chromodomain of histone methyltransferase SUV39H1, and similar proteins; CHRomatin Organization Modifier (chromo) domain of human SUV39H1, a histone lysine methyltransferase (HMT) which catalyzes di- and tri-methylation of lysine 9 of histone H3 (H3K9me2/3), leading to heterochromatin formation and gene silencing. H3K9me2/3 represents a specific mark for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3, and/or CBX5) proteins to methylated histones. SUV39H1 mainly functions in heterochromatin regions. The human SUV39H1/2, histone H3K9 methyltransferases, are the mammalian homologs of Drosophila Su(var)3-9 and Schizosaccharomyces pombe Clr4. SUV39H1 contains a chromodomain at its N-terminus and a SET domain at its C-terminus. Although the SET domain performs the catalytic activity, the chromodomain of SUV39H1 is essential for the catalytic activity of SUV39H1. A chromodomain is a conserved region of about 50 amino acids, found in a variety of chromosomal proteins, and which appears to play a role in the functional organization of the eukaryotic nucleus. The chromodomain is implicated in the binding, of the proteins in which it is found, to methylated histone tails and maybe RNA. A chromodomain may occur as a single instance, in a tandem arrangement, or followed by a related chromo shadow domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 301171605  47 YEVEYLCDYKVVKDMEYYLVKWKGWPDSTNTWEPLQNLKCPLLLQQFSN 95
Cdd:cd18639    1 YEVEYLCDYKKIREQEYYLVKWKGYPDSENTWEPRQNLKCSRLLKQFHK 49

chromodomain of histone methyltransferase SUV39H1, and similar proteins; CHRomatin Organization Modifier (chromo) domain of human SUV39H1, a histone lysine methyltransferase (HMT) which catalyzes di- and tri-methylation of lysine 9 of histone H3 (H3K9me2/3), leading to heterochromatin formation and gene silencing. H3K9me2/3 represents a specific mark for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3, and/or CBX5) proteins to methylated histones. SUV39H1 mainly functions in heterochromatin regions. The human SUV39H1/2, histone H3K9 methyltransferases, are the mammalian homologs of Drosophila Su(var)3-9 and Schizosaccharomyces pombe Clr4. SUV39H1 contains a chromodomain at its N-terminus and a SET domain at its C-terminus. Although the SET domain performs the catalytic activity, the chromodomain of SUV39H1 is essential for the catalytic activity of SUV39H1. A chromodomain is a conserved region of about 50 amino acids, found in a variety of chromosomal proteins, and which appears to play a role in the functional organization of the eukaryotic nucleus. The chromodomain is implicated in the binding, of the proteins in which it is found, to methylated histone tails and maybe RNA. A chromodomain may occur as a single instance, in a tandem arrangement, or followed by a related chromo shadow domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 301171605  47 YEVEYLCDYKVVKDMEYYLVKWKGWPDSTNTWEPLQNLKCPLLLQQFSN 95
Cdd:cd18639    1 YEVEYLCDYKKIREQEYYLVKWKGYPDSENTWEPRQNLKCSRLLKQFHK 49

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 301171605  104 VITSEEAERRGQFY-----DNKGITYLFDLDyESDEFTVD--AARYGNVSHFVNHSCDPNLQVFNVFIDnldtRLPRIAL 176
Cdd:pfam00856  24 LITKEEADKRELLYydkleLRLWGPYLFTLD-EDSEYCIDarALYYGNWARFINHSCDPNCEVRVVYVN----GGPRIVI 98

                          90
                  ....*....|....*.
gi 301171605  177 FSTRTINAGEELTFDY 192
Cdd:pfam00856  99 FALRDIKPGEELTIDY 114

Chromo (CHRromatin organization MOdifier) domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 301171605   47 YEVEYLCDYKVVKD-MEYYLVKWKGWPDSTNTWEPLQNL-KCPLLLQQF 93
Cdd:pfam00385   1 YEVERILDHRKDKGgKEEYLVKWKGYPYDENTWEPEENLsKCPELIEEF 49

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 301171605 100 YLSQVITSEEAERRGQFYDNKGITYLFDLDYESD--EFTVDAARYGNVSHFVNHSCDPNLQVFNVFIDNLDTRLPRIALF 177
Cdd:cd10542  117 YVGEIITSEEAERRGKIYDANGRTYLFDLDYNDDdcEYTVDAAYYGNISHFINHSCDPNLAVYAVWINHLDPRLPRIAFF 196

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 301171605 178 STRTINAGEELTFDYQMKGSGDISSdsiDHSPAKKRVRTVCKCGAVTCRGYL 229
Cdd:cd10542  197 AKRDIKAGEELTFDYLMTGTGGSSE---STIPKPKDVRVPCLCGSKNCRKYL 245

SET domain (including pre-SET and post-SET domains) found in SET domain bifurcated 1 (SETDB1) and 2 (SETDB2), suppressor of variegation 3-9 homologs, SUV39H1 and SUV39H2, euchromatic histone-lysine N-methyltransferase EHMT1 and EHMT2, and similar proteins; The family includes SET domain bifurcated 1 (SETDB1) and 2 (SETDB2), suppressor of variegation 3-9 homologs, SUV39H1 and SUV39H2, euchromatic histone-lysine N-methyltransferase EHMT1 and EHMT2. SETDB1 (EC 2.1.1.43; also termed ERG-associated protein with SET domain (ESET), histone H3-K9 methyltransferase 4, H3-K9-HMTase 4, or lysine N-methyltransferase 1E (KMT1E)) acts as a histone-lysine N-methyltransferase that specifically trimethylates 'Lys-9' of histone H3 (H3K9me3). It mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. SETDB2 (EC 2.1.1.43; also termed chronic lymphocytic leukemia deletion region gene 8 protein (CLLD8), or lysine N-methyltransferase 1F (KMT1F)) acts as a histone-lysine N-methyltransferase that specifically trimethylates 'Lys-9' of histone H3 (H3K9me3). It is involved in left-right axis specification in early development and mitosis. 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. EHMT1 (also termed Eu-HMTase1, G9a-like protein 1, GLP, GLP1, histone H3-K9 methyltransferase 5, H3-K9-HMTase 5, lysine N-methyltransferase 1D, or KMT1D) and EHMT2 (also termed Eu-HMTase2, HLA-B-associated transcript 8, histone H3-K9 methyltransferase 3, H3-K9-HMTase 3, lysine N-methyltransferase 1C, KMT1C, or protein G9a), both act as histone-lysine N-methyltransferases that specifically mono- and dimethylate 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. This family also includes the pre-SET domain, which is found in a number of histone methyltransferases (HMTase), N-terminal to the SET domain. Pre-SET domain is a zinc binding motif which contains 9 conserved cysteines that coordinate three zinc ions. It is thought that this region plays a structural role in stabilizing SET domains. Most family members, except for Arabidopsis thaliana SUVH9, contain a post-SET domain which harbors a zinc-binding site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301171605 100 YLSQVITSEEAERRGQFYDNKGITYLFDLDYESD------EFTVDAARYGNVSHFVNHSCDPNLQVFNVFIDNLDTRLPR 173
Cdd:cd10538  118 YVGEVITTSEADRRGKIYDKSGGSYLFDLDEFSDsdgdgeELCVDATFCGNVSRFINHSCDPNLFPFNVVIDHDDLRYPR 197

                         90       100
                 ....*....|....*....|
gi 301171605 174 IALFSTRTINAGEELTFDYQ 193
Cdd:cd10538  198 IALFATRDILPGEELTFDYG 217

chromodomain of histone methyltransferase SUV39H1, and similar proteins; CHRomatin Organization Modifier (chromo) domain of human SUV39H1, a histone lysine methyltransferase (HMT) which catalyzes di- and tri-methylation of lysine 9 of histone H3 (H3K9me2/3), leading to heterochromatin formation and gene silencing. H3K9me2/3 represents a specific mark for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3, and/or CBX5) proteins to methylated histones. SUV39H1 mainly functions in heterochromatin regions. The human SUV39H1/2, histone H3K9 methyltransferases, are the mammalian homologs of Drosophila Su(var)3-9 and Schizosaccharomyces pombe Clr4. SUV39H1 contains a chromodomain at its N-terminus and a SET domain at its C-terminus. Although the SET domain performs the catalytic activity, the chromodomain of SUV39H1 is essential for the catalytic activity of SUV39H1. A chromodomain is a conserved region of about 50 amino acids, found in a variety of chromosomal proteins, and which appears to play a role in the functional organization of the eukaryotic nucleus. The chromodomain is implicated in the binding, of the proteins in which it is found, to methylated histone tails and maybe RNA. A chromodomain may occur as a single instance, in a tandem arrangement, or followed by a related chromo shadow domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 301171605  47 YEVEYLCDYKVVKDMEYYLVKWKGWPDSTNTWEPLQNLKCPLLLQQFSN 95
Cdd:cd18639    1 YEVEYLCDYKKIREQEYYLVKWKGYPDSENTWEPRQNLKCSRLLKQFHK 49

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 301171605   100 YLSQVITSEEAERRGQFYDNKGI--TYLFDLDyesDEFTVDAARYGNVSHFVNHSCDPNLQVFNVFIDNLDtrlpRIALF 177
Cdd:smart00317  30 YVGEIITSEEAEERPKAYDTDGAkaFYLFDID---SDLCIDARRKGNLARFINHSCEPNCELLFVEVNGDD----RIVIF 102

                           90
                   ....*....|....*.
gi 301171605   178 STRTINAGEELTFDYQ 193
Cdd:smart00317 103 ALRDIKPGEELTIDYG 118

SET domain (including pre-SET and post-SET domains) found in euchromatic histone-lysine N-methyltransferase EHMT1, EHMT2 and similar proteins; This family includes EHMT1 (also termed Eu-HMTase1, G9a-like protein 1, GLP, GLP1, histone H3-K9 methyltransferase 5, H3-K9-HMTase 5, lysine N-methyltransferase 1D, or KMT1D) and EHMT2 (also termed Eu-HMTase2, HLA-B-associated transcript 8, histone H3-K9 methyltransferase 3, H3-K9-HMTase 3, lysine N-methyltransferase 1C, KMT1C, or protein G9a), both act as histone-lysine N-methyltransferases that specifically mono- and dimethylate 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301171605 100 YLSQVITSEEAERRGqfyDNkgiTYLFDLD-YESDEFTVDAARYGNVSHFVNHSCDPNLQVFNVFIDNLDTRLPRIALFS 178
Cdd:cd10543  120 YIGELISDSEADSRE---DD---SYLFDLDnKDGETYCIDARRYGNISRFINHLCEPNLIPVRVFVEHQDLRFPRIAFFA 193

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 301171605 179 TRTINAGEELTFDYqmkGSG--DIssdsidhspakKRVRTVCKCGAVTCR 226
Cdd:cd10543  194 SRDIKAGEELGFDY---GEKfwRI-----------KGKYFTCRCGSPKCK 229

SET domain (including post-SET domain) found in SET domain-containing protein 2 (SETD2) and similar proteins; SETD2 (also termed HIF-1, huntingtin yeast partner B, huntingtin-interacting protein 1 (HIP-1), huntingtin-interacting protein B, lysine N-methyltransferase 3A or protein-lysine N-methyltransferase SETD2) acts as histone-lysine N-methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using demethylated 'Lys-36' (H3K36me2) as substrate. It has been shown that methylation is a posttranslational modification of dynamic microtubules and that SETD2 methylates alpha-tubulin at lysine 40, the same lysine that is marked by acetylation on microtubules. Methylation of microtubules occurs during mitosis and cytokinesis and can be ablated by SETD2 deletion, which causes mitotic spindle and cytokinesis defects, micronuclei, and polyploidy.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301171605 100 YLSQVITSEEAERRGQFYDNKGITYLFDLDYESDEFtVDAARYGNVSHFVNHSCDPN--LQVFNVfidnldTRLPRIALF 177
Cdd:cd19172   31 YVGEVLDEKEFKRRMKEYAREGNRHYYFMALKSDEI-IDATKKGNLSRFINHSCEPNceTQKWTV------NGELRVGFF 103

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 301171605 178 STRTINAGEELTFDYQMKGSGDIssdsidhspAKKrvrtvCKCGAVTCRGYL 229
Cdd:cd19172  104 AKRDIPAGEELTFDYQFERYGKE---------AQK-----CYCGSPNCRGYI 141

SET domain (including post-SET domain) found in SET domain-containing protein 2 (SETD2), nuclear SETD2 (NSD2), ASH1-like protein (ASH1L) and similar proteins; This family includes SET domain-containing protein 2 (SETD2), nuclear SETD2 (NSD2) and ASH1-like protein (ASH1L), which function as histone-lysine N-methyltransferases. SETD2 specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using demethylated 'Lys-36' (H3K36me2) as substrate. NSD2 shows histone H3 'Lys-27' (H3K27me) methyltransferase activity. ASH1L specifically methylates 'Lys-36' of histone H3 (H3K36me). The family also includes Arabidopsis thaliana ASH1-related protein 3 (ASHR3) and similar proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301171605 100 YLSQVITSEEAERRGQFYDNKGITYLFDLDYESDEFtVDAARYGNVSHFVNHSCDPNL--QVFNVFIDnldtrlPRIALF 177
Cdd:cd10531   29 YVGEVIDKKEFKERLDEYEELGKSNFYILSLSDDVV-IDATRKGNLSRFINHSCEPNCetQKWIVNGE------YRIGIF 101

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 301171605 178 STRTINAGEELTFDYQMKGSGDISsdsidhspakkrvrTVCKCGAVTCR 226
Cdd:cd10531  102 ALRDIPAGEELTFDYNFVNYNEAK--------------QVCLCGAQNCR 136

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 301171605  98 HNYLSQVITSEEAERRGQFYDNKGITYLFDLDYESDeFTVDAARYGNVSHFVNHSCDPNL--QVFNVfidNLDTRlprIA 175
Cdd:cd19173   29 IEYVGELIDEEECRRRLKKAHENNITNFYMLTLDKD-RIIDAGPKGNLSRFMNHSCQPNCetQKWTV---NGDTR---VG 101

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 301171605 176 LFSTRTINAGEELTFDYQMKGSGDissdsidhspakkrVRTVCKCGAVTCRGYL 229
Cdd:cd19173  102 LFAVRDIPAGEELTFNYNLDCLGN--------------EKKVCRCGAPNCSGFL 141

SET domain (including pre-SET and post-SET domains) found in SET domain and mariner transposase fusion protein (SETMAR) and similar proteins; SETMAR (also termed metnase) is a DNA-binding protein that is indirectly recruited to sites of DNA damage through protein-protein interactions. It has a sequence-specific DNA-binding activity recognizing the 19-mer core of the 5'-terminal inverted repeats (TIRs) of the Hsmar1 element and displays a DNA nicking and end joining activity. SETMAR also acts as a histone-lysine N-methyltransferase that methylates 'Lys-4' and 'Lys-36' of histone H3. It specifically mediates dimethylation of H3 'Lys-36' at sites of DNA double-strand break and may recruit proteins required for efficient DSB repair through non-homologous end-joining.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301171605 100 YLSQVITSEEAERRGQFYDNKGITYLFDL-DYESD----EFTVDAARYGNVSHFVNHSCDPNLQVFNVFIDNLdtrLPRI 174
Cdd:cd10544  119 YAGEVIGFEEARRRTKSQTKGDMNYIIVLrEHLSSgkvlETFVDPTYIGNIGRFLNHSCEPNLFMVPVRVDSM---VPKL 195

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 301171605 175 ALFSTRTINAGEELTFDYQMKGSGDISSDSI---DHSPAKKrvrtVCKCGAVTCRGYL 229
Cdd:cd10544  196 ALFAARDIVAGEELSFDYSGEFSNSVESVTLarqDESKSRK----PCLCGAENCRGFL 249

SET domain (including pre-SET and post-SET domains) found in euchromatic histone-lysine N-methyltransferase 2 (EHMT2) and similar proteins; EHMT2 (also termed Eu-HMTase2, HLA-B-associated transcript 8, histone H3-K9 methyltransferase 3, H3-K9-HMTase 3, lysine N-methyltransferase 1C (KMT1C), or protein G9a) acts as a histone-lysine N-methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301171605 100 YLSQVITSEEAERRgqfydnKGITYLFDLDYESDE-FTVDAARYGNVSHFVNHSCDPNLQVFNVFIDNLDTRLPRIALFS 178
Cdd:cd10533  120 YVGELISDAEADVR------EDDSYLFDLDNKDGEvYCIDARYYGNISRFINHLCDPNIIPVRVFMLHQDLRFPRIAFFS 193

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 301171605 179 TRTINAGEELTFDYqmkgsGDISSDsidhspAKKRVRTvCKCGAVTCR 226
Cdd:cd10533  194 SRDIRTGEELGFDY-----GDRFWD------IKSKYFT-CQCGSEKCK 229

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 301171605 100 YLSQVITSEEAERRGQFYD--NKGItYLFDLDyesDEFTVDAARYGNVSHFVNHSCDPNLQVFNVFIDnldtRLPRIALF 177
Cdd:cd19171   43 YIGEIIRNEVANRREKIYEsqNRGI-YMFRID---NDWVIDATMTGGPARYINHSCNPNCVAEVVTFD----KEKKIIII 114

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 301171605 178 STRTINAGEELTFDYQMkgsgDISSDSiDHSPakkrvrtvCKCGAVTCRGYL 229
Cdd:cd19171  115 SNRRIAKGEELTYDYKF----DFEDDQ-HKIP--------CLCGAPNCRKWM 153

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301171605 100 YLSQVITSEEAERRGQFyDNKGITYLFDLDyesDEFTVDAARYGNVSHFVNHSCDPNLQvfnvfidnLDTRLPRIALFST 179
Cdd:COG2940   35 YPGEVITWAEAERREPH-KEPLHTYLFELD---DDGVIDGALGGNPARFINHSCDPNCE--------ADEEDGRIFIVAL 102

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 301171605 180 RTINAGEELTFDYqmkgsgdisSDSIDHSPAKkrvrtvCKCGavTCRG 227
Cdd:COG2940  103 RDIAAGEELTYDY---------GLDYDEEEYP------CRCP--NCRG 133

SET domain (including post-SET domain) found in nuclear SET domain-containing protein 2 (NSD2) and similar proteins; 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-36' (H3K36me) methyltransferase activity. NSD2 has been shown to mediate di- and trimethylation of H3K36 and dimethylation of H4K20 in different systems, and has been characterized as a transcriptional repressor interacting with histone deacetylase HDAC1 and histone demethylase LSD1. NSD2 mediates constitutive NF-kappaB signaling for cancer cell proliferation, survival and tumor growth. It is highly overexpressed in several types of human cancers, including small-cell lung cancers, neuroblastoma, carcinomas of stomach and colon, and bladder cancers, and its overexpression tends to be associated with tumor aggressiveness. WHSC1 is frequently deleted in Wolf-Hirschhorn syndrome (WHS).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301171605  92 QFSNDkhnYLSQVITSEEAERRGQFYDNKGITYLFDLDYESDEFtVDAARYGNVSHFVNHSCDPNLQVFNVFIdNLDTrl 171
Cdd:cd19211   26 EFVNE---YVGELIDEEECMARIKHAHENDITHFYMLTIDKDRI-IDAGPKGNYSRFMNHSCQPNCETQKWTV-NGDT-- 98

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 301171605 172 pRIALFSTRTINAGEELTFDYQMKGSGDissdsidhspakkrVRTVCKCGAVTCRGYL 229
Cdd:cd19211   99 -RVGLFAVCDIPAGTELTFNYNLDCLGN--------------EKTVCRCGAPNCSGFL 141

SET domain found in Legionella pneumophila type IV secretion system effector LegAS4 and similar proteins; LegAS4 is a type IV secretion system effector of Legionella pneumophila. It contains a SET domain that is involved in the modification of Lys4 of histone H3 (H3K4) in the nucleolus of the host cell, thereby enhancing heterochromatic rDNA transcription. It also contains an ankyrin repeat domain of unknown function at its C-terminal region.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301171605 100 YLSQVITSEEAERRGQFYdnKGITYLFDLDYesDEFTVDAARYGNVSHFVNHSCDPNLQVFNVFIDnldtRLPRIALFST 179
Cdd:cd10522   32 YTGEVLDRWEEDRDSVYH--YDPLYPFDLNG--DILVIDAGKKGNLTRFINHSDQPNLELIVRTLK----GEQHIGFVAI 103

                         90
                 ....*....|...
gi 301171605 180 RTINAGEELTFDY 192
Cdd:cd10522  104 RDIKPGEELFISY 116

SET domain found in enhancer of zeste homolog 2 (EZH2) and similar proteins; EZH2 (EC 2.1.1.43), also termed lysine N-methyltransferase 6, or ENX-1, or histone-lysine N-methyltransferase EZH2, is a catalytic subunit of the polycomb repressive complex 2 (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. It can mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. PRC2 is involved in several cancers; EZH2 is overexpressed in breast, liver and prostate cancer, while point mutations in EZH2 alter the substrate preference and product specificity of PRC2 in Non-Hodgkin lymphomas (NHLs). Thus, PRC2 is a popular target for cancer therapeutics.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301171605 100 YLSQVITSEEAERRGQFYDNKGITYLFDLDyesDEFTVDAARYGNVSHFVNHSCDPNLQVfNVFIDNLDTrlpRIALFST 179
Cdd:cd19218   33 YCGEIISQDEADRRGKVYDKYMCSFLFNLN---NDFVVDATRKGNKIRFANHSVNPNCYA-KVMMVNGDH---RIGIFAK 105

                         90
                 ....*....|....
gi 301171605 180 RTINAGEELTFDYQ 193
Cdd:cd19218  106 RAIQTGEELFFDYR 119

SET domain (including pre-SET and post-SET domains) found in SET domain bifurcated 1 (SETDB1), SET domain bifurcated 2 (SETDB2), and similar proteins; SETDB1 (EC 2.1.1.43; also termed ERG-associated protein with SET domain (ESET), histone H3-K9 methyltransferase 4, H3-K9-HMTase 4, or lysine N-methyltransferase 1E (KMT1E)) acts as a histone-lysine N-methyltransferase that specifically trimethylates 'Lys-9' of histone H3 (H3K9me3). It mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. SETDB2 (EC 2.1.1.43; also termed chronic lymphocytic leukemia deletion region gene 8 protein (CLLD8), or lysine N-methyltransferase 1F (KMT1F)) acts as a histone-lysine N-methyltransferase that specifically trimethylates 'Lys-9' of histone H3 (H3K9me3). It is involved in left-right axis specification in early development and mitosis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301171605 100 YLSQVITSEEAERRGQFydnKGITYLFDLDY-ESDEFTVDAARYGNVSHFVNHSCDPNLQVFNVFIDNLDTRLPRIALFS 178
Cdd:cd10541  121 YAGKILTDDFADKEGLE---MGDEYFANLDHiEESCYIIDAKLEGNLGRYLNHSCSPNLFVQNVFVDTHDLRFPWVAFFA 197

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 301171605 179 TRTINAGEELTFDYQMKgsgdissdsIDHSPAKKrvrTVCKCGAVTCRGYL 229
Cdd:cd10541  198 SKRIKAGTELTWDYNYE---------VGSVEGKE---LLCCCGSNECRGRL 236

SET domain (including post-SET domain) found in nuclear receptor-binding SET domain-containing protein 1 (NSD1) and similar proteins; 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. NSD1 is altered in approximately 10% of head and neck cancer patients with 55% decrease in risk of death in NSD1-mutated versus non-mutated patients; its disruption promotes favorable chemotherapeutic responses linked to hypomethylation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301171605  92 QFSNDkhnYLSQVITSEEAERRGQFYDNKGITYLFDLDYESDEFtVDAARYGNVSHFVNHSCDPNLQVfNVFIDNLDTrl 171
Cdd:cd19210   26 EFVNE---YVGELIDEEECRARIRYAQEHDITNFYMLTLDKDRI-IDAGPKGNYARFMNHCCQPNCET-QKWTVNGDT-- 98

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 301171605 172 pRIALFSTRTINAGEELTFDYQMK--GSGdissdsidhspakkrvRTVCKCGAVTCRGYL 229
Cdd:cd19210   99 -RVGLFALCDIKAGTELTFNYNLEclGNG----------------KTVCKCGAPNCSGFL 141

SET domain (including post-SET domain) found in nuclear receptor-binding SET domain-containing protein 3 (NSD3) and similar proteins; 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. NSD3 is amplified and overexpressed in multiple cancer types, including acute myeloid leukemia (AML), breast, lung, pancreatic and bladder cancers, as well as squamous cell carcinoma of the head and neck (SCCHN). NSD3 contributes to tumorigenesis by interacting with bromodomain-containing protein 4 (BRD4), the bromodomain and extraterminal (BET) protein, which is a potential therapeutic target in acute myeloid leukemia (AML). NSD3 is amplified in primary tumors and cell lines from breast carcinoma, and can promote the cell viability of small-cell lung cancer and pancreatic ductal adenocarcinoma. High NSD3 expression is implicated in poor grade and heavy smoking history in SCCHN. Thus, NSD3 may serve as a potential druggable target for selective cancer therapy.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301171605  85 KCPLLLQQFSNDkhnYLSQVITSEEAERRGQFYDNKGITYLFDLDYESDEFtVDAARYGNVSHFVNHSCDPNLQVfNVFI 164
Cdd:cd19212   19 KRSIKKGEFVNE---YVGELIDEEECRLRIKRAHENSVTNFYMLTVTKDRI-IDAGPKGNYSRFMNHSCNPNCET-QKWT 93

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 301171605 165 DNLDTrlpRIALFSTRTINAGEELTFDYQMKGSGDissdsidhspakkrVRTVCKCGAVTCRGYL 229
Cdd:cd19212   94 VNGDV---RVGLFALCDIPAGMELTFNYNLDCLGN--------------GRTECHCGADNCSGFL 141

CHROMO (CHRromatin Organization Modifier) domains and chromo shadow domains; Members of this group are chromodomains or chromo shadow domains; these are SH3-fold-beta-barrel domains of the chromo-like superfamily. Chromodomains lack the first strand of the SH3-fold-beta-barrel, this first strand is altered by insertion in the chromo shadow domains. The chromodomain is a conserved region of about 50 amino acids, found in a variety of chromosomal proteins, and which appears to play a role in the functional organization of the eukaryotic nucleus. The chromodomain is implicated in the binding, of the proteins in which it is found, to methylated histone tails and maybe RNA. Chromodomain-containing proteins include: i) those having an N-terminal chromodomain followed by a related chromo shadow domain, such as Drosophila and human heterochromatin protein Su(var)205 (HP1), and mammalian modifier 1 and 2; ii) those having a single chromodomain, such as Drosophila protein Polycomb (Pc), mammalian modifier 3, human Mi-2 autoantigen, and several yeast and Caenorhabditis elegans proteins of unknown function; iii) those having paired tandem chromodomains, such as mammalian DNA-binding/helicase proteins CHD-1 to CHD-4 and yeast protein CHD1; (iv) and elongation factor eEF3, a member of the ATP-binding cassette (ABC) family of proteins, that serves an essential function in the translation cycle of fungi. eEF3 is a soluble factor lacking a transmembrane domain and having two ABC domains arranged in tandem, with a unique chromodomain inserted within the ABC2 domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 301171605  47 YEVEYLCDYKVVKDMEYYLVKWKGWPDSTNTWEPLQNLK-CPLLLQQF 93
Cdd:cd00024    1 YEVEKILDHRVRKGKLEYLVKWKGYPPEENTWEPEENLTnAPELIKEY 48

SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain superfamily; The Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain superfamily corresponds to SET domain-containing lysine methyltransferases, which catalyze site and state-specific methylation of lysine residues in histones that are fundamental in epigenetic regulation of gene activation and silencing in eukaryotic organisms. 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 has 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 N-SET and C-SET. C-SET forms an unusual and conserved knot-like structure of probable functional importance. In addition to N-SET and C-SET, an insert region (I-SET) and flanking regions of high structural variability form part of the overall structure. Some family members contain a pre-SET domain, which is found in a number of histone methyltransferases (HMTase), and a post-SET domain, which harbors a zinc-binding site.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 301171605 145 VSHFVNHSCDPNLQVFNVFIDnldtRLPRIALFSTRTINAGEELTFDY 192
Cdd:cd08161   28 LARFINHSCEPNCEFEEVYVG----GKPRVFIVALRDIKAGEELTVDY 71

chromodomain of insect HP1a; CHRomatin Organization Modifier (chromo) domain of insect HP1a. HP1a is a member of the heterochromatin protein family, and is enriched in the heterochromatin and associated with centromeres. HP1 has diverse functions in heterochromatin formation and impacts both gene expression and gene silencing. HP1 has two conserved protein-protein interaction domains, a single N-terminal chromodomain (CD) which can bind to histone proteins via methylated lysine residues, and a related C-terminal chromo shadow domain (CSD) which is responsible for the homodimerization and interaction with a number of chromatin-associated non-histone proteins; a flexible hinge region separates the CD and CSD and may bind nucleic acid. HP1 is a highly conserved non-histone chromosomal protein that is evolutionarily conserved from fission yeast to plants and animals. In Drosophila, there are at least five HP1 family proteins, this subgroup includes the CD of Drosophila melanogaster HP1a.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 301171605  47 YEVEYLCDYKVVKDMEYYLVKWKGWPDSTNTWEPLQNLKCPLLLQQF 93
Cdd:cd18653    2 YAVEKICDRRVRKGKVEYYLKWKGYPETENTWEPEENLDCQDLIQQY 48

chromodomain of heterochromatin protein 1 proteins, including HP1alpha, HP1beta, and HP1gamma; CHRomatin Organization Modifier (chromo) domain of mammalian HP1alpha (Cbx5), HP1beta (Cbx1), HP1gamma (Cbx5), and similar proteins. HP1 has diverse functions in heterochromatin formation and impacts both gene expression and gene silencing. HP1 has two conserved protein-protein interaction domains, a single N-terminal chromodomain (CD) which can bind to histone proteins via methylated lysine residues, and a related C-terminal chromo shadow domain (CSD) which is responsible for the homodimerization and interaction with a number of chromatin-associated non-histone proteins; a flexible hinge region separates the CD and CSD and may bind nucleic acid. HP1 is a highly conserved non-histone chromosomal protein that is evolutionarily conserved from fission yeast to plants and animals. There are three human homologs of HP1 proteins: HP1alpha (also known as Cbx5), HP1beta (also known as Cbx1), and HP1gamma (also known as Cbx3).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 301171605  47 YEVEYLCDYKVVKDMEYYLVKWKGWPDSTNTWEPLQNLKCPLLLQQFSN 95
Cdd:cd18631    2 YVVEKVLDRRVVKGKVEYLLKWKGYPDEDNTWEPEENLDCPDLIAEFEE 50

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 301171605 100 YLSQVITSEEAERRGQFYD--NKGItYLFDLDyesDEFTVDAARYGNVSHFVNHSCDPNLQVFNVFIDNLDtrlpRIALF 177
Cdd:cd19209   45 YIGTIIRNEVANRREKIYEeqNRGI-YMFRIN---NEHVIDATLTGGPARYINHSCAPNCVAEVVTFDKED----KIIII 116

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 301171605 178 STRTINAGEELTFDYQMkgsgDISSDSIDhspakkrvrTVCKCGAVTCRGYL 229
Cdd:cd19209  117 SSRRIPKGEELTYDYQF----DFEDDQHK---------IPCHCGAWNCRKWM 155

SET domain (including post-SET domain) found in histone-lysine N-methyltransferase 2C (KMT2C) and similar proteins; KMT2C (EC2.1.1.43; also termed lysine N-methyltransferase 2C, homologous to ALR protein (HALR) myeloid/lymphoid, or mixed-lineage leukemia protein 3 (MLL3)), acts as a histone methyltransferase that methylates 'Lys-4' of histone H3 (H3K4me) and may be involved in leukemogenesis and developmental disorder. KMT2C is a catalytic subunit of MLL2/3 complex, a coactivator complex of nuclear receptors, involved in transcriptional coactivation. Overexpression of KMT2C is associated with estrogen receptor-positive breast cancer; KMT2C mediates the estrogen dependence of breast cancer through regulation of estrogen receptor alpha (ERalpha) enhancer function. KMT2C is frequently mutated in certain populations with diffuse-type gastric adenocarcinomas (DGA); its loss promotes epithelial-to-mesenchymal transition (EMT) and is associated with worse overall survival.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301171605 100 YLSQVITSEEAERRGQFYD--NKGItYLFDLDyesDEFTVDAARYGNVSHFVNHSCDPNLQVFNVFIDnldtRLPRIALF 177
Cdd:cd19208   44 YIGTIIRNEVANRKEKLYEsqNRGV-YMFRID---NDHVIDATLTGGPARYINHSCAPNCVAEVVTFE----KGHKIIIS 115

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 301171605 178 STRTINAGEELTFDYQMkgsgDISSDsidhspakkRVRTVCKCGAVTCRGYL 229
Cdd:cd19208  116 SSRRIQKGEELCYDYKF----DFEDD---------QHKIPCHCGAVNCRKWM 154