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        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1191805951   3 KIYSRGELHHFIDGFNEEKSNWLRYVNPAHSAREQNLAACQNGMNIYFYTIKPIPANQELLVWYCRDFAERL 74
Cdd:cd19187    57 RIYSNGEFYHYIDGFDPSKSNWMRYVNPAHSLQEQNLVACQIGMNIYFYTVKPIPPNQELLVWYCREFARRL 128

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*.
gi 1191805951 515 NLKTHLRLHSGEKPYQCKVCPAKFTQ 540
Cdd:pfam13465   1 NLKRHMRTHTGEKPYKCPECGKSFKS 26

PR-SET domain found in PR domain zinc finger protein 1 (PRDM1) and similar proteins; PRDM1 (also termed BLIMP-1, beta-interferon gene positive regulatory domain I-binding factor, PR domain-containing protein 1, positive regulatory domain I-binding factor 1, PRDI-BF1, or PRDI-binding factor 1) acts as a transcription factor that mediates a transcriptional program in various innate and adaptive immune tissue-resident lymphocyte T cell types such as tissue-resident memory T (Trm), natural killer (trNK) and natural killer T (NKT) cells and negatively regulates gene expression of proteins that promote the egress of tissue-resident T-cell populations from non-lymphoid organs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1191805951   3 KIYSRGELHHFIDGFNEEKSNWLRYVNPAHSAREQNLAACQNGMNIYFYTIKPIPANQELLVWYCRDFAERL 74
Cdd:cd19187    57 RIYSNGEFYHYIDGFDPSKSNWMRYVNPAHSLQEQNLVACQIGMNIYFYTVKPIPPNQELLVWYCREFARRL 128

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1191805951   9 ELHHFIDGFNEEKSNWLRYVNpaHSAREQNLAACQ---NGMNIYFYTIKPIPANQELLVWY 66
Cdd:pfam00856  56 DSEYCIDARALYYGNWARFIN--HSCDPNCEVRVVyvnGGPRIVIFALRDIKPGEELTIDY 114

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*.
gi 1191805951 515 NLKTHLRLHSGEKPYQCKVCPAKFTQ 540
Cdd:pfam13465   1 NLKRHMRTHTGEKPYKCPECGKSFKS 26

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*.
gi 1191805951 459 NLKVHLRVHSGERPFKCQTCNKGFTQ 484
Cdd:pfam13465   1 NLKRHMRTHTGEKPYKCPECGKSFKS 26

PR-SET domain found in PR domain zinc finger protein 1 (PRDM1) and similar proteins; PRDM1 (also termed BLIMP-1, beta-interferon gene positive regulatory domain I-binding factor, PR domain-containing protein 1, positive regulatory domain I-binding factor 1, PRDI-BF1, or PRDI-binding factor 1) acts as a transcription factor that mediates a transcriptional program in various innate and adaptive immune tissue-resident lymphocyte T cell types such as tissue-resident memory T (Trm), natural killer (trNK) and natural killer T (NKT) cells and negatively regulates gene expression of proteins that promote the egress of tissue-resident T-cell populations from non-lymphoid organs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1191805951   3 KIYSRGELHHFIDGFNEEKSNWLRYVNPAHSAREQNLAACQNGMNIYFYTIKPIPANQELLVWYCRDFAERL 74
Cdd:cd19187    57 RIYSNGEFYHYIDGFDPSKSNWMRYVNPAHSLQEQNLVACQIGMNIYFYTVKPIPPNQELLVWYCREFARRL 128

PR-SET domain found in PR domain zinc finger protein 12 (PRDM12) and similar proteins; PRDM12 (also termed PR domain-containing protein 12) acts as a transcription factor that is involved in the positive regulation of histone H3-K9 dimethylation.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1191805951   6 SRGELHHFIDGFNEEKSNWLRYVNPAHSAREQNLAACQNGMNIYFYTIKPIPANQELLVWYCRDFAERLHYP 77
Cdd:cd19196    59 EDGTVSHFIDASQENHRSWMTFVNCARNEQEQNLEVVQIGESIYYRAIKDIPPDQELLVWYGNSYNTFLGIP 130

PR-SET domain found in PR domain zinc finger protein 10 (PRDM10) and similar proteins; PRDM10 (also termed PR domain-containing protein 10, or tristanin) may be involved in transcriptional regulation.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1191805951  13 FIDGFNEEKSNWLRYVNPAHSAREQNLAACQNGMNIYFYTIKPIPANQELLVWYCRDFAERL 74
Cdd:cd19194    66 YFDLSDENKCNWMMFVRPAQNHLEQNLVAYQYGQEIYFTTIKNIEPKQELKVWYAASYAEFL 127

PR-SET domain found in PR domain zinc finger protein 14 (PRDM14) and similar proteins; PRDM14 (also termed PR domain-containing protein 14) acts as a transcription factor that has both positive and negative roles on transcription. It acts on regulating epigenetic modifications in the cells, playing a key role in the regulation of cell pluripotency, epigenetic reprogramming, differentiation and development. Aberrant PRDM14 expression is associated with tumorigenesis, cell migration and cell chemotherapeutic drugs resistance.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1191805951   1 MEKIYSRGELHHFIDGfNEEKSNWLRYVNPAHSAREQNLAACQNGMNIYFYTIKPIPANQELLVWY 66
Cdd:cd19198    56 MWEIFEDGKLSHFIDG-RGSTGNWMSYVNCARYAEEQNLIAIQCQGQIFYESCKEILQGQELLVWY 120

PR-SET domain found in PR domain zinc finger protein 2 (PRDM2) and similar proteins; PRDM2 (also termed GATA-3-binding protein G3B, lysine N-methyltransferase 8, MTB-or MTE-binding protein, PR domain-containing protein 2, retinoblastoma protein-interacting zinc finger protein, or zinc finger protein RIZ) is S-adenosyl-L-methionine-dependent histone methyltransferase that specifically methylates 'Lys-9' of histone H3. It may function as a DNA-binding transcription factor.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1191805951  14 IDGFNEEKSNWLRYVNPAHSAREQNLAACQNGMNIYFYTIKPIPANQELLVWY 66
Cdd:cd19188    66 VDASDPTKGNWLRYVNWARSGEEQNLFPLQINRAIYYKTLKPIAPGEELLCWY 118

PR-SET domain found in PR domain zinc finger protein 15 (PRDM15) and similar proteins; PRDM15 (also termed PR domain-containing protein 15, or zinc finger protein 298 (ZNF298)) may be involved in transcriptional regulation. It plays an essential role as a chromatin factor that modulates the transcription of upstream regulators of WNT and MAPK-ERK signaling to safeguard naive pluripotency.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1191805951   3 KIYSRGELHHFIDGFNEEKSNWLRYVNPAHSAREQNLAACQNGMNIYFYTIKPIPANQELLVWYCRDFAERL 74
Cdd:cd19199    55 KVFEKDGSVVYLDTSNEDDCNWMMFVRPATDVEHQNLTAYQQGEDIYFTTSRDIQPGAELRVWYAAFYAKKM 126

PR-SET domain found in PR domain zinc finger protein 8 (PRDM8) and similar proteins; PRDM8 (also termed PR domain-containing protein 8) may function as histone methyltransferase, preferentially acting on 'Lys-9' of histone H3.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1191805951  15 DGFNEEKSNWLRYVNPAHSAREQNLAA-CQNGMNIYFYTIKPIPANQELLVWYCRDFAERL 74
Cdd:cd19192    71 CNGSSEPSDWLRLVQPARDRHEQNLEAfRKNEGQVYFRTLRRIRKGEELLVWYSDELAELL 131

PR-SET domain found in zinc finger protein ZFPM1, ZFPM2 and similar proteins; ZFPM1 (also termed friend of GATA protein 1, FOG-1, friend of GATA 1, zinc finger protein 89A, or zinc finger protein multitype 1) functions as a transcription regulator that plays an essential role in erythroid and megakaryocytic cell differentiation. ZFPM2 (also termed friend of GATA protein 2, FOG-2, friend of GATA 2, zinc finger protein 89B, or zinc finger protein multitype 2) functions as a transcription regulator that plays a central role in heart morphogenesis and development of coronary vessels from epicardium, by regulating genes that are essential during cardiogenesis.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1191805951  19 EEKSNWLRYVNPAHSAREQNLAACQNGMNIYFYTIKPIPANQELLVWYCRDF 70
Cdd:cd19201    70 EDSGTWLKLVRSADDEDEANLILYFKGGQIWCEVTKDIPPGEELILVLREPL 121

PR-SET domain found in PR domain zinc finger protein 13 (PRDM13) and similar proteins; PRDM13 (also termed PR domain-containing protein 13) may be involved in transcriptional regulation. It mediates the balance of inhibitory and excitatory neurons in somatosensory circuits.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1191805951   7 RGELHHFIDGFNEEKSNWLRYVNPAHSAREQNLAACQN--GMNIYFYTIKPIPANQELLVWY 66
Cdd:cd19197    34 RVRGDYLVDESGSPATEWIGLVRAARNNQEQNLEAIADlpGGQIFYRALRDIQPGEELTVWY 95

PR-SET domain found in PR domain zinc finger protein 16 (PRDM16), MDS1 and EVI1 complex locus protein and similar proteins; PRDM16 (also termed PR domain-containing protein 16, transcription factor MEL1, or MDS1/EVI1-like gene 1) functions as a transcriptional regulator. PRDM16 is preferentially expressed by hematopoietic and neuronal stem cells. It is closely related to paralog of PRDM3 (also termed MDS1 and EVI1 complex locus protein, ecotropic virus integration site 1 protein, EVI-1, myelodysplasia syndrome 1 protein, myelodysplasia syndrome-associated protein 1, or MECOM) which is a nuclear transcription factor essential for the proliferation/maintenance of hematopoietic stem cells (HSCs). PRDM3 and PRDM16 are both directly linked to various aspects of oncogenic transformation.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1191805951   8 GELHHFIDGFNEEKSNWLRYVNPAHSAREQNLAACQNGMNIYFYTIKPIPANQELLV 64
Cdd:cd19200    65 GKVKFWIDASEPGTGNWMKYIRSAPSCEQQNLMACQIDEQIYYKVVRDIQPGEELLL 121

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*.
gi 1191805951 487 HLQKHYLVHTGEKPHECQVCHKRFSS 512
Cdd:pfam13465   1 NLKRHMRTHTGEKPYKCPECGKSFKS 26

FOG: Zn-finger [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191805951 440 NGKIKYECNVCAKTFGQLSNLKVHLRVHSGER-PFKCQTCNKGFTQLAHLQKHY--LVHTGE--KPHEC--QVCHKRFSS 512
Cdd:COG5048   256 SASESPRSSLPTASSQSSSPNESDSSSEKGFSlPIKSKQCNISFSRSSPLTRHLrsVNHSGEslKPFSCpySLCGKLFSR 335

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1191805951 513 TSNLKTHLRLHSGEKPYQCK--VCPAKFTQFVHLKLHKRLHTRERPHK 558
Cdd:COG5048   336 NDALKRHILLHTSISPAKEKllNSSSKFSPLLNNEPPQSLQQYKDLKN 383

Zinc-finger double domain;

                          10        20
                  ....*....|....*....|....*.
gi 1191805951 543 HLKLHKRLHTRERPHKCAHCHKSYIH 568
Cdd:pfam13465   1 NLKRHMRTHTGEKPYKCPECGKSFKS 26

Zinc finger, C2H2 type; The C2H2 zinc finger is the classical zinc finger domain. The two conserved cysteines and histidines co-ordinate a zinc ion. The following pattern describes the zinc finger. #-X-C-X(1-5)-C-X3-#-X5-#-X2-H-X(3-6)-[H/C] Where X can be any amino acid, and numbers in brackets indicate the number of residues. The positions marked # are those that are important for the stable fold of the zinc finger. The final position can be either his or cys. The C2H2 zinc finger is composed of two short beta strands followed by an alpha helix. The amino terminal part of the helix binds the major groove in DNA binding zinc fingers. The accepted consensus binding sequence for Sp1 is usually defined by the asymmetric hexanucleotide core GGGCGG but this sequence does not include, among others, the GAG (=CTC) repeat that constitutes a high-affinity site for Sp1 binding to the wt1 promoter.

                          10        20
                  ....*....|....*....|...
gi 1191805951 501 HECQVCHKRFSSTSNLKTHLRLH 523
Cdd:pfam00096   1 YKCPDCGKSFSRKSNLKRHLRTH 23

Zinc finger, C2H2 type; The C2H2 zinc finger is the classical zinc finger domain. The two conserved cysteines and histidines co-ordinate a zinc ion. The following pattern describes the zinc finger. #-X-C-X(1-5)-C-X3-#-X5-#-X2-H-X(3-6)-[H/C] Where X can be any amino acid, and numbers in brackets indicate the number of residues. The positions marked # are those that are important for the stable fold of the zinc finger. The final position can be either his or cys. The C2H2 zinc finger is composed of two short beta strands followed by an alpha helix. The amino terminal part of the helix binds the major groove in DNA binding zinc fingers. The accepted consensus binding sequence for Sp1 is usually defined by the asymmetric hexanucleotide core GGGCGG but this sequence does not include, among others, the GAG (=CTC) repeat that constitutes a high-affinity site for Sp1 binding to the wt1 promoter.

                          10        20
                  ....*....|....*....|...
gi 1191805951 445 YECNVCAKTFGQLSNLKVHLRVH 467
Cdd:pfam00096   1 YKCPDCGKSFSRKSNLKRHLRTH 23

Zinc finger, C2H2 type; The C2H2 zinc finger is the classical zinc finger domain. The two conserved cysteines and histidines co-ordinate a zinc ion. The following pattern describes the zinc finger. #-X-C-X(1-5)-C-X3-#-X5-#-X2-H-X(3-6)-[H/C] Where X can be any amino acid, and numbers in brackets indicate the number of residues. The positions marked # are those that are important for the stable fold of the zinc finger. The final position can be either his or cys. The C2H2 zinc finger is composed of two short beta strands followed by an alpha helix. The amino terminal part of the helix binds the major groove in DNA binding zinc fingers. The accepted consensus binding sequence for Sp1 is usually defined by the asymmetric hexanucleotide core GGGCGG but this sequence does not include, among others, the GAG (=CTC) repeat that constitutes a high-affinity site for Sp1 binding to the wt1 promoter.

                          10        20
                  ....*....|....*....|...
gi 1191805951 473 FKCQTCNKGFTQLAHLQKHYLVH 495
Cdd:pfam00096   1 YKCPDCGKSFSRKSNLKRHLRTH 23

Putative transcriptional repressor regulating G2/M transition [Transcription / Cell division and chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191805951 493 LVHTGEKPHECQV--CHKRFSSTSNLKTHlRLHSGekpyqckvCPAKFTQFVHLKLHKRLHTRERPHKCAHCHKSYIHLC 570
Cdd:COG5189   342 LKVKDGKPYKCPVegCNKKYKNQNGLKYH-MLHGH--------QNQKLHENPSPEKMNIFSAKDKPYRCEVCDKRYKNLN 412

                  ....*..
gi 1191805951 571 SLKVHLK 577
Cdd:COG5189   413 GLKYHRK 419