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 568930457    1 MWEVYYPNLGWMCIDATDPEKGNWLRYVNWACSGEEQNLFPLEINRAIYYKTLKPIAPGEELLVWYNGEDN 71
Cdd:cd19188    53 MWEIYGPKRGWMCVDASDPTKGNWLRYVNWARSGEEQNLFPLQINRAIYYKTLKPIAPGEELLCWYNGEDN 123

C2H2-type zinc finger; This family contains a number of divergent C2H2 type zinc fingers.

                           10        20
                   ....*....|....*....|....
gi 568930457   404 HPCKYCKKVFGTHTNMRRHQRRVH 427
Cdd:pfam13894    1 FKCPICGKSFSSKKSLKRHLKTHH 24

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568930457    1 MWEVYYPNLGWMCIDATDPEKGNWLRYVNWACSGEEQNLFPLEINRAIYYKTLKPIAPGEELLVWYNGEDN 71
Cdd:cd19188    53 MWEIYGPKRGWMCVDASDPTKGNWLRYVNWARSGEEQNLFPLQINRAIYYKTLKPIAPGEELLCWYNGEDN 123

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 568930457     5 YYPNLGWMCIDATDPEKGNWLRYVNWACsgeEQN----LFPLEINRAIYYKTLKPIAPGEELLVWYN 67
Cdd:pfam00856   52 TLDEDSEYCIDARALYYGNWARFINHSC---DPNcevrVVYVNGGPRIVIFALRDIKPGEELTIDYG 115

C2H2-type zinc finger; This family contains a number of divergent C2H2 type zinc fingers.

                           10        20
                   ....*....|....*....|....
gi 568930457   404 HPCKYCKKVFGTHTNMRRHQRRVH 427
Cdd:pfam13894    1 FKCPICGKSFSSKKSLKRHLKTHH 24

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568930457    1 MWEVYYPNLGWMCIDATDPEKGNWLRYVNWACSGEEQNLFPLEINRAIYYKTLKPIAPGEELLVWYNGEDN 71
Cdd:cd19188    53 MWEIYGPKRGWMCVDASDPTKGNWLRYVNWARSGEEQNLFPLQINRAIYYKTLKPIAPGEELLCWYNGEDN 123

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568930457    2 WEVYYPNLGWMCIDATDPEKGNWLRYVNWACSGEEQNLFPLEINRAIYYKTLKPIAPGEELLVWY 66
Cdd:cd19187    56 WRIYSNGEFYHYIDGFDPSKSNWMRYVNPAHSLQEQNLVACQIGMNIYFYTVKPIPPNQELLVWY 120

PR-SET domain found in PRDM (PRDI-BF1 and RIZ homology domain) family of proteins; PRDM family of proteins is defined based on the conserved N-terminal PR domain, which is closely related to the Su(var)3-9, enhancer of zeste, and trithorax (SET) domains of histone methyltransferases, and is specifically called PR-SET domain. The family consists of 17 members in primates. PRDMs play diverse roles in cell-cycle regulation, differentiation, and meiotic recombination. The family also contains zinc finger protein ZFPM1 and ZFPM2. 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
                  ....*....|....*....|....*....|....*....|....*
gi 568930457   23 NWLRYVNWACSGEEQNLFPLEINRAIYYKTLKPIAPGEELLVWYN 67
Cdd:cd10534    39 NWMRFVRPARNEEEQNLVAYQHGGQIYFRTTRDIPPGEELLVWYS 83

PR-SET domain found in PR domain zinc finger protein 16 (PRDM16) and similar proteins; PRDM16, also termed PR domain-containing protein 16, or transcription factor MEL1, or MDS1/EVI1-like gene 1, functions as a transcriptional regulator. PRDM16 is preferentially expressed by hematopoietic and neuronal stem cells and is closely related to paralog of PRDM3, both of which are directly linked to various aspects of oncogenic transformation.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568930457   13 CIDATDPEKGNWLRYVNWACSGEEQNLFPLEINRAIYYKTLKPIAPGEELLVW 65
Cdd:cd19213    97 CVDAGQAGAGSWLKYIRVACSCDEQNLTACQINEQIYYKVIKDIEPGEELLVY 149

PR-SET domain found in PR domain zinc finger protein 6 (PRDM6) and similar proteins; PRDM6 (also termed PR domain-containing protein 6) is a putative histone-lysine N-methyltransferase that acts as a transcriptional repressor of smooth muscle gene expression. It may specifically methylate 'Lys-20' of histone H4 when associated with other proteins and in vitro.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568930457    1 MWEVYYPNlGWMC--IDATDPEKGNWLRYVNWACSGEEQNLFPLEINRAIYYKTLKPIAPGEELLVWYN 67
Cdd:cd19191    54 LWEIYDQE-GTLQhfIDGGDPSKSSWMRYIRCARHCGEQNLTVVQYRGCIFYRACRDIPRGTELLVWYD 121

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 568930457    1 MWEVYYP-NLGWMcIDATdPEKGNWLRYVNWACSGEEQNLFPLEINRAIYYKTLKPIAPGEELLVWY 66
Cdd:cd19198    56 MWEIFEDgKLSHF-IDGR-GSTGNWMSYVNCARYAEEQNLIAIQCQGQIFYESCKEILQGQELLVWY 120

PR-SET domain found in PR domain zinc finger protein 4 (PRDM4) and similar proteins; PRDM4 (also termed PR domain-containing protein 4, or PFM1) may function as a transcription factor involved in cell differentiation.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568930457    1 MWEVYYPNLGWMCIDATDPEKGNWLRYVNWACSGEEQNLFPLEINRAIYYKTLKPIAPGEELLVWY 66
Cdd:cd19189    59 IWKIYHNDVLEFCIITTDENECNWMMFVRKARTREEQNLVAYPHDGKIYFCTSRDIPPDQELLFYY 124

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
                  ....*....|....*....|....*....|....*....|....*...
gi 568930457   20 EKGNWLRYVNWACSGEEQNLFPLEINRAIYYKTLKPIAPGEELLVWYN 67
Cdd:cd19201    71 DSGTWLKLVRSADDEDEANLILYFKGGQIWCEVTKDIPPGEELILVLR 118

PR-SET domain found in PR domain zinc finger protein 11 (PRDM11) and similar proteins; PRDM11 (also termed PR domain-containing protein 11) may be involved in transcription regulation.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568930457    2 WEVYYPNLGWMCIDATDPEKGNWLRYVNWACSGEEQNLFPLEINRAIYYKTLKPIAPGEELLVWYNGE 69
Cdd:cd19195    53 WLIVDKNNRYKSIDGSDETKANWMRYVVISREEREQNLLAFQHSEQIYFRACRDIRPGEKLRVWYSED 120

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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568930457   15 DATDPEKGNWLRYVNWACSGEEQNL-FPLEINRAIYYKTLKPIAPGEELLVWYNGE 69
Cdd:cd19192    71 CNGSSEPSDWLRLVQPARDRHEQNLeAFRKNEGQVYFRTLRRIRKGEELLVWYSDE 126

PR-SET domain found in PR domain zinc finger protein 5 (PRDM5) and similar proteins; PRDM5 (also termed PR domain-containing protein 5) is a sequence-specific DNA-binding transcription factor that represses transcription at least in part by recruitment of the histone methyltransferase EHMT2/G9A and histone deacetylases such as HDAC1.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568930457    1 MWEVYYPNLGWMCI-DATDPEKGNWLRYVNWACSGEEQNLFPLEINRAIYYKTLKPIAPGEELLVWYNGED 70
Cdd:cd19190    56 MWEVRGSKGEVLYIlDASNPRHSNWLRFVHEAPSQEQKNLAAIQEGENIFYLAVDDIETDTELLIGYLDSD 126

SET domain found in Schizossacharomyces pombe Set7 and similar proteins; Schizosaccharomyces pombe Set7 is a novel histone-lysine N-methyltransferase. The family also includes a viral histone H3 lysine 27 methyltransferase from Paramecium bursaria Chlorella virus 1 (PBCV-1).

                          10        20
                  ....*....|....*....|....*
gi 568930457   45 NRAIYYKTLKPIAPGEELLVWYNGE 69
Cdd:cd10540    85 NQTIVFYALRDIEAGEELTINYGDD 109

C2H2-type zinc finger; This family contains a number of divergent C2H2 type zinc fingers.

                           10        20
                   ....*....|....*....|...
gi 568930457   283 FPCQHCERKFATKQGLERHMHIH 305
Cdd:pfam13894    1 FKCPICGKSFSSKKSLKRHLKTH 23