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 528509339 1389 CSLCQQHGDAKPNDAGRLLYIGQNEWAHVNCCIWSAEV-QETNGALLHVHSAVARGRFMRCERCGQTGATVGCCLTSCQS 1467
Cdd:cd15664     1 CALCGVYGDDEPNDAGRLLYCGQDEWVHINCALWSAEVfEEDDGSLQNVHSAVSRGRMMKCELCGKPGATVGCCLKSCPA 80

                          90       100
                  ....*....|....*....|....*
gi 528509339 1468 NYHFMCARASNCVFQHDKKVYCYKH 1492
Cdd:cd15664    81 NYHFMCARKAECVFQDDKKVFCPAH 105

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 528509339 1149 FCTVCLKCYEEHEFDSSMMQCARCAHWVHPKCEGLTDDLHEILCRLRGkSLVFSCAPC 1206
Cdd:cd15593     1 YCPICLKCYEDNDYESKMMQCAKCDHWVHAKCEGLSDELYEILSSLPD-SVVYSCAPC 57

F/Y rich C-terminus; This region is normally found in the trithorax/ALL1 family proteins. It is similar to SMART:SM00542.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509339  2559 QPHLIFQITSEDGFSVEADSMDVAWKAVMDGVQEARIGCRMEQLPFNSINGARVLGVLHDAVLFLLEQLQGASLCQKHRF 2638
Cdd:pfam05965    1 GPLFRVTVEEDPDESFEGSSPTKCWSMVLERVQELRREAGLKLKLPESISGEDMFGLTHPAVVRLIESLPGAEKCTNYKF 80

                   ...
gi 528509339  2639 RFH 2641
Cdd:pfam05965   81 RYG 83

F/Y-rich N-terminus; This region is normally found in the trithorax/ALL1 family proteins. It is similar to SMART:SM00541.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 528509339  1539 GSLHVKNLGVLTELSA---NSGKLYPVGYQCSRWYWSTVDPRRRCRYTCKV 1586
Cdd:pfam05964    1 GSLTVLSLGEIVPDRPafhTERYIYPVGYKSTRLYWSTKDPRKRCRYTCEI 51

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 528509339 1389 CSLCQQHGDAKPNDAGRLLYIGQNEWAHVNCCIWSAEV-QETNGALLHVHSAVARGRFMRCERCGQTGATVGCCLTSCQS 1467
Cdd:cd15664     1 CALCGVYGDDEPNDAGRLLYCGQDEWVHINCALWSAEVfEEDDGSLQNVHSAVSRGRMMKCELCGKPGATVGCCLKSCPA 80

                          90       100
                  ....*....|....*....|....*
gi 528509339 1468 NYHFMCARASNCVFQHDKKVYCYKH 1492
Cdd:cd15664    81 NYHFMCARKAECVFQDDKKVFCPAH 105

SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain; Putative methyl transferase, based on outlier plant homologues

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509339   2725 VGVYRSAIHGRGLFCKRNIEAGEMVIEYAGNVIRAVLTDKREKYYDSKGI-GCYMFRIDDFDVVDATMHGNAARFINHSC 2803
Cdd:smart00317    3 LEVFKSPGKGWGVRATEDIPKGEFIGEYVGEIITSEEAEERPKAYDTDGAkAFYLFDIDSDLCIDARRKGNLARFINHSC 82

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|..
gi 528509339   2804 DPNCYSRVINVEGQKHIVIFALRKIYRGEELTYDYKFPIEDA 2845
Cdd:smart00317   83 EPNCELLFVEVNGDDRIVIFALRDIKPGEELTIDYGSDYANE 124

SET domain; SET domains are protein lysine methyltransferase enzymes. SET domains appear to be protein-protein interaction domains. It has been demonstrated that SET domains mediate interactions with a family of proteins that display similarity with dual-specificity phosphatases (dsPTPases). A subset of SET domains have been called PR domains. These domains are divergent in sequence from other SET domains, but also appear to mediate protein-protein interaction. The SET domain consists of two regions known as SET-N and SET-C. SET-C forms an unusual and conserved knot-like structure of probably functional importance. Additionally to SET-N and SET-C, an insert region (SET-I) and flanking regions of high structural variability form part of the overall structure.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509339  2734 GRGLFCKRNIEAGEMVIEYAGN-VIRAVLTDKREKYYDSKGI----GCYMFRIDDFD--VVDAT--MHGNAARFINHSCD 2804
Cdd:pfam00856    1 GRGLFATEDIPKGEFIGEYVEVlLITKEEADKRELLYYDKLElrlwGPYLFTLDEDSeyCIDARalYYGNWARFINHSCD 80

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 528509339  2805 PNCYSRVINVEGQKHIVIFALRKIYRGEELTYDYK 2839
Cdd:pfam00856   81 PNCEVRVVYVNGGPRIVIFALRDIKPGEELTIDYG 115

PHD finger 1 found in Histone-lysine N-methyltransferase 2B (KMT2B); KMT2B, also termed trithorax homolog 2 or WW domain-binding protein 7 (WBP-7), is encoded by the gene that was first named myeloid/lymphoid or mixed-lineage leukemia 2 (MLL2), a second human homolog of Drosophila trithorax, located on chromosome 19. It belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2) and is vital for normal mammalian embryonic development. KMT2B functions as the catalytic subunit in the MLL2 complex, which contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex. The MLL2 complex is highly active and specific for histone 3 lysine 4 (H3K4) methylation, which stimulates chromatin transcription in a SAM- and H3K4-dependent manner. Moreover, KMT2B plays a critical role in memory formation through 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. KMT2B contains a CxxC (x for any residue) zinc finger domain, three plant homeodomain (PHD) fingers, an extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain. This model corresponds to the first PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 528509339 1016 VCLLCASKGQHEMVYCQMCCEPFHHFCLPPDDRPKEENKENWCCRRC 1062
Cdd:cd15589     1 VCLLCASKGQHELLFCQVCCEPFHRFCLEESERPLPEQEENWCCRRC 47

PHD domain 2 found in Histone-lysine N-methyltransferase 2B (KMT2B); KMT2B, also termed trithorax homolog 2 or WW domain-binding protein 7 (WBP-7), is encoded by the gene that was first named myeloid/lymphoid or mixed-lineage leukemia 2 (MLL2), a second human homolog of Drosophila trithorax, located on chromosome 19. It belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2) and is vital for normal mammalian embryonic development. KMT2B functions as the catalytic subunit in the MLL2 complex, which contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex. The MLL2 complex is highly active and specific for histone 3lysine 4 (H3K4) methylation, which stimulates chromatin transcription in a SAM- and H3K4-dependent manner. Moreover, KMT2B plays a critical role in memory formation through 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. KMT2B contains a CxxC (x for any residue) zinc finger domain, three plant homeodomain (PHD), an extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain. This model corresponds to the second PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 528509339 1064 FCHVCGRKSKQTKPVLQCKRCMYCYHPSCLGPTYPKP-VKMNTSWVCMLC 1112
Cdd:cd15591     1 FCHVCGRKNKESKPLLECERCRNCYHPACLGPNYPKPaNRKKRPWICSAC 50

F/Y-rich N-terminus; This region is normally found in the trithorax/ALL1 family proteins. It is similar to SMART:SM00541.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 528509339  1539 GSLHVKNLGVLTELSA---NSGKLYPVGYQCSRWYWSTVDPRRRCRYTCKV 1586
Cdd:pfam05964    1 GSLTVLSLGEIVPDRPafhTERYIYPVGYKSTRLYWSTKDPRKRCRYTCEI 51

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509339  1416 HVNCCIWSAEV----QETNGALL-HVHSAVARGRFMRCERCGQ-TGATVGCCLTSCQSNYHFMCARASNCVFQHDK---- 1485
Cdd:pfam13771    1 HVVCALWSPELvqrgNDSMGFPIeDIEKIPKRRWKLKCYLCKKkGGACIQCSKKNCRRAFHVTCALEAGLLMQFDEdngt 80

                   ....*...
gi 528509339  1486 -KVYCYKH 1492
Cdd:pfam13771   81 fKSYCKKH 88

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        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 528509339  1016 VCLLCASKG-QHEMVYCQMCCEPFHHFCLPPDDRPKEENKENWCCRRCKFC 1065
Cdd:pfam00628    1 YCAVCGKSDdGGELVQCDGCDDWFHLACLGPPLDPAEIPSGEWLCPECKPK 51

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        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 528509339  1064 FCHVCGRKSKQTKpVLQCKRCMYCYHPSCLGPTYPKPVKMNTSWVCMLCIRC 1115
Cdd:pfam00628    1 YCAVCGKSDDGGE-LVQCDGCDDWFHLACLGPPLDPAEIPSGEWLCPECKPK 51

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 528509339   1149 FCTVCLKCYEehefDSSMMQCARCAHWVHPKCEGLTDDLHEilcrlrgKSLVFSCAPC 1206
Cdd:smart00249    1 YCSVCGKPDD----GGELLQCDGCDRWYHQTCLGPPLLEEE-------PDGKWYCPKC 47

SET domain (including post-SET domain) found in histone-lysine N-methyltransferase 2A (KMT2A) and similar proteins; KMT2A (EC2.1.1.43; also termed lysine N-methyltransferase 2A, ALL-1, CXXC-type zinc finger protein 7 (CXXC7), myeloid/lymphoid or mixed-lineage leukemia (MLL), myeloid/lymphoid or mixed-lineage leukemia protein 1 (MLL1), trithorax-like protein (TRX1), or zinc finger protein HRX) acts as a histone methyltransferase that plays an essential role in early development and hematopoiesis. It is a catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509339 2710 VAMRFRHLEKTSKEAVGVYRSAIHGRGLFCKRNIEAGEMVIEYAGNVIRAVLTDKREKYYDSKGIGCYMFRIDDFDVVDA 2789
Cdd:cd19206     1 MPMRFRHLKKTSKEAVGVYRSPIHGRGLFCKRNIDAGEMVIEYSGNVIRSILTDKREKYYDSKGIGCYMFRIDDSEVVDA 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528509339 2790 TMHGNAARFINHSCDPNCYSRVINVEGQKHIVIFALRKIYRGEELTYDYKFPIEDADNKLHCNCGARRCRRFLN 2863
Cdd:cd19206    81 TMHGNAARFINHSCEPNCYSRVINIDGQKHIVIFAMRKIYRGEELTYDYKFPIEDASNKLPCNCGAKKCRKFLN 154

SET domain (including post-SET domain) found in SET domain-containing proteins (SETD1A/SETD1B), histone-lysine N-methyltransferases (KMT2A/KMT2B/KMT2C/KMT2D) and similar proteins; This family includes SET domain-containing protein 1A (SETD1A), 1B (SETD1B), as well as histone-lysine N-methyltransferase 2A (KMT2A), 2B (KMT2B), 2C (KMT2C), 2D (KMT2D). These proteins are histone-lysine N-methyltransferases (EC 2.1.1.43) that specifically methylate 'Lys-4' of histone H3 (H3K4me).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509339 2710 VAMRFRHLEKTSKEAVGVYRSAIHGRGLFCKRNIEAGEMVIEYAGNVIRAVLTDKREKYYDSKGI-GCYMFRIDDFDVVD 2788
Cdd:cd10518     1 MSKRFRQLRSRLKERLRVGKSGIHGWGLFAKRPIAAGEMVIEYVGEVIRPIVADKREKRYDEEGGgGTYMFRIDEDLVID 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528509339 2789 ATMHGNAARFINHSCDPNCYSRVINVEGQKHIVIFALRKIYRGEELTYDYKFPIEDaDNKLHCNCGARRCR 2859
Cdd:cd10518    81 ATKKGNIARFINHSCDPNCYAKIITVDGEKHIVIFAKRDIAPGEELTYDYKFPIED-EEKIPCLCGAPNCR 150

SET domain (including post-SET domain) found in histone-lysine N-methyltransferase 2C (KMT2C), 2D (KMT2D) and similar proteins; This family includes KMT2C and KMT2D. Both, KMT2C (also termed HALR or MLL3) and KMT2D (also termed ALR or MLL2), act as histone methyltransferases that methylate 'Lys-4' of histone H3 (H3K4me). They are subunits of MLL2/3 complex, a coactivator complex of nuclear receptors, involved in transcriptional coactivation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509339 2714 FRHLEKTSKEAVGVYRSAIHGRGLFCKRNIEAGEMVIEYAGNVIRAVLTDKREKYYDSKGIGCYMFRIDDFDVVDATMHG 2793
Cdd:cd19171     5 YRKLKTEWRSNVYLARSRIQGLGLYAARDIEKHTMVIEYIGEIIRNEVANRREKIYESQNRGIYMFRIDNDWVIDATMTG 84

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 528509339 2794 NAARFINHSCDPNCYSRVINVEGQKHIVIFALRKIYRGEELTYDYKFPIEDADNKLHCNCGARRCRRFL 2862
Cdd:cd19171    85 GPARYINHSCNPNCVAEVVTFDKEKKIIIISNRRIAKGEELTYDYKFDFEDDQHKIPCLCGAPNCRKWM 153

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 528509339 1387 RQCSLCQQHGDAKPNDAGRLLYIGQNEWAHVNCCIWSAEV-QETNGALLHVHSAVARGRFMRCERCGQTGATVGCCLTSC 1465
Cdd:cd15693     1 RQCALCLKYGDDSANDAGRLLYIGQNEWTHVNCALWSAEVfEDDDGSLKNVHMAVIRGKQLRCEFCQKPGATVGCCLTSC 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 528509339 1466 QSNYHFMCARASNCVFQHDKKVYCYKHRELI 1496
Cdd:cd15693    81 TSNYHFMCSRAKNCVFLEDKKVYCQRHKDLI 111

Extended PHD finger found in histone-lysine N-methyltransferase 2B (KMT2B); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This subfamily includes the ePHD finger of KMT2B. KMT2B is also called trithorax homolog 2 or WW domain-binding protein 7 (WBP-7). KMT2B is encoded by the gene that was first named myeloid/lymphoid or mixed-lineage leukemia 2 (MLL2), a second human homolog of Drosophila trithorax, located on chromosome 19. It belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2) and is vital for normal mammalian embryonic development. KMT2B functions as the catalytic subunit in the MLL2 complex, which contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex. The MLL2 complex is highly active and specific for histone 3 lysine 4 (H3K4) methylation, which stimulates chromatin transcription in a SAM- and H3K4-dependent manner. Moreover, KMT2B 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. KMT2B contains a CxxC (x for any residue) zinc finger domain, three PHD fingers, this 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 528509339 1389 CSLCQQHGDAKPNDAGRLLYIGQNEWAHVNCCIWSAEV-QETNGALLHVHSAVARGRFMRCERCGQTGATVGCCLTSCQS 1467
Cdd:cd15694     1 CALCLKYGDADSKDAGRLLYIGQNEWTHVNCAIWSAEVfEENDGSLKNVHAAVARGRQMRCEHCQKIGATVGCCLSACLS 80

                          90       100
                  ....*....|....*....|....*
gi 528509339 1468 NYHFMCARASNCVFQHDKKVYCYKH 1492
Cdd:cd15694    81 NFHFMCARASRCCFQDDKKVFCQKH 105

SET domain (including post-SET domain) found in SET domain-containing protein 1A (SETD1A) and similar proteins; SETD1A (EC2.1.1.43), also termed lysine N-methyltransferase 2F, or Set1/Ash2 histone methyltransferase complex subunit SET1, is a histone-lysine N-methyltransferase that specifically methylates 'Lys-4' of histone H3 (H3K4me), when part of the SET1 histone methyltransferase (HMT) complex, but not if the neighboring 'Lys-9' residue is already methylated. Human SET domain containing protein 1A (hSETD1A) expression occurs at a high rate in hepatocellular carcinoma patients and controls tumor metastasis in breast cancer by activating MMP expression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509339 2719 KTSKEAVGVYRSAIHGRGLFCKRNIEAGEMVIEYAGNVIRAVLTDKREKYYDSKGIGC-YMFRIDDFDVVDATMHGNAAR 2797
Cdd:cd19204    10 KFRKKKLRFGRSRIHEWGLFAMEPIAADEMVIEYVGQNIRQVVADMREKRYVQEGIGSsYLFRVDHDTIIDATKCGNLAR 89

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 528509339 2798 FINHSCDPNCYSRVINVEGQKHIVIFALRKIYRGEELTYDYKFPIEdaDNKLHCNCGARRCRRFLN 2863
Cdd:cd19204    90 FINHCCTPNCYAKVITIESQKKIVIYSKQPIGVNEEITYDYKFPIE--DNKIPCLCGTENCRGTLN 153

SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain; Putative methyl transferase, based on outlier plant homologues

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509339   2725 VGVYRSAIHGRGLFCKRNIEAGEMVIEYAGNVIRAVLTDKREKYYDSKGI-GCYMFRIDDFDVVDATMHGNAARFINHSC 2803
Cdd:smart00317    3 LEVFKSPGKGWGVRATEDIPKGEFIGEYVGEIITSEEAEERPKAYDTDGAkAFYLFDIDSDLCIDARRKGNLARFINHSC 82

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|..
gi 528509339   2804 DPNCYSRVINVEGQKHIVIFALRKIYRGEELTYDYKFPIEDA 2845
Cdd:smart00317   83 EPNCELLFVEVNGDDRIVIFALRDIKPGEELTIDYGSDYANE 124

SET domain (including post-SET domain) found in histone-lysine N-methyltransferase 2D (KMT2D) and similar proteins; KMT2D (EC2.1.1.43; also termed lysine N-methyltransferase 2D, ALL1-related protein (ALR), or myeloid/lymphoid or mixed-lineage leukemia protein 2 (MLL2)), acts as histone methyltransferase that methylates 'Lys-4' of histone H3 (H3K4me). It is a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription. KMT2D is a subunit of MLL2/3 complex, a coactivator complex of nuclear receptors, involved in transcriptional coactivation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509339 2713 RFRHLEKTSKEAVGVYRSAIHGRGLFCKRNIEAGEMVIEYAGNVIRAVLTDKREKYYDSKGIGCYMFRIDDFDVVDATMH 2792
Cdd:cd19209     6 QYRRLKTEWKNNVYLARSRIQGLGLYAAKDLEKHTMVIEYIGTIIRNEVANRREKIYEEQNRGIYMFRINNEHVIDATLT 85

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509339 2793 GNAARFINHSCDPNCYSRVINVEGQKHIVIFALRKIYRGEELTYDYKFPIEDADNKLHCNCGARRCRRFL 2862
Cdd:cd19209    86 GGPARYINHSCAPNCVAEVVTFDKEDKIIIISSRRIPKGEELTYDYQFDFEDDQHKIPCHCGAWNCRKWM 155

SET domain-containing protein (function unknown) [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509339 2729 RSAIHGRGLFCKRNIEAGEMVIEYAGNVIRAvltDKREKYYDSKGIGC-YMFRIDDFDVVDATMHGNAARFINHSCDPNC 2807
Cdd:COG2940    12 PSPIHGRGVFATRDIPKGTLIGEYPGEVITW---AEAERREPHKEPLHtYLFELDDDGVIDGALGGNPARFINHSCDPNC 88

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 528509339 2808 YSRVINvegqKHIVIFALRKIYRGEELTYDYKFPIEDADnkLHCNCgaRRCR 2859
Cdd:COG2940    89 EADEED----GRIFIVALRDIAAGEELTYDYGLDYDEEE--YPCRC--PNCR 132

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 528509339 1389 CSLCQQHGDAKPNDAGRLLYIGQNEWAHVNCCIWSAEVQET-NGALLHVHSAVARGRFMRCERCGQTGATVGCCLTSCQS 1467
Cdd:cd15666     1 CVLCGGEGDGDTDGPGRLLNLDVDKWVHLNCALWSYEVYETqNGALMNVEEALRRALTTTCSHCGRTGATVPCFKPRCAN 80

                          90       100
                  ....*....|....*....|....*
gi 528509339 1468 NYHFMCARASNCVFQHDKKVYCYKH 1492
Cdd:cd15666    81 VYHLPCAIKDGCMFFKDKTMLCPSH 105

SET domain found in enhancer of zeste homolog 1 (EZH1), zeste homolog 2 (EZH2) and similar proteins; The family includes EZH1 and EZH2. EZH1 (EC 2.1.1.43; also termed ENX-2, or histone-lysine N-methyltransferase EZH1) is a catalytic subunit of the PRC2/EED-EZH1 complex, which methylates 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. EZH2 (EC 2.1.1.43; also termed lysine N-methyltransferase 6, ENX-1, or histone-lysine N-methyltransferase EZH2) is a catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Both, EZH1 and EZH2, can mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509339 2723 EAVGVYRSAIHGRGLFCKRNIEAGEMVIEYAGNVIRAVLTDKREKYYDSKGIGcYMFRIDDFDVVDATMHGNAARFINHS 2802
Cdd:cd10519     1 KRLLLGKSDVAGWGLFLKEPIKKDEFIGEYTGELISQDEADRRGKIYDKYNSS-YLFNLNDQFVVDATRKGNKIRFANHS 79

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 528509339 2803 CDPNCYSRVINVEGQKHIVIFALRKIYRGEELTYDY 2838
Cdd:cd10519    80 SNPNCYAKVMMVNGDHRIGIFAKRDIEAGEELFFDY 115

PHD finger 3 found in Histone-lysine N-methyltransferase 2B (KMT2B); KMT2B, also termed trithorax homolog 2 or WW domain-binding protein 7 (WBP-7), is encoded by the gene that was first named myeloid/lymphoid or mixed-lineage leukemia 2 (MLL2), a second human homolog of Drosophila trithorax, located on chromosome 19. It belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2) and is vital for normal mammalian embryonic development. KMT2B functions as the catalytic subunit in the MLL2 complex, which contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex. The MLL2 complex is highly active and specific for histone 3 lysine 4 (H3K4) methylation, which stimulates chromatin transcription in a SAM- and H3K4-dependent manner. Moreover, KMT2B plays a critical role in memory formation through 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. KMT2B contains a CxxC (x for any residue) zinc finger domain, three plant homeodomain (PHD) fingers, an extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain. This model corresponds to the third PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 528509339 1149 FCTVCLKCYEEHEFDSSMMQCARCAHWVHPKCEGLTDDLHEILCRLRGkSLVFSCAPC 1206
Cdd:cd15593     1 YCPICLKCYEDNDYESKMMQCAKCDHWVHAKCEGLSDELYEILSSLPD-SVVYSCAPC 57

SET domain (including pre-SET and post-SET domains) found in suppressor of variegation 3-9 homologs, SUV39H1, SUV39H2 and similar proteins; This family includes SUV39H1 (also termed histone H3-K9 methyltransferase 1, H3-K9-HMTase 1, lysine N-methyltransferase 1A, KMT1A, position-effect variegation 3-9 homolog, SUV39H, or Su(var)3-9 homolog 1) and SUV39H2 (also termed histone H3-K9 methyltransferase 2, H3-K9-HMTase 2, lysine N-methyltransferase 1B, KMT1B, or Su(var)3-9 homolog 2), both act as histone-lysine N-methyltransferases that specifically trimethylate 'Lys-9' of histone H3 (H3K9me3) using monomethylated H3 'Lys-9' as substrate. They mainly function in heterochromatin regions, thereby playing central roles in the establishment of constitutive heterochromatin at pericentric and telomere regions. Also included are Schizosaccharomyces pombe H3K9 methyltransferase Clr4 (SUV39H homolog) and Neurospora crassa DIM-5, both of which also methylate 'Lys-9' of histone H3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509339 2734 GRGLFCKRNIEAGEMVIEYAGNVIRAVLTDKREKYYDSKGIgCYMFRIDDFD-----VVDATMHGNAARFINHSCDPN-- 2806
Cdd:cd10542    99 GWGVKTLEDIKKGTFVMEYVGEIITSEEAERRGKIYDANGR-TYLFDLDYNDddceyTVDAAYYGNISHFINHSCDPNla 177

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 528509339 2807 CYSRVINVEGQK--HIVIFALRKIYRGEELTYDYKFPIEDADN----------KLHCNCGARRCRRFL 2862
Cdd:cd10542   178 VYAVWINHLDPRlpRIAFFAKRDIKAGEELTFDYLMTGTGGSSestipkpkdvRVPCLCGSKNCRKYL 245

SET domain (including post-SET domain) found in nuclear SET domain-containing proteins, NSD1, NSD2, NSD3 and similar proteins; The nuclear receptor-binding SET Domain (NSD) family of histone H3 lysine 36 methyltransferases is comprised of NSD1, NSD2, and NSD3, which are primarily known to be involved in chromatin integrity and gene expression through mono-, di-, or tri-methylating lysine 36 of histone H3 (H3K36), respectively. NSD1 (EC 2.1.1.43; also termed histone-lysine N-methyltransferase H3 lysine-36 and H4 lysine-20 specific, androgen receptor coactivator 267 kDa protein (ARA267), androgen receptor-associated protein of 267 kDa, H3-K36-HMTase, H4-K20-HMTase, lysine N-methyltransferase 3B (KMT3B) or NR-binding SET domain-containing protein 1) functions as a histone-lysine N-methyltransferase that preferentially methylates 'Lys-36' of histone H3 and 'Lys-20' of histone H4. NSD2 (EC 2.1.1.43; also termed multiple myeloma SET domain-containing protein (MMSET), protein trithorax-5 (TRX5), or wolf-Hirschhorn syndrome candidate 1 protein (WHSC1)) acts as histone-lysine N-methyltransferase with histone H3 'Lys-27' (H3K27me) methyltransferase activity. NSD3 (EC 2.1.1.43; also termed protein whistle, WHSC1-like 1 isoform 9 with methyltransferase activity to lysine, Wolf-Hirschhorn syndrome candidate 1-like protein 1 (WHSC1L1), or WHSC1-like protein 1) functions as a histone-lysine N-methyltransferase that preferentially methylates 'Lys-4' and 'Lys-27' of histone H3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528509339 2727 VYRSAIHGRGLFCKRNIEAGEMVIEYAGNVIRAVLTDKREKYYDSKGI-GCYMFRIDDFDVVDATMHGNAARFINHSCDP 2805
Cdd:cd19173     6 PFKTGDRGWGLRTKRDIKKGDFVIEYVGELIDEEECRRRLKKAHENNItNFYMLTLDKDRIIDAGPKGNLSRFMNHSCQP 85

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 528509339 2806 NCYSRVINVEGQKHIVIFALRKIYRGEELTYDYKFpiEDADN-KLHCNCGARRCRRFL 2862
Cdd:cd19173    86 NCETQKWTVNGDTRVGLFAVRDIPAGEELTFNYNL--DCLGNeKKVCRCGAPNCSGFL 141