RNA recognition motif in the Set1-like family of histone-lysine N-methyltransferases; This subfamily corresponds to the RRM of the Set1-like family of histone-lysine N-methyltransferases which includes Set1A and Set1B that are ubiquitously expressed vertebrates histone methyltransferases exhibiting high homology to yeast Set1. Set1A and Set1B proteins exhibit a largely non-overlapping subnuclear distribution in euchromatic nuclear speckles, strongly suggesting that they bind to a unique set of target genes and thus make non-redundant contributions to the epigenetic control of chromatin structure and gene expression. With the exception of the catalytic component, the subunit composition of the Set1A and Set1B histone methyltransferase complexes are identical. Each complex contains six human homologs of the yeast Set1/COMPASS complex, including Set1A or Set1B, Ash2 (homologous to yeast Bre2), CXXC finger protein 1 (CFP1; homologous to yeast Spp1), Rbbp5 (homologous to yeast Swd1), Wdr5 (homologous to yeast Swd3), and Wdr82 (homologous to yeast Swd2). The genomic targeting of these complexes is determined by the identity of the catalytic subunit present in each histone methyltransferase complex. Thus, the Set1A and Set1B complexes may exhibit both overlapping and non-redundant properties. Both Set1A and Set1B contain an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), an N- SET domain, and a C-terminal catalytic SET domain followed by a post-SET domain. In contrast to Set1B, Set1A additionally contains an HCF-1 binding motif that interacts with HCF-1 in vivo.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366751   99 PAVEVTIVNLNDNIDKQFLASMLDKCGTSDEINIYHHPITNKHLGIARIVFDSTKGARQFVEKYNQKSVMGKILDVFCDP 178
Cdd:cd12304     1 PPREVTFANLNDNINEGFLKDMCKKYGEVEEVKIYFHPKTGKHLGLARVVFDTTKGAKDCVEKLNQTSVMGNIIHVFLDP 80

                          90
                  ....*....|...
gi 281366751  179 FGATLKKSLESLT 191
Cdd:cd12304    81 KGRIIARLYEDIV 93

U2 snRNP auxilliary factor, large subunit, splicing factor; These splicing factors consist of an N-terminal arginine-rich low complexity domain followed by three tandem RNA recognition motifs (pfam00076). The well-characterized members of this family are auxilliary components of the U2 small nuclear ribonuclearprotein splicing factor (U2AF). These proteins are closely related to the CC1-like subfamily of splicing factors (TIGR01622). Members of this subfamily are found in plants, metazoa and fungi.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366751   255 RDKERERDRhfkERSR-HSSERSYDRDRGMREnvgtsirrrrtfyrrrssdiSPEDSRDILIMTRERSRDSDSRPRDYCR 333
Cdd:TIGR01642    1 RDEEPDRER---EKSRgRDRDRSSERPRRRSR--------------------DRSRFRDRHRRSRERSYREDSRPRDRRR 57

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 281366751   334 SRERESFRDRKRSHEKGRDQPReKREHYYNSSKDREYRGRDRDRSAEIDQRDR 386
Cdd:TIGR01642   58 YDSRSPRSLRYSSVRRSRDRPR-RRSRSVRSIEQHRRRLRDRSPSNQWRKDDK 109

RNA recognition motif in the Set1-like family of histone-lysine N-methyltransferases; This subfamily corresponds to the RRM of the Set1-like family of histone-lysine N-methyltransferases which includes Set1A and Set1B that are ubiquitously expressed vertebrates histone methyltransferases exhibiting high homology to yeast Set1. Set1A and Set1B proteins exhibit a largely non-overlapping subnuclear distribution in euchromatic nuclear speckles, strongly suggesting that they bind to a unique set of target genes and thus make non-redundant contributions to the epigenetic control of chromatin structure and gene expression. With the exception of the catalytic component, the subunit composition of the Set1A and Set1B histone methyltransferase complexes are identical. Each complex contains six human homologs of the yeast Set1/COMPASS complex, including Set1A or Set1B, Ash2 (homologous to yeast Bre2), CXXC finger protein 1 (CFP1; homologous to yeast Spp1), Rbbp5 (homologous to yeast Swd1), Wdr5 (homologous to yeast Swd3), and Wdr82 (homologous to yeast Swd2). The genomic targeting of these complexes is determined by the identity of the catalytic subunit present in each histone methyltransferase complex. Thus, the Set1A and Set1B complexes may exhibit both overlapping and non-redundant properties. Both Set1A and Set1B contain an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), an N- SET domain, and a C-terminal catalytic SET domain followed by a post-SET domain. In contrast to Set1B, Set1A additionally contains an HCF-1 binding motif that interacts with HCF-1 in vivo.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366751   99 PAVEVTIVNLNDNIDKQFLASMLDKCGTSDEINIYHHPITNKHLGIARIVFDSTKGARQFVEKYNQKSVMGKILDVFCDP 178
Cdd:cd12304     1 PPREVTFANLNDNINEGFLKDMCKKYGEVEEVKIYFHPKTGKHLGLARVVFDTTKGAKDCVEKLNQTSVMGNIIHVFLDP 80

                          90
                  ....*....|...
gi 281366751  179 FGATLKKSLESLT 191
Cdd:cd12304    81 KGRIIARLYEDIV 93

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366751 1501 KKQLKFAKSAIHDWGLFAMEPIAADEMVIEYVGQMIRPVVADLRETKYEAIGIgssYLFRIDMETIIDATKCGNLARFIN 1580
Cdd:COG2940     5 HPRIEVRPSPIHGRGVFATRDIPKGTLIGEYPGEVITWAEAERREPHKEPLHT---YLFELDDDGVIDGALGGNPARFIN 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 281366751 1581 HSCNPNCYAkvitIESEKKIVIYSKQPIGINEEITYDYKFPLEDEKIPCLCGaqGCRGT 1639
Cdd:COG2940    82 HSCDPNCEA----DEEDGRIFIVALRDIAAGEELTYDYGLDYDEEEYPCRCP--NCRGT 134

COMPASS (Complex proteins associated with Set1p) component N; The n-SET or N-SET domain is a component of the COMPASS complex, associated with SET1, conserved in yeasts and in other eukaryotes up to humans. The COMPASS complex functions to methylate the fourth lysine of Histone 3 and for the silencing of genes close to the telomeres of chromosomes. This domain promotes trimethylation in conjunction with an RRM domain and is necessary for binding of the Spp1 component of COMPASS into the complex.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366751  1352 DAEDINFIKMSYLDHLHKEPYAMFLNNTHWVDHCTTDRAF--WPPPSKKRRK-DDELIRHKTGCARTEGFYKLDVREKAK 1428
Cdd:pfam11764   15 DDEDLKFLKKVLADLLQDDNSSDIGNLEYWAWKQKEIKALnrLRGPTEKEKKiEGYYVPNPTGCARTEGYKKIPDSEKSK 94

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 281366751  1429 HKYH---YAKA-NTEDSFNEDRSDEPTALTNHHHNKLISK-MQGISREARSNQRRLLTAFGSM-----GESELLKFNQ 1496
Cdd:pfam11764   95 YLPHrrkVQKPrETRQAHAKEDPAAAAAAAALAAEKSVSKgEISSSRVNRANNRRFVADINAQkaalgTESDLLSLNQ 172

RNA recognition motif;

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 281366751    107 NLNDNIDKQFLASMLDKCGTSDEINIYHHPITNKHLGIARIVFDSTKGARQFVEKYNQKSVMGKILDV 174
Cdd:smart00360    6 NLPPDTTEEELRELFSKFGKVESVRLVRDKETGKSKGFAFVEFESEEDAEKALEALNGKELDGRPLKV 73

transcription termination factor Rho; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366751  245 PNRSRDRNWNRDKERERDRHFKERSRHSSERSYDRDRGMRENVGTSirRRRTFYRRRSSDISPEDSRDilimTRERSRDS 324
Cdd:PRK12678  145 AGEGGEQPATEARADAAERTEEEERDERRRRGDREDRQAEAERGER--GRREERGRDGDDRDRRDRRE----QGDRREER 218

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 281366751  325 DSRPRDYCRSRERESFRDRKRSHEKGRDQPREKREHYYNSSKDREYRGRDRDRsaeidQRDRG 387
Cdd:PRK12678  219 GRRDGGDRRGRRRRRDRRDARGDDNREDRGDRDGDDGEGRGGRRGRRFRDRDR-----RGRRG 276

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 281366751 1489 SELLKFNQLKFRKKQLKFAKSAIHDWGLFAMEPIAADEMVIEYVGQMIRPVVADLRETKYEAIGIGSSYLFRIDMETIID 1568
Cdd:cd19204     1 SDLLKLNQLKFRKKKLRFGRSRIHEWGLFAMEPIAADEMVIEYVGQNIRQVVADMREKRYVQEGIGSSYLFRVDHDTIID 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 281366751 1569 ATKCGNLARFINHSCNPNCYAKVITIESEKKIVIYSKQPIGINEEITYDYKFPLEDEKIPCLCGAQGCRGTLN 1641
Cdd:cd19204    81 ATKCGNLARFINHCCTPNCYAKVITIESQKKIVIYSKQPIGVNEEITYDYKFPIEDNKIPCLCGTENCRGTLN 153

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 281366751 1490 ELLKFNQLKFRKKQ-LKFAKSAIHDWGLFAMEPIAADEMVIEYVGQMIRPVVADLRETKYEAIGIGSSYLFRIDMETIID 1568
Cdd:cd10518     1 MSKRFRQLRSRLKErLRVGKSGIHGWGLFAKRPIAAGEMVIEYVGEVIRPIVADKREKRYDEEGGGGTYMFRIDEDLVID 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366751 1569 ATKCGNLARFINHSCNPNCYAKVITIESEKKIVIYSKQPIGINEEITYDYKFPLED-EKIPCLCGAQGCR 1637
Cdd:cd10518    81 ATKKGNIARFINHSCDPNCYAKIITVDGEKHIVIFAKRDIAPGEELTYDYKFPIEDeEKIPCLCGAPNCR 150

SET domain (including post-SET domain) found in histone-lysine N-methyltransferase 2A (KMT2A), 2B (KMT2B) and similar proteins; This family includes KMT2A and KMT2B. Both KMT2A (also termed ALL-1 or CXXC7 or MLL or MLL1 or TRX1 or HRX) and KMT2B (also termed MLL4 or TRX2) act as histone methyltransferases that methylate 'Lys-4' of histone H3 (H3K4me).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366751 1508 KSAIHDWGLFAMEPIAADEMVIEYVGQMIRPVVADLRETKYEAIGIGSsYLFRIDMETIIDATKCGNLARFINHSCNPNC 1587
Cdd:cd19170    20 RSPIHGRGLFCKRNIDAGEMVIEYAGEVIRSVLTDKREKYYESKGIGC-YMFRIDDDEVVDATMHGNAARFINHSCEPNC 98

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 281366751 1588 YAKVITIESEKKIVIYSKQPIGINEEITYDYKFPLEDEKIPCLCGAQGCRGTLN 1641
Cdd:cd19170    99 YSRVVNIDGKKHIVIFALRRILRGEELTYDYKFPIEDVKIPCTCGSKKCRKYLN 152

RNA recognition motif in the Set1-like family of histone-lysine N-methyltransferases; This subfamily corresponds to the RRM of the Set1-like family of histone-lysine N-methyltransferases which includes Set1A and Set1B that are ubiquitously expressed vertebrates histone methyltransferases exhibiting high homology to yeast Set1. Set1A and Set1B proteins exhibit a largely non-overlapping subnuclear distribution in euchromatic nuclear speckles, strongly suggesting that they bind to a unique set of target genes and thus make non-redundant contributions to the epigenetic control of chromatin structure and gene expression. With the exception of the catalytic component, the subunit composition of the Set1A and Set1B histone methyltransferase complexes are identical. Each complex contains six human homologs of the yeast Set1/COMPASS complex, including Set1A or Set1B, Ash2 (homologous to yeast Bre2), CXXC finger protein 1 (CFP1; homologous to yeast Spp1), Rbbp5 (homologous to yeast Swd1), Wdr5 (homologous to yeast Swd3), and Wdr82 (homologous to yeast Swd2). The genomic targeting of these complexes is determined by the identity of the catalytic subunit present in each histone methyltransferase complex. Thus, the Set1A and Set1B complexes may exhibit both overlapping and non-redundant properties. Both Set1A and Set1B contain an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), an N- SET domain, and a C-terminal catalytic SET domain followed by a post-SET domain. In contrast to Set1B, Set1A additionally contains an HCF-1 binding motif that interacts with HCF-1 in vivo.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366751   99 PAVEVTIVNLNDNIDKQFLASMLDKCGTSDEINIYHHPITNKHLGIARIVFDSTKGARQFVEKYNQKSVMGKILDVFCDP 178
Cdd:cd12304     1 PPREVTFANLNDNINEGFLKDMCKKYGEVEEVKIYFHPKTGKHLGLARVVFDTTKGAKDCVEKLNQTSVMGNIIHVFLDP 80

                          90
                  ....*....|...
gi 281366751  179 FGATLKKSLESLT 191
Cdd:cd12304    81 KGRIIARLYEDIV 93

SET domain (including post-SET domain) found in histone-lysine N-methyltransferase 2B (KMT2B) and similar proteins; KMT2B (EC2.1.1.43; also termed lysine N-methyltransferase 2B, myeloid/lymphoid or mixed-lineage leukemia protein 4 (MLL2/MLL4), trithorax homolog 2 (TRX2), or WW domain-binding protein 7 (WBP-7)), acts as a histone methyltransferase that methylates 'Lys-4' of histone H3 (H3K4me). It is required during the transcriptionally active period of oocyte growth for the establishment and/or maintenance of bulk H3K4 trimethylation (H3K4me3), global transcriptional silencing that precedes resumption of meiosis, oocyte survival and normal zygotic genome activation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366751 1492 LKFNQLKFRKKQ-LKFAKSAIHDWGLFAMEPIAADEMVIEYVGQMIRPVVADLRETKYEAIGIGSsYLFRIDMETIIDAT 1570
Cdd:cd19207     3 MRFRHLKKTSKEaVGVYRSAIHGRGLFCKRNIDAGEMVIEYSGIVIRSVLTDKREKFYDSKGIGC-YMFRIDDFDVVDAT 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 281366751 1571 KCGNLARFINHSCNPNCYAKVITIESEKKIVIYSKQPIGINEEITYDYKFPLED--EKIPCLCGAQGCRGTLN 1641
Cdd:cd19207    82 MHGNAARFINHSCEPNCYSRVIHVEGQKHIVIFALRKIYRGEELTYDYKFPIEDasNKLPCNCGAKRCRRFLN 154

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 281366751   1504 LKFAKSAIHDWGLFAMEPIAADEMVIEYVGQMIRPVVADLRETKYEAIGIGSSYLFRIDMETIIDATKCGNLARFINHSC 1583
Cdd:smart00317    3 LEVFKSPGKGWGVRATEDIPKGEFIGEYVGEIITSEEAEERPKAYDTDGAKAFYLFDIDSDLCIDARRKGNLARFINHSC 82

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|..
gi 281366751   1584 NPNCYAKVITIESEKKIVIYSKQPIGINEEITYDYKFPLEDE 1625
Cdd:smart00317   83 EPNCELLFVEVNGDDRIVIFALRDIKPGEELTIDYGSDYANE 124

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 281366751 1514 WGLFAMEPIAADEMVIEYVGQMIRPVVADLRETKYEAIGIGSSYLFRIDMETIIDATKCGNLARFINHSCNPNCYAKVIT 1593
Cdd:cd10531    12 WGVKAKEDIQKGEFIIEYVGEVIDKKEFKERLDEYEELGKSNFYILSLSDDVVIDATRKGNLSRFINHSCEPNCETQKWI 91

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 281366751 1594 IESEKKIVIYSKQPIGINEEITYDYKFPLE-DEKIPCLCGAQGCR 1637
Cdd:cd10531    92 VNGEYRIGIFALRDIPAGEELTFDYNFVNYnEAKQVCLCGAQNCR 136

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 281366751 1501 KKQLKFAKSAIHDWGLFAMEPIAADEMVIEYVGQMIRPVVADLRETKYEAIGIGSsYLFRIDMETIIDATKCGNLARFIN 1580
Cdd:cd19209    15 KNNVYLARSRIQGLGLYAAKDLEKHTMVIEYIGTIIRNEVANRREKIYEEQNRGI-YMFRINNEHVIDATLTGGPARYIN 93

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 281366751 1581 HSCNPNCYAKVITIESEKKIVIYSKQPIGINEEITYDYKFPLEDEK--IPCLCGAQGCR 1637
Cdd:cd19209    94 HSCAPNCVAEVVTFDKEDKIIIISSRRIPKGEELTYDYQFDFEDDQhkIPCHCGAWNCR 152

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 281366751 1514 WGLFAMEPIAADEMVIEYVGQMIRPVVADLRETKYEAIGIGSSYLFRIDMETIIDATKCGNLARFINHSCNPNCYAKVIT 1593
Cdd:cd19172    14 WGLRAAEDLPKGTFVIEYVGEVLDEKEFKRRMKEYAREGNRHYYFMALKSDEIIDATKKGNLSRFINHSCEPNCETQKWT 93

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 281366751 1594 IESEKKIVIYSKQPIGINEEITYDYKFPL-EDEKIPCLCGAQGCRGTL 1640
Cdd:cd19172    94 VNGELRVGFFAKRDIPAGEELTFDYQFERyGKEAQKCYCGSPNCRGYI 141

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 281366751  1514 WGLFAMEPIAADEMVIEYVG-QMIRPVVADLRETKYEAIGIG---SSYLFRID--METIIDAT--KCGNLARFINHSCNP 1585
Cdd:pfam00856    2 RGLFATEDIPKGEFIGEYVEvLLITKEEADKRELLYYDKLELrlwGPYLFTLDedSEYCIDARalYYGNWARFINHSCDP 81

                           90       100       110
                   ....*....|....*....|....*....|....
gi 281366751  1586 NCYAKVITIESEKKIVIYSKQPIGINEEITYDYK 1619
Cdd:pfam00856   82 NCEVRVVYVNGGPRIVIFALRDIKPGEELTIDYG 115

COMPASS (Complex proteins associated with Set1p) component N; The n-SET or N-SET domain is a component of the COMPASS complex, associated with SET1, conserved in yeasts and in other eukaryotes up to humans. The COMPASS complex functions to methylate the fourth lysine of Histone 3 and for the silencing of genes close to the telomeres of chromosomes. This domain promotes trimethylation in conjunction with an RRM domain and is necessary for binding of the Spp1 component of COMPASS into the complex.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366751  1352 DAEDINFIKMSYLDHLHKEPYAMFLNNTHWVDHCTTDRAF--WPPPSKKRRK-DDELIRHKTGCARTEGFYKLDVREKAK 1428
Cdd:pfam11764   15 DDEDLKFLKKVLADLLQDDNSSDIGNLEYWAWKQKEIKALnrLRGPTEKEKKiEGYYVPNPTGCARTEGYKKIPDSEKSK 94

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 281366751  1429 HKYH---YAKA-NTEDSFNEDRSDEPTALTNHHHNKLISK-MQGISREARSNQRRLLTAFGSM-----GESELLKFNQ 1496
Cdd:pfam11764   95 YLPHrrkVQKPrETRQAHAKEDPAAAAAAAALAAEKSVSKgEISSSRVNRANNRRFVADINAQkaalgTESDLLSLNQ 172

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 281366751 1514 WGLFAMEPIAADEMVIEYVGQMIRPVVADLRETKYEAIGIgsSYLFRIDMETI-----IDATKCGNLARFINHSCNPN-- 1586
Cdd:cd10542   100 WGVKTLEDIKKGTFVMEYVGEIITSEEAERRGKIYDANGR--TYLFDLDYNDDdceytVDAAYYGNISHFINHSCDPNla 177

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 281366751 1587 CYAKVIT--IESEKKIVIYSKQPIGINEEITYDYKFPL------------EDEKIPCLCGAQGCRGTL 1640
Cdd:cd10542   178 VYAVWINhlDPRLPRIAFFAKRDIKAGEELTFDYLMTGtggssestipkpKDVRVPCLCGSKNCRKYL 245

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 281366751 1503 QLKFAKSAIHDWGLFAMEPIAADEMVIEYVGQMIRPVVADLRETKYEAIGIGSSYLFRIDMETIIDATKCGNLARFINHS 1582
Cdd:cd19211     3 ETKIIKTEGKGWGLIAKRDIKKGEFVNEYVGELIDEEECMARIKHAHENDITHFYMLTIDKDRIIDAGPKGNYSRFMNHS 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 281366751 1583 CNPNCYAKVITIESEKKIVIYSKQPIGINEEITYDYKFP-LEDEKIPCLCGAQGCRGTL 1640
Cdd:cd19211    83 CQPNCETQKWTVNGDTRVGLFAVCDIPAGTELTFNYNLDcLGNEKTVCRCGAPNCSGFL 141

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 281366751 1500 RKKQLKFAKSAIHDWGLFAMEPIAADEMVIEYVGQMIRPVVADLRETKYEAIGigSSYLFRID---------METIIDAT 1570
Cdd:cd10538    87 LQARLQVFRTSKKGWGVRSLEFIPKGSFVCEYVGEVITTSEADRRGKIYDKSG--GSYLFDLDefsdsdgdgEELCVDAT 164

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 281366751 1571 KCGNLARFINHSCNPNCyaKVITIESEK------KIVIYSKQPIGINEEITYDY 1618
Cdd:cd10538   165 FCGNVSRFINHSCDPNL--FPFNVVIDHddlrypRIALFATRDILPGEELTFDY 216

RNA recognition motif in vertebrate histone-lysine N-methyltransferase Setd1B (Set1B); This subgroup corresponds to the RRM of Setd1B, also termed SET domain-containing protein 1B (Set1B), or lysine N-methyltransferase 2G, a ubiquitously expressed vertebrates histone methyltransferase that exhibits high homology to yeast Set1. Set1B is localized to euchromatic nuclear speckles and associates with a complex containing six human homologs of the yeast Set1/COMPASS complex, including CXXC finger protein 1 (CFP1; homologous to yeast Spp1), Rbbp5 (homologous to yeast Swd1), Ash2 (homologous to yeast Bre2), Wdr5 (homologous to yeast Swd3), and Wdr82 (homologous to yeast Swd2). Set1B complex is a histone methyltransferase that produces trimethylated histone H3 at Lys4. Set1B contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), an N- SET domain, and a C-terminal catalytic SET domain followed by a post-SET domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366751   99 PAVEVTIVNLNDNIDKQFLASMLDKCGTSDEINIYHHPITNKHLGIARIVFDSTKGARQFVEKYNQKSVMGKILDVFCDP 178
Cdd:cd12549     1 PPKQVTFAKLNDNIRENFLRDMCKKYGEVEEVEILYNPKNKKHLGIAKVVFATVKGAKDAVQHLHNTSVMGNIIHVELDT 80

                          90
                  ....*....|..
gi 281366751  179 FGATLKKSLESL 190
Cdd:cd12549    81 KGETRMRFYELL 92

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 281366751 1514 WGLFAMEPIAADEMVIEYVGQMIRPVVADLRETKYEAIGIGSSYLFRIDMETIIDATKCGNLARFINHSCNPNCYAKVIT 1593
Cdd:cd19210    14 WGLRCKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDITNFYMLTLDKDRIIDAGPKGNYARFMNHCCQPNCETQKWT 93

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 281366751 1594 IESEKKIVIYSKQPIGINEEITYDYKFP-LEDEKIPCLCGAQGCRGTL 1640
Cdd:cd19210    94 VNGDTRVGLFALCDIKAGTELTFNYNLEcLGNGKTVCKCGAPNCSGFL 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 281366751 1502 KQLKFAKSAIHDWGLFAMEPIAADEMVIEYVGQMI-----RPVVADLRETKyeaigigSSYLFRID--------METIID 1568
Cdd:cd10544    90 FKLQVFKTPKKGWGLRTLEFIPKGRFVCEYAGEVIgfeeaRRRTKSQTKGD-------MNYIIVLRehlssgkvLETFVD 162

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366751 1569 ATKCGNLARFINHSCNPNCYAKVITIESE-KKIVIYSKQPIGINEEITYDY-----------KFPLEDE---KIPCLCGA 1633
Cdd:cd10544   163 PTYIGNIGRFLNHSCEPNLFMVPVRVDSMvPKLALFAARDIVAGEELSFDYsgefsnsvesvTLARQDEsksRKPCLCGA 242

                  ....*..
gi 281366751 1634 QGCRGTL 1640
Cdd:cd10544   243 ENCRGFL 249

SET domain found in SET domain-containing protein 8 (SETD8) and similar proteins; SETD8 (EC 2.1.1.43; also termed N-lysine methyltransferase KMT5A, H4-K20-HMTase KMT5A, lysine N-methyltransferase 5A, lysine-specific methylase 5A, PR/SET domain-containing protein 07, PR-Set7 or PR/SET07) is a nucleosomal histone-lysine N-methyltransferase that specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). It plays a central role in the silencing of euchromatic genes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366751 1515 GLFAMEPIAADEMVIEYVGQMIRPVVADLRETKYEAIGIGSSYL--FRIDMETI-IDATK-CGNLARFINHSC-NPNCYA 1589
Cdd:cd10528    30 GVIATRPFEKGDFVVEYHGDLITITEAKKREALYAKDPSTGCYMyyFQYKGKTYcVDATKeSGRLGRLINHSKkKPNLKT 109

                          90       100
                  ....*....|....*....|....*....
gi 281366751 1590 KVITIESEKKIVIYSKQPIGINEEITYDY 1618
Cdd:cd10528   110 KLLVIDGVPHLILVAKRDIKPGEELLYDY 138

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.