MYST -like histone acetyltransferase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  538 SVIEFGKYEIQTWYSSPYPQEYARLPKLYLCEFCLKYMKSKNILLRHSKKCGWFHPPANEIYR----RKDLSVFEVDGNM 613
Cdd:PLN00104   171 ATIELGRYEIDTWYFSPFPPEYNDCSKLYFCEFCLKFMKRKEQLQRHMKKCDLKHPPGDEIYRhptrQEGLSMFEVDGKK 250

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  614 SKIYCQNLCLLAKLFLDHKTLYYDVEPFLFYVLTKNDEKGCHLVGYFSKEKLCQQKYNVSCIMIMPQHQRQGFGRFLIDF 693
Cdd:PLN00104   251 NKVYCQNLCYLAKLFLDHKTLYYDVDLFLFYVLCECDDRGCHMVGYFSKEKHSEEDYNLACILTLPPYQRKGYGKFLIAF 330

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  694 SYLLSRREGQAGSPEKPLSDLGRLSYLAYWKSVILEYLyHHHERHISIKAISRATGMCPHDIATTLQHLHMIDKRDGRFV 773
Cdd:PLN00104   331 SYELSKREGKVGTPERPLSDLGLVSYRGYWTRVLLEIL-KKHKGNISIKELSDMTAIKAEDIVSTLQSLNLIQYRKGQHV 409

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1625649087  774 IIRREKLILSHMEKLKtcSRANELDPDSLRWTP 806
Cdd:PLN00104   410 ICADPKVLEEHLKAAG--RGGLEVDPSKLIWTP 440

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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1625649087  271 TCSACRVQGrNADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15527      1 TCSVCQDSG-NADNLLFCDACDKGFHMECHDPPLTRMPKGKWVCQIC 46

MYST -like histone acetyltransferase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  538 SVIEFGKYEIQTWYSSPYPQEYARLPKLYLCEFCLKYMKSKNILLRHSKKCGWFHPPANEIYR----RKDLSVFEVDGNM 613
Cdd:PLN00104   171 ATIELGRYEIDTWYFSPFPPEYNDCSKLYFCEFCLKFMKRKEQLQRHMKKCDLKHPPGDEIYRhptrQEGLSMFEVDGKK 250

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  614 SKIYCQNLCLLAKLFLDHKTLYYDVEPFLFYVLTKNDEKGCHLVGYFSKEKLCQQKYNVSCIMIMPQHQRQGFGRFLIDF 693
Cdd:PLN00104   251 NKVYCQNLCYLAKLFLDHKTLYYDVDLFLFYVLCECDDRGCHMVGYFSKEKHSEEDYNLACILTLPPYQRKGYGKFLIAF 330

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  694 SYLLSRREGQAGSPEKPLSDLGRLSYLAYWKSVILEYLyHHHERHISIKAISRATGMCPHDIATTLQHLHMIDKRDGRFV 773
Cdd:PLN00104   331 SYELSKREGKVGTPERPLSDLGLVSYRGYWTRVLLEIL-KKHKGNISIKELSDMTAIKAEDIVSTLQSLNLIQYRKGQHV 409

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1625649087  774 IIRREKLILSHMEKLKtcSRANELDPDSLRWTP 806
Cdd:PLN00104   410 ICADPKVLEEHLKAAG--RGGLEVDPSKLIWTP 440

Histone acetyltransferase (MYST family) [Chromatin structure and dynamics];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  540 IEFGKYEIQTWYSSPYPQEYARLPKLYLCEFCLKYMKSKNILLRHSKKCGWFHPPANEIYRRKDLSVFEVDGNMSKIYCQ 619
Cdd:COG5027    133 IKLGNYEIEPWYFSPYPEEFSDLDIVYICEFCLKYYGSQTSLVRHRKKCSLQHPPGNEIYRDKYISFFEIDGRKQRLYCR 212

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  620 NLCLLAKLFLDHKTLYYDVEPFLFYVLTKNDEKGCHLVGYFSKEKLCQQKYNVSCIMIMPQHQRQGFGRFLIDFSYLLSR 699
Cdd:COG5027    213 NLCLLSKLFLDHKTLYYDVDPFLFYVLTERGDTGCHLVGYFSKEKESEQDYNLACILTLPPYQRRGYGKLLIDFSYLLSQ 292

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  700 REGQAGSPEKPLSDLGRLSYLAYWKSVILEYLYHHHERHISIKAISRATGMCPHDIATTLQHLHMIDKRDGRFVI-IRRE 778
Cdd:COG5027    293 KEGKVGSPEKPLSDLGLLSYRAYWSEIVAKLLLKMDKEITDINEISKETGMSTDDVIHTLEALNILREYKGQYIIsLNSD 372

                          250       260
                   ....*....|....*....|....*..
gi 1625649087  779 KLilshMEKLKTCSRANE-LDPDSLRW 804
Cdd:COG5027    373 KL----HNYLRLWSKKRRrINPDLLLW 395

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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1625649087  271 TCSACRVQGrNADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15527      1 TCSVCQDSG-NADNLLFCDACDKGFHMECHDPPLTRMPKGKWVCQIC 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 1625649087   271 TCSACRvQGRNADNMLFCDSCDRGFHMECCDPPL-SRMPKGMWICQVC 317
Cdd:smart00249    1 YCSVCG-KPDDGGELLQCDGCDRWYHQTCLGPPLlEEEPDGKWYCPKC 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        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1625649087  215 ICSFClgtkesNREKKPEELLSCADCGSSGHPSCLKFcPELTTNVKALRWQCIECKTC 272
Cdd:pfam00628    1 YCAVC------GKSDDGGELVQCDGCDDWFHLACLGP-PLDPAEIPSGEWLCPECKPK 51

linker histone 1 and histone 5 domains; the basic subunit of chromatin is the nucleosome, consisting of an octamer of core histones, two full turns of DNA, a linker histone (H1 or H5) and a variable length of linker DNA; H1/H5 are chromatin-associated proteins that bind to the exterior of nucleosomes and dramatically stabilize the highly condensed states of chromatin fibers; stabilization of higher order folding occurs through electrostatic neutralization of the linker DNA segments, through a highly positively charged carboxy- terminal domain known as the AKP helix (Ala, Lys, Pro); thought to be involved in specific protein-protein and protein-DNA interactions and play a role in suppressing core histone tail domain acetylation in the chromatin fiber

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1625649087  114 AIEGLEEPNGSSLKNIEKYLRSQSDLTSTTNNPafqqRLRLGAKRAVNNGRLLK 167
Cdd:cd00073     14 AIKALKERKGSSLQAIKKYIEAKYKVDDENFNK----LLKLALKKGVAKGKLVQ 63

MYST -like histone acetyltransferase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  538 SVIEFGKYEIQTWYSSPYPQEYARLPKLYLCEFCLKYMKSKNILLRHSKKCGWFHPPANEIYR----RKDLSVFEVDGNM 613
Cdd:PLN00104   171 ATIELGRYEIDTWYFSPFPPEYNDCSKLYFCEFCLKFMKRKEQLQRHMKKCDLKHPPGDEIYRhptrQEGLSMFEVDGKK 250

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  614 SKIYCQNLCLLAKLFLDHKTLYYDVEPFLFYVLTKNDEKGCHLVGYFSKEKLCQQKYNVSCIMIMPQHQRQGFGRFLIDF 693
Cdd:PLN00104   251 NKVYCQNLCYLAKLFLDHKTLYYDVDLFLFYVLCECDDRGCHMVGYFSKEKHSEEDYNLACILTLPPYQRKGYGKFLIAF 330

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  694 SYLLSRREGQAGSPEKPLSDLGRLSYLAYWKSVILEYLyHHHERHISIKAISRATGMCPHDIATTLQHLHMIDKRDGRFV 773
Cdd:PLN00104   331 SYELSKREGKVGTPERPLSDLGLVSYRGYWTRVLLEIL-KKHKGNISIKELSDMTAIKAEDIVSTLQSLNLIQYRKGQHV 409

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1625649087  774 IIRREKLILSHMEKLKtcSRANELDPDSLRWTP 806
Cdd:PLN00104   410 ICADPKVLEEHLKAAG--RGGLEVDPSKLIWTP 440

Histone acetyltransferase (MYST family) [Chromatin structure and dynamics];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  540 IEFGKYEIQTWYSSPYPQEYARLPKLYLCEFCLKYMKSKNILLRHSKKCGWFHPPANEIYRRKDLSVFEVDGNMSKIYCQ 619
Cdd:COG5027    133 IKLGNYEIEPWYFSPYPEEFSDLDIVYICEFCLKYYGSQTSLVRHRKKCSLQHPPGNEIYRDKYISFFEIDGRKQRLYCR 212

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  620 NLCLLAKLFLDHKTLYYDVEPFLFYVLTKNDEKGCHLVGYFSKEKLCQQKYNVSCIMIMPQHQRQGFGRFLIDFSYLLSR 699
Cdd:COG5027    213 NLCLLSKLFLDHKTLYYDVDPFLFYVLTERGDTGCHLVGYFSKEKESEQDYNLACILTLPPYQRRGYGKLLIDFSYLLSQ 292

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  700 REGQAGSPEKPLSDLGRLSYLAYWKSVILEYLYHHHERHISIKAISRATGMCPHDIATTLQHLHMIDKRDGRFVI-IRRE 778
Cdd:COG5027    293 KEGKVGSPEKPLSDLGLLSYRAYWSEIVAKLLLKMDKEITDINEISKETGMSTDDVIHTLEALNILREYKGQYIIsLNSD 372

                          250       260
                   ....*....|....*....|....*..
gi 1625649087  779 KLilshMEKLKTCSRANE-LDPDSLRW 804
Cdd:COG5027    373 KL----HNYLRLWSKKRRrINPDLLLW 395

histone acetyltransferase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  502 KDVVTE---EDLDVFKQAQELSWEKIECESGVEDCGrypsVIEFGKYEIQTWYSSPYPQEYAR----LPKLYLCEFCLKY 574
Cdd:PLN03239    40 EDVVATiaaPELDEHEGLDDAALKEHEEVTKVKNVA----FLELGPYQMDTWYFSPLPKELFKaggfIDVLYVCEFSFGF 115

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  575 MKSKNILLRHSKKC---GWFHPPANEIYRRKDLSVFEVDGNMSKIYCQNLCLLAKLFLDHKTLYYDVEPFLFYVLTKNDE 651
Cdd:PLN03239   116 FARKSELLRFQAKElpkERRHPPGNEIYRCGDLAMFEVDGFEERIYCQNLCYIAKLFLDHKTLYFDVDPFLFYVLCEVDE 195

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649087  652 KGCHLVGYFSKEKLCQQKYNVSCIMIMPQHQRQGFGRFLIDFSYLLSRREGQAGSPEKPLSDLGRLSYLAYWKSVILEYL 731
Cdd:PLN03239   196 RGFHPVGYYSKEKYSDVGYNLACILTFPAHQRKGYGRFLIAFSYELSKKEEKVGSPEKPMSDLGQQAYIPYWGSTIVDFL 275

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1625649087  732 YHH--HERHISIKAISRATGMCPHDIATTLQHLHMIDKRDGRFvIIRREKLILSHMEKlKTCSRANELDPDSLRWTP 806
Cdd:PLN03239   276 LNHsgNDSSLSIMDIAKKTSIMAEDIVFALNQLGILKFINGIY-FIAAEKGLLEELAE-KHPVKEPRVDPSKLHWTP 350

PHD finger 1 found in monocytic leukemia zinc finger protein-related factor (MORF); 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 histone acetyltransferase (HAT) activity. It can interact with the Runt-domain transcription factor Runx2 and form a tetrameric complex with BRPFs, ING5, and EAF6. MORF and monocytic leukemia zinc-finger protein (MOZ) 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. MORF contains an N-terminal region containing two plant homeodomain (PHD) fingers, a putative HAT domain, an acidic region, and a C-terminal Ser/Met-rich domain. The model corresponds to the first PHD finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1625649087  212 PIPICSFCLGTKESNREKKPEELLSCADCGSSGHPSCLKFCPELTTNVKALRWQCIECK 270
Cdd:cd15689      1 PIPICSFCLGTKESNREKKPEELLSCADCGSSGHPSCLKFCPELTANVKALRWQCIECK 59

PHD finger 1 found in monocytic leukemia zinc-finger protein (MOZ); 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 and MOZ-related factor (MORF) are catalytic subunits of histone acetyltransferase (HAT) complexes that are required for normal developmental programs, such as hematopoiesis, neurogenesis, and skeletogenesis, and implicated in human leukemias. It 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. The model corresponds to the first PHD finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1625649087  212 PIPICSFCLGTKESNREKKPEELLSCADCGSSGHPSCLKFCPELTTNVKALRWQCIECK 270
Cdd:cd15688      1 PIPICSFCLGTKEQNREKKPEELISCADCGNSGHPSCLKFSPELTVRVKALRWQCIECK 59

PHD finger 1 found in monocytic leukemia zinc-finger protein (MOZ), its factor (MORF), and d4 gene family proteins; MOZ 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 and 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) 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 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 lymphoma genesis and bone development, and its homologs. This family also includes three members of the d4 gene family, DPF1 (neuro-d4), DPF2 (ubi-d4/Requiem), and DPF3 (cer-d4), which function as transcription factors and are involved in transcriptional regulation of genes via changing the condensed/decondensed state of chromatin in nucleus. DPF2 is ubiquitously expressed and it acts as a transcription factor that may participate in developmentally programmed cell death. DPF1 and DPF3 are expressed predominantly in neural tissues, and they may be involved in the transcription regulation of neuro specific gene clusters. All family members contain two plant homeodomain (PHD) fingers. This model corresponds to the first PHD finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1625649087  215 ICSFCLGTKE-SNREKKPEELLSCADCGSSGHPSCLKFCPELTTNVKALRWQCIEC 269
Cdd:cd15526      1 ICDFCLGTDEkNNKTGEPEELISCADCGSSGHPSCLKFSPGLTDAVKSYRWQCIEC 56

PHD finger 1 found in d4 gene family proteins; The family includes proteins coded by three members of the d4 gene family, DPF1 (neuro-d4), DPF2 (ubi-d4/Requiem), and DPF3 (cer-d4), which function as transcription factors and are involved in transcriptional regulation of genes by changing the condensed/decondensed state of chromatin in the nucleus. DPF2 is ubiquitously expressed and it acts as a transcription factor that may participate in developmentally programmed cell death. DPF1 and DPF3 are expressed predominantly in neural tissues, and they may be involved in the transcription regulation of neuro-specific gene clusters. The d4 family proteins show distinct domain organization with domain 2/3 in the N-terminal region, a Cys2His2 (C2H2) zinc finger or Kruppel-type zinc finger in the central part and two adjacent plant homeodomain (PHD) fingers (d4-domain) in the C-terminal part of the molecule. This model corresponds to the first PHD finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1625649087  216 CSFCLG-TKESNREKKPEELLSCADCGSSGHPSCLKFCPELTTNVKALRWQCIEC 269
Cdd:cd15619      2 CDFCLGdAKENKKTGQPEELVSCSDCGRSGHPSCLQFTPNMTISVKKYRWQCIEC 56

PHD finger 1 found in D4, zinc and double PHD fingers family 3 (DPF3); DPF3, also termed BRG1-associated factor 45C (BAF45C), or zinc finger protein cer-d4, is encoded by a neuro-specific gene, cer-d4. It functions as a new epigenetic key factor for heart and muscle development and may be involved in the transcription regulation of neuro-specific gene clusters. It interacts with the BAF chromatin remodeling complex and binds methylated and acetylated lysine residues of histone 3 and 4. DPF3 contains a nuclear localization signal in the N-terminal region, a Cys2His2 (C2H2) zinc finger or Kruppel-type zinc-finger and a sequence of negatively charged amino acids in the central region, and a cysteine/histidine-rich region that is composed of two adjacent plant homeodomain (PHD) fingers (d4-domain) in the C-terminal part of the molecule. This model corresponds to the first PHD finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1625649087  216 CSFCLGTKESNREK-KPEELLSCADCGSSGHPSCLKFCPELTTNVKALRWQCIECK 270
Cdd:cd15692      2 CDFCLGGSNMNKKSgRPEELVSCADCGRSGHPTCLQFTVNMTEAVKTYQWQCIECK 57

PHD finger found in bromodomain adjacent to zinc finger domain protein 1A (BAZ1A); BAZ1A, also termed ATP-dependent chromatin-remodeling protein, or ATP-utilizing chromatin assembly and remodeling factor 1 (ACF1), or CHRAC subunit ACF1, or Williams syndrome transcription factor-related chromatin-remodeling factor 180 (WCRF180), or WALp1, is a subunit of the conserved imitation switch (ISWI)-family ATP-dependent chromatin assembly and remodeling factor (ACF)/chromatin accessibility complex (CHRAC) chromatin remodeling complex, which is required for DNA replication through heterochromatin. It alters the remodeling properties of the ATPase motor protein sucrose nonfermenting-2 homolog (SNF2H). Moreover, BAZ1A and its complexes play important roles in DNA double-strand break (DSB) repair. It is essential for averting improper gene expression during spermatogenesis. It also regulates transcriptional repression of vitamin D3 receptor-regulated genes. BAZ1A contains a WAC motif, a DDT domain, BAZ 1 and BAZ 2 motifs, a WAKZ (WSTF/Acf1/KIAA0314/ZK783.4) motif, a plant homeodomain (PHD) finger, and a bromodomain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1625649087  272 CSACRVQGrNADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15627      2 CRICRRKG-DAEKMLLCDGCDRGHHMYCLRPPLKKVPEGDWFCPDC 46

PHD finger 1 found in PHD finger protein 10 (PHF10) and similar proteins; PHF10, also termed BRG1-associated factor 45a (BAF45a), or XAP135, is a ubiquitously expressed transcriptional regulator that is required for maintaining the undifferentiated status of neuroblasts. It contains a SAY (supporter of activation of yellow) domain and two adjacent plant homeodomain (PHD) fingers. This model corresponds to the first PHD finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1625649087  215 ICSFCLGTKESNrEKKPEELLSCADCGSSGHPSCLKFCPELTTNVKALRWQCIEC 269
Cdd:cd15528      1 VCGICEKGGKSN-KGEPEELIHCSQCGNSGHPSCLEMSDEMVAVIKTYPWQCMEC 54

PHD finger 1 found in Schizosaccharomyces pombe Lid2 complex component Lid2p and similar proteins; Lid2p is a trimethyl H3K4 (H3K4me3) demethylase responsible for H3K4 hypomethylation in heterochromatin. It interacts with the histone lysine-9 methyltransferase, Clr4, through the Dos1/Clr8-Rik1 complex, and mediates H3K9 methylation and small RNA production. It also acts cooperatively with the histone modification enzymes Set1 and Lsd1 and plays an essential role in cross-talk between H3K4 and H3K9 methylation in euchromatin. Lid2p contains a JmjC domain, three PHD fingers and a JmjN domain. This model corresponds to the first PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1625649087  271 TCSACRVqGRNADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15519      1 GCEVCGL-DDNEGEVLLCDGCDAEYHTSCLDPPLGEIPPGTWFCPSC 46

PHD finger 2 found in d4 gene family proteins; The family includes proteins coded by three members of the d4 gene family, DPF1 (neuro-d4), DPF2 (ubi-d4/Requiem), and DPF3 (cer-d4), which function as transcription factors and are involved in transcriptional regulation of genes by changing the condensed/decondensed state of chromatin in the nucleus. DPF2 is ubiquitously expressed and it acts as a transcription factor that may participate in developmentally programmed cell death. DPF1 and DPF3 are expressed predominantly in neural tissues, and they may be involved in the transcription regulation of neuro-specific gene clusters. The d4 family proteins show distinct domain organization with domain 2/3 in the N-terminal region, a Cys2His2 (C2H2) zinc finger or Kruppel-type zinc finger in the central part and two adjacent plant homeodomain (PHD) fingers (d4-domain) in the C-terminal part of the molecule. This model corresponds to the second PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1625649087  271 TCSACRVQgRNADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15530      1 SCSLCGTS-ENDDQLLFCDDCDRGYHMYCLSPPMSEPPEGSWSCHLC 46

PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) finger typically characterized as Cys4HisCys3, and a non-canonical extended PHD finger, characterized as Cys2HisCys5HisCys2His. Variations include the RAG2 PHD finger characterized by Cys3His2Cys2His and the PHD finger 5 found in nuclear receptor-binding SET domain-containing proteins characterized by Cys4HisCys2His. The PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. Single or multiple copies of PHD fingers have been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors. The PHD finger domain SF is structurally similar to the RING and FYVE_like superfamilies.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1625649087  271 TCSACRVQGRNADNMLFCDSCDRGFHMECCDPPLSR-MPKGMWICQVC 317
Cdd:cd15489      1 SCIVCGKGGDLGGELLQCDGCGKWFHADCLGPPLSSfVPNGKWICPVC 48

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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1625649087  272 CSACRVQGRnadnMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15523      2 CSVCRKSGE----LLMCDTCSLVYHLDCLDPPLKTIPKGMWICPKC 43

PHD finger 1 found in Lysine-specific demethylase KDM5A, KDM5B, KDM5C, KDM5D and similar proteins; The JARID subfamily within the JmjC proteins includes Lysine-specific demethylase KDM5A, KDM5B, KDM5C, KDM5D and a Drosophila homolog, protein little imaginal discs (Lid). KDM5A was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation. It is involved in transcription through interacting with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK and BMAL1. KDM5B has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of the pregnant female and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis. Both KDM5A and KDM5B function as trimethylated histone H3 lysine 4 (H3K4me3) demethylases. KDM5C is a H3K4 trimethyl-histone demethylase that catalyzes demethylation of H3K4me3 and H3K4me2 to H3K4me1. It plays a role in neuronal survival and dendrite development. KDM5C defects are associated with X-linked mental retardation (XLMR). KDM5D is a male-specific antigen that shows a demethylase activity specific for di- and tri-methylated histone H3K4 (H3K4me2 and H3K4me3), and has a male-specific function as a histone H3K4 demethylase by recruiting a meiosis-regulatory protein, MSH5, to condensed DNA. KDM5D directly interacts with a polycomb-like protein Ring6a/MBLR, and plays a role in regulation of transcriptional initiation through H3K4 demethylation. This family also includes Drosophila melanogaster protein little imaginal discs (Lid) that functions as a JmjC-dependent H3K4me3 demethylase, which is required for dMyc-induced cell growth. It positively regulates Hox gene expression in S2 cells. Members in this family contain the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as two or three plant homeodomain (PHD) fingers. This model corresponds to the first PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1625649087  269 CKTCSacrvQGRNADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15515      2 CQVCG----RGDDEDKLLLCDGCDDSYHTFCLIPPLPDIPPGDWRCPKC 46

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1625649087  271 TCSACRvQGRNADNMLFCDSCDRGFHMECCDppLSRMPKGMWICQVC 317
Cdd:cd15529      1 TCTKCG-DPHDEDKMMFCDQCDRGYHTFCVG--LRSIPDGRWICPLC 44

Domain in histone families 1 and 5;

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1625649087   113 RAIEGLEEPNGSSLKNIEKYLRSQSDLTSttnnPAFQQRLRLGAKRAVNNGRLLK 167
Cdd:smart00526   13 EAISALKERKGSSLQAIKKYIEANYKVLP----NNFRKLLKLALKRLVASGKLVQ 63

PHD finger found in PHD and RING finger domain-containing protein 1 (PHRF1); PHRF1, also termed KIAA1542, or CTD-binding SR-like protein rA9, is a ubiquitin ligase that induces the ubiquitination of TGIF (TG-interacting factor) at lysine 130. It acts as a tumor suppressor that promotes the transforming growth factor (TGF)-beta cytostatic program through selective release of TGIF-driven promyelocytic leukemia protein (PML) inactivation. PHRF1 contains a plant homeodomain (PHD) finger and a RING finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1625649087  275 CRVQGR--NADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15536      2 CEVCGRsdREDRLLLCDGCDAGYHMECLTPPLDEVPIEEWFCPEC 46

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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1625649087  272 CSACRVQGRNAdNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15510      2 CQACRQPGDDT-KMLVCETCDKGYHTSCLRPVMSSIPKYGWKCKNC 46

PHD finger found in bromodomain adjacent to zinc finger domain protein 1B (BAZ1B); BAZ1B, also termed Tyrosine-protein kinase BAZ1B, or Williams syndrome transcription factor (WSTF), or Williams-Beuren syndrome chromosomal region 10 protein, Williams-Beuren syndrome chromosomal region 9 protein, or WALp2, is a multifunctional protein implicated in several nuclear processes, including replication, transcription, and the DNA damage response. BAZ1B/WSTF, together with the imitation switch (ISWI) ATPase, forms a WSTF-ISWI chromatin remodeling complex (WICH), which transiently associates with the human inactive X chromosome (Xi) during late S-phase prior to BRCA1 and gamma-H2AX. Moreover, BAZ1B/WSTF, SNF2h, and nuclear myosin 1 (NM1) forms the chromatin remodeling complex B-WICH that is involved in regulating rDNA transcription. BAZ1B contains a WAC motif, a DDT domain, BAZ 1 and BAZ 2 motifs, a WAKZ (WSTF/Acf1/KIAA0314/ZK783.4) motif, a plant homeodomain (PHD) finger, and a bromodomain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1625649087  272 CSACRVQGrNADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15628      2 CKVCRKKG-EDDKLILCDECNQAFHLFCLRPALYEVPDGEWMCPAC 46

PHD finger 2 found in Histone-lysine N-methyltransferase 2D (KMT2D); KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named myeloid/lymphoid or mixed-lineage leukemia 4 (MLL4), a fourth human homolog of Drosophila trithorax, located on chromosome 12. KMT2D enzymatically generates trimethylated histone H3 Lys 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 asHOXA1-3 and NESTIN. It 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 KMT2D. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2D contains the catalytic domain SET, five 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 second PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1625649087  272 CSACRVQGRNAdNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15595      2 CQTCRKPGEDS-KMLVCEACDKGYHTFCLKPAMESLPTDSWKCKAC 46

PHD finger found in PHD finger protein 21B (PHF21B); PHF21B is a plant homeodomain (PHD) finger-containing protein whose biological function remains unclear. It shows high sequence similarity with PHF21A, which is associated with LSD1, a lysine (K)-specific histone demethylase and inhibits LSD1-mediated histone demethylation in vitro. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1625649087  272 CSACRVQGrnadNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15524      2 CAACKRGG----NLQPCGTCPRAYHLDCLDPPLKTAPKGVWVCPKC 43

PHD finger 1 found in Lysine-specific demethylase 5A (KDM5A); KDM5A (also termed Histone demethylase JARID1A, Jumonji/ARID domain-containing protein 1A, or Retinoblastoma-binding protein 2 (RBBP-2 or RBP2)) was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation. It is involved in transcription through interacting with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK and BMAL1. KDM5A functions as a trimethylated histone H3 lysine 4 (H3K4me3) demethylase that belongs to the JARID subfamily within the JmjC proteins. It also displays DNA-binding activities that can recognize the specific DNA sequence CCGCCC. KDM5A contains the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers. This model corresponds to the first PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1625649087  272 CSACrVQGRNADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15602      2 CLFC-GRGNNEDKLLLCDGCDDSYHTFCLIPPLPDVPKGDWRCPKC 46

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 1625649087  215 ICSFClgtkesNREKKPEELLSCADCGSSGHPSCLKFcPELTTNVKALRWQCIECKTC 272
Cdd:pfam00628    1 YCAVC------GKSDDGGELVQCDGCDDWFHLACLGP-PLDPAEIPSGEWLCPECKPK 51

PHD finger 1 found in bromodomain and PHD finger-containing transcription factor (BPTF); BPTF, also termed nucleosome-remodeling factor subunit BPTF, or fetal Alz-50 clone 1 protein (FAC1), or fetal Alzheimer antigen, functions as a transcriptional regulator that exhibits altered expression and subcellular localization during neuronal development and neurodegenerative diseases such as Alzheimer's disease. It interacts with the human orthologue of the Kelch-like Ech-associated protein (Keap1). Its function and subcellular localization can be regulated by Keap1. Moreover, BPTF is a novel DNA-binding protein that recognizes the DNA sequence CACAACAC and represses transcription through this site in a phosphorylation-dependent manner. Furthermore, BPTF interacts with the Myc-associated zinc finger protein (ZF87/MAZ) and alters its transcriptional activity, which has been implicated in gene regulation in neurodegeneration. Some family members contain two or three plant homeodomain (PHD) fingers, which may be involved in complex formation with histone H3 trimethylated at K4 (H3K4me3). This family corresponds to the first PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1625649087  275 CRVQGRNADnMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15559      2 CRVCHKLGD-LLCCETCSAVYHLECVDPPLEEVPEEDWQCEVC 43

PHD finger found in ubiquitin-like PHD and RING finger domain-containing protein UHRF1 and UHRF2; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumour suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of transcription factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. 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. Both UHRF1 and UHRF2 contain 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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1625649087  274 ACRVQG--RNADNMLFCDSCDRGFHMECCDPPLSRMPKG-MWICQVC 317
Cdd:cd15525      1 ACHVCGgkQDPEKQLLCDECDMAYHLYCLDPPLTSLPDDdEWYCPDC 47

PHD finger 1 found in polycomb repressive complex 2 (PRC2)-associated polycomb-like (PCL) family proteins MTF2, PHF19, and similar proteins; The family includes two PCL family proteins, metal-response element-binding transcription factor 2 (MTF2/PCL2) and PHF19/PCL3, which are homologs of PHD finger protein1 (PHF1). PCL family proteins are accessory components of the polycomb repressive complex 2 (PRC2) core complex and all contain an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain. They specifically recognize tri-methylated H3K36 (H3K36me3) through their N-terminal Tudor domains. The interaction between their Tudor domains and H3K36me3 is critical for both the targeting and spreading of PRC2 into active chromatin regions and for the maintenance of optimal repression of poised developmental genes where PCL proteins, H3K36me3, and H3K27me3 coexist. Moreover, unlike other PHD finger-containing proteins, the first PHD fingers of PCL proteins do not display histone H3K4 binding affinity and they do not affect the Tudor domain binding to histones. This model corresponds to the first PHD finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1625649087  271 TCSACrvQGRNA---DNMLFCDSCDRGFHMECCDPPLSRMPK---GMWICQVC 317
Cdd:cd15499      1 TCSIC--GGAEArdgNEILICDKCDKGYHQLCHSPKVRTSPLegdEKWFCSRC 51