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 1498523212 1004 CVLCPIRDNDNEPNGkqyppdPLKRTEHNHWAHIRCSVWNNKLIFGTPNLEPVLGLAQDVRHSGTGICFICKTGVGVCIN 1083
Cdd:cd15571      1 CALCPRSGGALKGGG------ALKTTSDGLWVHVVCALWSPEVYFDDGTLLEVEGVSKIPKRRKKLKCSICGKRGGACIQ 74

                           90       100
                   ....*....|....*....|....*....
gi 1498523212 1084 CR--CCGMEYHAGCAHRHNYVFGFELLPE 1110
Cdd:cd15571     75 CSypGCPRSFHVSCAIRAGCLFEFEDGPG 103

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
                   ....*....|....*....|....*....|....*....|....*....|
gi 1498523212  944 ACNVCG---VSNERMILSCSGCQMCVHRECYGVtaeePQLMSGGWYCDLC 990
Cdd:cd15492      1 VCDVCLdgeSEDDNEIVFCDGCNVAVHQSCYGI----PLIPEGDWFCRKC 46

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 1498523212 1004 CVLCPIRDNDNEPNGkqyppdPLKRTEHNHWAHIRCSVWNNKLIFGTPNLEPVLGLAQDVRHSGTGICFICKTGVGVCIN 1083
Cdd:cd15571      1 CALCPRSGGALKGGG------ALKTTSDGLWVHVVCALWSPEVYFDDGTLLEVEGVSKIPKRRKKLKCSICGKRGGACIQ 74

                           90       100
                   ....*....|....*....|....*....
gi 1498523212 1084 CR--CCGMEYHAGCAHRHNYVFGFELLPE 1110
Cdd:cd15571     75 CSypGCPRSFHVSCAIRAGCLFEFEDGPG 103

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1498523212  941 LKDACNVCGVS---NERMILSCSGCQMCVHRECYGVtaeePQLMSGGWYCDLCTNdAKPNVNThyqCVLCPIRDNdnepn 1017
Cdd:COG5141    192 FDDICTKCTSThneNSNAIVFCDGCEICVHQSCYGI----QFLPEGFWLCRKCIY-GEYQIRC---CSFCPSSDG----- 258

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1498523212 1018 gkqyppdPLKRTEHNHWAHIRCSVWNNKLIFG-TPNLEPVLGLAQDVRHSGTGICFICKTGVGVCINC--RCCGMEYHAG 1094
Cdd:COG5141    259 -------AFKQTSDGRWGHVICAMFNPELSFGhLLSKDPIDNIASVSSSRWKLGCLICKEFGGTCIQCsyFNCTRAYHVT 331

                   ....*..
gi 1498523212 1095 CAHRHNY 1101
Cdd:COG5141    332 CARRAGY 338

Bromo adjacent homology domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1498523212   117 TYAPGDHCYIVSEPPGEPYYIGRIMDFVINEENptvtdgNTDKHwstlnprqkypasqflFQVNWFYRPKDISKHVA--- 193
Cdd:smart00439    1 TISVGDFVLVEPDDADEPYYIGRIEEIFETKKN------SESKM----------------VRVRWFYRPEETVLEKAalf 58

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....
gi 1498523212   194 DSRLLYATMHSDICSLQSMRGKCIVTHRTD--IIDIEDYRTKPNHFYFTQFYDR 245
Cdd:smart00439   59 DKNEVFLSDEYDTVPLSDIIGKCNVLYKSDypGLRPEGSIGEPDVFFCESAYDP 112

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        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1498523212  944 ACNVCG---VSNERMILSCSGCQMCVHRECYGVtaeePQLMSGGWYCDLC 990
Cdd:cd15492      1 VCDVCLdgeSEDDNEIVFCDGCNVAVHQSCYGI----PLIPEGDWFCRKC 46

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 1498523212   294 CVTCSNWSSPDDSVECAHCRTNFHMMCVTPPLFKKPTRGfGWSCAAC 340
Cdd:smart00249    2 CSVCGKPDDGGELLQCDGCDRWYHQTCLGPPLLEEEPDG-KWYCPKC 47

Myb-Like Dna-Binding Domain of MTA3 and related proteins; Members in this SANT/myb family include domains found in mouse metastasis-associated protein 3 (MTA3) proteins and arginine-glutamic dipeptide (RERE) repeats proteins. SANT (SWI3, ADA2, N-CoR and TFIIIB) DNA-binding domains are a diverse set of proteins that share a common 3 alpha-helix bundle. MTA3 has been shown to interact with nucleosome remodeling and deacetylase (NuRD) proteins CHD4 and HDAC1, and the core cohesin complex protein RAD21 in the ovary, and regulate G2/M progression in proliferating granulosa cells. RERE belongs to the atrophin family and has been identified as a nuclear receptor corepressor; altered expression levels of RERE are associated with cancer in humans while mutations of Rere in mice cause failure in closing the anterior neural tube and fusion of the telencephalic and optic vesicles during embryogenesis.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1498523212  586 FSAEDKRRFEEGVSKYGSELHPVTLE-IGTQTPGHVVRYYYNWKK 629
Cdd:cd11661      2 WSESEAKLFEEGLRKYGKDFHDIRQDfLPWKSVGELVEFYYMWKK 46

Myb-like DNA-binding domain; This family contains the DNA binding domains from Myb proteins, as well as the SANT domain family.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1498523212  586 FSAEDKRRFEEGVSKYGSELHPVTLEIGTQTPGHVVRYYYNWK 628
Cdd:pfam00249    4 WTPEEDELLLEAVEKLGNRWKKIAKLLPGRTDNQCKNRWQNYL 46

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 1498523212 1004 CVLCPIRDNDNEPNGkqyppdPLKRTEHNHWAHIRCSVWNNKLIFGTPNLEPVLGLAQDVRHSGTGICFICKTGVGVCIN 1083
Cdd:cd15571      1 CALCPRSGGALKGGG------ALKTTSDGLWVHVVCALWSPEVYFDDGTLLEVEGVSKIPKRRKKLKCSICGKRGGACIQ 74

                           90       100
                   ....*....|....*....|....*....
gi 1498523212 1084 CR--CCGMEYHAGCAHRHNYVFGFELLPE 1110
Cdd:cd15571     75 CSypGCPRSFHVSCAIRAGCLFEFEDGPG 103

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1498523212  941 LKDACNVCGVS---NERMILSCSGCQMCVHRECYGVtaeePQLMSGGWYCDLCTNdAKPNVNThyqCVLCPIRDNdnepn 1017
Cdd:COG5141    192 FDDICTKCTSThneNSNAIVFCDGCEICVHQSCYGI----QFLPEGFWLCRKCIY-GEYQIRC---CSFCPSSDG----- 258

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1498523212 1018 gkqyppdPLKRTEHNHWAHIRCSVWNNKLIFG-TPNLEPVLGLAQDVRHSGTGICFICKTGVGVCINC--RCCGMEYHAG 1094
Cdd:COG5141    259 -------AFKQTSDGRWGHVICAMFNPELSFGhLLSKDPIDNIASVSSSRWKLGCLICKEFGGTCIQCsyFNCTRAYHVT 331

                   ....*..
gi 1498523212 1095 CAHRHNY 1101
Cdd:COG5141    332 CARRAGY 338

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 1498523212 1004 CVLCPIRDNDNEPNGKQYP---PDPLKRTEHNHWAHIRCSVWNNKLIFGTP-NLEPVLGLAQDVRHSGTGICFICKTGVG 1079
Cdd:cd15667      1 CSLCNAKESNYELAKKQSPrtrPDALKCTSNGTWCHVLCALFNEDIKFGNSkSLQPILNTESVLLKGSRQKCEICKVSGG 80

                           90       100       110
                   ....*....|....*....|....*....|
gi 1498523212 1080 VCINCRCCGMEYHAGCAH-RHNYVFGFELL 1108
Cdd:cd15667     81 GLVKCEVCDDRFHVSCAQdTPGFKLGFKKE 110

PHD-zinc-finger like domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1498523212 1003 QCVLCPIRDndnepngkqyppDPLKRTEHNHWAHIRCSVWNNKLIFG-TPNLEPV-LGLAQDVRHSGTgiCFICKTGVGV 1080
Cdd:pfam13832    2 RCCLCPLRG------------GALKQTSDGRWVHVLCAIFVPEVRFGnVATMEPIdVSRIPPERWKLK--CVFCKKRSGA 67

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1498523212 1081 CINC--RCCGMEYHAGCAHRHNYVFGFELLP 1109
Cdd:pfam13832   68 CIQCskGRCTTAFHVTCAQAAGVYMEPEDWP 98

BAH, or Bromo Adjacent Homology domain (also called ELM1 and BAM for Bromo Adjacent Motif). BAH domains have first been described as domains found in the polybromo protein and Yeast Rsc1/Rsc2 (Remodeling of the Structure of Chromatin). They also occur in mammalian DNA methyltransferases and the MTA1 subunits of histone deacetylase complexes. A BAH domain is also found in Yeast Sir3p and in the origin receptor complex protein 1 (Orc1p), where it was found to interact with the N-terminal lobe of the silence information regulator 1 protein (Sir1p), confirming the initial hypothesis that BAH plays a role in protein-protein interactions.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1498523212  115 GTTYAPGDHCYIVSE--PPGEPYYIGRIMDFVineenptvTDGNTDKHwstlnprqkypasqflFQVNWFYRPKDISKHV 192
Cdd:cd04370      1 GITYEVGDSVYVEPDdsIKSDPPYIARIEELW--------EDTNGSKQ----------------VKVRWFYRPEETPKGL 56

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1498523212  193 ---ADSRLLYATMHSDICSLQSMRGKCIVTH--RTDIIDIEDYRTKPNHFYFTQFYDR 245
Cdd:cd04370     57 spfALRRELFLSDHLDEIPVESIIGKCKVLFvsEFEGLKQRPNKIDTDDFFCRLAYDP 114

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 1498523212 1004 CVLCPIRDNdnepngkqyppdPLKRTEHNHWAHIRCSVWNNKLIFG-TPNLEPVLGLAQDVRHSGTGICFICK-TGVGVC 1081
Cdd:cd15703      1 CVLCPNKGG------------AFKQTSDGRWAHVVCAIWIPEVCFAnTVFLEPVEGVNNIPPARWKLTCYLCKqKGRGAA 68

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1498523212 1082 INCR--CCGMEYHAGCAHRHNYVFGFELLPESEVrpgyplvefNGKRGGMCATTYCYWH 1138
Cdd:cd15703     69 IQCHkvNCYTAFHVTCAQRAGLFMKIEPVRETGL---------NGTTFTVRKTAYCENH 118

BAH, or Bromo Adjacent Homology domain, as present in MTA1 and similar proteins. The Metastasis-associated protein MTA1 is part of the NURD (nucleosome remodeling and deacetylating) complex and plays a role in cellular transformation and metastasis. BAH domains are found in a variety of proteins playing roles in transcriptional silencing and the remodeling of chromatin. It is assumed that in most or all of these instances the BAH domain mediates protein-protein interactions.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1498523212  115 GTTYAPGDHCYIVSEPpGEPYYIGRIMDFvineeNPTVTDGntdkhwstlnprqkypasqFLFQVNWFYRPKDISKHV-- 192
Cdd:cd04709      1 ANMYRVGDYVYFESSP-NNPYLIRRIEEL-----NKTARGH-------------------VEAKVVCYYRRRDIPDSLyq 55

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1498523212  193 -ADS----------------------RLLYATMHSDICSLQSMRGKCIVTHRTDIIDIEDYRTKPNHFYFTQFYD 244
Cdd:cd04709     56 lADQhrreleeksddltpkqrhqlrhRELFLSRQVETLPATHIRGKCSVTLLNDTESARSYLAREDTFFYSLVYD 130

PHD finger found in Arabidopsis thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like protein ATX3, ATX4, ATX5, and similar proteins; The family includes A. thaliana 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. They show distinct phylogenetic origins from the ATX1 and ATX2 family. They are multi-domain containing proteins that consist of an N-terminal PWWP domain, 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 1498523212  945 CNVCGVSNERMILSCSGCQMCVHRECYGVTAEEPQlmsGGWYCDLC 990
Cdd:cd15495      5 CNEGEDDDNNPLITCNRCQISVHQKCYGIREVDPD---GSWVCRAC 47

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
                   ....*....|....*....|....*....|....*
gi 1498523212  956 ILSCSGCQMCVHRECYGVtaeEPQLMSGGWYCDLC 990
Cdd:pfam13831    4 LVYCSKCSVQVHASCYGV---PPIPDGDGWKCRRC 35

Extended PHD finger found in protein Jade-2 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Jade-2. Jade-2, also termed PHD finger protein 15 (PHF15), is a plant homeodomain (PHD) zinc finger protein that is closely related to Jade-1, which functions as an essential regulator of multiple cell signaling pathways. Like Jade-1, Jade-2 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, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. Jade-2 contains 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 1498523212 1004 CVLCPIRDNDNEPNgkqyppdplkrTEHNHWAHIRCSVWNNKLIFGTP-NLEPVLGLAQDVRHSGTGICFICKTGVGVCI 1082
Cdd:cd15705      1 CLLCPKRGGALKPT-----------RSGTKWVHVSCALWIPEVSIGCPeKMEPITKISHIPASRWALSCSLCKECTGTCI 69

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1498523212 1083 NCR--CCGMEYHAGCAHRHNYVFGFELLPESEVR 1114
Cdd:cd15705     70 QCSmpSCITAFHVTCAFDHGLEMRTTLADNDEVK 103

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 1498523212 1004 CVLCPIRDNdnepngkqyppdPLKRTEH-NHWAHIRCSVWNNKLIFGTPN-LEPVLGLAQDVRHSGTGICFICKTGVGVC 1081
Cdd:cd15706      1 CLLCPKTGG------------AMKATRTgTKWAHVSCALWIPEVSIACPErMEPITKVSHIPPSRWALVCSLCKLKTGAC 68

                           90       100
                   ....*....|....*....|.
gi 1498523212 1082 INC--RCCGMEYHAGCAHRHN 1100
Cdd:cd15706     69 IQCsvKSCITAFHVTCAFEHS 89

PHD finger 3 found in PHD finger protein 14 (PHF14) and similar proteins; 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 a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His. It can interact with histones through its PHD fingers. The model corresponds to the third PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1498523212  293 ECVTCSNWSSPDDSVECAHCRTNFHMMCVTPPLFKKPT-RGFGWSCAAC 340
Cdd:cd15563      1 ECCVCKQTGDNSQLVRCDECKLCYHFGCLDPPLKKSPKqRGYGWVCEEC 49

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 1498523212   294 CVTCSNWSSPDDSVECAHCRTNFHMMCVTPPLFKKPTRGfGWSCAAC 340
Cdd:smart00249    2 CSVCGKPDDGGELLQCDGCDRWYHQTCLGPPLLEEEPDG-KWYCPKC 47

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.

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                   ....*....|....*....|....*....|....*....|....*....
gi 1498523212  945 CNVCGVSNE---RMILSCSGCQMCVHRECYGVTAEEPQLMsggWYCDLC 990
Cdd:cd15494      2 CSVCGEDEEyedNLLLQCDKCRMMVHMRCYGVLEPPPGAL---WLCNLC 47

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.

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                   ....*....|....*....|....*....|....*....|....*...
gi 1498523212  945 CNVCG--VSNERMILSCSGCQMCVHRECYGVTAEEPQLmSGGWYCDLC 990
Cdd:cd15489      2 CIVCGkgGDLGGELLQCDGCGKWFHADCLGPPLSSFVP-NGKWICPVC 48

Myb-Like Dna-Binding Domain of MTA3 and related proteins; Members in this SANT/myb family include domains found in mouse metastasis-associated protein 3 (MTA3) proteins and arginine-glutamic dipeptide (RERE) repeats proteins. SANT (SWI3, ADA2, N-CoR and TFIIIB) DNA-binding domains are a diverse set of proteins that share a common 3 alpha-helix bundle. MTA3 has been shown to interact with nucleosome remodeling and deacetylase (NuRD) proteins CHD4 and HDAC1, and the core cohesin complex protein RAD21 in the ovary, and regulate G2/M progression in proliferating granulosa cells. RERE belongs to the atrophin family and has been identified as a nuclear receptor corepressor; altered expression levels of RERE are associated with cancer in humans while mutations of Rere in mice cause failure in closing the anterior neural tube and fusion of the telencephalic and optic vesicles during embryogenesis.

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                   ....*....|....*....|....*....|....*....|....*
gi 1498523212  586 FSAEDKRRFEEGVSKYGSELHPVTLE-IGTQTPGHVVRYYYNWKK 629
Cdd:cd11661      2 WSESEAKLFEEGLRKYGKDFHDIRQDfLPWKSVGELVEFYYMWKK 46

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1498523212 1036 HIRCSVWNNKLIFGTP--NLEPVLGLAQDVRHSGTGICFICKTGVGVCINCR--CCGMEYHAGCAHRHNYVFGFE 1106
Cdd:pfam13771    1 HVVCALWSPELVQRGNdsMGFPIEDIEKIPKRRWKLKCYLCKKKGGACIQCSkkNCRRAFHVTCALEAGLLMQFD 75

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.

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                   ....*....|....*....|....*....|....*....|....*....|.
gi 1498523212  945 CNVC---GVSNERMILSCSGCQMCVHRECYGVtaeePQLMSGGWYCDLCTN 992
Cdd:cd15677      4 CCICmdgECQNSNVILFCDMCNLAVHQECYGV----PYIPEGQWLCRHCLQ 50

PHD finger found in Jumonji domain-containing protein 2B (JMJD2B); JMJD2B, also termed lysine-specific demethylase 4B (KDM4B), or JmjC domain-containing histone demethylation protein 3B (JHDM3B), specifically antagonizes the trimethyl group from H3K9 in pericentric heterochromatin and reduces H3K36 methylation in mammalian cells. It plays an essential role in the growth regulation of cancer cells by modulating the G1-S transition and promotes cell-cycle progression through the regulation of cyclin-dependent kinase 6 (CDK6). It interacts with heat shock protein 90 (Hsp90) and its stability can be regulated by Hsp90. JMJD2B also functions as a direct transcriptional target of p53, which induces its expression through promoter binding. Moreover, JMJD2B expression can be controlled by hypoxia-inducible factor 1alpha (HIF1alpha) in colorectal cancer and estrogen receptor alpha (ERalpha) in breast cancer. It is also involved in bladder, lung, and gastric cancer. JMJD2B contains jmjN and jmjC domains in the N-terminal region, followed by a canonical Cys4HisCys3 PHD finger, a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, and a Tudor domain. This model corresponds to the canonical Cys4HisCys3 PHD finger.

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                   ....*....|....*....|....*....|....*.
gi 1498523212  955 MILSCSGCQMCVHRECYGVtaeEPQLMSGGWYCDLC 990
Cdd:cd15576     67 VLLSCAKCCLQVHASCYGV---NPDLVNEGWTCSRC 99

BAH, or Bromo Adjacent Homology domain, second copy present in DNA (Cytosine-5)-methyltransferases (DCM) from plants. DNA methylation, or the covalent addition of a methyl group to cytosine within the context of the CpG dinucleotide, has profound effects on the genome. These effects include transcriptional repression via inhibition of transcription factor binding, the recruitment of methyl-binding proteins and their associated chromatin remodeling factors, X chromosome inactivation, imprinting, and the suppression of parasitic DNA sequences. DNA methylation is also essential for proper embryonic development and is an important player in both DNA repair and genome stability. BAH domains are found in a variety of proteins playing roles in transcriptional silencing and the remodeling of chromatin. It is assumed that in most or all of these instances the BAH domain mediates protein-protein interactions.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1498523212  166 PRQKYPASqFLFQVNWFYRPKDISKHVA---DSRLLYATMHSDICSLQSMRGKCIVTHRTDIIDIEDYRTKPNHFYFTQF 242
Cdd:cd04708     56 SKQADVAS-TQVKVRRFYRPEDVSPEKAyasDIREVYYSEDTLTVPVEAVEGKCEVRKKSDLPDSDAPVIFEHVFFCELL 134

                   ...
gi 1498523212  243 YDR 245
Cdd:cd04708    135 YDP 137

PHD finger found in bromodomain and PHD finger-containing (BRPF) proteins; The family of BRPF proteins includes BRPF1, BRD1/BRPF2, and BRPF3. They 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. This model corresponds to the canonical Cys4HisCys3 PHD finger.

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                   ....*....|....*....|....*....|....*....|....*.
gi 1498523212  945 CNVCGVSNERMILSCSGCQMCVHRECYGVtaeePQLMSGGWYCDLC 990
Cdd:cd15572      7 CLDGECQNSNVILFCDMCNLAVHQECYGV----PYIPEGQWLCRRC 48

PHD finger 2 found in monocytic leukemia zinc-finger protein (MOZ) and its factor (MORF); MOZ, also termed histone acetyltransferase KAT6A, YBF2/SAS3, SAS2 and TIP60 protein 3 (MYST-3), or runt-related transcription factor-binding protein 2, or zinc finger protein 220, is a MYST-type histone acetyltransferase (HAT) that functions as a coactivator for acute myeloid leukemia 1 protein (AML1)- and p53-dependent transcription. It possesses intrinsic HAT activity to acetylate both itself and lysine (K) residues on histone H2B, histone H3 (K14) and histone H4 (K5, K8, K12 and K16) in vitro and H3K9 in vivo. MOZ-related factor (MORF), also termed MOZ2, or histone acetyltransferase KAT6B, or MOZ, YBF2/SAS3, SAS2 and TIP60 protein 4 (MYST4), is a ubiquitously expressed transcriptional regulator with intrinsic HAT activity. It can interact with the Runt-domain transcription factor Runx2 and form a tetrameric complex with BRPFs, ING5, and EAF6. Both MOZ and MORF are catalytic subunits of HAT complexes that are required for normal developmental programs, such as hematopoiesis, neurogenesis, and skeletogenesis, and are also implicated in human leukemias. MOZ is also the catalytic subunit of a tetrameric inhibitor of growth 5 (ING5) complex, which specifically acetylates nucleosomal histone H3K14. Moreover, MOZ and MORF are involved in regulating transcriptional activation mediated by Runx2 (or Cbfa1), a Runt-domain transcription factor known to play important roles in T cell lymphomagenesis and bone development, and its homologs. MOZ contains a linker histone 1 and histone 5 domains and two plant homeodomain (PHD) fingers. In contrast, MORF contains an N-terminal region containing two PHD fingers, a putative HAT domain, an acidic region, and a C-terminal Ser/Met-rich domain. The family corresponds to the first PHD finger.

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                   ....*....|....*....|....*....|....*....|....*..
gi 1498523212  294 CVTCSNWSSPDDSVECAHCRTNFHMMCVTPPLFKKPTRgfGWSCAAC 340
Cdd:cd15527      2 CSVCQDSGNADNLLFCDACDKGFHMECHDPPLTRMPKG--KWVCQIC 46

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.

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                   ....*....|....*....|....*....|....*....|....*.
gi 1498523212  945 CNVCGVSNERMILSCSGCQMCVHRECYGVtaeePQLMSGGWYCDLC 990
Cdd:cd15676     13 CNDGECQNSNVILFCDMCNLAVHQECYGV----PYIPEGQWLCRRC 54

PHD finger 1 found in Histone-lysine N-methyltransferase 2C (KMT2C) and 2D (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, several plant homeodomain (PHD) fingers, two extended PHD (ePHD) fingers, Cys2HisCys5HisCys2His, a RING finger, an HMG (high-mobility group)-binding motif, and two FY-rich regions. This model corresponds to the first PHD finger.

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                   ....*....|....*....|....*....|....*....|....*...
gi 1498523212  293 ECVTCSNWSSPDDSVECAHCRTNFHMMCVTPPLFKKPTRGFGWSCAAC 340
Cdd:cd15509      1 NCAVCDSPGDLSDLLFCTSCGQHYHGSCLDPAVRPTPLVRAGWQCPEC 48

PHD finger found in protein Jade-1 and similar proteins; Jade-1, also termed PHD finger protein 17 (PHF17), is a novel binding partner of von Hippel-Lindau (VHL) tumor suppressor Pvhl, a key regulator of the cellular oxygen sensing pathway. It is highly expressed in renal proximal tubules. Jade-1 functions as an essential regulator of multiple cell signaling pathways. It may be involved in the serine/threonine kinase AKT/AKT1 pathway during renal cancer pathogenesis and normally prevents renal epithelial cell proliferation and transformation. It also acts as a pro-apoptotic and growth suppressive ubiquitin ligase to inhibit canonical Wnt downstream effector beta-catenin for proteasomal degradation, and as a transcription factor associated with histone acetyltransferase activity and with increased abundance of cyclin-dependent kinase inhibitor p21. Moreover, Jade-1 is required for ING4 and ING5 to associate with histone acetyltransferase (HAT) HBO1 and Eaf6 to form a HBO1 complex, and plays a role in epithelial cell regeneration. It has also been identified as a novel component of the nephrocystin protein (NPHP) complex and interacts with the ciliary protein nephrocystin-4 (NPHP4). Jade-1 contains a canonical Cys4HisCys3 plant homeodomain (PHD) finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, both of which are zinc-binding motifs. This model corresponds to the canonical Cys4HisCys3 PHD finger.

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                   ....*....|....*....|....*....|....*....|....*....|
gi 1498523212  945 CNVC----GVSNERMILsCSGCQMCVHRECYGVTaeepQLMSGGWYCDLC 990
Cdd:cd15679      2 CDVCqspdGEDGNEMVF-CDKCNICVHQACYGIL----KVPEGSWLCRTC 46