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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 528476774  129 RCICGFTHDDGYMICCDKCSVWQHIDCMGIDRQHIPETYLCERC 172
Cdd:cd15550     1 RCICGFEHDDGFMICCDKCSVWQHGDCMGIDRENIPDSYLCEQC 44

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528476774   541 ELIEDLEEKTSVSNEVeMESEEQIAERRRKMTREERKMEAILQAFAR-MEKREKRREQALERI 602
Cdd:pfam13868  117 EAEEKLEKQRQLREEI-DEFNEEQAEWKELEKEEEREEDERILEYLKeKAEREEEREAEREEI 178

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 528476774  129 RCICGFTHDDGYMICCDKCSVWQHIDCMGIDRQHIPETYLCERC 172
Cdd:cd15550     1 RCICGFEHDDGFMICCDKCSVWQHGDCMGIDRENIPDSYLCEQC 44

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 528476774   344 LKAVRDLAADSLIIEYRGKVMLRQ----QFEANGYFFKRPYPFVLFYSKFD-GLEMCVDARSF--GNEARFIRRSCTPNA 416
Cdd:pfam00856    4 LFATEDIPKGEFIGEYVEVLLITKeeadKRELLYYDKLELRLWGPYLFTLDeDSEYCIDARALyyGNWARFINHSCDPNC 83

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 528476774   417 EVRHVIEEGMLHLYIYSLRSISKGSEITigfdYDYG 452
Cdd:pfam00856   84 EVRVVYVNGGPRIVIFALRDIKPGEELT----IDYG 115

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 528476774   129 RC-ICGFTHDDGYMICCDKCSVWQHIDCMGI---DRQHIPETYLCERCQPR 175
Cdd:pfam00628    1 YCaVCGKSDDGGELVQCDGCDDWFHLACLGPpldPAEIPSGEWLCPECKPK 51

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528476774  682 PSSPGDTLEPLMAETQdiemPVAPEADAPPTQPPETSPPHSGSPAPTCRSGQKYPKTKKHLVSEWMGVDKQERVASRTPE 761
Cdd:PHA03247 2598 PRAPVDDRGDPRGPAP----PSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRA 2673

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528476774  762 PPPERPLRISSDPEVLATqLNSLPGMSCSSHVYSTPKHYVRFSSPFLanrsPSTPGVPTGRRRS---------REMPETP 832
Cdd:PHA03247 2674 AQASSPPQRPRRRAARPT-VGSLTSLADPPPPPPTPEPAPHALVSAT----PLPPGPAAARQASpalpaapapPAVPAGP 2748

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528476774  833 TSTGSCKKRWLKQALEEEGSTSP-----GGGRPFLLIPSESPLSPSING--ESCSPLPLNGSCSLPELPTPLKKRRLCSL 905
Cdd:PHA03247 2749 ATPGGPARPARPPTTAGPPAPAPpaapaAGPPRRLTRPAVASLSESRESlpSPWDPADPPAAVLAPAAALPPAASPAGPL 2828

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528476774  906 DPCMSETSTPYGSPCATPTRTESTE---APGTPSLLATPPRPRPEEPSTEPSTPLQMPNHPLLQESESSMDSSPDGSRRP 982
Cdd:PHA03247 2829 PPPTSAQPTAPPPPPGPPPPSLPLGgsvAPGGDVRRRPPSRSPAAKPAAPARPPVRRLARPAVSRSTESFALPPDQPERP 2908

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|
gi 528476774  983 STQDVERPPSLLASPSVRNvSSDTAPQESSKSMGSLSPQP 1022
Cdd:PHA03247 2909 PQPQAPPPPQPQPQPPPPP-QPQPPPPPPPRPQPPLAPTT 2947

Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 viral late glycoprotein, also termed gp350/220. It is the most abundantly expressed glycoprotein in the viral envelope of the Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies in vivo.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528476774   795 STPKHYVRFS--------SPFLANRSPSTPGVPTGRRRSREMPE---TPTSTGSCKKRWLKQALEEEGSTSpgGGRPFLL 863
Cdd:pfam05109  413 TTTTHKVIFSkapestttSPTLNTTGFAAPNTTTGLPSSTHVPTnltAPASTGPTVSTADVTSPTPAGTTS--GASPVTP 490

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528476774   864 IPS--------ESPLSPSINGESCSPLPlNGSCSLPELPTPLKKrrlcSLDPCMSETSTPYGSPCATPTRTESTEAPGTP 935
Cdd:pfam05109  491 SPSprdngtesKAPDMTSPTSAVTTPTP-NATSPTPAVTTPTPN----ATSPTLGKTSPTSAVTTPTPNATSPTPAVTTP 565

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528476774   936 SLLATPPRPRPEEPSTEPSTPLQMPNHPLLQEsessmdSSPDGSRRPSTQDVERPPSLLASPSVRNVSSDTAPQE--SSK 1013
Cdd:pfam05109  566 TPNATIPTLGKTSPTSAVTTPTPNATSPTVGE------TSPQANTTNHTLGGTSSTPVVTSPPKNATSAVTTGQHniTSS 639

                          250
                   ....*....|
gi 528476774  1014 SMGSLSPQPS 1023
Cdd:pfam05109  640 STSSMSLRPS 649

SET domain (including post-SET domain) found in SET domain-containing protein 5 (SETD5) and similar proteins; SETD5 is a probable transcriptional regulator that acts via the formation of large multiprotein complexes that modify and/or remodel the chromatin. SETD5 loss-of-function mutations are a likely cause of a familial syndromic intellectual disability with variable phenotypic expression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528476774  335 SQVQKNKRILKAVRDLAADSLIIEYRGKVMLRQQFEANGYFFKRPYPFVLFYSKFDGLEMCVDARSFGNEARFIRRSCTP 414
Cdd:cd19181    12 TRVQKHRKILRAARDLALDTLIIEYRGKVMLRQQFEVNGHFFKRPYPFVLFYSKFNGVEMCVDARTFGNDARFIRRSCTP 91

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 528476774  415 NAEVRHVIEEGMLHLYIYSLRSISKGSEITIGFDYDYGSCKYKVDCACVKGNPECPVLK 473
Cdd:cd19181    92 NAEVRHMIADGMIHLCIYAVAAIAKDAEVTIAFDYEYSNCNYKVDCACHKGNRNCPVQK 150

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 528476774  129 RCICGFTHDDGYMICCDKCSVWQHIDCMGIDRQHIPETYLCERC 172
Cdd:cd15550     1 RCICGFEHDDGFMICCDKCSVWQHGDCMGIDRENIPDSYLCEQC 44

SET domain (including post-SET domain) found in Schizosaccharomyces pombe SET domain-containing protein 3 (SETD3) and similar proteins; Schizosaccharomyces pombe SETD3 functions as a transcriptional regulator that acts via the formation of large multiprotein complexes that modify and/or remodel the chromatin. It is required for both, gene activation and repression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528476774  344 LKAVRDLAADSLIIEYRGKVMLRQQFEA---NGY-FFKRPYPFVLFYSKfdgLEMCVDARSFGNEARFIRRSCTPNAEVR 419
Cdd:cd19183    16 LFADRPIPAGDPIQELLGEIGLQSEYIAdpeNQYqILGAPKPHVFFHPQ---SPLYIDTRRSGSVARFIRRSCRPNAELV 92

                          90       100       110
                  ....*....|....*....|....*....|...
gi 528476774  420 HVI--EEGMLHLYIYSLRSISKGSEITIGFDYD 450
Cdd:cd19183    93 TVAsdSGSVLKFVLYASRDISPGEEITIGWDWD 125

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528476774  346 AVRDLAADSLIIEYRGKVMLRQQFEANGYFFKRPYPFVLFYSKFDGlemcVDARSFGNEARFIRRSCTPNAEVRhvIEEG 425
Cdd:COG2940    22 ATRDIPKGTLIGEYPGEVITWAEAERREPHKEPLHTYLFELDDDGV----IDGALGGNPARFINHSCDPNCEAD--EEDG 95

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 528476774  426 mlHLYIYSLRSISKGSEITIgfDY--DYGSCKYkvDCACVK 464
Cdd:COG2940    96 --RIFIVALRDIAAGEELTY--DYglDYDEEEY--PCRCPN 130

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 528476774  346 AVRDLAADSLIIEYRGKVMLRQQFEANGYFfkrpYPFVLFYSKFDGLEMCVDARSFGNEARFIRRSCTPNAEVRHVIEEG 425
Cdd:cd10522    19 AAETIAKGEFVGEYTGEVLDRWEEDRDSVY----HYDPLYPFDLNGDILVIDAGKKGNLTRFINHSDQPNLELIVRTLKG 94

                          90       100
                  ....*....|....*....|....*.
gi 528476774  426 MLHLYIYSLRSISKGSEITIGFDYDY 451
Cdd:cd10522    95 EQHIGFVAIRDIKPGEELFISYGPKY 120

PHD finger found in Arabidopsis thaliana PHD finger protein MALE MEIOCYTE DEATH 1 (MMD1), PHD finger protein MALE STERILITY 1 (MS1), and similar proteins; MMD1 is a plant homeodomain (PHD) finger protein expressed in male meiocytes. It is encoded by the gene DUET, which is required for male meiotic chromosome organization and progression. MMD1 has been implicated in the regulation of gene expression during meiosis. The mmd1 mutation triggers cell death in male meiocytes. MS1 is a nuclear transcriptional activator that is important for tapetal development and pollen wall biosynthesis. It contains a Leu zipper-like domain and a PHD finger motif, both of which are essential for its function.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 528476774  130 CICGFTHDDG-YMICCDKCSVWQHIDCMGI-DRQHIPETYLCERC 172
Cdd:cd15556     2 CSCGTRDDDGeRMIACDVCEVWQHTRCVGIaDNEEPPDHFLCRRC 46

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 528476774  346 AVRDLAADSLIIEYRGKV-------MLRQQFEANG----YFFKrpypfvlfyskFDGlEMCVDARSFGNEARFIRRSCTP 414
Cdd:cd10518    30 AKRPIAAGEMVIEYVGEVirpivadKREKRYDEEGgggtYMFR-----------IDE-DLVIDATKKGNIARFINHSCDP 97

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 528476774  415 NAEVRHVIEEGMLHLYIYSLRSISKGSEITigfdYDYGSC---KYKVDCACvkGNPEC 469
Cdd:cd10518    98 NCYAKIITVDGEKHIVIFAKRDIAPGEELT----YDYKFPiedEEKIPCLC--GAPNC 149

SET domain (including post-SET domain) found in SET domain-containing protein 1 (SETD1) and similar proteins; This family includes SET domain-containing protein 1A (SETD1A) and SET domain-containing protein 1B (SETD1B). These proteins are histone-lysine N-methyltransferases that specifically methylate '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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528476774  344 LKAVRDLAADSLIIEYRGKVmLRQ--------QFEANG----YFFKRPYPFVLfyskfdglemcvDARSFGNEARFIRRS 411
Cdd:cd19169    27 LFALEPIAADEMVIEYVGQV-IRQsvaderekRYEAIGigssYLFRVDDDTII------------DATKCGNLARFINHS 93

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528476774  412 CTPNAEVRHVIEEGMLHLYIYSLRSISKGSEITigfdYDYgscKY-----KVDCACvkGNPEC 469
Cdd:cd19169    94 CNPNCYAKIITVESQKKIVIYSKRPIAVNEEIT----YDY---KFpiedeKIPCLC--GAPQC 147

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 528476774  344 LKAVRDLAADSLIIEYRGKVMLRQQFEANgyffKRPYPFVL---FYskFDGL--EMCVDARSFGNEARFIRRSCTPNAEV 418
Cdd:cd19172    16 LRAAEDLPKGTFVIEYVGEVLDEKEFKRR----MKEYAREGnrhYY--FMALksDEIIDATKKGNLSRFINHSCEPNCET 89

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 528476774  419 RHVIEEGMLHLYIYSLRSISKGSEITigFDYD---YGSCKYKvdCACvkGNPEC 469
Cdd:cd19172    90 QKWTVNGELRVGFFAKRDIPAGEELT--FDYQferYGKEAQK--CYC--GSPNC 137

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 528476774   129 RC-ICGFTHDDGYMICCDKCSVWQHIDCMGI---DRQHIPETYLCERCQPR 175
Cdd:pfam00628    1 YCaVCGKSDDGGELVQCDGCDDWFHLACLGPpldPAEIPSGEWLCPECKPK 51

PHD finger found in PHD finger protein 20-like protein 1 (P20L1); P20L1 is an active malignant brain tumor (MBT) domain-containing protein that binds to monomethylated lysine 142 on DNA (Cytosine-5) Methyltransferase 1 (DNMT1) (DNMT1K142me1) and colocalizes at the perinucleolar space in a SET7-dependent manner. Its MBT domain reads and controls enzyme levels of methylated DNMT1 in cells, thus representing a novel antagonist of DNMT1 proteasomal degradation. In addition to the MBT domain, PHF20L1 also contains two Tudor domains, a plant homeodomain (PHD) finger and the putative DNA-binding domains, AT hook and Cys2His2-type zinc finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 528476774  129 RCICGFTHDDGYMICCDKCSVWQHIDCMGIDRQHIPETYLCERCQ 173
Cdd:cd15633     1 RCICEMDEENGFMIQCEECLCWQHSVCMGLLEESIPEQYICYICR 45

PHD finger found in PHD finger protein 3 (PHF3), and death-inducer obliterator variants Dido1, Dido2, and Dido3; PHF3 is a human homolog of yeast protein bypass of Ess1 (Bye1), a nuclear protein with a domain resembling the central domain in the transcription elongation factor TFIIS. It is ubiquitously expressed in normal tissues including brain, but its expression is significantly reduced or lost in glioblastomas. PHF3 contains an N-terminal plant homeodomain (PHD) finger, a central RNA polymerase II (Pol II)-binding TFIIS-like domain (TLD) domain, and a C-terminal Spen paralogue and orthologue C-terminal (SPOC) domain. This family also includes Dido gene encoding three alternative splicing variants (Dido1, 2, and 3), which have been implicated in a number of cellular processes such as apoptosis and chromosomal segregation, particularly in the hematopoietic system. Dido1 is important for maintaining embryonic stem (ES) cells and directly regulates the expression of pluripotency factors. It is the shortest isoform that contains only a highly conserved PHD finger responsible for the binding of histone H3 with a higher affinity for trimethylated lysine4 (H3K4me3). Gene Dido1 is a Bone morphogenetic protein (BMP) target gene and promotes BMP-induced melanoma progression. It also triggers apoptosis after nuclear translocation and caspase upregulation. Dido3 is the largest isoform and is ubiquitously expressed in all human tissues. It is dispensable for ES cell self-renewal and pluripotency, but is involved in the maintenance of stem cell genomic stability and tumorigenesis. Dido3 contains a PHD finger, a transcription elongation factor S-II subunit M (TFSIIM) domain, a SPOC module, and a long C-terminal region (CT) of unknown homology.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 528476774  130 CICGFTHDDGYMICCDKCSVWQHIDCMGIDRQHIP------ETYLCERC 172
Cdd:cd15552     2 CICRKPHNNRFMICCDRCEEWFHGDCVGITEAQGKemeeniEEYVCPKC 50

PHD finger found in PHD finger protein 20 (PHF20) and PHD finger protein 20-like protein 1 (P20L1); PHF20, also termed Glioma-expressed antigen 2, or hepatocellular carcinoma-associated antigen 58, or novel zinc finger protein, or transcription factor TZP (referring to Tudor and zinc finger domain containing protein), is a regulator of NF-kappaB activation by disrupting recruitment of PP2A to p65. It also functions as a transcription factor that binds Akt and plays a role in Akt cell survival/growth signaling. Moreover, it transcriptionally regulates p53. The phosphorylation of PHF20 on Ser291 mediated by protein kinase B (PKB) is essential in tumorigenesis via the regulation of p53 mediated signaling. P20L1 is an active malignant brain tumor (MBT) domain-containing protein that binds to monomethylated lysine 142 on DNA (Cytosine-5) Methyltransferase 1 (DNMT1) (DNMT1K142me1) and colocalizes at the perinucleolar space in a SET7-dependent manner. Its MBT domain reads and controls enzyme levels of methylated DNMT1 in cells, thus representing a novel antagonist of DNMT1 proteasomal degradation. Both PHF20 and PHF20L1 contain an N-terminal MBT domain, two Tudor domains, a plant homeodomain (PHD) finger and the putative DNA-binding domains, AT hook and Cys2His2-type zinc finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 528476774  129 RCICGFTHDDGYMICCDKCSVWQHIDCMGIDRQ-HIPETYLCERC 172
Cdd:cd15549     1 HCICGVNEENGLMIQCELCLCWQHGVCMGIEEEeSVPERYVCYVC 45

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 528476774  344 LKAVRDLAADSLIIEYRGKVM------LRQ-QFEANG---YFFKRPYPFVlfyskfdglemcVDARSFGNEARFIRRSCT 413
Cdd:cd19171    28 LYAARDIEKHTMVIEYIGEIIrnevanRREkIYESQNrgiYMFRIDNDWV------------IDATMTGGPARYINHSCN 95

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 528476774  414 PN--AEVRHVIEEgmLHLYIYSLRSISKGSEITIGFDYDYGSCKYKVDCACvkGNPEC 469
Cdd:cd19171    96 PNcvAEVVTFDKE--KKIIIISNRRIAKGEELTYDYKFDFEDDQHKIPCLC--GAPNC 149

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 528476774  344 LKAVRDLAADSLIIEYRGKV---------MLRQQFEANGYFFKRPYPFvlfYSKFDGLEMCVDARSFGNEARFIRRSCTP 414
Cdd:cd10538   103 VRSLEFIPKGSFVCEYVGEVittseadrrGKIYDKSGGSYLFDLDEFS---DSDGDGEELCVDATFCGNVSRFINHSCDP 179

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 528476774  415 N-AEVRHVIEEGMLHLY---IYSLRSISKGSEITigfdYDYG 452
Cdd:cd10538   180 NlFPFNVVIDHDDLRYPriaLFATRDILPGEELT----FDYG 217

PHD finger found in PHD finger protein 20 (PHF20); PHF20, also termed Glioma-expressed antigen 2, or hepatocellular carcinoma-associated antigen 58, or novel zinc finger protein, or transcription factor TZP (referring to Tudor and zinc finger domain containing protein), is a regulator of NF-kappaB activation by disrupting recruitment of PP2A to p65. It also functions as a transcription factor that binds Akt and plays a role in Akt cell survival/growth signaling. Moreover, it transcriptionally regulates p53. The phosphorylation of PHF20 on Ser291 mediated by protein kinase B (PKB) is essential in tumorigenesis via the regulation of p53 mediated signaling. PHF20 contains an N-terminal malignant brain tumor (MBT) domain, two Tudor domains, a plant homeodomain (PHD) finger and the putative DNA-binding domains, AT hook and Cys2His2-type zinc finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 528476774  129 RCICGFTHDDGYMICCDKCSVWQHIDCMGIDRQHIPETYLCERC 172
Cdd:cd15634     1 RCICEVQEENDFMIQCEECLCWQHGVCMGLLEDNVPEKYTCYIC 44

SET domain (including pre-SET and post-SET domains) found in suppressor of variegation 3-9 homolog 2 (SUV39H2) and similar proteins; SUV39H2 (EC 2.1.1.43; also termed histone H3-K9 methyltransferase 2, H3-K9-HMTase 2, lysine N-methyltransferase 1B (KMT1B), or Su(var)3-9 homolog 2) acts as a histone-lysine N-methyltransferase that specifically trimethylates 'Lys-9' of histone H3 (H3K9me3) using monomethylated H3 'Lys-9' as substrate. It mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528476774  344 LKAVRDLAADSLIIEYRGKVMLRQQFEANGYFFKRPYPFVLFYSKFDGLEMCVDARSFGNEARFIRRSCTPNAEVRHVIE 423
Cdd:cd10532    99 VKTLQKIKKNSFVMEYVGEVITSEEAERRGQFYDSKGITYLFDLDYESDEFTVDAARYGNVSHFVNHSCDPNLQVFNVFI 178

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528476774  424 EGM----LHLYIYSLRSISKGSEITigFDY-------------DYGSCKYKVDCACVKGNPEC 469
Cdd:cd10532   179 DNLdtrlPRIALFSTRTIKAGEELT--FDYqmkgsgdlssdsiDNSPAKKRVRTVCKCGAVTC 239

SET domain (including post-SET domain) found in SET domain-containing protein 1B (SETD1B) and similar proteins; SETD1B (EC2.1.1.43), also termed lysine N-methyltransferase 2G, 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. Loss of SETD1B occurs in up to half the gastric and colorectal cancers, most commonly via SETD1B mutations, while de novo variants in SETD1B are associated with intellectual disability, epilepsy and autism.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528476774  344 LKAVRDLAADSLIIEYRGKV-------MLRQQFEANG----YFFKRPYpfvlfyskfdglEMCVDARSFGNEARFIRRSC 412
Cdd:cd19205    28 LFAMEPIAADEMVIEYVGQNirqviadMREKRYEDEGigssYMFRVDH------------DTIIDATKCGNFARFINHSC 95

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 528476774  413 TPNAEVRHVIEEGMLHLYIYSLRSISKGSEITigFDYDYGSCKYKVDCAC 462
Cdd:cd19205    96 NPNCYAKVITVESQKKIVIYSKQHINVNEEIT--YDYKFPIEDVKIPCLC 143

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
                  ....*....|....*....|....*....|....*....|....*.
gi 528476774  130 CICGFTHDD-GYMICCDKCSVWQHIDCMGID--RQHIPETYLCERC 172
Cdd:cd15489     3 IVCGKGGDLgGELLQCDGCGKWFHADCLGPPlsSFVPNGKWICPVC 48

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 528476774  390 DGLEMCVDARSFGNEARFIRRSCTPNA-EVRHVIEEGMLH---LYIYSLRSISKGSEitIGFDY--DYGSCKYK-VDCAC 462
Cdd:cd10543   146 DGETYCIDARRYGNISRFINHLCEPNLiPVRVFVEHQDLRfprIAFFASRDIKAGEE--LGFDYgeKFWRIKGKyFTCRC 223

                  ....*..
gi 528476774  463 vkGNPEC 469
Cdd:cd10543   224 --GSPKC 228

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 528476774  349 DLAADSLIIEYRGKVMlrQQFEAN--GYFFKRPYPFVLFYSKFDGlemCVDARSFGNEARFIRRSCTPNAEVRHVIEEGM 426
Cdd:cd10519    20 PIKKDEFIGEYTGELI--SQDEADrrGKIYDKYNSSYLFNLNDQF---VVDATRKGNKIRFANHSSNPNCYAKVMMVNGD 94

                          90       100
                  ....*....|....*....|....*
gi 528476774  427 LHLYIYSLRSISKGSEITigFDYDY 451
Cdd:cd10519    95 HRIGIFAKRDIEAGEELF--FDYGY 117

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 528476774  342 RILKAVRDLAADSLIIEYRGKVM-------LRQQFEAN---GYFfkrpypfvLFYSKFDGLEMCVDA-RSFGNEARFIRR 410
Cdd:cd10528    29 RGVIATRPFEKGDFVVEYHGDLItiteakkREALYAKDpstGCY--------MYYFQYKGKTYCVDAtKESGRLGRLINH 100