

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 1237937754 318 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQID-VGRIPLQRLKLKCIFCRHRVkrvsGACIQCSYGRCP 396
Cdd:cd15662     1 CCLCPVVGGALKPTTDGRWAHLACAIWIPETCLLDVKTMEPVDgINAISKERWELSCTICKQRY----GACIQCSNNSCR 76

                          90
                  ....*....|....*.
gi 1237937754 397 ASFHVTCAHAAGVLME 412
Cdd:cd15662    77 VAYHPLCARAAGLCME 92

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937754 318 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFCRHR---VKRVSGACIQCSYGR 394
Cdd:cd15708     5 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIVLQSVPHERYNKTCYICDEQgreSKAATGACMTCNKHG 84

                          90
                  ....*....|....*...
gi 1237937754 395 CPASFHVTCAHAAGVLME 412
Cdd:cd15708    85 CRQAFHVTCAQLAGLLCE 102

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 1237937754 318 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLK-CIFCRHRVKRVSGACIQCSYGRCP 396
Cdd:cd15674     1 CELCPNRGGIFKETDTGRWVHLVCALYTPGVAFGDVDKLSPVTLTEMNYSKWGAReCSLCEDPRFARTGVCISCDAGMCK 80

                          90
                  ....*....|....*....
gi 1237937754 397 ASFHVTCAHAAGVLMEPDD 415
Cdd:cd15674    81 SYFHVTCAQREGLLSEATD 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 1237937754 318 CCLCNLRGGALKQTKN-NKWAHVMCAVAVPEVRFtNVPERTQ--IDVGRIPLQRLKLKCIFCRHrvkrVSGACIQCSYGR 394
Cdd:cd15705     1 CLLCPKRGGALKPTRSgTKWVHVSCALWIPEVSI-GCPEKMEpiTKISHIPASRWALSCSLCKE----CTGTCIQCSMPS 75

                          90
                  ....*....|....*..
gi 1237937754 395 CPASFHVTCAHAAGVLM 411
Cdd:cd15705    76 CITAFHVTCAFDHGLEM 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 1237937754 318 CCLCNLRGGALKQTK-NNKWAHVMCAVAVPEVRFTNVpERTQIDVG--RIPLQRLKLKCIFCrhrvKRVSGACIQCSygR 394
Cdd:cd15663     1 CCLCPVKGGALKPTDvEGLWVHVTCAWFRPEVCFKNE-EKMEPAVGllRIPLSTFLKACVIC----KQIHGSCTQCC--K 73

                          90
                  ....*....|....*...
gi 1237937754 395 CPASFHVTCAHAAGVLME 412
Cdd:cd15663    74 CATYFHAMCASRAGYHME 91

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 1237937754 536 GEVVQVKWPDGKLYGAKYFGSNIAHMYQVEFEDGS 570
Cdd:pfam18104   1 GQDVIARWTDGRYYLGKFIGIHTQTFYEVEFEDGS 35

PHD-finger; PHD folds into an interleaved type of Zn-finger chelating 2 Zn ions in a similar manner to that of the RING and FYVE domains. Several PHD fingers have been identified as binding modules of methylated histone H3.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1237937754 275 TSLLISCAKCCVRVHASCYGIPSHEICDGWLCARC 309
Cdd:pfam13831   1 TSPLVYCSKCSVQVHASCYGVPPIPDGDGWKCRRC 35

PHD finger found in Jumonji domain-containing protein 2 (JMJD2) family of histone demethylases; JMJD2 proteins, also termed lysine-specific demethylase 4 histone demethylases (KDM4), have been implicated in various cellular processes including DNA damage response, transcription, cell cycle regulation, cellular differentiation, senescence, and carcinogenesis. They selectively catalyze the demethylation of di- and trimethylated H3K9 and H3K36. This model contains only three JMJD2 proteins, JMJD2A-C, which all contain jmjN and jmjC domains in the N-terminal region, followed by a Cys4HisCys3 canonical PHD finger, a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, and a Tudor domain. JMJD2D is not included in this family, since it lacks both PHD and Tudor domains and has a different substrate specificity. JMJD2A-C are required for efficient cancer cell growth. This model corresponds to the Cys4HisCys3 canonical PHD finger.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 1237937754 278 LISCAKCCVRVHASCYGIPSHE-ICDGWLCARC 309
Cdd:cd15493    10 LLVCSRCCVCVHASCYGVPDIPgDGEGWKCDRC 42

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937754 318 CCLCNLRGG---------------ALKQTKNNKWAHVMCAVAVPEVRFTNvPERTQ--IDVGRIPLQRLKLKCIFCRHRV 380
Cdd:cd15667     1 CSLCNAKESnyelakkqsprtrpdALKCTSNGTWCHVLCALFNEDIKFGN-SKSLQpiLNTESVLLKGSRQKCEICKVSG 79

                          90       100
                  ....*....|....*....|....
gi 1237937754 381 krvsGACIQCSygRCPASFHVTCA 404
Cdd:cd15667    80 ----GGLVKCE--VCDDRFHVSCA 97

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 1237937754 318 CCLCNLRG-------GALKQTKNNKWAHVMCAVAVPEVrFTNVPERTQ-----IDVGRiplqrlKLKCIFCRHRvkrvsG 385
Cdd:cd15664     1 CALCGVYGddepndaGRLLYCGQDEWVHINCALWSAEV-FEEDDGSLQnvhsaVSRGR------MMKCELCGKP-----G 68

                          90       100
                  ....*....|....*....|....*....
gi 1237937754 386 ACIQCSYGRCPASFHVTCAHAAGVLMEPD 414
Cdd:cd15664    69 ATVGCCLKSCPANYHFMCARKAECVFQDD 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 1237937754 318 CCLCNLRG-------GALKQTKNNKWAHVMCAVAVPEV------RFTNVPErtqidvgriPLQR-LKLKCIFCRHRvkrv 383
Cdd:cd15666     1 CVLCGGEGdgdtdgpGRLLNLDVDKWVHLNCALWSYEVyetqngALMNVEE---------ALRRaLTTTCSHCGRT---- 67

                          90       100
                  ....*....|....*....|.
gi 1237937754 384 sGACIQCSYGRCPASFHVTCA 404
Cdd:cd15666    68 -GATVPCFKPRCANVYHLPCA 87

Extended PHD finger 2 found in histone-lysine N-methyltransferase 2C (KMT2C); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the second ePHD finger of KMT2C. 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. KMT2C contains PHD fingers, two ePHD fingers, an ATPase alpha beta signature, a high mobility group (HMG)-1 box, a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain and two FY (phenylalanine tyrosine)-rich domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1237937754 318 CCLCNLRGGALKQTKN-------NKWAHVMCAVAVPEVRFTNVPERTQIDVGripLQR-LKLKCIFCRHrvkrvSGACIQ 389
Cdd:cd15697     1 CCFCHEEGDGLTDGPArllnldlDLWVHLNCALWSTEVYETQAGALINVELA---LRRgLQMKCVFCHK-----TGATSG 72

                          90
                  ....*....|....*...
gi 1237937754 390 CSYGRCPASFHVTCAHAA 407
Cdd:cd15697    73 CHRLRCTNVYHFTCAIKA 90

PHD finger found in Arabidopsis thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like protein ATX3, ATX4, ATX5, and similar proteins; The family includes A. thaliana ATX3 (also termed protein SET domain group 14, or trithorax-homolog protein 3), ATX4 (also termed protein SET domain group 16, or trithorax-homolog protein 4) and ATX5 (also termed protein SET domain group 29, or trithorax-homolog protein 5), which belong to the histone-lysine methyltransferase family. They show distinct phylogenetic origins from the ATX1 and ATX2 family. They are multi-domain containing proteins that consist of an N-terminal PWWP domain, a canonical Cys4HisCys3 plant homeodomain (PHD) finger, a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, and a C-terminal SET domain; this model corresponds to the Cys4HisCys3 canonical PHD finger.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1237937754 271 EEDGTSLLISCAKCCVRVHASCYGIPSHEICDGWLCARC 309
Cdd:cd15495     9 EDDDNNPLITCNRCQISVHQKCYGIREVDPDGSWVCRAC 47

PHD finger found in mixed lineage leukemia 5 (MLL5); MLL5 is a histone methyltransferase that plays a key role in hematopoiesis, spermatogenesis and cell cycle progression. It contains a single plant homeodomain (PHD) finger followed by a catalytic SET domain. MLL5 can be recruited to E2F1-responsive promoters to stimulate H3K4 trimethylation and transcriptional activation by binding to the cell cycle regulator host cell factor (HCF-1), thereby facilitating the cell cycle G1 to S phase transition. It is also involved in mitotic fidelity and genomic integrity by modulating the stability of the chromosomal passenger complex (CPC) via the interaction with Borealin. Moreover, MLL5 is a component of a complex associated with retinoic acid receptor that requires GlcN Acylation of its SET domain in order to activate its histone lysine methyltransferase activity. It also participates in the camptothecin (CPT)-induced p53 activation. Furthermore, MLL5 indirectly regulates H3K4 methylation, represses cyclin A2 (CycA) expression, and promotes myogenic differentiation.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1237937754 272 EDGTSLLISCAKCCVRVHASCYGIPSHEICDGWLCARC 309
Cdd:cd15550     7 EHDDGFMICCDKCSVWQHGDCMGIDRENIPDSYLCEQC 44

Extended PHD finger found in histone-lysine N-methyltransferase 2A (KMT2A); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This subfamily includes the ePHD finger of KMT2A. KMT2A also termed ALL-1, or CXXC-type zinc finger protein 7, or myeloid/lymphoid or mixed-lineage leukemia protein 1 (MLL1), or trithorax-like protein (Htrx), or zinc finger protein HRX, is a histone methyltransferase that belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2). It 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, which also contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex. The MLL1 complex is highly active and specific for H3K4methylation. KMT2A contains a CxxC (x for any residue) zinc finger domain, three PHD fingers, a Bromodomain domain, this extended PHD 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 1237937754 317 ECCLCNLRG-------GALKQTKNNKWAHVMCAVAVPEVrFTNVPERTQiDVGRIPLQRLKLKCIFCRHrvkrvSGACIQ 389
Cdd:cd15693     2 QCALCLKYGddsandaGRLLYIGQNEWTHVNCALWSAEV-FEDDDGSLK-NVHMAVIRGKQLRCEFCQK-----PGATVG 74

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1237937754 390 CSYGRCPASFHVTCAHAAGVLMEPDDWPYvvnitCFRHK 428
Cdd:cd15693    75 CCLTSCTSNYHFMCSRAKNCVFLEDKKVY-----CQRHK 108

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
                  ....*....|....*....|....*....|....*....
gi 1237937754 273 DGTSLLISCAKCCVRVHASCYGIPSHEIC--DGWLCARC 309
Cdd:cd15489    10 DLGGELLQCDGCGKWFHADCLGPPLSSFVpnGKWICPVC 48