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 20129223  184 CELCPNKGGIYKETDVGKWVHLICALYVPGVAFGEVEQLSSVTLFEMQYSKWGAKVCSLCENALFARTGVCIGCDAGMCK 263
Cdd:cd15674    1 CELCPNRGGIFKETDTGRWVHLVCALYTPGVAFGDVDKLSPVTLTEMNYSKWGARECSLCEDPRFARTGVCISCDAGMCK 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 20129223  264 TYFHVTCAQVAGFLIEAHHEDDAADPFYAHCKVH 297
Cdd:cd15674   81 SYFHVTCAQREGLLSEATDEEDIADPFYAYCKQH 114

PHD finger 2 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 second PHD finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 20129223  586 SCGICKRSKDQHLLVKCDTCNLHYHLGCLNPPLTRPPKKSKQYGWQCSEC 635
Cdd:cd15562    1 SCGICKKSNDQHLLALCDTCKLYYHLGCLDPPLTRMPKKTKNSGWQCSEC 50

transport protein TonB; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20129223   854 FYVPANAVRSVDEASRPTSVETVEDSVQGAEQALA----PIVLPAASPQKVREPKETAASASVNPTPSPKRKVSPrKASP 929
Cdd:PRK10819   31 LYTSVHQVIELPAPAQPISVTMVAPADLEPPQAVQpppePVVEPEPEPEPIPEPPKEAPVVIPKPEPKPKPKPKP-KPKP 109

                  ....*....
gi 20129223   930 RKPRVGRPR 938
Cdd:PRK10819  110 VKKVEEQPK 118

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 20129223  184 CELCPNKGGIYKETDVGKWVHLICALYVPGVAFGEVEQLSSVTLFEMQYSKWGAKVCSLCENALFARTGVCIGCDAGMCK 263
Cdd:cd15674    1 CELCPNRGGIFKETDTGRWVHLVCALYTPGVAFGDVDKLSPVTLTEMNYSKWGARECSLCEDPRFARTGVCISCDAGMCK 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 20129223  264 TYFHVTCAQVAGFLIEAHHEDDAADPFYAHCKVH 297
Cdd:cd15674   81 SYFHVTCAQREGLLSEATDEEDIADPFYAYCKQH 114

PHD finger 2 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 second PHD finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 20129223  586 SCGICKRSKDQHLLVKCDTCNLHYHLGCLNPPLTRPPKKSKQYGWQCSEC 635
Cdd:cd15562    1 SCGICKKSNDQHLLALCDTCKLYYHLGCLDPPLTRMPKKTKNSGWQCSEC 50

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 20129223  949 SCCVCSQTGKSNQVVTCDECHRHYHFACLDPPLKKSPKIRGYSWHCADC 997
Cdd:cd15563    1 ECCVCKQTGDNSQLVRCDECKLCYHFGCLDPPLKKSPKQRGYGWVCEEC 49

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
                   ....*....|....*....|....*....|....*....|....*....
gi 20129223    587 CGICKRSKDQHLLVKCDTCNLHYHLGCLNPPLTRPPKKSKqyGWQCSEC 635
Cdd:pfam00628    2 CAVCGKSDDGGELVQCDGCDDWFHLACLGPPLDPAEIPSG--EWLCPEC 48

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 20129223    950 CCVCSQTGKSNQVVTCDECHRHYHFACLDPPLKKSPKIRGySWHCADCDP 999
Cdd:pfam00628    2 CAVCGKSDDGGELVQCDGCDDWFHLACLGPPLDPAEIPSG-EWLCPECKP 50

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
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 20129223     120 MCCVClgERSDDVNEIVECDSCGVSVHEGCYGVSDNVSIsstnstcSTEPWFCEAC 175
Cdd:smart00249    1 YCSVC--GKPDDGGELLQCDGCDRWYHQTCLGPPLLEEE-------PDGKWYCPKC 47

transport protein TonB; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 20129223   854 FYVPANAVRSVDEASRPTSVETVEDSVQGAEQALA----PIVLPAASPQKVREPKETAASASVNPTPSPKRKVSPrKASP 929
Cdd:PRK10819   31 LYTSVHQVIELPAPAQPISVTMVAPADLEPPQAVQpppePVVEPEPEPEPIPEPPKEAPVVIPKPEPKPKPKPKP-KPKP 109

                  ....*....
gi 20129223   930 RKPRVGRPR 938
Cdd:PRK10819  110 VKKVEEQPK 118

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 20129223  184 CELCPNKGGIYKETDVGKWVHLICALYVPGVAFGEVEQLSSVTLFEMQYSKWGAKVCSLCENALFARTGVCIGCDAGMCK 263
Cdd:cd15674    1 CELCPNRGGIFKETDTGRWVHLVCALYTPGVAFGDVDKLSPVTLTEMNYSKWGARECSLCEDPRFARTGVCISCDAGMCK 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 20129223  264 TYFHVTCAQVAGFLIEAHHEDDAADPFYAHCKVH 297
Cdd:cd15674   81 SYFHVTCAQREGLLSEATDEEDIADPFYAYCKQH 114

PHD finger 2 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 second PHD finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 20129223  586 SCGICKRSKDQHLLVKCDTCNLHYHLGCLNPPLTRPPKKSKQYGWQCSEC 635
Cdd:cd15562    1 SCGICKKSNDQHLLALCDTCKLYYHLGCLDPPLTRMPKKTKNSGWQCSEC 50

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 20129223  949 SCCVCSQTGKSNQVVTCDECHRHYHFACLDPPLKKSPKIRGYSWHCADC 997
Cdd:cd15563    1 ECCVCKQTGDNSQLVRCDECKLCYHFGCLDPPLKKSPKQRGYGWVCEEC 49

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 20129223  184 CELCPNKGGIYKE------TDVGKWVHLICALYVPGVAFGEVEQLSSVTLFEMQYSKWGAKvCSLCENalfaRTGVCIGC 257
Cdd:cd15571    1 CALCPRSGGALKGggalktTSDGLWVHVVCALWSPEVYFDDGTLLEVEGVSKIPKRRKKLK-CSICGK----RGGACIQC 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 20129223  258 DAGMCKTYFHVTCAQVAGFLIEAHhedDAADPFYAHCKVH 297
Cdd:cd15571   76 SYPGCPRSFHVSCAIRAGCLFEFE---DGPGNFVVYCPKH 112

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 20129223  184 CELCPNKGGIYKETDVGKWVHLICALYVPGVAFGEVEQLSSVTLFEMQYSKWgAKVCSLCENA---LFARTGVCIGCDAG 260
Cdd:cd15672    1 CELCPHKDGALKRTDNGGWAHVVCALYIPEVRFGNVATMEPIILQDVPQDRF-NKTCYICEEQgreSKASTGACMQCNKS 79

                         90
                 ....*....|....*....
gi 20129223  261 MCKTYFHVTCAQVAGFLIE 279
Cdd:cd15672   80 GCKQSFHVTCAQMAGLLCE 98

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 20129223  184 CELCPNKGGIYKETDVGKWVHLICALYVPGVAFGEVEQLSSVTLFE-MQYSKWGAKvCSLCENalfaRTGVCIGCDAGMC 262
Cdd:cd15670    1 CVLCPNKGGAFKQTDDGRWAHVVCALWIPEVSFANTVFLEPIDGIQnIPKARWKLT-CYICKK----RMGACIQCHKKNC 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 20129223  263 KTYFHVTCAQVAGFLIEAHHEDDAADPFY------AHCKVH 297
Cdd:cd15670   76 YTAFHVTCAQQAGLYMKIEPVKDPGNGTSdsvrkeAYCDKH 116

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 20129223    204 HLICALYVPGVAF-GEVEQLSSVTLFEMQYSKWGAKVCSLCENalfaRTGVCIGCDAGMCKTYFHVTCAQVAGFLIEahh 282
Cdd:pfam13771    1 HVVCALWSPELVQrGNDSMGFPIEDIEKIPKRRWKLKCYLCKK----KGGACIQCSKKNCRRAFHVTCALEAGLLMQ--- 73

                           90
                   ....*....|....*
gi 20129223    283 EDDAADPFYAHCKVH 297
Cdd:pfam13771   74 FDEDNGTFKSYCKKH 88

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 20129223  184 CELCPNKGGIYKETDVGKWVHLICALYVPGVAFGEVEQLSSVTLFEMQYSKWGaKVCSLCENA---LFARTGVCIGCDAG 260
Cdd:cd15709    5 CELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPIVLQYVPHDRFN-KTCYICEEQgreSKAASGACMTCNRH 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 20129223  261 MCKTYFHVTCAQVAGFLIEAHHEDDAADPFYAHCKVHSEK 300
Cdd:cd15709   84 GCRQAFHVTCAQMAGLLCEEEVLEVDNVKYCGYCKYHFNK 123

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 20129223  184 CELCPNKGGIYKETDVGKWVHLICALYVPGVAFGE---VEQLSSVTlfEMQYSKWGAkVCSLCENalfARTGVCIGCDAG 260
Cdd:cd15702    1 CVLCPNKGGAFKKTDDDRWGHVVCALWIPEVGFANtvfIEPIDGVR--NIPPARWKL-TCYLCKQ---KGVGACIQCHKA 74

                         90
                 ....*....|....*....
gi 20129223  261 MCKTYFHVTCAQVAGFLIE 279
Cdd:cd15702   75 NCYTAFHVTCAQKAGLYMK 93

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 20129223  181 EPDCELCPNKGGIYKETDVG-KWVHLICALYVPGVAFGEVEQLSSVTLFEMQYSKWGAKVCSLCENalfaRTGVCIGCDA 259
Cdd:cd15704    1 QPKCLLCPKKGGAMKPTRSGtKWVHVSCALWIPEVSIGSPEKMEPITKVSHIPSSRWALVCSLCNE----KVGASIQCSV 76

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 20129223  260 GMCKTYFHVTCAQVAGFLIEAHHEDDAADPFYAHCKVHS 298
Cdd:cd15704   77 KNCRTAFHVTCAFDRGLEMKTILAENDEVKFKSYCPKHS 115

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 20129223  184 CELCPNKGGIYKETDVGKWVHLICALYVPGVAFGEVEQLSSVT-LFEMQYSKWGAkVCSLCENalfARTGVCIGCDAGMC 262
Cdd:cd15703    1 CVLCPNKGGAFKQTSDGRWAHVVCAIWIPEVCFANTVFLEPVEgVNNIPPARWKL-TCYLCKQ---KGRGAAIQCHKVNC 76

                         90
                 ....*....|....*..
gi 20129223  263 KTYFHVTCAQVAGFLIE 279
Cdd:cd15703   77 YTAFHVTCAQRAGLFMK 93

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        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 20129223  586 SCGICKRSKDQHLLVKCDTCNLHYHLGCLNPPLTRPPKKsKQYGWQCSEC 635
Cdd:cd15563    1 ECCVCKQTGDNSQLVRCDECKLCYHFGCLDPPLKKSPKQ-RGYGWVCEEC 49

PHD finger 2 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 second PHD finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 20129223  949 SCCVCSQTGKSNQVVTCDECHRHYHFACLDPPLKKSP-KIRGYSWHCADC 997
Cdd:cd15562    1 SCGICKKSNDQHLLALCDTCKLYYHLGCLDPPLTRMPkKTKNSGWQCSEC 50

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 20129223  184 CELCPNKGGIYKETDVGKWVHLICALYVPGVAFGEVEQLSSVTLFEMQYSKWGAKvCSLCENALFARTGVCIGCDAGMCK 263
Cdd:cd15713    1 CCLCSLRGGALQRANDDKWVHVMCAVAVLEARFVNIAERSPVDVSKIPLQRFKLK-CIFCKKRRKRTAGCCVQCSHGRCP 79

                         90       100       110
                 ....*....|....*....|....*....|....
gi 20129223  264 TYFHVTCAQVAGFLIeahHEDDAADPFYAHCKVH 297
Cdd:cd15713   80 TSFHASCAQAAGVMM---QPDDWPFVVFITCFRH 110

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.

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gi 20129223  121 CCVCLGERSDDVNEIVECDSCGVSVHEGCYGVsdnvsisstnSTCSTEPWFCEAC 175
Cdd:cd15492    2 CDVCLDGESEDDNEIVFCDGCNVAVHQSCYGI----------PLIPEGDWFCRKC 46

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.

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gi 20129223  184 CELCPNKGGIYKETDVGKWVHLICALYVPGVAFGEVEQLSSV-TLFEMQYSKWgAKVCSLCEnalfARTGVCIGCDAGMC 262
Cdd:cd15662    1 CCLCPVVGGALKPTTDGRWAHLACAIWIPETCLLDVKTMEPVdGINAISKERW-ELSCTICK----QRYGACIQCSNNSC 75

                         90       100
                 ....*....|....*....|..
gi 20129223  263 KTYFHVTCAQVAGFLIEAHHED 284
Cdd:cd15662   76 RVAYHPLCARAAGLCMEVADEG 97

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.

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gi 20129223     587 CGICKRSKDQHLLVKCDTCNLHYHLGCLNPPLTRPPKKSKqygWQCSEC 635
Cdd:smart00249    2 CSVCGKPDDGGELLQCDGCDRWYHQTCLGPPLLEEEPDGK---WYCPKC 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.

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                   ....*....|....*....|....*....|....*....|....*....|
gi 20129223    950 CCVCSQTGKSNQVVTCDECHRHYHFACLDPPLKKSPKIRGySWHCADCDP 999
Cdd:pfam00628    2 CAVCGKSDDGGELVQCDGCDDWFHLACLGPPLDPAEIPSG-EWLCPECKP 50

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 20129223  121 CCVCLGERSDDVNEIVECDSCGVSVHEGCYGVSDNVSISStnstcstepWFCEAC 175
Cdd:cd15495    2 CAVCNEGEDDDNNPLITCNRCQISVHQKCYGIREVDPDGS---------WVCRAC 47

PHD finger 2 found in PHD finger protein 12 (PHF12), yeast Rco1, and similar proteins; PHF12, also termed PHD factor 1 (Pf1), is a plant homeodomain (PHD) zinc finger-containing protein that bridges the transducin-like enhancer of split (TLE) corepressor to the mSin3A-histone deacetylase (HDAC)-complex, and further represses transcription at targeted genes. PHF12 also interacts with MRG15 (mortality factor-related genes on chromosome 15), a member of the mortality factor (MORF) family of proteins implicated in regulating cellular senescence. PHF12 contains two plant homeodomain (PHD) zinc fingers followed by a polybasic region. The PHD fingers function downstream of phosphoinositide signaling triggered by the interaction between polybasic regions and phosphoinositides. This subfamily also includes yeast transcriptional regulatory protein Rco1 and similar proteins. Rco1 is a component of the Rpd3S histone deacetylase complex that plays an important role at actively transcribed genes. Rco1 contains two PHD fingers, which are required for the methylation of histone H3 lysine 36 (H3K36) nucleosome recognition by Rpd3S. This model corresponds to the second PHD finger.

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gi 20129223  587 CGICKRSKDQHLLVKCDTCNLHYHLGCLNPPLTRPPKKSKqygWQC 632
Cdd:cd15534    2 CFKCNRSCRVAPLIQCDYCPLLFHLDCLDPPLTHPPATGR---WMC 44

PHD finger 1 found in Saccharomyces cerevisiae SANT domain-containing protein 2 (Snt2p) and similar proteins; Snt2p 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 Cys4HisCys3 plant homeodomain (PHD) fingers, a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, and a SANT (SWI3, ADA2, N-CoR and TFIIIB) DNA-binding domain; this model corresponds to the first canonical Cys4HisCys3 PHD finger.

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gi 20129223  586 SCGICKR--SKDQHllVKCDTCNLHYHLGCLNPPLTRPPKKSkqYGWQCSEC 635
Cdd:cd15497    1 SCKVCKEwcASDDS--VRCDECKVSYHLLCVDPPLTKKPNRG--FVWSCAPC 48

PHD finger found in ubiquitin-like PHD and RING finger domain-containing protein 2 (UHRF2); UHRF2 (also termed Np95/ICBP90-like RING finger protein (NIRF), Np95-like RING finger protein, nuclear protein 97, nuclear zinc finger protein Np97, RING finger protein 107, or E3 ubiquitin-protein ligase UHRF2) was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs,p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) by interacting with the HBV core protein and promoting its degradation. UHRF2 contains an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal RING finger.

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gi 20129223  949 SCCVCSQTGKSNQVVTCDECHRHYHFACLDPPLKKSPKIRgySWHCADC 997
Cdd:cd15617    1 SCYVCGGKQDAHMQLLCDECNMAYHIYCLNPPLDKIPEDE--DWYCPSC 47

PHD finger 2 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, five plant homeodomain (PHD) fingers, two extended PHD (ePHD) fingers, Cys2HisCys5HisCys2His, a RING finger, an HMG (high-mobilitygroup)-binding motif, and two FY-rich regions. This model corresponds to the second PHD finger.

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gi 20129223  587 CGICKRSKDQHLLVKCDTCNLHYHLGCLNPPLTRPPKkskqYGWQCSEC 635
Cdd:cd15510    2 CQACRQPGDDTKMLVCETCDKGYHTSCLRPVMSSIPK----YGWKCKNC 46

PHD finger found in PHD finger protein 21A (PHF21A); PHF21A (also termed BHC80a or BRAF35-HDAC complex protein BHC80) along with HDAC1/2, CtBP1, CoREST, and BRAF35, is associated with LSD1, a lysine (K)-specific histone demethylase. It inhibits LSD1-mediated histone demethylation in vitro. PHF21A is predominantly present in the central nervous system and spermatogenic cells and is one of the six components of BRAF-HDAC complex (BHC) involved in REST-dependent transcriptional repression of neuron-specific genes in non-neuronal cells. It acts as a scaffold protein in BHC in neuronal as well as non-neuronal cells and also plays a role in spermatogenesis. PHF21A contains a C-terminal plant homeodomain (PHD) finger that is responsible for the binding directly to each of five other components of BHC, and of organizing BHC mediating transcriptional repression.

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gi 20129223  950 CCVCSQTGksnQVVTCDECHRHYHFACLDPPLKKSPKirgYSWHCADC 997
Cdd:cd15523    2 CSVCRKSG---ELLMCDTCSLVYHLDCLDPPLKTIPK---GMWICPKC 43

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 20129223  121 CCVCLGERSDDVNEIVECD--SCGVSVHEGCYGVsdnvsisstnSTCSTEPWFCEAC 175
Cdd:cd15574    2 CCVCSDERGWAENPLVYCDghGCNVAVHQACYGI----------VQVPTGPWFCRKC 48