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 568933383  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 568933383   561 MESEEQIAERKRKMTREERKMEAILQAFARL-EKREKRREQALERISTAKTEVKPE-CKESQVIAD---------AEVVQ 629
Cdd:pfam13868  133 DEFNEEQAEWKELEKEEEREEDERILEYLKEkAEREEEREAEREEIEEEKEREIARlRAQQEKAQDekaerdelrAKLYQ 212

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 568933383   630 EQVKEETAIKPAAAKVNRTKQRKSFSRSRTHIGQQRRRHR 669
Cdd:pfam13868  213 EEQERKERQKEREEAEKKARQRQELQQAREEQIELKERRL 252

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 568933383  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 568933383   343 LKSAKDLPPDALIIEYRGKFML-------REQFEANGYFFKRPYPFVLFYSKFHglEMCVDARTF--GNEARFIRRSCTP 413
Cdd:pfam00856    4 LFATEDIPKGEFIGEYVEVLLItkeeadkRELLYYDKLELRLWGPYLFTLDEDS--EYCIDARALyyGNWARFINHSCDP 81

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 568933383   414 NAEVRHEIEEGTIHLYIYSIQSIPKGTEITIafdfDYG 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 568933383   120 RC-ICGFTHDDGYMICCDKCSVWQHIDCMGI---DRQHIPDTYLCERCQPR 166
Cdd:pfam00628    1 YCaVCGKSDDGGELVQCDGCDDWFHLACLGPpldPAEIPSGEWLCPECKPK 51

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 568933383  1308 PDTSQSPSKTSKPGSPGPInpaqshgkiLTKPDSHWEATATVSEADNSVHQNPEPQHRQLSSNTPALSQNHA----PQAH 1383
Cdd:pfam05109  449 PSSTHVPTNLTAPASTGPT---------VSTADVTSPTPAGTTSGASPVTPSPSPRDNGTESKAPDMTSPTSavttPTPN 519

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933383  1384 ALSANDQLPQKLPSA---------PTKLHCPPSPHTENP-PKSSTPHTPVQHGYLSPKPPSQHLGSPfrPHHSQSPQVG- 1452
Cdd:pfam05109  520 ATSPTPAVTTPTPNAtsptlgktsPTSAVTTPTPNATSPtPAVTTPTPNATIPTLGKTSPTSAVTTP--TPNATSPTVGe 597

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933383  1453 -TPQRETQRNFYAAAQN---LQANPQQATSGalftqTPSGQSSATYSQFNQQSLNSTAPPPPPPPPPSSYYQNQQP---- 1524
Cdd:pfam05109  598 tSPQANTTNHTLGGTSStpvVTSPPKNATSA-----VTTGQHNITSSSTSSMSLRPSSISETLSPSTSDNSTSHMPllts 672

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*.
gi 568933383  1525 --SANFQNYNQLK-GSLSQQTVFTSGPnQALPGSTSQQSVPGHHVT 1567
Cdd:pfam05109  673 ahPTGGENITQVTpASTSTHHVSTSSP-APRPGTTSQASGPGNSST 717

N-terminal domain of Kruppel-like factor 10; Kruppel-like factor 10 (KLF10; also known as Krueppel-like factor 10; early growth response(EGR)-alpha/EGRA; TGFbeta inducible early gene-1/TIEG1) is a protein that in humans is encoded by the KLF10 gene. KLF10 was first identified in human osteoblasts and plays a role in mediating estrogen (E2) signaling in bone and skeletal homeostasis and a regulatory role in tumor formation and metastasis. It may also play a role in adipocyte differentiation and adipose tissue function. KLF9, KLF10, KLF11, KLF13, KLF14, and KLF16 share a conserved a-helical motif AA/VXXL that mediates their binding to Sin3A and their activities as transcriptional repressors. KLF10 belongs to a family of proteins, called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specificity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the N-terminal domain of KLF10.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933383 1698 HSASGQALHHPPHQGPPLFPASAHPAVPPYPSQAT---HHTTLGpgpqhQPSGTGPHCPLPVAGPHLQPQGPNSIPTPTA 1774
Cdd:cd21572    71 HPPSAATLHPPAAQPPEEQHLSAETAASQQRFQCTsviRHTADA-----QPCSCSSCPSSPSVVPSVPAGVAGVSPVPVY 145

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 568933383 1775 SGFCP--HPHPGSVALPHGVQGPQQASPVPAQIPIHRAQVPP 1814
Cdd:cd21572   146 CQILPvsSSSTTVVAAQAPLPQPQQQAASPAQVFLMGGQVPK 187

superantigen-like protein SSL4; Reviewed;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933383 1368 SSNTPALSQNHAPQAHALSANDQLPQKLPSAPTklhcPPSPHTENPPKSSTPHTpvqhgylspkPPSQHLGSPFRPHHSQ 1447
Cdd:PRK13042   29 NATTPSSTKVEAPQSTPPSTKVEAPQSKPNATT----PPSTKVEAPQQTPNATT----------PSSTKVETPQSPTTKQ 94

                          90
                  ....*....|....*.
gi 568933383 1448 SPQVGTPQRETQRNFY 1463
Cdd:PRK13042   95 VPTEINPKFKDLRAYY 110

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933383  1703 QALHHPPHQGPPLFPASAHPAVPPYPSQATHHTTLGPGPQHQPsgtgPHCPLPVAGPH-LQPQGPNSIPTPTasgfcPHP 1781
Cdd:pfam03154  175 QAQSGAASPPSPPPPGTTQAATAGPTPSAPSVPPQGSPATSQP----PNQTQSTAAPHtLIQQTPTLHPQRL-----PSP 245

                           90       100       110
                   ....*....|....*....|....*....|...
gi 568933383  1782 HPGSVALPHGVQgPQQASPVPAQIPIHRAQVPP 1814
Cdd:pfam03154  246 HPPLQPMTQPPP-PSQVSPQPLPQPSLHGQMPP 277

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 568933383 1695 SGHHSASGQALHHP----PHQGPPLFPASAHPAVPPYPSQATHhttlGPGPQHQPSGTGP----HCPLPvagphlqPQGP 1766
Cdd:NF040555   17 HGPAAGWSPAAHHPgpphPQGPAPVPPPAPGFPAPPGPQPGWH----PPAPQHAPAPPAPdttgHVQLP-------PGGP 85

                  ....*.
gi 568933383 1767 NSIPTP 1772
Cdd:NF040555   86 VPMPSP 91

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 568933383  334 SHIQKNKKILKSAKDLPPDALIIEYRGKFMLREQFEANGYFFKRPYPFVLFYSKFHGLEMCVDARTFGNEARFIRRSCTP 413
Cdd:cd19181    12 TRVQKHRKILRAARDLALDTLIIEYRGKVMLRQQFEVNGHFFKRPYPFVLFYSKFNGVEMCVDARTFGNDARFIRRSCTP 91

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568933383  414 NAEVRHEIEEGTIHLYIYSIQSIPKGTEITIAFDFDYGNCKYKVDCACLKENPECPVLK 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 568933383  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 568933383  343 LKSAKDLPPDALIIEYRGKFMLREQFEA---NGY-FFKRPYPFVLFYSKfhgLEMCVDARTFGNEARFIRRSCTPNAE-V 417
Cdd:cd19183    16 LFADRPIPAGDPIQELLGEIGLQSEYIAdpeNQYqILGAPKPHVFFHPQ---SPLYIDTRRSGSVARFIRRSCRPNAElV 92

                          90       100       110
                  ....*....|....*....|....*....|...
gi 568933383  418 RHEIEEGT-IHLYIYSIQSIPKGTEITIAFDFD 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 568933383  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 568933383  346 AKDLPPDALIIEYRGKFMLREQFEANGYFFKRPYPFVLFYSKFHGlemcVDARTFGNEARFIRRSCTPNAEVRheIEEGT 425
Cdd:COG2940    23 TRDIPKGTLIGEYPGEVITWAEAERREPHKEPLHTYLFELDDDGV----IDGALGGNPARFINHSCDPNCEAD--EEDGR 96

                          90       100
                  ....*....|....*....|....*.
gi 568933383  426 IhlYIYSIQSIPKGTEITIafdfDYG 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 568933383  346 AKDLPPDALIIEYRGKFMLREQFEANGYFfkrpYPFVLFYSKFHGLEMCVDARTFGNEARFIRRSCTPNAEVRHEIEEGT 425
Cdd:cd10522    20 AETIAKGEFVGEYTGEVLDRWEEDRDSVY----HYDPLYPFDLNGDILVIDAGKKGNLTRFINHSDQPNLELIVRTLKGE 95

                          90       100
                  ....*....|....*....|....*.
gi 568933383  426 IHLYIYSIQSIPKGTEITIafdfDYG 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 568933383  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 568933383    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 568933383  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 568933383  343 LKSAKDLPPDALIIEYRGKFMLREQFEANgyfFKRPYpfvLFYSKFHGLEMC----VDARTFGNEARFIRRSCTPNAEVR 418
Cdd:cd19174    14 VRTKEPIKAGQFIIEYVGEVVSEQEFRRR---MIEQY---HNHSHHYCLNLDsgmvIDGYRMGNEARFVNHSCDPNCEMQ 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 568933383  419 HEIEEGTIHLYIYSIQSIPKGTEITIAFDFDYGNCKYKVDCACLKEN 465
Cdd:cd19174    88 KWSVNGVYRIGLFALKDIPAGEELTYDYNFHSFNVEKQQPCKCGSPN 134

SET domain (including post-SET domain) found in Arabidopsis thaliana ASH1-related protein 3 (ASHR3) and similar proteins; This family includes Arabidopsis thaliana ASH1-related protein 3 (ASHR3, also termed protein SET DOMAIN GROUP 4 or protein stamen loss), ASH1 homolog 3 (ASHH3, also termed protein SET DOMAIN GROUP 7) and homolog 4 (ASHH4, also termed protein SET DOMAIN GROUP 24). They all function as histone-lysine N-methyltransferases (EC 2.1.1.43).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933383  343 LKSAKDLPPDALIIEYRGK-----------FMLREQFEANgyffkrpypfvlFYSKFHGLEMCVDARTFGNEARFIRRSC 411
Cdd:cd19175    14 LVADEDINAGEFIIEYVGEviddktceerlWDMKHKGEKN------------FYMCEIDKDMVIDATFKGNLSRFINHSC 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568933383  412 TPNAEVRHEIEEGTIHLYIYSIQSIPKGTEITIAFDF-DYGNckyKVDCAC 461
Cdd:cd19175    82 DPNCELQKWQVDGETRIGVFAIRDIKKGEELTYDYQFvQFGA---DQDCHC 129

SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain superfamily; The Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain superfamily corresponds to SET domain-containing lysine methyltransferases, which catalyze site and state-specific methylation of lysine residues in histones that are fundamental in epigenetic regulation of gene activation and silencing in eukaryotic organisms. SET domains appear to be protein-protein interaction domains. It has been demonstrated that SET domains mediate interactions with a family of proteins that display similarity with dual-specificity phosphatases (dsPTPases). A subset of SET domains has been called PR domains. These domains are divergent in sequence from other SET domains, but also appear to mediate protein-protein interaction. The SET domain consists of two regions known as N-SET and C-SET. C-SET forms an unusual and conserved knot-like structure of probable functional importance. In addition to N-SET and C-SET, an insert region (I-SET) and flanking regions of high structural variability form part of the overall structure. Some family members contain a pre-SET domain, which is found in a number of histone methyltransferases (HMTase), and a post-SET domain, which harbors a zinc-binding site.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568933383  403 EARFIRRSCTPNAEVRHEIEEGTIHLYIYSIQSIPKGTEITiafdFDYG 451
Cdd:cd08161    28 LARFINHSCEPNCEFEEVYVGGKPRVFIVALRDIKAGEELT----VDYG 72

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 568933383  345 SAKDLPPDALIIEYRGKFM------LREQ-FEANG----YFFKrpypfvlfYSKFHglemCVDArTF-GNEARFIRRSCT 412
Cdd:cd10518    30 AKRPIAAGEMVIEYVGEVIrpivadKREKrYDEEGgggtYMFR--------IDEDL----VIDA-TKkGNIARFINHSCD 96

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568933383  413 PNAEVRHEIEEGTIHLYIYSIQSIPKGTEITIAFDFDYGNCKyKVDCAClkENPEC 468
Cdd:cd10518    97 PNCYAKIITVDGEKHIVIFAKRDIAPGEELTYDYKFPIEDEE-KIPCLC--GAPNC 149

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 568933383  318 KSELSTNNSLFRppveSHIQKNKkiLKSAKDLPPDALIIEYRGKfMLREQFeANgyffKRPypfVLFYSKFHGLEM---- 393
Cdd:cd19171     9 KTEWRSNVYLAR----SRIQGLG--LYAARDIEKHTMVIEYIGE-IIRNEV-AN----RRE---KIYESQNRGIYMfrid 73

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568933383  394 ---CVDARTFGNEARFIRRSCTPN--AEVRHEieEGTIHLYIYSIQSIPKGTEITIAFDFDYGNCKYKVDCAC 461
Cdd:cd19171    74 ndwVIDATMTGGPARYINHSCNPNcvAEVVTF--DKEKKIIIISNRRIAKGEELTYDYKFDFEDDQHKIPCLC 144

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 568933383  343 LKSAKDLPPDALIIEYRGKFMLREQFEANGYFF---KRPYPFVLFYSKFHGlEMCVDARTFGNEARFIRRSCTPNAEVRH 419
Cdd:cd10542   102 VKTLEDIKKGTFVMEYVGEIITSEEAERRGKIYdanGRTYLFDLDYNDDDC-EYTVDAAYYGNISHFINHSCDPNLAVYA 180

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 568933383  420 E-IEEGTIHLY---IYSIQSIPKGTEITiafdFDY 450
Cdd:cd10542   181 VwINHLDPRLPriaFFAKRDIKAGEELT----FDY 211

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 568933383  121 CICGFTHDD-GYMICCDKCSVWQHIDCMGID--RQHIPDTYLCERC 163
Cdd:cd15489     3 IVCGKGGDLgGELLQCDGCGKWFHADCLGPPlsSFVPNGKWICPVC 48

PHD finger found in PHD finger protein 13 (PHF13); PHF13, also termed survival time-associated PHD finger protein in ovarian cancer 1 (SPOC1), is a novel plant homeodomain (PHD) finger-containing protein that shows strong expression in spermatogonia and ovarian cancer cells, modulates chromatin structure and mitotic chromosome condensation, and is important for proper cell division. It is also required for spermatogonial stem cell differentiation and sustained spermatogenesis. The overexpression of PHF13 associates with unresectable carcinomas and shorter survival in ovarian cancer.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 568933383  121 CICGFTHDDGYMICCDKCSVWQHIDCMGIDRQHIPDTYLCERCQ 164
Cdd:cd15632     4 CFCMKPFAGRPMIECNECHTWIHLSCAKIRKSNVPEVYVCQKCR 47

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 568933383  395 VDARTFGNEARFIRRSCTPNAEVRHEIEEGTIHLYIYSIQSIPKGTEITIAFDFDYGNCKYKVDCAC 461
Cdd:cd19207    78 VDATMHGNAARFINHSCEPNCYSRVIHVEGQKHIVIFALRKIYRGEELTYDYKFPIEDASNKLPCNC 144

PHD finger found in Transcription factor 19 (TCF-19), Lysine-specific demethylase KDM5A and KDM5B, and other similar proteins; TCF-19 was identified as a putative trans-activating factor with expression beginning at the late G1-S boundary in dividing cells. It functions as a novel islet factor necessary for proliferation and survival in the INS-1 beta cell line. It plays an important role in susceptibility to both Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM); it has been suggested that it may positively impact beta cell mass under conditions of beta cell stress and increased insulin demand. KDM5A was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation. It is involved in transcription through interaction with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK, and BMAL1. KDM5B has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of the pregnant female and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis. Both KDM5A and KDM5B function as trimethylated histone H3 lysine 4 (H3K4me3) demethylases. This family also includes Caenorhabditis elegans Lysine-specific demethylase 7 homolog (ceKDM7A). ceKDM7A (also termed JmjC domain-containing protein 1.2, PHD finger protein 8 homolog, or PHF8 homolog) is a plant homeodomain (PHD)- and JmjC domain-containing protein that functions as a histone demethylase specific for H3K9me2 and H3K27me2. The binding of the PHD finger to H3K4me3 guides H3K9me2- and H3K27me2-specific demethylation by its catalytic JmjC domain in a trans-histone regulation mechanism. In addition, this family includes plant protein OBERON 1 and OBERON 2, Alfin1-like (AL) proteins, histone acetyltransferases (HATs) HAC, and AT-rich interactive domain-containing protein 4 (ARID4).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568933383  122 ICG-FTH-DDGYMICCDKCSVWQHIDCMGID--RQHIPDTYLCERC 163
Cdd:cd15517     4 ICNlETAaVDELWVQCDGCDKWFHQFCLGLSneRYADEDKFKCPNC 49