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 109255247  755 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFCRHRVKRVSGACIQCSYGRCPA 834
Cdd:cd15715     1 CCLCNLRGGALKQTSDDKWAHVMCAVALPEVRFINVVERTPIDISRIPLQRLKLKCIFCRNRIKRVSGACIQCSYGRCPA 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 109255247  835 SFHVTCAHAAGVLMEPDDWPYVVNITCFRH 864
Cdd:cd15715    81 SFHVTCAHAAGVLMEPDDWPYVVFITCFRH 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 109255247   177 YLYFGMWKTTFAWHTEDMDLYSINYLHFGEPKSWYAIPPEHGKRLERLAQgffPSSSQGCDAFLRHKMTLISPSVLKKYG 256
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLYSINYLHFGAPKVWYIIPPEYAEKFEKVLS---DHFGGEQPDDLLHLNTIISPKQLRENG 77

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 109255247   257 IPFDKITQEAGEFMITFPYGYHAGFNHGFNCAESTNF 293
Cdd:pfam02373   78 IPVYRFVQKPGEFVFTFPGWYHQVFNLGFNIAEAVNF 114

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 109255247  879 ISVGQTVITKHRNTRYYSCRVMAVTSQTFYEVMFDDGSFSRDTFPEDIVSRDCL 932
Cdd:cd20465     1 ISVGQTVISKHRNTRYYSCRVTEVTSQTFYEVMFDDGSFSRDTFPEDIVSRDCL 54

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 109255247  755 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFCRHRVKRVSGACIQCSYGRCPA 834
Cdd:cd15715     1 CCLCNLRGGALKQTSDDKWAHVMCAVALPEVRFINVVERTPIDISRIPLQRLKLKCIFCRNRIKRVSGACIQCSYGRCPA 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 109255247  835 SFHVTCAHAAGVLMEPDDWPYVVNITCFRH 864
Cdd:cd15715    81 SFHVTCAHAAGVLMEPDDWPYVVFITCFRH 110

PHD-zinc-finger like domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109255247   753 AECCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFCRHRvkrvSGACIQCSYGRC 832
Cdd:pfam13832    1 VRCCLCPLRGGALKQTSDGRWVHVLCAIFVPEVRFGNVATMEPIDVSRIPPERWKLKCVFCKKR----SGACIQCSKGRC 76

                           90       100       110
                   ....*....|....*....|....*....|...
gi 109255247   833 PASFHVTCAHAAGVLMEPDDWP-YVVNITCFRH 864
Cdd:pfam13832   77 TTAFHVTCAQAAGVYMEPEDWPnVVVIAYCQKH 109

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 109255247  936 PPAEGEVVQVKWPDGKLYGAKYFGSNIAHMYQVEFEDGSQIAMKREDIYTLDEELPKRVK 995
Cdd:cd20468     1 PPAEGEVVQVKWPDGLLYGAKYLGSNIAHMYQVEFEDGSQIVMKREDIYTLDEELPKKVK 60

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109255247  708 EEDGTSLLISCAKCCVRVHASCYGIPshEICDG-WLCARCKRNAWTAECCL-CNLRGGALKQTKNNKWAHVMCAVAVPEV 785
Cdd:COG5141   203 HNENSNAIVFCDGCEICVHQSCYGIQ--FLPEGfWLCRKCIYGEYQIRCCSfCPSSDGAFKQTSDGRWGHVICAMFNPEL 280

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 109255247  786 RFTNVPERTQID-VGRIPLQRLKLKCIFCRHRVkrvsGACIQCSYGRCPASFHVTCAHAAGVLM 848
Cdd:COG5141   281 SFGHLLSKDPIDnIASVSSSRWKLGCLICKEFG----GTCIQCSYFNCTRAYHVTCARRAGYFD 340

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

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 109255247    148 DEWNIARLNTVLDVVEEeCGISIEGVNT-PYLYFGMWKTTFAWHTEDMDLysINYLHFGEP 207
Cdd:smart00558    1 QLWNLAKLPFKLNLLSD-LPEDIPGPDVgPYLYMGMAGSTTPWHIDDYDL--VNYLHQGAG 58

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 109255247   882 GQTVITKHRNTRYYSCRVMAVTSQTFYEVMFDDGS 916
Cdd:pfam18104    1 GQDVIARWTDGRYYLGKFIGIHTQTFYEVEFEDGS 35

jmjN domain;

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 109255247    17 MTFRPSMEEFREFNKYLAYMESKGAhRAGLAKVIP 51
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 109255247    935 GPPAEGEVVQVKWPDGKLYGAKYFGSNIAHMYQVEFED-GSQIAMKREDIYTLDEEL 990
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        50
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 109255247    810 CIFCRHRVKrvSGACIQCSygRCPASFHVTCAHAAGVLMEPDDwpyvvNITCFRH 864
Cdd:smart00249    2 CSVCGKPDD--GGELLQCD--GCDRWYHQTCLGPPLLEEEPDG-----KWYCPKC 47

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 109255247  755 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFCRHRVKRVSGACIQCSYGRCPA 834
Cdd:cd15715     1 CCLCNLRGGALKQTSDDKWAHVMCAVALPEVRFINVVERTPIDISRIPLQRLKLKCIFCRNRIKRVSGACIQCSYGRCPA 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 109255247  835 SFHVTCAHAAGVLMEPDDWPYVVNITCFRH 864
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 109255247  644 HCAICTLLMPYHKPDSSNEENDARWET-KLDEVVTSEGKTKPLIPEMCFIYSEENIEYSPPNAFLEEDGTSLLISCAKCC 722
Cdd:cd15577     1 HCAICTLFMPYYKPDALNEENSAQWEMeLPAAPCISMRKTKPLIPEMCFIYREENCEPSPPNALLQEDGTSLLISCAKCC 80

                          90       100
                  ....*....|....*....|....
gi 109255247  723 VRVHASCYGIPSHEICDGWLCARC 746
Cdd:cd15577    81 VQVHASCYGVPSHEIHDGWLCARC 104

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 109255247  755 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFCRHRVKRVSGACIQCSYGRCPA 834
Cdd:cd15713     1 CCLCSLRGGALQRANDDKWVHVMCAVAVLEARFVNIAERSPVDVSKIPLQRFKLKCIFCKKRRKRTAGCCVQCSHGRCPT 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 109255247  835 SFHVTCAHAAGVLMEPDDWPYVVNITCFRH 864
Cdd:cd15713    81 SFHASCAQAAGVMMQPDDWPFVVFITCFRH 110

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109255247   177 YLYFGMWKTTFAWHTEDMDLYSINYLHFGEPKSWYAIPPEHGKRLERLAQgffPSSSQGCDAFLRHKMTLISPSVLKKYG 256
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLYSINYLHFGAPKVWYIIPPEYAEKFEKVLS---DHFGGEQPDDLLHLNTIISPKQLRENG 77

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 109255247   257 IPFDKITQEAGEFMITFPYGYHAGFNHGFNCAESTNF 293
Cdd:pfam02373   78 IPVYRFVQKPGEFVFTFPGWYHQVFNLGFNIAEAVNF 114

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 109255247  879 ISVGQTVITKHRNTRYYSCRVMAVTSQTFYEVMFDDGSFSRDTFPEDIVSRDCL 932
Cdd:cd20465     1 ISVGQTVISKHRNTRYYSCRVTEVTSQTFYEVMFDDGSFSRDTFPEDIVSRDCL 54

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 109255247  644 HCAICTLLMPYHKPDSSNEENDARWETKLdevVTSEGKTKPLIPEMCFIYSEENIEYSPPNAFLEEDGTSLLISCAKCCV 723
Cdd:cd15575     1 HCAVCMLFQTYQVDCWGGHNSSSGVAASE---ARIKKKTKPLIPEMCFTSTGCNTDLNLSTPYLEEDGTSILVTCKKCCV 77

                          90       100
                  ....*....|....*....|...
gi 109255247  724 RVHASCYGIPSHEICDGWLCARC 746
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 109255247  755 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQID-VGRIPLQRLKLKCIFCRHRVkrvsGACIQCSYGRCP 833
Cdd:cd15670     1 CVLCPNKGGAFKQTDDGRWAHVVCALWIPEVSFANTVFLEPIDgIQNIPKARWKLTCYICKKRM----GACIQCHKKNCY 76

                          90
                  ....*....|....*.
gi 109255247  834 ASFHVTCAHAAGVLME 849
Cdd:cd15670    77 TAFHVTCAQQAGLYMK 92

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 109255247  879 ISVGQTVITKHRNTRYYSCRVMAVTSQTFYEVMFDDGSFSRDTFPEDIVSRDC 931
Cdd:cd20391     1 ISVGQRVIAKHKNGRYYEAEVVDLTTQTFYEVNFDDGSFSDDLPPEDIVSYNC 53

second Tudor domain found in Jumonji domain-containing protein 2A (JMJD2A) and similar proteins; JMJD2A, also called lysine-specific demethylase 4A (KDM4A), or JmjC domain-containing histone demethylation protein 3A (JHDM3A), catalyzes the demethylation of di- and trimethylated H3K9 and H3K36. It is involved in carcinogenesis and functions as a transcription regulator that may either stimulate or repress gene transcription. It associates with nuclear receptor corepressor complex or histone deacetylases. Moreover, JMJD2A forms complexes with both the androgen and estrogen receptor (ER), and plays an essential role in growth of both ER-positive and -negative breast tumors. It is also involved in prostate, colon, and lung cancer progression. JMJD2A contains jmjN and jmjC domains in the N-terminal region, followed by a canonical plant homeodomain (PHD) domain, a noncanonical extended PHD domain, and tandem Tudor domains. The model corresponds to the second Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 109255247  936 PPAEGEVVQVKWPDGKLYGAKYFGSNIAHMYQVEFEDGSQIAMKREDIYTLDEELP 991
Cdd:cd20466     1 PPAEGEVVQVRWTDGQVYGAKFVASHPIQMYQVEFEDGSQLVVKRDDVYTLDEELP 56

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 109255247  755 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQID-VGRIPLQRLKLKCIFCRhrvKRVSGACIQCSYGRCP 833
Cdd:cd15701     1 CALCPNKGGAFKQTDDGRWAHVVCALWIPEVCFANTVFLEPIDsIEHIPPARWKLTCYICK---QRGSGACIQCHKANCY 77

                          90
                  ....*....|....*.
gi 109255247  834 ASFHVTCAHAAGVLME 849
Cdd:cd15701    78 TAFHVTCAQQAGLYMK 93

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 109255247  755 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFC---RHRVKRVSGACIQCSYGR 831
Cdd:cd15672     1 CELCPHKDGALKRTDNGGWAHVVCALYIPEVRFGNVATMEPIILQDVPQDRFNKTCYICeeqGRESKASTGACMQCNKSG 80

                          90
                  ....*....|....*...
gi 109255247  832 CPASFHVTCAHAAGVLME 849
Cdd:cd15672    81 CKQSFHVTCAQMAGLLCE 98

first Tudor domain found in Jumonji domain-containing protein 2A (JMJD2A) and similar proteins; JMJD2A, also called lysine-specific demethylase 4A (KDM4A), or JmjC domain-containing histone demethylation protein 3A (JHDM3A), catalyzes the demethylation of di- and trimethylated H3K9 and H3K36. It is involved in carcinogenesis and functions as a transcription regulator that may either stimulate or repress gene transcription. It associates with nuclear receptor corepressor complex or histone deacetylases. Moreover, JMJD2A forms complexes with both the androgen and estrogen receptor (ER), and plays an essential role in growth of both ER-positive and -negative breast tumors. It is also involved in prostate, colon, and lung cancer progression. JMJD2A contains jmjN and jmjC domains in the N-terminal region, followed by a canonical plant homeodomain (PHD) domain, a noncanonical extended PHD domain, and tandem Tudor domains. The model corresponds to the first Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 109255247  879 ISVGQTVITKHRNTRYYSCRVMAVTSQTFYEVMFDDGSFSRDTFPEDIVSRDCLK 933
Cdd:cd20463     1 ITAGQKVISKHKNGRFYQCEVVRLTKETFYEVNFDDGSFSDNLYPEDIVSQDCLQ 55

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 109255247  879 ISVGQTVITKHRNTRYYSCRVMAVTSQTFYEVMFDDGSFSRDTFPEDIVSRDCL 932
Cdd:cd20464     1 VSLGQVVITKNRNGLYYRCRVIGTATQTFYEVNFDDGSYSDNVYPESITSRDCL 54

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 109255247   775 HVMCAVAVPEVRFTNVPERTQ--IDVGRIPLQRLKLKCIFCRHRVkrvsGACIQCSYGRCPASFHVTCAHAAGVLME 849
Cdd:pfam13771    1 HVVCALWSPELVQRGNDSMGFpiEDIEKIPKRRWKLKCYLCKKKG----GACIQCSKKNCRRAFHVTCALEAGLLMQ 73

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 109255247  755 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFCRHR---VKRVSGACIQCSYGR 831
Cdd:cd15708     5 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIVLQSVPHERYNKTCYICDEQgreSKAATGACMTCNKHG 84

                          90
                  ....*....|....*...
gi 109255247  832 CPASFHVTCAHAAGVLME 849
Cdd:cd15708    85 CRQAFHVTCAQLAGLLCE 102

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109255247  755 CCLCNLRGGALKQTK-NNKWAHVMCAVAVPEVRFTnVPERTQ--IDVGRIPLQRLKLKCIFCRHRvkrvSGACIQCSYGR 831
Cdd:cd15706     1 CLLCPKTGGAMKATRtGTKWAHVSCALWIPEVSIA-CPERMEpiTKVSHIPPSRWALVCSLCKLK----TGACIQCSVKS 75

                          90
                  ....*....|....*...
gi 109255247  832 CPASFHVTCAHAAGVLME 849
Cdd:cd15706    76 CITAFHVTCAFEHSLEMK 93

Extended PHD finger found in protein AF-17 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of AF-17. AF-17, also termed ALL1-fused gene from chromosome 17 protein, is encoded by gene AF17 that has been identified in hematological malignancies as a translocation partner of the mixed lineage leukemia gene MLL. It is a putative transcription factor that may play a role in multiple signaling pathways. It is involved in chromatin-mediated gene regulation mechanisms. It functions as a component of the multi-subunit Dot1 complex (Dotcom) and plays a role in the Wnt/Wingless signaling pathway. It also seems to be a downstream target of the beta-catenin/T-cell factor pathway, and participates in G2-M progression. Moreover, it may function as an important regulator of ENaC-mediated Na+ transport and thus blood pressure. AF-17 contains an N-terminal plant homeodomain (PHD) finger followed by a non-canonical ePHD finger.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109255247  755 CCLCNLRGGALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFCRHR---VKRVSGACIQCSYGR 831
Cdd:cd15709     5 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPIVLQYVPHDRFNKTCYICEEQgreSKAASGACMTCNRHG 84

                          90       100
                  ....*....|....*....|
gi 109255247  832 CPASFHVTCAHAAGVLMEPD 851
Cdd:cd15709    85 CRQAFHVTCAQMAGLLCEEE 104

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 109255247  754 ECCLCNLRGGALKQTKN-NKWAHVMCAVAVPEVRFTNvPERTQ--IDVGRIPLQRLKLKCIFCRHRVkrvsGACIQCSYG 830
Cdd:cd15704     3 KCLLCPKKGGAMKPTRSgTKWVHVSCALWIPEVSIGS-PEKMEpiTKVSHIPSSRWALVCSLCNEKV----GASIQCSVK 77

                          90
                  ....*....|....*....
gi 109255247  831 RCPASFHVTCAHAAGVLME 849
Cdd:cd15704    78 NCRTAFHVTCAFDRGLEMK 96

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

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 109255247    148 DEWNIARLNTVLDVVEEeCGISIEGVNT-PYLYFGMWKTTFAWHTEDMDLysINYLHFGEP 207
Cdd:smart00558    1 QLWNLAKLPFKLNLLSD-LPEDIPGPDVgPYLYMGMAGSTTPWHIDDYDL--VNYLHQGAG 58

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 109255247   882 GQTVITKHRNTRYYSCRVMAVTSQTFYEVMFDDGS 916
Cdd:pfam18104    1 GQDVIARWTDGRYYLGKFIGIHTQTFYEVEFEDGS 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 109255247  715 LISCAKCCVRVHASCYGIPSHE-ICDGWLCARC 746
Cdd:cd15493    10 LLVCSRCCVCVHASCYGVPDIPgDGEGWKCDRC 42

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

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 109255247    879 ISVGQTVITKHRNTRYYSCRVMAVTSQTFYEVMFDDGSFSRDTFPEDIVSRDCLK 933
Cdd:smart00333    3 FKVGDKVAARWEDGEWYRARIVKVDGEQLYEVFFIDYGNEEVVPPSDLRQLPEEL 57

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 109255247  755 CCLCNLRGG---------------ALKQTKNNKWAHVMCAVAVPEVRFTNvPERTQ--IDVGRIPLQRLKLKCIFCRHRV 817
Cdd:cd15667     1 CSLCNAKESnyelakkqsprtrpdALKCTSNGTWCHVLCALFNEDIKFGN-SKSLQpiLNTESVLLKGSRQKCEICKVSG 79

                          90       100
                  ....*....|....*....|....
gi 109255247  818 krvsGACIQCSygRCPASFHVTCA 841
Cdd:cd15667    80 ----GGLVKCE--VCDDRFHVSCA 97

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 109255247    935 GPPAEGEVVQVKWPDGKLYGAKYFGSNIAHMYQVEFED-GSQIAMKREDIYTLDEEL 990
Cdd:smart00333    1 PTFKVGDKVAARWEDGEWYRARIVKVDGEQLYEVFFIDyGNEEVVPPSDLRQLPEEL 57

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 109255247  755 CCLCNLRG-------GALKQTKNNKWAHVMCAVAVPEV------RFTNVPErtqidvgriPLQR-LKLKCIFCRHRvkrv 820
Cdd:cd15666     1 CVLCGGEGdgdtdgpGRLLNLDVDKWVHLNCALWSYEVyetqngALMNVEE---------ALRRaLTTTCSHCGRT---- 67

                          90       100
                  ....*....|....*....|.
gi 109255247  821 sGACIQCSYGRCPASFHVTCA 841
Cdd:cd15666    68 -GATVPCFKPRCANVYHLPCA 87

Extended PHD finger 2 found in histone-lysine N-methyltransferase 2D (KMT2D); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the second ePHD finger of KMT2D. KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named myeloid/lymphoid or mixed-lineage leukemia 4 (MLL4), a fourth human homolog of Drosophila trithorax, located on chromosome 12. KMT2D enzymatically generates trimethylated histone H3 Lys 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. It 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 KMT2D. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2D contains the catalytic domain SET, five PHD fingers, two ePHD fingers, a RING finger, an HMG (high-mobility group)-binding motif, and two FY-rich regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109255247  755 CCLCNLRG-------GALKQTKNNKWAHVMCAVAVPEVRFTNVPERTQIDVGripLQR-LKLKCIFCRHrvkrvSGACIQ 826
Cdd:cd15698     1 CCFCHEEGdgatdgpARLLNLDLDLWVHLNCALWSTEVYETQGGALMNVEVA---LHRgLLTKCSLCQK-----TGATNS 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 109255247  827 CSYGRCPASFHVTCAHAAGVLMEPDDwpyvvNITCFRHKV 866
Cdd:cd15698    73 CNRLRCPNVYHFACAIRAKCMFFKDK-----TMLCPMHKL 107