Extended PHD finger found in Arabidopsis thaliana ATX1, -2, and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This subfamily includes the ePHD finger of A. thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like proteins ATX1, -2, and similar proteins. ATX1 and -2 are sister paralogs originating from a segmental chromosomal duplication; they are plant counterparts of the Drosophila melanogaster trithorax (TRX) and mammalian mixed-lineage leukemia (MLL1) proteins. ATX1 (also known as protein SET domain group 27, or trithorax-homolog protein 1/TRX-homolog protein 1), is a methyltransferase that trimethylates histone H3 at lysine 4 (H3K4me3). It also acts as a histone modifier and as a positive effector of gene expression. ATX1 regulates transcription from diverse classes of genes implicated in biotic and abiotic stress responses. It is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways. ATX2 (also known as protein SET domain group 30, or trithorax-homolog protein 2/TRX-homolog protein 2), is involved in dimethylating histone H3 at lysine 4 (H3K4me2). ATX1 and ATX2 are multi-domain proteins that consist of an N-terminal PWWP domain, FYRN- and FYRC (DAST, domain associated with SET in trithorax) domains, a canonical PHD finger, this non-canonical ePHD finger, and a C-terminal SET domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  685 CCLCPVVGGAMKPTTDGRWAHLACAIWIPETCLLDVKKMEPIDGVKKVSKDRWKLLCSICGVSYGACIQCSNNTCRVAYH 764
Cdd:cd15662     1 CCLCPVVGGALKPTTDGRWAHLACAIWIPETCLLDVKTMEPVDGINAISKERWELSCTICKQRYGACIQCSNNSCRVAYH 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 240254018  765 PLCARAAGLCVELADEDRlfllsmdDDEADQCIRLLSFCKRH 806
Cdd:cd15662    81 PLCARAAGLCMEVADEGG-------EDPGDQGLRLLSYCPRH 115

PHD finger found in Arabidopsis thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like protein ATX1, ATX2, and similar proteins; The family includes A. thaliana ATX1 and ATX2, both of which are sister paralogs originating from a segmental chromosomal duplication. They are plant counterparts of the Drosophila melanogaster trithorax (TRX) and mammalian mixed-lineage leukemia (MLL1) proteins. ATX1, also termed protein SET domain group 27, or trithorax-homolog protein 1 (TRX-homolog protein 1), is a methyltransferase that trimethylates histone H3 at lysine 4 (H3K4me3). It also acts as a histone modifier and as a positive effector of gene expression. ATX1regulates transcription from diverse classes of genes implicated in biotic and abiotic stress responses. It is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways. ATX2, also termed protein SET domain group 30, or trithorax-homolog protein 2 (TRX-homolog protein 2), is involved in dimethylating histone H3 at lysine 4 (H3K4me2). Both ATX1 and ATX2 are multi-domain containing proteins that consist of an N-terminal PWWP domain, FYRN- and FYRC (DAST, domain associated with SET in trithorax) domains, a canonical Cys4HisCys3 plant homeodomain (PHD) finger, a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, and a C-terminal SET domain; this model corresponds to the Cys4HisCys3 canonical PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 240254018  628 KCNVCHMDEEYENNLFLQCDKCRMMVHTRCYGQLEPHNGILWLCNLC 674
Cdd:cd15494     1 KCSVCGEDEEYEDNLLLQCDKCRMMVHMRCYGVLEPPPGALWLCNLC 47

Tudor-like Agenet domain found in Arabidopsis thaliana proteins EMSY-LIKE 1-4 (AtEML1-4) and similar proteins; This family includes Arabidopsis thaliana proteins EMSY-LIKE 1-4 (AtEML1-4), histone-lysine N-methyltransferase trithorax-like proteins ATX1-2 (AtATX1-2), histone-lysine N-methyltransferase ASHH3, DNA mismatch repair protein MSH6, and similar proteins. EMSY-like proteins contain an EMSY N-terminal domain, a central Tudor-like Agenet domain, and a C-terminal coiled-coil motif. AtEML1, AtEML2, and likely AtEML4, contribute to RPP7-mediated immunity. Besides this, AtEML1 and AtEML2 participate in a second EDM2-dependent function and affect floral transition. ATX-like proteins are plant counterparts of the Drosophila melanogaster trithorax (TRX) and mammalian mixed-lineage leukemia (MLL1) proteins. ATX1, also called protein SET domain group 27, or trithorax-homolog protein 1 (TRX-homolog protein 1), is a methyltransferase that trimethylates histone H3 at lysine 4 (H3K4me3). It also acts as a histone modifier and as a positive effector of gene expression. ATX1regulates transcription from diverse classes of genes implicated in biotic and abiotic stress responses. It is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways. ATX2, also called protein SET domain group 30, or trithorax-homolog protein 2 (TRX-homolog protein 2), is involved in dimethylating histone H3 at lysine 4 (H3K4me2). Both ATX1 and ATX2 are multi-domain proteins that consist of an N-terminal Tudor-like Agenet domain, a PWWP domain, FYRN- and FYRC (DAST, domain associated with SET in trithorax) domains, a canonical plant homeodomain (PHD) domain, a non-canonical extended PHD (ePHD) domain, and a C-terminal SET domain. ASHR3, also called protein SET DOMAIN GROUP 7, functions as a histone-lysine N-methyltransferase (EC 2.1.1.43). It contains a SET domain and a Tudor-like Agenet domain. AtMSH6, also called MutS protein homolog 6, is a component of the post-replicative DNA mismatch repair system (MMR). It forms a heterodimer with MutS alpha (MSH2-MSH6 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. AtMSH6 contains a Tudor-like Agenet domain and a MutS domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 240254018  221 IGLQCKVFWPLDAVWYPGSIVGYNVETKHHIVKYGDGDGEELALRREKIKF 271
Cdd:cd20404     1 VGRRVRVYWPEDGTWYEGVVVDYDPSTGKHRVEYDDGDEEEVDLWRELVEW 51

Extended PHD finger found in Arabidopsis thaliana ATX1, -2, and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This subfamily includes the ePHD finger of A. thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like proteins ATX1, -2, and similar proteins. ATX1 and -2 are sister paralogs originating from a segmental chromosomal duplication; they are plant counterparts of the Drosophila melanogaster trithorax (TRX) and mammalian mixed-lineage leukemia (MLL1) proteins. ATX1 (also known as protein SET domain group 27, or trithorax-homolog protein 1/TRX-homolog protein 1), is a methyltransferase that trimethylates histone H3 at lysine 4 (H3K4me3). It also acts as a histone modifier and as a positive effector of gene expression. ATX1 regulates transcription from diverse classes of genes implicated in biotic and abiotic stress responses. It is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways. ATX2 (also known as protein SET domain group 30, or trithorax-homolog protein 2/TRX-homolog protein 2), is involved in dimethylating histone H3 at lysine 4 (H3K4me2). ATX1 and ATX2 are multi-domain proteins that consist of an N-terminal PWWP domain, FYRN- and FYRC (DAST, domain associated with SET in trithorax) domains, a canonical PHD finger, this non-canonical ePHD finger, and a C-terminal SET domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  685 CCLCPVVGGAMKPTTDGRWAHLACAIWIPETCLLDVKKMEPIDGVKKVSKDRWKLLCSICGVSYGACIQCSNNTCRVAYH 764
Cdd:cd15662     1 CCLCPVVGGALKPTTDGRWAHLACAIWIPETCLLDVKTMEPVDGINAISKERWELSCTICKQRYGACIQCSNNSCRVAYH 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 240254018  765 PLCARAAGLCVELADEDRlfllsmdDDEADQCIRLLSFCKRH 806
Cdd:cd15662    81 PLCARAAGLCMEVADEGG-------EDPGDQGLRLLSYCPRH 115

PHD-zinc-finger like domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018   683 PRCCLCPVVGGAMKPTTDGRWAHLACAIWIPETCLLDVKKMEPIDgVKKVSKDRWKLLCSICGVSYGACIQCSNNTCRVA 762
Cdd:pfam13832    1 VRCCLCPLRGGALKQTSDGRWVHVLCAIFVPEVRFGNVATMEPID-VSRIPPERWKLKCVFCKKRSGACIQCSKGRCTTA 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 240254018   763 YHPLCARAAGLCVELADEDrlfllsmdddeadqCIRLLSFCKRH 806
Cdd:pfam13832   80 FHVTCAQAAGVYMEPEDWP--------------NVVVIAYCQKH 109

PHD zinc finger-containing protein [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  616 YRPVRVEWKDLDKCNVCHMDEEYENNLFLQCDKCRMMVHTRCYGQLEPHNGiLWLCNLCRPVALDIppRCCL-CPVVGGA 694
Cdd:COG5141   183 VEPIEPSDEFDDICTKCTSTHNENSNAIVFCDGCEICVHQSCYGIQFLPEG-FWLCRKCIYGEYQI--RCCSfCPSSDGA 259

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  695 MKPTTDGRWAHLACAIWIPETCLLDVKKMEPIDGVKKVSKDRWKLLCSICGVSYGACIQCSNNTCRVAYHPLCARAAGLc 774
Cdd:COG5141   260 FKQTSDGRWGHVICAMFNPELSFGHLLSKDPIDNIASVSSSRWKLGCLICKEFGGTCIQCSYFNCTRAYHVTCARRAGY- 338

                         170       180       190
                  ....*....|....*....|....*....|..
gi 240254018  775 veladedrLFLLSMDDDEADQCIRLLSFCKRH 806
Cdd:COG5141   339 --------FDLNIYSHNGISYCIDHEPLCRKH 362

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 240254018   930 GFGIFAKLPHRAGDMVIEYTGE-LVRPPIADKREHLIY--NSMVGAGTYMFRID--NERVIDATRT--GSIAHLINHSCE 1002
Cdd:pfam00856    1 GRGLFATEDIPKGEFIGEYVEVlLITKEEADKRELLYYdkLELRLWGPYLFTLDedSEYCIDARALyyGNWARFINHSCD 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 240254018  1003 PNCYSRVISVNGDEHIIIFAKRDVAKWEELTYDY 1036
Cdd:pfam00856   81 PNCEVRVVYVNGGPRIVIFALRDIKPGEELTIDY 114

FY-rich domain, C-terminal region; is sometimes closely juxtaposed with the N-terminal region (FYRN), but sometimes is far distant. Unknown function, but occurs frequently in chromatin-associated proteins.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018    524 VFRVTTNS--GEQFKGDTPSACWNKIYNRIKKIQIASDNPDVLGEglHESGTDMFGFSNPEVDKLIQGLLQSRPPSKVSQ 601
Cdd:smart00542    1 LFRVEIESdpGEVFKGESPEKCWEMVLERVQEARIAADLLQLLPE--GVSGEEMFGLSSPAVVKLIEALPGVHQCTNYWF 78

                    ....*....
gi 240254018    602 RkYSSGKYQ 610
Cdd:smart00542   79 R-YHRSPLL 86

Tudor-like Agenet domain found in Arabidopsis thaliana proteins EMSY-LIKE 1-4 (AtEML1-4) and similar proteins; This family includes Arabidopsis thaliana proteins EMSY-LIKE 1-4 (AtEML1-4), histone-lysine N-methyltransferase trithorax-like proteins ATX1-2 (AtATX1-2), histone-lysine N-methyltransferase ASHH3, DNA mismatch repair protein MSH6, and similar proteins. EMSY-like proteins contain an EMSY N-terminal domain, a central Tudor-like Agenet domain, and a C-terminal coiled-coil motif. AtEML1, AtEML2, and likely AtEML4, contribute to RPP7-mediated immunity. Besides this, AtEML1 and AtEML2 participate in a second EDM2-dependent function and affect floral transition. ATX-like proteins are plant counterparts of the Drosophila melanogaster trithorax (TRX) and mammalian mixed-lineage leukemia (MLL1) proteins. ATX1, also called protein SET domain group 27, or trithorax-homolog protein 1 (TRX-homolog protein 1), is a methyltransferase that trimethylates histone H3 at lysine 4 (H3K4me3). It also acts as a histone modifier and as a positive effector of gene expression. ATX1regulates transcription from diverse classes of genes implicated in biotic and abiotic stress responses. It is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways. ATX2, also called protein SET domain group 30, or trithorax-homolog protein 2 (TRX-homolog protein 2), is involved in dimethylating histone H3 at lysine 4 (H3K4me2). Both ATX1 and ATX2 are multi-domain proteins that consist of an N-terminal Tudor-like Agenet domain, a PWWP domain, FYRN- and FYRC (DAST, domain associated with SET in trithorax) domains, a canonical plant homeodomain (PHD) domain, a non-canonical extended PHD (ePHD) domain, and a C-terminal SET domain. ASHR3, also called protein SET DOMAIN GROUP 7, functions as a histone-lysine N-methyltransferase (EC 2.1.1.43). It contains a SET domain and a Tudor-like Agenet domain. AtMSH6, also called MutS protein homolog 6, is a component of the post-replicative DNA mismatch repair system (MMR). It forms a heterodimer with MutS alpha (MSH2-MSH6 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. AtMSH6 contains a Tudor-like Agenet domain and a MutS domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 240254018  221 IGLQCKVFWPLDAVWYPGSIVGYNVETKHHIVKYGDGDGEELALRREKIKF 271
Cdd:cd20404     1 VGRRVRVYWPEDGTWYEGVVVDYDPSTGKHRVEYDDGDEEEVDLWRELVEW 51

F/Y rich C-terminus; This region is normally found in the trithorax/ALL1 family proteins. It is similar to SMART:SM00542.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 240254018   522 RPVFRVT--TNSGEQFKGDTPSACWNKIYNRIKKIQIASDNPDVLGEGLheSGTDMFGFSNPEVDKLIQGL 590
Cdd:pfam05965    1 GPLFRVTveEDPDESFEGSSPTKCWSMVLERVQELRREAGLKLKLPESI--SGEDMFGLTHPAVVRLIESL 69

domain with conserved PWWP motif; conservation of Pro-Trp-Trp-Pro residues

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 240254018    313 FEPRDIIWAKLTGHAMWPAIIVDE----SVIVKRKGLNNKisggrsVLVQFFGTHDFARIQVK 371
Cdd:smart00293    1 FKPGDLVWAKMKGFPWWPALVISPkmtpDNIMKRKSDENL------YPVLFFGDKDTAWIPSS 57

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 240254018    629 CNVCHmdEEYENNLFLQCDKCRMMVHTRCYG---QLEPHNGIlWLCNLC 674
Cdd:smart00249    2 CSVCG--KPDDGGELLQCDGCDRWYHQTCLGpplLEEEPDGK-WYCPKC 47

Extended PHD finger found in Arabidopsis thaliana ATX1, -2, and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This subfamily includes the ePHD finger of A. thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like proteins ATX1, -2, and similar proteins. ATX1 and -2 are sister paralogs originating from a segmental chromosomal duplication; they are plant counterparts of the Drosophila melanogaster trithorax (TRX) and mammalian mixed-lineage leukemia (MLL1) proteins. ATX1 (also known as protein SET domain group 27, or trithorax-homolog protein 1/TRX-homolog protein 1), is a methyltransferase that trimethylates histone H3 at lysine 4 (H3K4me3). It also acts as a histone modifier and as a positive effector of gene expression. ATX1 regulates transcription from diverse classes of genes implicated in biotic and abiotic stress responses. It is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways. ATX2 (also known as protein SET domain group 30, or trithorax-homolog protein 2/TRX-homolog protein 2), is involved in dimethylating histone H3 at lysine 4 (H3K4me2). ATX1 and ATX2 are multi-domain proteins that consist of an N-terminal PWWP domain, FYRN- and FYRC (DAST, domain associated with SET in trithorax) domains, a canonical PHD finger, this non-canonical ePHD finger, and a C-terminal SET domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  685 CCLCPVVGGAMKPTTDGRWAHLACAIWIPETCLLDVKKMEPIDGVKKVSKDRWKLLCSICGVSYGACIQCSNNTCRVAYH 764
Cdd:cd15662     1 CCLCPVVGGALKPTTDGRWAHLACAIWIPETCLLDVKTMEPVDGINAISKERWELSCTICKQRYGACIQCSNNSCRVAYH 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 240254018  765 PLCARAAGLCVELADEDRlfllsmdDDEADQCIRLLSFCKRH 806
Cdd:cd15662    81 PLCARAAGLCMEVADEGG-------EDPGDQGLRLLSYCPRH 115

SET domain (including post-SET domain) found in SET domain-containing protein 1 (SETD1) and similar proteins; This family includes SET domain-containing protein 1A (SETD1A) and SET domain-containing protein 1B (SETD1B). These proteins are histone-lysine N-methyltransferases that specifically methylate 'Lys-4' of histone H3 (H3K4me) when part of the SET1 histone methyltransferase (HMT) complex, but not if the neighboring 'Lys-9' residue is already methylated.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  918 RKRLAFGKSGIHGFGIFAKLPHRAGDMVIEYTGELVRPPIADKREHLiYNSMVGAGTYMFRIDNERVIDATRTGSIAHLI 997
Cdd:cd19169    12 KKQLKFAKSRIHDWGLFALEPIAADEMVIEYVGQVIRQSVADEREKR-YEAIGIGSSYLFRVDDDTIIDATKCGNLARFI 90

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 240254018  998 NHSCEPNCYSRVISVNGDEHIIIFAKRDVAKWEELTYDYRFFSIDERLACYCGFPRCR 1055
Cdd:cd19169    91 NHSCNPNCYAKIITVESQKKIVIYSKRPIAVNEEITYDYKFPIEDEKIPCLCGAPQCR 148

PWWP domain found in Arabidopsis thaliana histone-lysine N-methyltransferase trithorax-like proteins ATX1, ATX2, and similar proteins; This family includes A. thaliana ATX1 and ATX2, which are sister paralogs originating from a segmental chromosomal duplication. They are plant counterparts of the Drosophila melanogaster trithorax (TRX) and mammalian mixed-lineage leukemia (MLL1) proteins. ATX1, also called protein SET domain group 27, or trithorax-homolog protein 1 (TRX-homolog protein 1), is a methyltransferase that trimethylates histone H3 at lysine 4 (H3K4me3). It also acts as a histone modifier and as a positive effector of gene expression. ATX1 regulates transcription from diverse classes of genes implicated in biotic and abiotic stress responses. It is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways. ATX2, also called protein SET domain group 30, or trithorax-homolog protein 2 (TRX-homolog protein 2), is involved in dimethylating histone H3 at lysine 4 (H3K4me2). Both ATX1 and ATX2 are multi-domain containing proteins that consist of an N-terminal PWWP domain, FYRN- and FYRC (DAST, domain associated with SET in trithorax) domains, a canonical plant homeodomain (PHD) domain, a non-canonical extended PHD (ePHD) domain, and a C-terminal SET domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  314 EPRDIIWAKLTGHAMWPAIIVDESVIVKRKGLNNKISGGRSVLVQFFGTHDFARIQVKQAVSFLKGLLSRSPLKCKQPRF 393
Cdd:cd20142     1 SPGDVVWAKVKGYPMWPALVIDEEHAERCGLEANRPGKKGTVPVQFFGTYEVARLNPKKVVGFSKGLDLKYHSKCKAPVF 80

                          90
                  ....*....|....*..
gi 240254018  394 EEAMEEAKMYLKEYKLP 410
Cdd:cd20142    81 RQALEEAERYLKEGKLP 97

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 240254018  906 MAEKYTFMKETYRKRLAFGKSGIHGFGIFAKLPHRAGDMVIEYTGELVRPPIADKREHliYNSMVGAGTYMFRIDNERVI 985
Cdd:cd19206     1 MPMRFRHLKKTSKEAVGVYRSPIHGRGLFCKRNIDAGEMVIEYSGNVIRSILTDKREK--YYDSKGIGCYMFRIDDSEVV 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 240254018  986 DATRTGSIAHLINHSCEPNCYSRVISVNGDEHIIIFAKRDVAKWEELTYDYRfFSIDE---RLACYCGFPRCRGVVN 1059
Cdd:cd19206    79 DATMHGNAARFINHSCEPNCYSRVINIDGQKHIVIFAMRKIYRGEELTYDYK-FPIEDasnKLPCNCGAKKCRKFLN 154

SET domain (including post-SET domain) found in SET domain-containing protein 1A (SETD1A) and similar proteins; SETD1A (EC2.1.1.43), also termed lysine N-methyltransferase 2F, or Set1/Ash2 histone methyltransferase complex subunit SET1, is a histone-lysine N-methyltransferase that specifically methylates 'Lys-4' of histone H3 (H3K4me), when part of the SET1 histone methyltransferase (HMT) complex, but not if the neighboring 'Lys-9' residue is already methylated. Human SET domain containing protein 1A (hSETD1A) expression occurs at a high rate in hepatocellular carcinoma patients and controls tumor metastasis in breast cancer by activating MMP expression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  918 RKRLAFGKSGIHGFGIFAKLPHRAGDMVIEYTGELVRPPIADKREHLIYNSMVGAgTYMFRIDNERVIDATRTGSIAHLI 997
Cdd:cd19204    13 KKKLRFGRSRIHEWGLFAMEPIAADEMVIEYVGQNIRQVVADMREKRYVQEGIGS-SYLFRVDHDTIIDATKCGNLARFI 91

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 240254018  998 NHSCEPNCYSRVISVNGDEHIIIFAKRDVAKWEELTYDYRFFSIDERLACYCGFPRCRGVVN 1059
Cdd:cd19204    92 NHCCTPNCYAKVITIESQKKIVIYSKQPIGVNEEITYDYKFPIEDNKIPCLCGTENCRGTLN 153

SET domain found in enhancer of zeste homolog 1 (EZH1), zeste homolog 2 (EZH2) and similar proteins; The family includes EZH1 and EZH2. EZH1 (EC 2.1.1.43; also termed ENX-2, or histone-lysine N-methyltransferase EZH1) is a catalytic subunit of the PRC2/EED-EZH1 complex, which methylates 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. EZH2 (EC 2.1.1.43; also termed lysine N-methyltransferase 6, ENX-1, or histone-lysine N-methyltransferase EZH2) is a catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Both, EZH1 and EZH2, can mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  919 KRLAFGKSGIHGFGIFAKLPHRAGDMVIEYTGELVRPPIADKREHLIYNSMVgagTYMFRIDNERVIDATRTGSIAHLIN 998
Cdd:cd10519     1 KRLLLGKSDVAGWGLFLKEPIKKDEFIGEYTGELISQDEADRRGKIYDKYNS---SYLFNLNDQFVVDATRKGNKIRFAN 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 240254018  999 HSCEPNCYSRVISVNGDEHIIIFAKRDVAKWEELTYDYRF 1038
Cdd:cd10519    78 HSSNPNCYAKVMMVNGDHRIGIFAKRDIEAGEELFFDYGY 117

SET domain (including post-SET domain) found in SET domain-containing protein 1B (SETD1B) and similar proteins; SETD1B (EC2.1.1.43), also termed lysine N-methyltransferase 2G, is a histone-lysine N-methyltransferase that specifically methylates 'Lys-4' of histone H3 (H3K4me) when part of the SET1 histone methyltransferase (HMT) complex, but not if the neighboring 'Lys-9' residue is already methylated. Loss of SETD1B occurs in up to half the gastric and colorectal cancers, most commonly via SETD1B mutations, while de novo variants in SETD1B are associated with intellectual disability, epilepsy and autism.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  918 RKRLAFGKSGIHGFGIFAKLPHRAGDMVIEYTGELVRPPIADKREHLIYNSMVGAgTYMFRIDNERVIDATRTGSIAHLI 997
Cdd:cd19205    13 KKKLKFCKSHIHDWGLFAMEPIAADEMVIEYVGQNIRQVIADMREKRYEDEGIGS-SYMFRVDHDTIIDATKCGNFARFI 91

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 240254018  998 NHSCEPNCYSRVISVNGDEHIIIFAKRDVAKWEELTYDYRFFSIDERLACYCGFPRCRGVVN 1059
Cdd:cd19205    92 NHSCNPNCYAKVITVESQKKIVIYSKQHINVNEEITYDYKFPIEDVKIPCLCGSENCRGTLN 153

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  918 RKRLAFGKSGIHGFGIFAKLPHRAGDMVIEYTGELVRPPIADKREHliynSMVGAGTYMFRIDNERVIDATRTGSIAHLI 997
Cdd:COG2940     5 HPRIEVRPSPIHGRGVFATRDIPKGTLIGEYPGEVITWAEAERREP----HKEPLHTYLFELDDDGVIDGALGGNPARFI 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  998 NHSCEPNCYSRVIsvngDEHIIIFAKRDVAKWEELTYDYRFFSIDERLACYCgfPRCRGV 1057
Cdd:COG2940    81 NHSCDPNCEADEE----DGRIFIVALRDIAAGEELTYDYGLDYDEEEYPCRC--PNCRGT 134

Extended PHD finger found in protein Jade-1, Jade-2, Jade-3 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Jade-1 (PHF17), Jade-2 (PHF15), and Jade-3 (PHF16); each of these proteins is required for ING4 and ING5 to associate with histone acetyltransferase (HAT) HBO1 and EAF6 to form a HBO1 complex that has a histone H4-specific acetyltransferase activity, has reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. This family also contains Drosophila melanogaster PHD finger protein rhinoceros (RNO). It is a novel plant homeodomain (PHD)-containing nuclear protein that may function as a transcription factor that antagonizes Ras signaling by regulating transcription of key EGFR/Ras pathway regulators in the Drosophila eye. All Jade proteins contain a canonical PHD finger followed by this non-canonical ePHD finger, both of which are zinc-binding motifs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  685 CCLCPVVGGAMKPTTDGR-WAHLACAIWIPETCLLDVKKMEPIDGVKKVSKDRWKLLCSICGVSYGACIQCSNNTCRVAY 763
Cdd:cd15671     1 CVLCPKKGGAMKSTKSGTkWVHVSCALWIPEVSIGCPEKMEPITKISHIPMSRWALVCVLCKEKTGACIQCSVKSCKTAF 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 240254018  764 HPLCARAAGLcveladEDRLFLLSMDDDeadqcIRLLSFCKRH 806
Cdd:cd15671    81 HVTCAFQHGL------EMKTILEDEDDE-----VKFKSYCPKH 112

Extended plant homeodomain (PHD) finger, characterized by Cys2HisCys5HisCys2His; PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. The extended PHD finger is characterized as Cys2HisCys5HisCys2His, which has 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  685 CCLCPVVGGAMK------PTTDGRWAHLACAIWIPETCLLDVKKMEpIDGVKKVSKDRWKLLCSICGVSYGACIQCSNNT 758
Cdd:cd15571     1 CALCPRSGGALKgggalkTTSDGLWVHVVCALWSPEVYFDDGTLLE-VEGVSKIPKRRKKLKCSICGKRGGACIQCSYPG 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 240254018  759 CRVAYHPLCARAAGLCVELADEDRLFLLsmdddeadqcirllsFCKRH 806
Cdd:cd15571    80 CPRSFHVSCAIRAGCLFEFEDGPGNFVV---------------YCPKH 112

SET domain (including post-SET domain) found in histone-lysine N-methyltransferase 2C (KMT2C) and similar proteins; KMT2C (EC2.1.1.43; also termed lysine N-methyltransferase 2C, homologous to ALR protein (HALR) myeloid/lymphoid, or mixed-lineage leukemia protein 3 (MLL3)), acts as a histone methyltransferase that methylates 'Lys-4' of histone H3 (H3K4me) and may be involved in leukemogenesis and developmental disorder. KMT2C is a catalytic subunit of MLL2/3 complex, a coactivator complex of nuclear receptors, involved in transcriptional coactivation. Overexpression of KMT2C is associated with estrogen receptor-positive breast cancer; KMT2C mediates the estrogen dependence of breast cancer through regulation of estrogen receptor alpha (ERalpha) enhancer function. KMT2C is frequently mutated in certain populations with diffuse-type gastric adenocarcinomas (DGA); its loss promotes epithelial-to-mesenchymal transition (EMT) and is associated with worse overall survival.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  905 SMAEKYTFMKETYRKRLAFGKSGIHGFGIFAKLPHRAGDMVIEYTGELVRPPIADKREHLiYNSMvGAGTYMFRIDNERV 984
Cdd:cd19208     1 SKSSQYRKMKTEWKSNVYLARSRIQGLGLYAARDIEKHTMVIEYIGTIIRNEVANRKEKL-YESQ-NRGVYMFRIDNDHV 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 240254018  985 IDATRTGSIAHLINHSCEPNCYSRVISVNGDEHIIIFAKRDVAKWEELTYDYRF-FSIDE-RLACYCGFPRCR 1055
Cdd:cd19208    79 IDATLTGGPARYINHSCAPNCVAEVVTFEKGHKIIISSSRRIQKGEELCYDYKFdFEDDQhKIPCHCGAVNCR 151

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 240254018  905 SMAEKYTFMKETYRKRLAFGKSGIHGFGIFAKLPHRAGDMVIEYTGELVRPPIADKREHlIYNSMvGAGTYMFRIDNERV 984
Cdd:cd19209     2 SKSSQYRRLKTEWKNNVYLARSRIQGLGLYAAKDLEKHTMVIEYIGTIIRNEVANRREK-IYEEQ-NRGIYMFRINNEHV 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 240254018  985 IDATRTGSIAHLINHSCEPNCYSRVISVNGDEHIIIFAKRDVAKWEELTYDYRF-FSIDE-RLACYCGFPRCR 1055
Cdd:cd19209    80 IDATLTGGPARYINHSCAPNCVAEVVTFDKEDKIIIISSRRIPKGEELTYDYQFdFEDDQhKIPCHCGAWNCR 152

Extended PHD finger found in bromodomain and PHD finger-containing protein 3 (BRPF3) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of BRPF3. BRF3 is a homolog of BRPF1 and BRPF2. It is a scaffold protein that forms a novel monocytic leukemic zinc finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complex with other regulatory subunits. BRPF3 contains a plant homeodomain (PHD) finger followed by this non-canonical ePHD finger, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  685 CCLCPVVGGAMKPTTDGRWAHLACAIWIPETCLLDVKKMEPIDGVKKVSKDRWKLLCSICGVS-YGACIQCSNNTCRVAY 763
Cdd:cd15703     1 CVLCPNKGGAFKQTSDGRWAHVVCAIWIPEVCFANTVFLEPVEGVNNIPPARWKLTCYLCKQKgRGAAIQCHKVNCYTAF 80

                          90
                  ....*....|
gi 240254018  764 HPLCARAAGL 773
Cdd:cd15703    81 HVTCAQRAGL 90

Extended PHD finger found in bromodomain and PHD finger-containing protein 1 (BRPF1) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of BRPF1. BRPF1, also termed peregrin, or protein Br140, is a multi-domain protein that binds histones, mediates monocytic leukemic zinc-finger protein (MOZ) -dependent histone acetylation, and is required for Hox gene expression and segmental identity. It is a close partner of the MOZ histone acetyltransferase (HAT) complex and a novel Trithorax group (TrxG) member with a central role during development. BRPF1 is primarily a nuclear protein that has a broad tissue distribution and is abundant in testes and spermatogonia. It contains a plant homeodomain (PHD) zinc finger followed by a non-canonical ePHD finger, a bromodomain and a proline-tryptophan-tryptophan-proline (PWWP) domain. This PHD finger binds to methylated lysine 4 of histone H3 (H3K4me), the bromodomain interacts with acetylated lysines on N-terminal tails of histones and other proteins, and the PWWP domain shows histone-binding and chromatin association properties. BRPF1 may be involved in chromatin remodeling.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 240254018  685 CCLCPVVGGAMKPTTDGRWAHLACAIWIPETCLLDVKKMEPIDGVKKVSKDRWKLLCSICGV-SYGACIQCSNNTCRVAY 763
Cdd:cd15701     1 CALCPNKGGAFKQTDDGRWAHVVCALWIPEVCFANTVFLEPIDSIEHIPPARWKLTCYICKQrGSGACIQCHKANCYTAF 80

                          90
                  ....*....|....
gi 240254018  764 HPLCARAAGLCVEL 777
Cdd:cd15701    81 HVTCAQQAGLYMKM 94