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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 255 CVLCPKKGGAMKTTRTGTKWAHVSCALWIPEVSIACPERMEPVTKISHIPPSRWALVCNLCKLKTGACIQCSVKSCITAF 334
Cdd:cd15706     1 CLLCPKTGGAMKATRTGTKWAHVSCALWIPEVSIACPERMEPITKVSHIPPSRWALVCSLCKLKTGACIQCSVKSCITAF 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2237445597 335 HVTCAFEHGLEMKTILDEGDEVKFKSFCLKH 365
Cdd:cd15706    81 HVTCAFEHSLEMKTILDEGDEVKFKSYCLKH 111

Enhancer of polycomb-like; This is a family of EPL1 (Enhancer of polycomb-like) proteins. The EPL1 protein is a member of a histone acetyltransferase complex which is involved in transcriptional activation of selected genes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597  90 PTPSLRiiseKVKEmlFVR-PRKYIRCSspESAEpgyintlEQAASTCRYDLDDMDIFWLQELNEDLGEMGYGPIDETLM 168
Cdd:pfam10513  94 PTPDAG----KFRE--FERpPASYIRFS--ETVE-------EELDEGVEYDMDEEDEAWLEELNEKRKSEGVEKISEDEF 158

                  ....*....
gi 2237445597 169 EKTIEVLER 177
Cdd:pfam10513 159 EILMDRFEK 167

Extended PHD finger found in protein Jade-3 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Jade-3. Jade-3, also termed PHD finger protein 16 (PHF16), is a plant homeodomain (PHD) zinc finger protein that is close related to Jade-1, which functions as an essential regulator of multiple cell signaling pathways. Like Jade-1, Jade-3 is required for ING4 and ING5 to associate with histone acetyl transferase (HAT) HBO1 and Eaf6 to form a HBO1 complex that has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. Jade-3 contains a canonical PHD domain followed by this non-canonical ePHD domain, both of which are zinc-binding motifs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 255 CVLCPKKGGAMKTTRTGTKWAHVSCALWIPEVSIACPERMEPVTKISHIPPSRWALVCNLCKLKTGACIQCSVKSCITAF 334
Cdd:cd15706     1 CLLCPKTGGAMKATRTGTKWAHVSCALWIPEVSIACPERMEPITKVSHIPPSRWALVCSLCKLKTGACIQCSVKSCITAF 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2237445597 335 HVTCAFEHGLEMKTILDEGDEVKFKSFCLKH 365
Cdd:cd15706    81 HVTCAFEHSLEMKTILDEGDEVKFKSYCLKH 111

PHD-zinc-finger like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 253 PQCVLCPKKGGAMKTTrTGTKWAHVSCALWIPEVSIACPERMEPVTkISHIPPSRWALVCNLCKLKTGACIQCSVKSCIT 332
Cdd:pfam13832   1 VRCCLCPLRGGALKQT-SDGRWVHVLCAIFVPEVRFGNVATMEPID-VSRIPPERWKLKCVFCKKRSGACIQCSKGRCTT 78

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2237445597 333 AFHVTCAFEHGLEMKtiLDEGDEVKFKSFCLKH 365
Cdd:pfam13832  79 AFHVTCAQAAGVYME--PEDWPNVVVIAYCQKH 109

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 2237445597 202 ICDVCRSPDseEGNDMVFCDKCNVCVHQACYGI----LKIPEGSWLCRSCV 248
Cdd:pfam00628   1 YCAVCGKSD--DGGELVQCDGCDDWFHLACLGPpldpAEIPSGEWLCPECK 49

Enhancer of polycomb-like; This is a family of EPL1 (Enhancer of polycomb-like) proteins. The EPL1 protein is a member of a histone acetyltransferase complex which is involved in transcriptional activation of selected genes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597  90 PTPSLRiiseKVKEmlFVR-PRKYIRCSspESAEpgyintlEQAASTCRYDLDDMDIFWLQELNEDLGEMGYGPIDETLM 168
Cdd:pfam10513  94 PTPDAG----KFRE--FERpPASYIRFS--ETVE-------EELDEGVEYDMDEEDEAWLEELNEKRKSEGVEKISEDEF 158

                  ....*....
gi 2237445597 169 EKTIEVLER 177
Cdd:pfam10513 159 EILMDRFEK 167

Extended PHD finger found in protein Jade-3 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Jade-3. Jade-3, also termed PHD finger protein 16 (PHF16), is a plant homeodomain (PHD) zinc finger protein that is close related to Jade-1, which functions as an essential regulator of multiple cell signaling pathways. Like Jade-1, Jade-3 is required for ING4 and ING5 to associate with histone acetyl transferase (HAT) HBO1 and Eaf6 to form a HBO1 complex that has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. Jade-3 contains a canonical PHD domain followed by this non-canonical ePHD domain, both of which are zinc-binding motifs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 255 CVLCPKKGGAMKTTRTGTKWAHVSCALWIPEVSIACPERMEPVTKISHIPPSRWALVCNLCKLKTGACIQCSVKSCITAF 334
Cdd:cd15706     1 CLLCPKTGGAMKATRTGTKWAHVSCALWIPEVSIACPERMEPITKVSHIPPSRWALVCSLCKLKTGACIQCSVKSCITAF 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2237445597 335 HVTCAFEHGLEMKTILDEGDEVKFKSFCLKH 365
Cdd:cd15706    81 HVTCAFEHSLEMKTILDEGDEVKFKSYCLKH 111

Extended PHD finger found in Drosophila melanogaster PHD finger protein rhinoceros (RNO) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Drosophila melanogaster RNO. RNO is a novel plant homeodomain (PHD)-containing nuclear protein that may function as a transcription factor that antagonizes Ras signaling by regulating the transcription of key EGFR/Ras pathway regulators in the Drosophila eye. RNO contains a canonical PHD domain followed by this non-canonical ePHD domain, both of which are zinc-binding motifs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 255 CVLCPKKGGAMKTTRTGTKWAHVSCALWIPEVSIACPERMEPVTKISHIPPSRWALVCNLCKLKTGACIQCSVKSCITAF 334
Cdd:cd15707     1 CILCPNKGGAMKSTRSGTKWAHVSCALWIPEVSIGCVEKMEPITKISSIPASRWALICVLCRERTGACIQCSVKTCKTAY 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2237445597 335 HVTCAFEHGLEMKTILDEG--DEVKFKSFCLKH 365
Cdd:cd15707    81 HVTCGFQHGLEMKTILDEEseDGVKLRSYCQKH 113

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 138 YDLDDMDIFWLQELNEDLGEmgyGPIDETLMEKTIEVLERHCHENMNHAIE-TVEGLGIEYDEDVICDVCRSPDSEEGND 216
Cdd:COG5141   133 YDLDEYDTMWLRYLNESAID---ENVSEEAFEIIVTRLEKEWFFFEHGLPDkHVEPIEPSDEFDDICTKCTSTHNENSNA 209

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 217 MVFCDKCNVCVHQACYGILKIPEGSWLCRSCVLGIYP--QCVLCPKKGGAMKTTRTGtKWAHVSCALWIPEVSIACPERM 294
Cdd:COG5141   210 IVFCDGCEICVHQSCYGIQFLPEGFWLCRKCIYGEYQirCCSFCPSSDGAFKQTSDG-RWGHVICAMFNPELSFGHLLSK 288

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 295 EPVTKISHIPPSRWALVCNLCKLKTGACIQCSVKSCITAFHVTCAFEHGLEMKTILDEG---DEVKFKSFCLKH------ 365
Cdd:COG5141   289 DPIDNIASVSSSRWKLGCLICKEFGGTCIQCSYFNCTRAYHVTCARRAGYFDLNIYSHNgisYCIDHEPLCRKHyplgyg 368

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 366 -SQNKPKLGDAEYHHHRVAEQSQAKSEKTSLRAQKLRELEEEF-----YTLVQVED-VAKEMELSAFTVDF--IYNYWKL 436
Cdd:COG5141   369 rMNGLRYFGYEKLRYKNPPTAIPRKVRAARPRATLFMKLCWKQppatpSVLSRVEAcDLKEKDRQDLPVNIfdICKYWEM 448

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2237445597 437 KRKSNFNKPLIpPKEEEENGLVQPKEESIHTRMRMFMHLRQDLERVRNLCYMISRREKLKLSHTKVQEQIFGL 509
Cdd:COG5141   449 KRKSEIGGPLV-ILPDIVYSLKTLEDWMSKRRMREVAKALQDQYQLLTLVESTAKRQLLKCQLSNLRKKFLNL 520

Extended PHD finger found in BRPF proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the ePHD finger of the family of BRPF proteins, which includes BRPF1, BRD1/BRPF2, and BRPF3. These are scaffold proteins that form monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complexes with other regulatory subunits, such as inhibitor of growth 5 (ING5) and Esa1-associated factor 6 ortholog (EAF6). BRPF proteins have multiple domains, including 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 lysine 4 of histone H3 (K4H3), 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 255 CVLCPKKGGAMKTTRTGtKWAHVSCALWIPEVSIACPERMEPVTKISHIPPSRWALVCNLCKLKTGACIQCSVKSCITAF 334
Cdd:cd15670     1 CVLCPNKGGAFKQTDDG-RWAHVVCALWIPEVSFANTVFLEPIDGIQNIPKARWKLTCYICKKRMGACIQCHKKNCYTAF 79

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 2237445597 335 HVTCAFEHGLEMK------TILDEGDEVKFKSFCLKH 365
Cdd:cd15670    80 HVTCAQQAGLYMKiepvkdPGNGTSDSVRKEAYCDKH 116

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 2237445597 255 CVLCPKKGGAMK-----TTRTGTKWAHVSCALWIPEVSIACPERMEPVtKISHIPPSRWALVCNLCKLKTGACIQCSVKS 329
Cdd:cd15571     1 CALCPRSGGALKgggalKTTSDGLWVHVVCALWSPEVYFDDGTLLEVE-GVSKIPKRRKKLKCSICGKRGGACIQCSYPG 79

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2237445597 330 CITAFHVTCAFEHGLEMktiLDEGDEVKFKSFCLKH 365
Cdd:cd15571    80 CPRSFHVSCAIRAGCLF---EFEDGPGNFVVYCPKH 112

PHD-like zinc-binding domain; The members of this family are annotated as containing PHD domain, but the zinc-binding region here is not typical of PHD domains. The conformation here is a well-conserved cysteine-histidine rich region spanning 90 residues, where the Cys and His are arranged as HxxC(31)CxxC(6)CxxCxxxxCxxxxHxxC (21)CxxH.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 276 HVSCALWIPEVSIAC-PERMEPVTKISHIPPSRWALVCNLCKLKTGACIQCSVKSCITAFHVTCAFEHGLEMKTildEGD 354
Cdd:pfam13771   1 HVVCALWSPELVQRGnDSMGFPIEDIEKIPKRRWKLKCYLCKKKGGACIQCSKKNCRRAFHVTCALEAGLLMQF---DED 77

                          90
                  ....*....|.
gi 2237445597 355 EVKFKSFCLKH 365
Cdd:pfam13771  78 NGTFKSYCKKH 88

Extended PHD finger found in bromodomain and PHD finger-containing protein 2 (BRPF2) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of BRPF2. BRPF2 also termed bromodomain-containing protein 1 (BRD1), or BR140-likeprotein, is encoded by BRL (BR140 Like gene). It is responsible for the bulk of the acetylation of H3K14 and forms a novel monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complex with HBO1 and ING4. The complex is required for full transcriptional activation of the erythroid-specific regulator genes essential for terminal differentiation and survival of erythroblasts in fetal liver. BRPF2 shows widespread expression and localizes to the nucleus within spermatocytes. It contains a cysteine rich region harboring a plant homeodomain (PHD) finger followed by a non-canonical ePHD finger, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 255 CVLCPKKGGAMKTTRTgTKWAHVSCALWIPEVSIACPERMEPVTKISHIPPSRWALVCNLCKLK-TGACIQCSVKSCITA 333
Cdd:cd15702     1 CVLCPNKGGAFKKTDD-DRWGHVVCALWIPEVGFANTVFIEPIDGVRNIPPARWKLTCYLCKQKgVGACIQCHKANCYTA 79

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2237445597 334 FHVTCAFEHGLEMK----TILDEGD---EVKFKSFCLKH 365
Cdd:cd15702    80 FHVTCAQKAGLYMKmepvKEVTGGGttfSVRKTAYCDAH 118

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 2237445597 255 CVLCPKKGGAMKTTRTGTkWAHVSCALWIPEVSIACPERMEPVTKISHIPPSRWALVCNLCKLKTGACIQCSVKSCITAF 334
Cdd:cd15662     1 CCLCPVVGGALKPTTDGR-WAHLACAIWIPETCLLDVKTMEPVDGINAISKERWELSCTICKQRYGACIQCSNNSCRVAY 79

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2237445597 335 HVTCAFEHGLEMKTILDEGDE-----VKFKSFCLKH 365
Cdd:cd15662    80 HPLCARAAGLCMEVADEGGEDpgdqgLRLLSYCPRH 115

Extended PHD finger found in Jumonji domain-containing protein 2 (JMJD2) family of histone demethylases; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of JMJD2 proteins. JMJD2 proteins, also termed lysine-specific demethylase 4 histone demethylases (KDM4), have been implicated in various cellular processes including DNA damage response, transcription, cell cycle regulation, cellular differentiation, senescence, and carcinogenesis. They selectively catalyze the demethylation of di- and trimethylated H3K9 and H3K36. This model contains three JMJD2 proteins, JMJD2A-C, which all contain jmjN and jmjC domains in the N-terminal region, followed by a canonical PHD finger, this non-canonical ePHD finger, and a Tudor domain. JMJD2D is not included in this family, since it lacks both PHD and Tudor domains and has a different substrate specificity. JMJD2A-C are required for efficient cancer cell growth.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 255 CVLCPKKGGAMKTTRTGtKWAHVSCALWIPEVSIACPERMEPVTkISHIPPSRWALVCNLCK------LKTGACIQCSVK 328
Cdd:cd15675     1 CCLCCLRGGALKPTTDG-RWAHVVCAIAIPEVRFSNVPERGPID-ISKIPPARLKLKCIYCSkitksmSHMGACIQCSTG 78

                          90       100
                  ....*....|....*....|
gi 2237445597 329 SCITAFHVTCAFEHGLEMKT 348
Cdd:cd15675    79 KCTTSFHVTCAHAAGVQMEP 98

PHD finger found in BRPF proteins, Jade proteins, protein AF-10, AF-17, and similar proteins; The family includes BRPF proteins, Jade proteins, protein AF-10 and AF-17. BRPF proteins are scaffold proteins that form monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complexes with other regulatory subunits, such as inhibitor of growth 5 (ING5) and Esa1-associated factor 6 ortholog (EAF6). BRPF proteins have multiple domains, including a canonical Cys4HisCys3 plant homeodomain (PHD) zinc finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, a bromodomain and a proline-tryptophan-tryptophan-proline (PWWP) domain. PHD and ePHD fingers both bind to lysine 4 of histone H3 (K4H3), bromodomains interact with acetylated lysines on N-terminal tails of histones and other proteins, and PWWP domains show histone-binding and chromatin association properties. Jade proteins are 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, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. AF-10, also termed ALL1 (acute lymphoblastic leukemia)-fused gene from chromosome 10 protein, is a transcription factor that has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. AF-17, also termed ALL1-fused gene from chromosome 17 protein, is a putative transcription factor that may play a role in multiple signaling pathways. All Jade proteins, AF-10, and AF-17 contain a canonical PHD finger followed by a non-canonical ePHD finger. This model corresponds to the canonical PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2237445597 203 CDVCRSPDSEEGNDMVFCDKCNVCVHQACYGILKIPEGSWLCRSC 247
Cdd:cd15492     2 CDVCLDGESEDDNEIVFCDGCNVAVHQSCYGIPLIPEGDWFCRKC 46

Extended PHD finger found in PHD finger protein 14 (PHF14) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of PHF14. PHF14 is a novel nuclear transcription factor that controls the proliferation of mesenchymal cells by directly repressing platelet-derived growth factor receptor-alpha (PDGFRalpha) expression. It also acts as an epigenetic regulator and plays an important role in the development of multiple organs in mammals. PHF14 contains three canonical plant homeodomain (PHD) fingers and this non-canonical ePHD finger. It can interact with histones through its PHD fingers.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 255 CVLCPKKGGAMKTTRTGtKWAHVSCALWIPEVSIACPERMEPVTkISHIPPSRW-ALVCNLCK----LKTGACIQCSVKS 329
Cdd:cd15674     1 CELCPNRGGIFKETDTG-RWVHLVCALYTPGVAFGDVDKLSPVT-LTEMNYSKWgARECSLCEdprfARTGVCISCDAGM 78

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2237445597 330 CITAFHVTCAFEHGLEMKTILDEGDEVKFKSFCLKH 365
Cdd:cd15674    79 CKSYFHVTCAQREGLLSEATDEEDIADPFYAYCKQH 114

Extended PHD finger found in Arabidopsis thaliana ATX3, -4, -5, 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 ATX3 (also termed protein SET domain group 14, or trithorax-homolog protein 3), ATX4 (also termed protein SET domain group 16, or trithorax-homolog protein 4) and ATX5 (also termed protein SET domain group 29, or trithorax-homolog protein 5), which belong to the histone-lysine methyltransferase family. These proteins show distinct phylogenetic origins from the family of ATX1 and ATX2. They are multi-domain proteins that consist of an N-terminal PWWP domain, a canonical PHD finger, this non-canonical extended PHD finger, and a C-terminal SET domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 255 CVLCPKKGGAMKTTRTGTKWAHVSCALWIPEVSIACPERMEPVTKISHIPPSRWALVCNLCKLKTGACIQCSvkSCITAF 334
Cdd:cd15663     1 CCLCPVKGGALKPTDVEGLWVHVTCAWFRPEVCFKNEEKMEPAVGLLRIPLSTFLKACVICKQIHGSCTQCC--KCATYF 78

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2237445597 335 HVTCAFEHG--LEMKTILDEGDEV-KFKSFCLKH 365
Cdd:cd15663    79 HAMCASRAGyhMELHCLEKNGVQItRMVSYCSFH 112

Extended PHD finger found in protein AF-10 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of AF-10. AF-10, also termed ALL1 (acute lymphoblastic leukaemia)-fused gene from chromosome 10 protein, is a transcription factor encoded by gene AF10, a translocation partner of the MLL (mixed-lineage leukaemia) oncogene in leukaemia. AF-10 has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. It plays a key role in the survival of uncommitted hematopoietic cells. Moreover, AF-10 functions as a follistatin-related gene (FLRG)-interacting protein. The interaction with FLRG enhances AF10-dependent transcription. It interacts with human counterpart of the yeast Dot1, hDOT1L, and may act as a bridge for the recruitment of hDOT1L to the genes targeted by MLL-AF10. It also interacts with the synovial sarcoma associated protein SYT protein and may play a role in synovial sarcomas and acute leukemias. AF-10 contains an N-terminal plant homeodomain (PHD) finger followed by this non-canonical ePHD finger.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 254 QCVLCPKKGGAMKTTRTGtKWAHVSCALWIPEVSIACPERMEPVTkISHIPPSRWALVCNLC-------KLKTGACIQCS 326
Cdd:cd15708     4 RCELCPHKDGALKRTDNG-GWAHVVCALYIPEVQFANVSTMEPIV-LQSVPHERYNKTCYICdeqgresKAATGACMTCN 81

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2237445597 327 VKSCITAFHVTCAFEHGLEMKTILDEGDEVKFKSFCLKH 365
Cdd:cd15708    82 KHGCRQAFHVTCAQLAGLLCEEEGNGADNVQYCGYCKYH 120

Extended PHD finger found in protein AF-17 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of AF-17. AF-17, also termed ALL1-fused gene from chromosome 17 protein, is encoded by gene AF17 that has been identified in hematological malignancies as a translocation partner of the mixed lineage leukemia gene MLL. It is a putative transcription factor that may play a role in multiple signaling pathways. It is involved in chromatin-mediated gene regulation mechanisms. It functions as a component of the multi-subunit Dot1 complex (Dotcom) and plays a role in the Wnt/Wingless signaling pathway. It also seems to be a downstream target of the beta-catenin/T-cell factor pathway, and participates in G2-M progression. Moreover, it may function as an important regulator of ENaC-mediated Na+ transport and thus blood pressure. AF-17 contains an N-terminal plant homeodomain (PHD) finger followed by a non-canonical ePHD finger.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 254 QCVLCPKKGGAMKTTRTGtKWAHVSCALWIPEVSIACPERMEPVTkISHIPPSRWALVCNLC-------KLKTGACIQCS 326
Cdd:cd15709     4 RCELCPHKDGALKRTDNG-GWAHVVCALYIPEVQFANVLTMEPIV-LQYVPHDRFNKTCYICeeqgresKAASGACMTCN 81

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2237445597 327 VKSCITAFHVTCAFEHGLEMKTILDEGDEVKFKSFCLKH 365
Cdd:cd15709    82 RHGCRQAFHVTCAQMAGLLCEEEVLEVDNVKYCGYCKYH 120

PHD finger found in bromodomain and PHD finger-containing protein 2 (BRPF2) and similar proteins; BRPF2, also termed bromodomain-containing protein 1 (BRD1), or BR140-like protein, is encoded by BRL (BR140 Like gene). It is responsible for the bulk of the acetylation of H3K14 and forms a novel monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complex with HBO1 and ING4. The complex is required for full transcriptional activation of the erythroid-specific regulator genes essential for terminal differentiation and survival of erythroblasts in fetal liver. BRPF2 shows widespread expression and localizes to the nucleus within spermatocytes. It contains a cysteine rich region harboring a canonical Cys4HisCys3 plant homeodomain (PHD) finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 2237445597 200 DVICDVCRSPDSEEGNDMVFCDKCNVCVHQACYGILKIPEGSWLCRSCV 248
Cdd:cd15677     1 DAVCCICMDGECQNSNVILFCDMCNLAVHQECYGVPYIPEGQWLCRHCL 49

PHD finger found in bromodomain and PHD finger-containing protein 1 (BRPF1) and similar proteins; 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 canonical Cys4HisCys3 plant homeodomain (PHD) zinc finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, a bromodomain and a proline-tryptophan-tryptophan-proline (PWWP) domain. PHD and ePHD fingers both bind to lysine 4 of histone H3 (K4H3), bromodomains interact with acetylated lysines on N-terminal tails of histones and other proteins, and PWWP domains show histone-binding and chromatin association properties. BRPF1 may be involved in chromatin remodeling. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2237445597 198 DEDVICDVCRSPDSEEGNDMVFCDKCNVCVHQACYGILKIPEGSWLCRSCV 248
Cdd:cd15676     5 DEDAVCCICNDGECQNSNVILFCDMCNLAVHQECYGVPYIPEGQWLCRRCL 55

Extended PHD finger found in Saccharomyces cerevisiae SANT domain-containing protein 2 (Snt2p) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Snt2p. Sntp2 is a yeast protein that may function in multiple stress pathways. It coordinates the transcriptional response to hydrogen peroxide-mediated oxidative stress through interaction with Ecm5 and the Rpd3 deacetylase. Snt2p contains a bromo adjacent homology (BAH) domain, two canonical PHD fingers, a non-canonical ePHD finger, and a SANT (SWI3, ADA2, N-CoR and TFIIIB) DNA-binding domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 255 CVLCPKKGG---------------AMKTTRTGTkWAHVSCALWIPEVSIACPERMEPVTKISHIPPSRWALVCNLCKLKT 319
Cdd:cd15667     1 CSLCNAKESnyelakkqsprtrpdALKCTSNGT-WCHVLCALFNEDIKFGNSKSLQPILNTESVLLKGSRQKCEICKVSG 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 320 GACIQCSVksCITAFHVTCA-----FEHGLEmKTILDEGDEVKFKSFCL--KHSQNKPKL 372
Cdd:cd15667    80 GGLVKCEV--CDDRFHVSCAqdtpgFKLGFK-KEYLSDDTENPFITDKVdnESYTLKPII 136

PHD finger found in protein AF-10 and AF-17; This family includes protein AF-10 and AF-17. AF-10, also termed ALL1 (acute lymphoblastic leukemia)-fused gene from chromosome 10 protein, is a transcription factor encoded by gene AF10, a translocation partner of the MLL (mixed-lineage leukemia) oncogene in leukemia. AF-10 has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. It plays a key role in the survival of uncommitted hematopoietic cells. Moreover, AF-10 functions as a follistatin-related gene (FLRG)-interacting protein. The interaction with FLRG enhances AF10-dependent transcription. It interacts with the human counterpart of the yeast Dot1, hDOT1L, and may act as a bridge for the recruitment of hDOT1L to the genes targeted by MLL-AF10. It also interacts with the synovial sarcoma associated SYT protein and may play a role in synovial sarcomas and acute leukemias. AF-17, also termed ALL1-fused gene from chromosome 17 protein, is encoded by gene AF17 that has been identified in hematological malignancies as translocation partners of the mixed lineage leukemia gene MLL. It is a putative transcription factor that may play a role in multiple signaling pathways. It is involved in chromatin-mediated gene regulation mechanisms. It functions as a component of the multi-subunit Dot1 complex (Dotcom) and plays a role in the Wnt/Wingless signaling pathway. It also seems to be a downstream target of the beta-catenin/T-cell factor pathway, and participates in G2-M progression. Moreover, it may function as an important regulator of ENaC-mediated Na+ transport and thus blood pressure. Both AF-10 and AF-17 contain an N-terminal canonical Cys4HisCys3 plant homeodomain (PHD) finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His. The PHD finger is involved in their homo-oligomerization. In the C-terminal region, they possess a leucine zipper domain and a glutamine-rich region. This family also includes ZFP-1, the Caenorhabditis elegans AF10 homolog. It was originally identified as a factor promoting RNAi interference in C. elegans. It also acts as a Dot1-interacting protein that opposes H2B ubiquitination to reduce polymerase II (Pol II) transcription. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2237445597 203 CDVCRSPDSEEGNDMVFCD--KCNVCVHQACYGILKIPEGSWLCRSC 247
Cdd:cd15574     2 CCVCSDERGWAENPLVYCDghGCNVAVHQACYGIVQVPTGPWFCRKC 48

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 2237445597  202 ICDVCRSPDseEGNDMVFCDKCNVCVHQACYGI---LKIPEGSWLCRSC 247
Cdd:smart00249   1 YCSVCGKPD--DGGELLQCDGCDRWYHQTCLGPpllEEEPDGKWYCPKC 47

PHD finger 2 found in PHD finger protein 10 (PHF10) and similar proteins; PHF10, also termed BRG1-associated factor 45a (BAF45a), or XAP135, is a ubiquitously expressed transcriptional regulator that is required for maintaining the undifferentiated status of neuroblasts. It contains a SAY (supporter of activation of yellow) domain and two adjacent plant homeodomain (PHD) fingers. This model corresponds to the second PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2237445597 203 CDVCRSPDSEEgnDMVFCDKCNVCVHQACYGILKIPEGSWLCRSC 247
Cdd:cd15529     2 CTKCGDPHDED--KMMFCDQCDRGYHTFCVGLRSIPDGRWICPLC 44

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 2237445597 202 ICDVCRSPDsEEGNDMVFCDKCNVCVHQACYGI---LKIPEGSWLCRSC 247
Cdd:cd15489     1 SCIVCGKGG-DLGGELLQCDGCGKWFHADCLGPplsSFVPNGKWICPVC 48

Extended PHD finger found in histone-lysine N-methyltransferase 2A (KMT2A); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This subfamily includes the ePHD finger of KMT2A. KMT2A also termed ALL-1, or CXXC-type zinc finger protein 7, or myeloid/lymphoid or mixed-lineage leukemia protein 1 (MLL1), or trithorax-like protein (Htrx), or zinc finger protein HRX, is a histone methyltransferase that belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2). It regulates chromatin-mediated transcription through the catalysis of methylation of histone 3 lysine 4 (H3K4), and is frequently rearranged in acute leukemia. KMT2A functions as the catalytic subunit in the MLL1 complex, which also contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex. The MLL1 complex is highly active and specific for H3K4methylation. KMT2A contains a CxxC (x for any residue) zinc finger domain, three PHD fingers, a Bromodomain domain, this extended PHD finger, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 254 QCVLCPKKGGAmKTTRTG-------TKWAHVSCALWIPEVSiacpERMEPVTKISHIPPSRWA-LVCNLCkLKTGACIQC 325
Cdd:cd15693     2 QCALCLKYGDD-SANDAGrllyigqNEWTHVNCALWSAEVF----EDDDGSLKNVHMAVIRGKqLRCEFC-QKPGATVGC 75

                          90
                  ....*....|....
gi 2237445597 326 SVKSCITAFHVTCA 339
Cdd:cd15693    76 CLTSCTSNYHFMCS 89

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 2237445597 203 CDVCRSPDSEEGNDMVFCDKCNVCVHQACYGILKIPEG-SWLCRSC 247
Cdd:cd15494     2 CSVCGEDEEYEDNLLLQCDKCRMMVHMRCYGVLEPPPGaLWLCNLC 47

Extended PHD finger 2 found in histone-lysine N-methyltransferase 2C (KMT2C) and 2D (KMT2D); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the second ePHD finger of KMT2C, and KMT2D. KMT2C, also termed myeloid/lymphoid or mixed-lineage leukemia protein 3 (MLL3), or homologous to ALR protein, is a histone H3 lysine 4 (H3K4) lysine methyltransferase that functions as a circadian factor contributing to genome-scale circadian transcription. It is a component of a large complex that acts as a coactivator of multiple transcription factors, including the bile acid (BA)-activated nuclear receptor, farnesoid X receptor (FXR), a critical player in BA homeostasis. The MLL3 complex is essential for p53 transactivation of small heterodimer partner (SHP). KMT2C is also a part of activating signal cointegrator-2 (ASC-2)-containing complex (ASCOM) that contains the transcriptional coactivator nuclear receptor coactivator 6 (NCOA6), KMT2C and its paralog MLL4. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named MLL4, a fourth human homolog of Drosophila trithorax, located on chromosome 12. It enzymatically generates trimethylated histone H3 Lysine 4 (H3K4me3). It plays an essential role in differentiating the human pluripotent embryonal carcinoma cell line NTERA-2 clone D1 (NT2/D1) stem cells by activating differentiation-specific genes, such as HOXA1-3 and NESTIN. KMT2D is also a part of ASCOM. Both KMT2C and KMT2D contain the catalytic domain SET, five PHD fingers, two ePHD fingers, a RING finger, an HMG (high-mobilitygroup)-binding motif, and two FY-rich regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 255 CVLCpKKGGAMKTTRTG-------TKWAHVSCALWIPEVS-----------IACpERMEPVTkishippsrwalvCNLCK 316
Cdd:cd15666     1 CVLC-GGEGDGDTDGPGrllnldvDKWVHLNCALWSYEVYetqngalmnveEAL-RRALTTT-------------CSHCG 65

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 2237445597 317 lKTGACIQCSVKSCITAFHVTCAFEHG---LEMKTIL 350
Cdd:cd15666    66 -RTGATVPCFKPRCANVYHLPCAIKDGcmfFKDKTML 101

Extended PHD finger found in histone-lysine N-methyltransferase 2B (KMT2B); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This subfamily includes the ePHD finger of KMT2B. KMT2B is also called trithorax homolog 2 or WW domain-binding protein 7 (WBP-7). KMT2B is encoded by the gene that was first named myeloid/lymphoid or mixed-lineage leukemia 2 (MLL2), a second human homolog of Drosophila trithorax, located on chromosome 19. It belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2) and is vital for normal mammalian embryonic development. KMT2B functions as the catalytic subunit in the MLL2 complex, which contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex. The MLL2 complex is highly active and specific for histone 3 lysine 4 (H3K4) methylation, which stimulates chromatin transcription in a SAM- and H3K4-dependent manner. Moreover, KMT2B plays a critical role in memory formation by mediating hippocampal H3K4 di- and trimethylation. It is also required for RNA polymerase II association and protection from DNA methylation at the MagohB CpG island promoter. KMT2B contains a CxxC (x for any residue) zinc finger domain, three PHD fingers, this ePHD finger, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 255 CVLCPKKGGAmKTTRTG-------TKWAHVSCALWIPEVSiacpERMEPVTKISHIPPSRW-ALVCNLCkLKTGACIQCS 326
Cdd:cd15694     1 CALCLKYGDA-DSKDAGrllyigqNEWTHVNCAIWSAEVF----EENDGSLKNVHAAVARGrQMRCEHC-QKIGATVGCC 74

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2237445597 327 VKSCITAFHVTCAfehglEMKTILDEGDEvkfKSFCLKH 365
Cdd:cd15694    75 LSACLSNFHFMCA-----RASRCCFQDDK---KVFCQKH 105

Extended PHD finger found in histone-lysine N-methyltransferase 2A (KMT2A) and 2B (KMT2B); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This subfamily includes the ePHD finger of histone-lysine N-methyltransferase trithorax (Trx) like proteins, KMT2A/MLL1 and KMT2B/MLL2. KMT2A and KMT2B comprise the mammalian Trx branch of COMPASS family, and are both essential for mammalian embryonic development. KMT2A regulates chromatin-mediated transcription through the catalysis of methylation of histone 3 lysine 4 (H3K4), and is frequently rearranged in acute leukemia. KMT2A functions as the catalytic subunit in the MLL1 complex. KMT2B is a second human homolog of Drosophila trithorax, located on chromosome 19 and functions as the catalytic subunit in the MLL2 complex. It plays a critical role in memory formation by mediating hippocampal H3K4 di- and trimethylation. It is also required for RNA polymerase II association and protection from DNA methylation at the MagohB CpG island promoter. Both KMT2A and KMT2B contain a CxxC (x for any residue) zinc finger domain, three PHD fingers, this extended PHD (ePHD) finger, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2237445597 255 CVLCPKKGGAmKTTRTG-------TKWAHVSCALWIPEVSiacpERMEPVTKISHIPPSRWALV-CNLCkLKTGACIQCS 326
Cdd:cd15664     1 CALCGVYGDD-EPNDAGrllycgqDEWVHINCALWSAEVF----EEDDGSLQNVHSAVSRGRMMkCELC-GKPGATVGCC 74

                          90
                  ....*....|...
gi 2237445597 327 VKSCITAFHVTCA 339
Cdd:cd15664    75 LKSCPANYHFMCA 87