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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233  177 YDLDQFDDTWLKIINgERALAgaPSITEDQFERVIEELEvRCWDKIQAMVKSEQGLGIEYDENV--ICDVCRSPDSEEAN 254
Cdd:COG5141    133 YDLDEYDTMWLRYLN-ESAID--ENVSEEAFEIIVTRLE-KEWFFFEHGLPDKHVEPIEPSDEFddICTKCTSTHNENSN 208

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233  255 EMVFCDSCNICVHQACYGITAIPSGQWLCRTCSMG--QRPDCVLCPNKGGAMKSTRSGhKWAHVSCALWIPEVSIGSVDR 332
Cdd:COG5141    209 AIVFCDGCEICVHQSCYGIQFLPEGFWLCRKCIYGeyQIRCCSFCPSSDGAFKQTSDG-RWGHVICAMFNPELSFGHLLS 287

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233  333 MEPITKISSIPASRWALICVLCRERVGACIQCSVKTCKTAYHVTCAFQHGLEMRAIIEDENAEDGVKLRSYCQKHSlnks 412
Cdd:COG5141    288 KDPIDNIASVSSSRWKLGCLICKEFGGTCIQCSYFNCTRAYHVTCARRAGYFDLNIYSHNGISYCIDHEPLCRKHY---- 363

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233  413 kkDKGPSNNNAGKSGSDEE--------DTKRKKQ--RRDMTSEEKTI-----VRKKRVQEIEAEFEKHVNIRDISCHLMD 477
Cdd:COG5141    364 --PLGYGRMNGLRYFGYEKlryknpptAIPRKVRaaRPRATLFMKLCwkqppATPSVLSRVEACDLKEKDRQDLPVNIFD 441

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233  478 VDQeaiyciynYWIIKRKSLRNESLIPHKwDDVDMVEHKHEPADIEKMKMFVHLRQDLERVRNLCYMVSRREKLSRSFFK 557
Cdd:COG5141    442 ICK--------YWEMKRKSEIGGPLVILP-DIVYSLKTLEDWMSKRRMREVAKALQDQYQLLTLVESTAKRQLLKCQLSN 512

                   ....*.
gi 1992621233  558 MREQTF 563
Cdd:COG5141    513 LRKKFL 518

MSCRAMM family adhesin clumping factor ClfA; Clumping factor A is an MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules). It is heavily studied in Staphylococcus aureus both for its biological role in adhesion and for its potential for vaccination. Features of the sequence, but also of other MSCRAMM adhesins, include a long run of Ser-Asp dipeptide repeats and a C-terminal cell wall anchoring LPXTG motif.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233 2620 NSASTSGDRIITPIrlkIARKSDGEGYVMA----SESDKSGATGNEKKKKLSNDDSGTAANNNQANDSSSDKQNSENSkl 2695
Cdd:NF033609   530 NNGSGSGDGIDKPV---VPEQPDEPGEIEPipedSDSDPGSDSGSDSSNSDSGSDSGSDSTSDSGSDSASDSDSASDS-- 604

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1992621233 2696 negDGNSRTDNVVDDKESSSHDDQKQAVGPNRSNTLPDPASVASNSKNSDEKTEHPSGELTSTD 2759
Cdd:NF033609   605 ---DSASDSDSASDSDSASDSDSASDSDSASDSDSASDSDSDSDSDSDSDSDSDSDSDSDSDSD 665

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233  177 YDLDQFDDTWLKIINgERALAgaPSITEDQFERVIEELEvRCWDKIQAMVKSEQGLGIEYDENV--ICDVCRSPDSEEAN 254
Cdd:COG5141    133 YDLDEYDTMWLRYLN-ESAID--ENVSEEAFEIIVTRLE-KEWFFFEHGLPDKHVEPIEPSDEFddICTKCTSTHNENSN 208

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233  255 EMVFCDSCNICVHQACYGITAIPSGQWLCRTCSMG--QRPDCVLCPNKGGAMKSTRSGhKWAHVSCALWIPEVSIGSVDR 332
Cdd:COG5141    209 AIVFCDGCEICVHQSCYGIQFLPEGFWLCRKCIYGeyQIRCCSFCPSSDGAFKQTSDG-RWGHVICAMFNPELSFGHLLS 287

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233  333 MEPITKISSIPASRWALICVLCRERVGACIQCSVKTCKTAYHVTCAFQHGLEMRAIIEDENAEDGVKLRSYCQKHSlnks 412
Cdd:COG5141    288 KDPIDNIASVSSSRWKLGCLICKEFGGTCIQCSYFNCTRAYHVTCARRAGYFDLNIYSHNGISYCIDHEPLCRKHY---- 363

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233  413 kkDKGPSNNNAGKSGSDEE--------DTKRKKQ--RRDMTSEEKTI-----VRKKRVQEIEAEFEKHVNIRDISCHLMD 477
Cdd:COG5141    364 --PLGYGRMNGLRYFGYEKlryknpptAIPRKVRaaRPRATLFMKLCwkqppATPSVLSRVEACDLKEKDRQDLPVNIFD 441

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233  478 VDQeaiyciynYWIIKRKSLRNESLIPHKwDDVDMVEHKHEPADIEKMKMFVHLRQDLERVRNLCYMVSRREKLSRSFFK 557
Cdd:COG5141    442 ICK--------YWEMKRKSEIGGPLVILP-DIVYSLKTLEDWMSKRRMREVAKALQDQYQLLTLVESTAKRQLLKCQLSN 512

                   ....*.
gi 1992621233  558 MREQTF 563
Cdd:COG5141    513 LRKKFL 518

PHD finger found in proteins Jade-1, Jade-2, Jade-3, and similar proteins; This family includes proteins Jade-1 (PHF17), Jade-2 (PHF15), and Jade-3 (PHF16), each of which 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. 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 Cys4HisCys3 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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1992621233  241 ICDVCRSPDSEEANEMVFCDSCNICVHQACYGITAIPSGQWLCRTC 286
Cdd:cd15573      1 VCDVCRSPDSEEGNEMVFCDKCNICVHQACYGIQKIPEGSWLCRTC 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 1992621233   241 ICDVCRSPDSEEanEMVFCDSCNICVHQACYGIT---AIPSGQWLCRTC 286
Cdd:smart00249    1 YCSVCGKPDDGG--ELLQCDGCDRWYHQTCLGPPlleEEPDGKWYCPKC 47

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        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233   350 ICVLCRERV--GACIQCSvkTCKTAYHVTCafqHGLEMRAIIEDENaedgvklrSYCQKH 407
Cdd:smart00249    1 YCSVCGKPDdgGELLQCD--GCDRWYHQTC---LGPPLLEEEPDGK--------WYCPKC 47

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 1992621233  294 CVLCPNKGGAMKSTRSGHKWAHVSCALWIPEVSIGSVDRMEPITKISSIPASRWALICVLCRERVGACIQCSVKTCKTAY 373
Cdd:cd15671      1 CVLCPKKGGAMKSTKSGTKWVHVSCALWIPEVSIGCPEKMEPITKISHIPMSRWALVCVLCKEKTGACIQCSVKSCKTAF 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1992621233  374 HVTCAFQHGLEMRAIIEDENaeDGVKLRSYCQKH 407
Cdd:cd15671     81 HVTCAFQHGLEMKTILEDED--DEVKFKSYCPKH 112

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 1992621233  294 CVLCPNKGGAMKSTRSGHKWAHVSCALWIPEVSIGSVDRMEPITKISSIPASRWALICVLCRERVGACIQCSVKTCKTAY 373
Cdd:cd15706      1 CLLCPKTGGAMKATRTGTKWAHVSCALWIPEVSIACPERMEPITKVSHIPPSRWALVCSLCKLKTGACIQCSVKSCITAF 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1992621233  374 HVTCAFQHGLEMRAIIEDenaEDGVKLRSYCQKH 407
Cdd:cd15706     81 HVTCAFEHSLEMKTILDE---GDEVKFKSYCLKH 111

Extended PHD finger found in protein Jade-1 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Jade-1. 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 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 ASA 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 plant homeodomain (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 1992621233  291 RPDCVLCPNKGGAMKSTRSGHKWAHVSCALWIPEVSIGSVDRMEPITKISSIPASRWALICVLCRERVGACIQCSVKTCK 370
Cdd:cd15704      1 QPKCLLCPKKGGAMKPTRSGTKWVHVSCALWIPEVSIGSPEKMEPITKVSHIPSSRWALVCSLCNEKVGASIQCSVKNCR 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1992621233  371 TAYHVTCAFQHGLEMRAIIEDenaEDGVKLRSYCQKHSLNK 411
Cdd:cd15704     81 TAFHVTCAFDRGLEMKTILAE---NDEVKFKSYCPKHSSTK 118

PHD-zinc-finger like domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233  292 PDCVLCPNKGGAMKSTrSGHKWAHVSCALWIPEVSIGSVDRMEPITkISSIPASRWALICVLCRERVGACIQCSVKTCKT 371
Cdd:pfam13832    1 VRCCLCPLRGGALKQT-SDGRWVHVLCAIFVPEVRFGNVATMEPID-VSRIPPERWKLKCVFCKKRSGACIQCSKGRCTT 78

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1992621233  372 AYHVTCAFQHGLEMRaiIEDenaEDGVKLRSYCQKH 407
Cdd:pfam13832   79 AFHVTCAQAAGVYME--PED---WPNVVVIAYCQKH 109

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 1992621233  294 CVLCPNKGGAMKSTRSGhKWAHVSCALWIPEVSIGSVDRMEPITKISSIPASRWALICVLCRERVGACIQCSVKTCKTAY 373
Cdd:cd15662      1 CCLCPVVGGALKPTTDG-RWAHLACAIWIPETCLLDVKTMEPVDGINAISKERWELSCTICKQRYGACIQCSNNSCRVAY 79

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1992621233  374 HVTCAFQHGLEMRAIIE--DENAEDGVKLRSYCQKH 407
Cdd:cd15662     80 HPLCARAAGLCMEVADEggEDPGDQGLRLLSYCPRH 115

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 1992621233  294 CVLCPNKGGAMKSTRSGHkWAHVSCALWIPEVSIGSVDRMEPITKISSIPASRWALICVLCRER-VGACIQCSVKTCKTA 372
Cdd:cd15701      1 CALCPNKGGAFKQTDDGR-WAHVVCALWIPEVCFANTVFLEPIDSIEHIPPARWKLTCYICKQRgSGACIQCHKANCYTA 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1992621233  373 YHVTCAFQHGLEMRAIIEDENAEDG----VKLRSYCQKHS 408
Cdd:cd15701     80 FHVTCAQQAGLYMKMEPVRETGANGtsfsVRKTAYCDIHT 119

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 1992621233  294 CVLCPNKGGAMKSTRSgHKWAHVSCALWIPEVSIGSVDRMEPITKISSIPASRWALICVLCRER-VGACIQCSVKTCKTA 372
Cdd:cd15702      1 CVLCPNKGGAFKKTDD-DRWGHVVCALWIPEVGFANTVFIEPIDGVRNIPPARWKLTCYLCKQKgVGACIQCHKANCYTA 79

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1992621233  373 YHVTCAFQHGLEMRAIIEDENAEDG----VKLRSYCQKH 407
Cdd:cd15702     80 FHVTCAQKAGLYMKMEPVKEVTGGGttfsVRKTAYCDAH 118

Extended PHD finger found in protein AF-10 and AF-17; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of AF-10 and AF-17. 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 the human counterpart of 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-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 plant homeodomain (PHD) finger followed by this non-canonical ePHD finger. 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 Dot1-interacting protein that opposes H2B ubiquitination to reduce polymerase II (Pol II) transcription.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233  294 CVLCPNKGGAMKSTRSGhKWAHVSCALWIPEVSIGSVDRMEPITkISSIPASRWALICVLCRER-------VGACIQCSV 366
Cdd:cd15672      1 CELCPHKDGALKRTDNG-GWAHVVCALYIPEVRFGNVATMEPII-LQDVPQDRFNKTCYICEEQgreskasTGACMQCNK 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1992621233  367 KTCKTAYHVTCAFQHGLemraIIEDE-NAEDGVKLRSYCQKH 407
Cdd:cd15672     79 SGCKQSFHVTCAQMAGL----LCEEAgNYSDNVKYCGYCSYH 116

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 1992621233  294 CVLCPNKGGAMKSTRSGHKWAHVSCALWIPEVSIGSVDRMEPITKISSIPASRWALICVLCRERVGACIQCSvkTCKTAY 373
Cdd:cd15663      1 CCLCPVKGGALKPTDVEGLWVHVTCAWFRPEVCFKNEEKMEPAVGLLRIPLSTFLKACVICKQIHGSCTQCC--KCATYF 78

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1992621233  374 HVTCAFQHGLEMRAIIEDENAEDGVKLRSYCQKH 407
Cdd:cd15663     79 HAMCASRAGYHMELHCLEKNGVQITRMVSYCSFH 112

PHD finger found in protein Jade-3 and similar proteins; Jade-3, also termed PHD finger protein 16 (PHF16), 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-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 Cys4HisCys3 PHD domain followed by a non-canonical extended PHD (ePHD) domain, Cys2HisCys5HisCys2His, both of which are zinc-binding motifs. This model corresponds to the canonical Cys4HisCys3 PHD finger.

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                   ....*....|....*....|....*....|....*....|....*....
gi 1992621233  241 ICDVCRSPDSEEANEMVFCDSCNICVHQACYGITAIPSGQWLCRTCSMG 289
Cdd:cd15681      1 ICDVCRSPDSEEGNDMVFCDKCNICVHQACYGILKVPEGSWLCRTCVLG 49

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233  291 RPDCVLCPNKGGAMKSTRSGhKWAHVSCALWIPEVSIGSVDRMEPITkISSIPASRWALICVLCRER-------VGACIQ 363
Cdd:cd15708      2 RVRCELCPHKDGALKRTDNG-GWAHVVCALYIPEVQFANVSTMEPIV-LQSVPHERYNKTCYICDEQgreskaaTGACMT 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1992621233  364 CSVKTCKTAYHVTCAFQHGLEMRaiiEDENAEDGVKLRSYCQKHsLNKSKKDK 416
Cdd:cd15708     80 CNKHGCRQAFHVTCAQLAGLLCE---EEGNGADNVQYCGYCKYH-YSKLKKSK 128

PHD finger found in protein Jade-2 and similar proteins; 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 Cys4HisCys3 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 1992621233  241 ICDVCRSPDSEEANEMVFCDSCNICVHQACYGITAIPSGQWLCRTC 286
Cdd:cd15680      1 VCDVCRSPEGEDGNEMVFCDKCNVCVHQACYGILKVPTGSWLCRTC 46

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 1992621233  241 ICDVCRSPDSEEANEMVFCDSCNICVHQACYGITAIPSGQWLCRTC 286
Cdd:cd15679      1 VCDVCQSPDGEDGNEMVFCDKCNICVHQACYGILKVPEGSWLCRTC 46

Extended PHD finger (ePHD) found in Jumonji domain-containing protein 2A (JMJD2A); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of JMJD2A. JMJD2A, also termed lysine-specific demethylase 4A (KDM4A), or JmjC domain-containing histone demethylation protein 3A (JHDM3A), catalyzes the demethylation of di- and trimethylated H3K9 and H3K36. It is involved in carcinogenesis and functions as a transcription regulator that may either stimulate or repress gene transcription. It associates with nuclear receptor co-repressor complex or histone deacetylases. Moreover, JMJD2A forms complexes with both the androgen and estrogen receptor (ER) and plays an essential role in growth of both ER-positive and -negative breast tumors. It is also involved in prostate, colon, and lung cancer progression. JMJD2A contains jmjN and jmjC domains in the N-terminal region, followed by a canonical PHD finger, this non-canonical ePHD finger, and a Tudor domain.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1992621233  294 CVLCPNKGGAMKSTrSGHKWAHVSCALWIPEVSIGSVDRMEPItKISSIPASRWALICVLCRERV----GACIQCSVKTC 369
Cdd:cd15713      1 CCLCSLRGGALQRA-NDDKWVHVMCAVAVLEARFVNIAERSPV-DVSKIPLQRFKLKCIFCKKRRkrtaGCCVQCSHGRC 78

                           90
                   ....*....|....*..
gi 1992621233  370 KTAYHVTCAFQHGLEMR 386
Cdd:cd15713     79 PTSFHASCAQAAGVMMQ 95

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 1992621233  237 DENVICDVCRSPDSEEANEMVFCDSCNICVHQACYGITAIPSGQWLCRTC 286
Cdd:cd15676      5 DEDAVCCICNDGECQNSNVILFCDMCNLAVHQECYGVPYIPEGQWLCRRC 54

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.

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                   ....*....|....*....|....*....|....*....|....*....|.
gi 1992621233  241 ICDVCRSPDseEANEMVFCDSCNICVHQACYGIT----AIPSGQWLCRTCS 287
Cdd:pfam00628    1 YCAVCGKSD--DGGELVQCDGCDDWFHLACLGPPldpaEIPSGEWLCPECK 49

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.

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                   ....*....|....*....|....*....|....*....|....*.
gi 1992621233  242 CDVCRSPDSEEANEMVFCDSCNICVHQACYGITAI-PSGQWLCRTC 286
Cdd:cd15495      2 CAVCNEGEDDDNNPLITCNRCQISVHQKCYGIREVdPDGSWVCRAC 47

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.

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                   ....*....|....*....|....*....|....*....|....*..
gi 1992621233  242 CDVCRSPDSEEANEMVFCD--SCNICVHQACYGITAIPSGQWLCRTC 286
Cdd:cd15574      2 CCVCSDERGWAENPLVYCDghGCNVAVHQACYGIVQVPTGPWFCRKC 48