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 767948259  120 RCICGFTHDDGYMICCDKCSVWQHIDCMGIDRQHIPDTYLCERC 163
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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948259   561 MESEEQIAERKRKMTREERKMEAILQAFARL-EKREKRREQALERISTAKTEVKT-------ECKDTQIVSD---AEVIQ 629
Cdd:pfam13868  133 DEFNEEQAEWKELEKEEEREEDERILEYLKEkAEREEEREAEREEIEEEKEREIArlraqqeKAQDEKAERDelrAKLYQ 212

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 767948259   630 EQAKEENASKPTPAKVNRTKQRKSFSRSRTHIGQQRRRHR 669
Cdd:pfam13868  213 EEQERKERQKEREEAEKKARQRQELQQAREEQIELKERRL 252

ARC105 or Med15 subunit of Mediator complex non-fungal; The approx. 70 residue Med15 domain of the ARC-Mediator co-activator is a three-helix bundle with marked similarity to the KIX domain. The sterol regulatory element binding protein (SREBP) family of transcription activators use the ARC105 subunit to activate target genes in the regulation of cholesterol and fatty acid homeostasis. In addition, Med15 is a critical transducer of gene activation signals that control early metazoan development.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948259  1463 GYLSPKPPSQQLGSPYRPHHSQSP-QVGTPQREPQRNFYPAAQNLPAntqqatsgtLFTQTPSGQSSATYSQFNQQSLNS 1541
Cdd:pfam09606  157 GMMQPSSGQPGSGTPNQMGPNGGPgQGQAGGMNGGQQGPMGGQMPPQ---------MGVPGMPGPADAGAQMGQQAQANG 227

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948259  1542 TAPPPPPPPPPSSSYYQNQQPSANfqnynqlkgslSQQTVFTSGPNQAlpgttsQQTVPGHHVTPGHFLPSQNPTIHHQT 1621
Cdd:pfam09606  228 GMNPQQMGGAPNQVAMQQQQPQQQ-----------GQQSQLGMGINQM------QQMPQGVGGGAGQGGPGQPMGPPGQQ 290

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948259  1622 AAAVVPPPPPPPPAPGPHLVQQPNSHQQ---HSVAHVVGPVHAVTPGSHIHSQTAGHHLPppppppgpaphhhppphpsT 1698
Cdd:pfam09606  291 PGAMPNVMSIGDQNNYQQQQTRQQQQQQggnHPAAHQQQMNQSVGQGGQVVALGGLNHLE-------------------T 351

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948259  1699 GLQGLQAQHQhvVNSAPPPPPPPPPSSVLASGHHTTSAQALHHPPHQGPPLFPSSAHPtvppypsqathhttlgpGPQHQ 1778
Cdd:pfam09606  352 WNPGNFGGLG--ANPMQRGQPGMMSSPSPVPGQQVRQVTPNQFMRQSPQPSVPSPQGP-----------------GSQPP 412

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 767948259  1779 PSGTGPHCPLPVTGPHLQPQ---GPNS---IPTPTASGFCPHPGSVALPHGVqGPQQ 1829
Cdd:pfam09606  413 QSHPGGMIPSPALIPSPSPQmsqQPAQqrtIGQDSPGGSLNTPGQSAVNSPL-NPQE 468

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 767948259  120 RCICGFTHDDGYMICCDKCSVWQHIDCMGIDRQHIPDTYLCERC 163
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 767948259   343 LKSAKDLPPDALIIEYRGKFML-------REQFEANGYFFKRPYPFVLFYSKFHglEMCVDARTF--GNEARFIRRSCTP 413
Cdd:pfam00856    4 LFATEDIPKGEFIGEYVEVLLItkeeadkRELLYYDKLELRLWGPYLFTLDEDS--EYCIDARALyyGNWARFINHSCDP 81

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 767948259   414 NAEVRHEIQDGTIHLYIYSIHSIPKGTEITIafdfDYG 451
Cdd:pfam00856   82 NCEVRVVYVNGGPRIVIFALRDIKPGEELTI----DYG 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 767948259   120 RC-ICGFTHDDGYMICCDKCSVWQHIDCMGI---DRQHIPDTYLCERCQPR 166
Cdd:pfam00628    1 YCaVCGKSDDGGELVQCDGCDDWFHLACLGPpldPAEIPSGEWLCPECKPK 51

104 kDa microneme/rhoptry antigen; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948259 1310 QAKGPVPSFSElmEDPD-----PENPEPTTTN-ECPSPDTSQNTCKSPPKMSKP----GSPGSVipaqAHGKIFTKPDPQ 1379
Cdd:PTZ00449  491 KSKKKLAPIEE--EDSDkhdepPEGPEASGLPpKAPGDKEGEEGEHEDSKESDEpkegGKPGET----KEGEVGKKPGPA 564

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948259 1380 WDSTVSaseaengvhlKTELQQKQLSNNNQALSKNHP--PQTHVRNSSEQ--LSQKLPSVPTKLHCPPSPHLENPPKSst 1455
Cdd:PTZ00449  565 KEHKPS----------KIPTLSKKPEFPKDPKHPKDPeePKKPKRPRSAQrpTRPKSPKLPELLDIPKSPKRPESPKS-- 632

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 767948259 1456 PHTPVqhgylSPKPPSqqlgSPYRPHHSQSPQVGTPQREPQRNFYPA 1502
Cdd:PTZ00449  633 PKRPP-----PPQRPS----SPERPEGPKIIKSPKPPKSPKPPFDPK 670

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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948259   561 MESEEQIAERKRKMTREERKMEAILQAFARL-EKREKRREQALERISTAKTEVKT-------ECKDTQIVSD---AEVIQ 629
Cdd:pfam13868  133 DEFNEEQAEWKELEKEEEREEDERILEYLKEkAEREEEREAEREEIEEEKEREIArlraqqeKAQDEKAERDelrAKLYQ 212

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 767948259   630 EQAKEENASKPTPAKVNRTKQRKSFSRSRTHIGQQRRRHR 669
Cdd:pfam13868  213 EEQERKERQKEREEAEKKARQRQELQQAREEQIELKERRL 252

AAA family ATPase Pro-rich N-terminal domain; This HMM describes an extremely rich N-terminal domain that is well-conserved for a family of AAA family ATPases seen in Streptomyces. The HMM was built to support correct structural annotation of this unusual, low-complexity domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948259 1728 ASGHHTTSAQALHHP----PHQGPPLFPSSAHPTVPPYPSQATHhttlGPGPQHQPSGTGP----HCPLPvtgphlqPQG 1799
Cdd:NF040555   16 GHGPAAGWSPAAHHPgpphPQGPAPVPPPAPGFPAPPGPQPGWH----PPAPQHAPAPPAPdttgHVQLP-------PGG 84

                  ....*..
gi 767948259 1800 PNSIPTP 1806
Cdd:NF040555   85 PVPMPSP 91

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948259  561 MESEEQIAERKRKMTREE--RKMEAILQAFARLEKREKRREQALERISTAKTEVKTECKDTqivsDAEVIQEQAKEENAS 638
Cdd:COG1579    94 LQKEIESLKRRISDLEDEilELMERIEELEEELAELEAELAELEAELEEKKAELDEELAEL----EAELEELEAEREELA 169

                          90
                  ....*....|....*...
gi 767948259  639 KPTPAKV----NRTKQRK 652
Cdd:COG1579   170 AKIPPELlalyERIRKRK 187

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 767948259  334 SHIQKNKKILKSAKDLPPDALIIEYRGKFMLREQFEANGYFFKRPYPFVLFYSKFHGLEMCVDARTFGNEARFIRRSCTP 413
Cdd:cd19181    12 TRVQKHRKILRAARDLALDTLIIEYRGKVMLRQQFEVNGHFFKRPYPFVLFYSKFNGVEMCVDARTFGNDARFIRRSCTP 91

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 767948259  414 NAEVRHEIQDGTIHLYIYSIHSIPKGTEITIAFDFDYGNCKYKVDCACLKENPECPVLK 472
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 767948259  120 RCICGFTHDDGYMICCDKCSVWQHIDCMGIDRQHIPDTYLCERC 163
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 767948259  343 LKSAKDLPPDALIIEYRGKFMLREQFEA---NGY-FFKRPYPFVLFYSKfhgLEMCVDARTFGNEARFIRRSCTPNAE-V 417
Cdd:cd19183    16 LFADRPIPAGDPIQELLGEIGLQSEYIAdpeNQYqILGAPKPHVFFHPQ---SPLYIDTRRSGSVARFIRRSCRPNAElV 92

                          90       100       110
                  ....*....|....*....|....*....|...
gi 767948259  418 RHEIQDGT-IHLYIYSIHSIPKGTEITIAFDFD 449
Cdd:cd19183    93 TVASDSGSvLKFVLYASRDISPGEEITIGWDWD 125

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 767948259  121 CICGFTHDDG-YMICCDKCSVWQHIDCMGI-DRQHIPDTYLCERC 163
Cdd:cd15556     2 CSCGTRDDDGeRMIACDVCEVWQHTRCVGIaDNEEPPDHFLCRRC 46

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948259  346 AKDLPPDALIIEYRGKFMLREQFEANGYFFKRPYPFVLFYSKFHGlemcVDARTFGNEARFIRRSCTPNAEVRHEiqDGT 425
Cdd:COG2940    23 TRDIPKGTLIGEYPGEVITWAEAERREPHKEPLHTYLFELDDDGV----IDGALGGNPARFINHSCDPNCEADEE--DGR 96

                          90       100
                  ....*....|....*....|....*.
gi 767948259  426 IhlYIYSIHSIPKGTEITIafdfDYG 451
Cdd:COG2940    97 I--FIVALRDIAAGEELTY----DYG 116

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 767948259  346 AKDLPPDALIIEYRGKFMLREQFEANGYFfkrpYPFVLFYSKFHGLEMCVDARTFGNEARFIRRSCTPNAEVRHEIQDGT 425
Cdd:cd10522    20 AETIAKGEFVGEYTGEVLDRWEEDRDSVY----HYDPLYPFDLNGDILVIDAGKKGNLTRFINHSDQPNLELIVRTLKGE 95

                          90       100
                  ....*....|....*....|....*.
gi 767948259  426 IHLYIYSIHSIPKGTEITIafdfDYG 451
Cdd:cd10522    96 QHIGFVAIRDIKPGEELFI----SYG 117

PHD domain found in Saccharomyces cerevisiae bypass of ESS1 protein 1 (Bye1p), the E3 Sumo Ligase SIZ1, and similar proteins; Yeast Bye1p is a nuclear transcription factor with a domain resembling the central domain in the transcription elongation factor TFIIS and plays an inhibitory role during transcription elongation. It functions as a multicopy suppressor of Ess1, a peptidyl-prolyl cis-trans isomerase involved in proline isomerization of the C-terminal domain (CTD) of RNA polymerase II (Pol II). Bye1p contains an N-terminal plant homeodomain (PHD) finger, a central Pol II-binding TFIIS-like domain (TLD) domain, and a C-terminal Spen paralogue and orthologue C-terminal (SPOC) domain. The PHD domain binds to a histone H3 tail peptide containing trimethylated lysine 4 (H3K4me3). The TLD domain is responsible for the association with chromatin. Plant SIZ1 protein is a SUMO (small ubiquitin-related modifier) E3 ligase that facilitates conjugation of SUMO to substrate target proteins (sumoylation) and belongs to the protein inhibitor of activated STAT (PIAS) protein family. It negatively regulates abscisic acid (ABA) signaling, which is dependent on the bZIP transcripton factor ABI5. It also modulates plant growth and plays a role in drought stress response likely through the regulation of gene expression. SIZ1 functions as a floral repressor that not only represses the salicylic acid (SA)-dependent pathway, but also promotes FLOWERING LOCUS C (FLC) expression by repressing FLOWERING LOCUS D (FLD) activity through sumoylation. SIZ1 contains a PHD finger, which specifically binds methylated histone H3 at lysine 4 and arginine 2.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 767948259  120 RCICGFTHDDGYMICCDKCSVWQHIDCMGI------DRQHIPDTYLCERC 163
Cdd:cd15570     1 RCPCGSSMEDGSMIQCEGCKTWQHMDCVLIpdkpadGLPELPSKFYCELC 50

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*
gi 767948259    121 CICGFTHDDGYMICCDKCSVWQHIDCMGI-DRQHIPD-TYLCERC 163
Cdd:smart00249    3 SVCGKPDDGGELLQCDGCDRWYHQTCLGPpLLEEEPDgKWYCPKC 47

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 767948259  121 CICGFTHDDGYMICCDKCSVWQHIDCMGIDRQHIPD------TYLCERC 163
Cdd:cd15552     2 CICRKPHNNRFMICCDRCEEWFHGDCVGITEAQGKEmeenieEYVCPKC 50

SET domain (including post-SET domain) found in ASH1-like protein (ASH1L) and similar proteins; ASH1L (EC 2.1.1.43; also termed absent small and homeotic disks protein 1 homolog, KMT2H, or lysine N-methyltransferase 2H) acts as histone-lysine N-methyltransferase that specifically methylates 'Lys-36' of histone H3 (H3K36me). It plays important roles in development; heterozygous mutation of ASH1L is associated with severe intellectual disability (ID) and multiple congenital anomaly (MCA).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948259  343 LKSAKDLPPDALIIEYRGKFMLREQFEANgyfFKRPYpfvLFYSKFHGLEMC----VDARTFGNEARFIRRSCTPNAEVR 418
Cdd:cd19174    14 VRTKEPIKAGQFIIEYVGEVVSEQEFRRR---MIEQY---HNHSHHYCLNLDsgmvIDGYRMGNEARFVNHSCDPNCEMQ 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 767948259  419 HEIQDGTIHLYIYSIHSIPKGTEITIAFDFDYGNCKYKVDCACLKEN 465
Cdd:cd19174    88 KWSVNGVYRIGLFALKDIPAGEELTYDYNFHSFNVEKQQPCKCGSPN 134

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 767948259  120 RCICGFTHDDGYMICCDKCSVWQHIDCMGIDRQ-HIPDTYLCERC 163
Cdd:cd15549     1 HCICGVNEENGLMIQCELCLCWQHGVCMGIEEEeSVPERYVCYVC 45

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 767948259  343 LKSAKDLPPDALIIEYRGKFMLREQFEANGYFFKRP---YPFVL---FYSKFHGLEMCVDARTFGNEARFIRRSCTPN-- 414
Cdd:cd10538   103 VRSLEFIPKGSFVCEYVGEVITTSEADRRGKIYDKSggsYLFDLdefSDSDGDGEELCVDATFCGNVSRFINHSCDPNlf 182

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 767948259  415 -AEVRHEIQDGTIH-LYIYSIHSIPKGTEITiafdFDYG 451
Cdd:cd10538   183 pFNVVIDHDDLRYPrIALFATRDILPGEELT----FDYG 217

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 767948259  343 LKSAKDLPPDALIIEYRGKfMLREQFeANgyffKRPypfVLFYSKFHGLEM-------CVDARTFGNEARFIRRSCTPN- 414
Cdd:cd19171    28 LYAARDIEKHTMVIEYIGE-IIRNEV-AN----RRE---KIYESQNRGIYMfridndwVIDATMTGGPARYINHSCNPNc 98

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 767948259  415 -AEVRHeiQDGTIHLYIYSIHSIPKGTEITIAFDFDYGNCKYKVDCAC 461
Cdd:cd19171    99 vAEVVT--FDKEKKIIIISNRRIAKGEELTYDYKFDFEDDQHKIPCLC 144

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948259  347 KDLPPDALIIEYRGKFMLREQFEANGYFFKrpypfvlfySKFHGLEM-------CVDARTFGNEARFIRRSCTPNAEVRH 419
Cdd:cd19206    32 RNIDAGEMVIEYSGNVIRSILTDKREKYYD---------SKGIGCYMfriddseVVDATMHGNAARFINHSCEPNCYSRV 102

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 767948259  420 EIQDGTIHLYIYSIHSIPKGTEITIAFDFDYGNCKYKVDCAC 461
Cdd:cd19206   103 INIDGQKHIVIFAMRKIYRGEELTYDYKFPIEDASNKLPCNC 144

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 767948259  343 LKSAKDLPPDALIIEYRGKFMLREQFEANGYFFKRPYPFVLFYSKFHglEMCVDARTFGNEARFIRRSCTPNAEVRHEIQ 422
Cdd:cd19209    30 LYAAKDLEKHTMVIEYIGTIIRNEVANRREKIYEEQNRGIYMFRINN--EHVIDATLTGGPARYINHSCAPNCVAEVVTF 107

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 767948259  423 DGTIHLYIYSIHSIPKGTEITIAFDFDYGNCKYKVDCAC 461
Cdd:cd19209   108 DKEDKIIIISSRRIPKGEELTYDYQFDFEDDQHKIPCHC 146

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767948259  395 VDARTFGNEARFIRRSCTPNAEVRHEIQDGTIHLYIYSIHSIPKGTEITIAFDFD-YGNCKYKvdCACLKEN 465
Cdd:cd19212    67 IDAGPKGNYSRFMNHSCNPNCETQKWTVNGDVRVGLFALCDIPAGMELTFNYNLDcLGNGRTE--CHCGADN 136

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 767948259  343 LKSAKDLPPDALIIEYRGKFMLREQFEANGYFF---KRPYPFVLFYSKFHGlEMCVDARTFGNEARFIRRSCTPNAEVRH 419
Cdd:cd10542   102 VKTLEDIKKGTFVMEYVGEIITSEEAERRGKIYdanGRTYLFDLDYNDDDC-EYTVDAAYYGNISHFINHSCDPNLAVYA 180

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 767948259  420 ---EIQDGTI-HLYIYSIHSIPKGTEITiafdFDY 450
Cdd:cd10542   181 vwiNHLDPRLpRIAFFAKRDIKAGEELT----FDY 211

PHD finger found in death-inducer obliterator variants Dido1, Dido2, and Dido3; This family includes three alternative splicing variants (Dido1, 2, and 3) encoded by the Dido gene, which have been implicated in a number of cellular processes such as apoptosis and chromosomal segregation, particularly in the hematopoietic system. Dido1, also termed DIO-1, or death-associated transcription factor 1 (DATF-1), 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 plant homeodomain (PHD) finger responsible for the binding of histone H3 with a higher affinity for trimethylated lysine 4 (H3K4me3). Gene Dido is a Bonemorphogenetic protein (BMP) target gene, which promotes BMP-induced melanoma progression. It also triggers apoptosis after nuclear translocation and caspase upregulation. Dido3 is the largest isoform ubiquitously expressed in all human tissues. It is dispensable for ES cell self-renewal and pluripotency, but 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, aspen paralog and ortholog (SPOC) module, and a long C-terminal region (CT) of unknown homology. Its PHD finger interacts with H3K4me3.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 767948259  121 CICGFTHDDGYMICCDKCSVWQHIDCMGIDR------QHIPDTYLCERC 163
Cdd:cd15639     6 CICRQPHNNRFMICCDRCEEWFHGDCVGITEargrllERNGEDYICPNC 54

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767948259  395 VDARTFGNEARFIRRSCTPNAEVRHEIQDGTIHLYIYSIHSIPKGTEITIAFDFDYGNCKYKVDCAC 461
Cdd:cd19207    78 VDATMHGNAARFINHSCEPNCYSRVIHVEGQKHIVIFALRKIYRGEELTYDYKFPIEDASNKLPCNC 144

PHD finger found in PHD finger protein 23 (PHF23); PHF23, also termed PHD-containing protein JUNE-1, is a hypothetical protein with a plant homeodomain (PHD) finger. It is encoded by gene PHF23 that acts as a candidate fusion partner for the nucleoporin gene NUP98. The NUP98-PHF23 fusion results from a cryptic translocation t(11;17)(p15;p13) in acute myeloid leukemia (AML).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 767948259  121 CICGFTHDDGYMICCDKCSVWQHIDCMGIDRQHIPDTYLCERC 163
Cdd:cd15631     2 CYCGKPFAGRPMIECSQCGTWIHLSCAKIKKSNVPDFFYCQKC 44