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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1625649045  212 PIPICSFCLGTKESNREKKPEELLSCADCGSSGHPSCLKFCPELTTNVKALRWQCIECK 270
Cdd:cd15689      1 PIPICSFCLGTKESNREKKPEELLSCADCGSSGHPSCLKFCPELTANVKALRWQCIECK 59

Domain in histone families 1 and 5;

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1625649045   113 RAIEGLEEPNGSSLKNIEKYLRSQSDLTSttnnPAFQQRLRLGAKRAVNNGRLLK 167
Cdd:smart00526   13 EAISALKERKGSSLQAIKKYIEANYKVLP----NNFRKLLKLALKRLVASGKLVQ 63

MOZ/SAS family; This region of these proteins has been suggested to be homologous to acetyltransferases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649045  484 PPANEIYRRKDLSVFEVDGNMSKIYCQNLCLLAKLFLDHKTLYYDVEPFLFYVLTKNDEKGCHLVGYFSKEKLCQQKYNV 563
Cdd:pfam01853    1 PPGNEIYRKGNISIFEVDGRKQKLYCQNLCLLAKLFLDHKTLYYDVEPFLFYVLTETDETGCHIVGYFSKEKESSDNYNL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649045  564 SCIMIMPQHQRQGFGRFLIDFSYLLSRREGQAGSPEKPLSDLGRLSYLAYWKSVILEYLYHHHERHISIKAISRATGMCP 643
Cdd:pfam01853   81 ACILTLPPYQRKGYGKLLIEFSYELSKREGKIGGPEKPLSDLGLLSYRSYWSEVILEYLLKHRKEGISIEDISKATGITP 160

                          170
                   ....*....|....*...
gi 1625649045  644 HDIATTLQHLHMIDKRDG 661
Cdd:pfam01853  161 EDIISTLQSLNMLKYYKG 178

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 1625649045  212 PIPICSFCLGTKESNREKKPEELLSCADCGSSGHPSCLKFCPELTTNVKALRWQCIECK 270
Cdd:cd15689      1 PIPICSFCLGTKESNREKKPEELLSCADCGSSGHPSCLKFCPELTANVKALRWQCIECK 59

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 1625649045  272 CSACRvQGRNADNMLFCDSCDRGFHMECCDPPLSRM--PKGMWICQVCRPK 320
Cdd:pfam00628    2 CAVCG-KSDDGGELVQCDGCDDWFHLACLGPPLDPAeiPSGEWLCPECKPK 51

Domain in histone families 1 and 5;

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1625649045   113 RAIEGLEEPNGSSLKNIEKYLRSQSDLTSttnnPAFQQRLRLGAKRAVNNGRLLK 167
Cdd:smart00526   13 EAISALKERKGSSLQAIKKYIEANYKVLP----NNFRKLLKLALKRLVASGKLVQ 63

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 1625649045   215 ICSFClgtkesNREKKPEELLSCADCGSSGHPSCLKfcPELTTNVKALRWQCIEC 269
Cdd:smart00249    1 YCSVC------GKPDDGGELLQCDGCDRWYHQTCLG--PPLLEEEPDGKWYCPKC 47

MOZ/SAS family; This region of these proteins has been suggested to be homologous to acetyltransferases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649045  484 PPANEIYRRKDLSVFEVDGNMSKIYCQNLCLLAKLFLDHKTLYYDVEPFLFYVLTKNDEKGCHLVGYFSKEKLCQQKYNV 563
Cdd:pfam01853    1 PPGNEIYRKGNISIFEVDGRKQKLYCQNLCLLAKLFLDHKTLYYDVEPFLFYVLTETDETGCHIVGYFSKEKESSDNYNL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649045  564 SCIMIMPQHQRQGFGRFLIDFSYLLSRREGQAGSPEKPLSDLGRLSYLAYWKSVILEYLYHHHERHISIKAISRATGMCP 643
Cdd:pfam01853   81 ACILTLPPYQRKGYGKLLIEFSYELSKREGKIGGPEKPLSDLGLLSYRSYWSEVILEYLLKHRKEGISIEDISKATGITP 160

                          170
                   ....*....|....*...
gi 1625649045  644 HDIATTLQHLHMIDKRDG 661
Cdd:pfam01853  161 EDIISTLQSLNMLKYYKG 178

probable histone acetyltransferase MYST; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649045  429 SVIEFGKYEIQTWYSSPYPQEYARLPKLYLCEFCLKYMKSKNILLRHSKKCGWFHPPANEIYRRKD---LSVFEVDGNMS 505
Cdd:PLN03238    21 EMIELGKYEMDTWYYSPYPEPYASCTKLYICEYCLKYMRKKKSLLRHLAKCDIRQPPGGGIYGAVTegpLSVFEVDGKKA 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649045  506 KIYCQNLCLLAKLFLDHKTLYYDVEPFLFYVLTKNDEKGCHLVGYFSKEKLCQQKYNVSCIMIMPQHQRQGFGRFLIDFS 585
Cdd:PLN03238   101 KVYCQNLCLLAKLFLDHKTLYYDVDPFLFYVMTEVDDHGSHIVGYFSKEKVSAEDYNLACILTLPPYQRKGYGKFLISFA 180

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649045  586 YLLSRREGQAGSPEKPLSDLGRLSYLAYWKSVILEYLyHHHERHISIKAISRATGMCPHDIATTLQHLHMIDKRDGRFVI 665
Cdd:PLN03238   181 YELSKREGKVGTPERPLSDLGKVSFRSYWTRVLLEQL-RDVKGDVSIKDLSLATGIRGEDIVSTLQSLNLIKYWKGQHVI 259

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1625649045  666 IRREKLILSHMeKLKTCSRANELDPDslRWTPI 698
Cdd:PLN03238   260 HVDQRVLDEHW-AKFAHQRVIEVDCL--HWQPL 289

histone acetyltransferase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649045  429 SVIEFGKYEIQTWYSSPYPQEYARLPKLYLCEFCLKYMKSKNILLRHSKKCGWFHPPANEIYRRKDLSVFEVDGNMSKIY 508
Cdd:PTZ00064   253 GRVRIGKFILDTWYFSPLPDEYQNVDTLHFCEYCLDFFCFEDELIRHLSRCQLRHPPGNEIYRKDNISVFEIDGALTRGY 332

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649045  509 CQNLCLLAKLFLDHKTLYYDVEPFLFYVLTKNDEKGCHLVGYFSKEKLCQQKYNVSCIMIMPQHQRQGFGRFLIDFSYLL 588
Cdd:PTZ00064   333 AENLCYLAKLFLDHKTLQYDVEPFLFYIVTEVDEEGCHIVGYFSKEKVSLLHYNLACILTLPCYQRKGYGKLLVDLSYKL 412

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1625649045  589 SRREGQAGSPEKPLSDLGRLSYLAYWKSVILEYLYHHHERH------------------ISIKAISRATGMCPHDIATTL 650
Cdd:PTZ00064   413 SLKEGKWGHPERPLSDLGRAIYNNWWAHRISEYLLEYFKQNkicerggskqplqvsnywKFIDNVVRSTGIRREDVIRIL 492

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1625649045  651 QHlhmidkrDGRFVIIRREKLILSHMEKLKTCSRAN-----ELDPDSLRWTP 697
Cdd:PTZ00064   493 EE-------NGIMRNIKDQHYIFCNQEFLKGIVKRSgrpgiTLIDKYFNWVP 537

PHD finger 1 found in monocytic leukemia zinc-finger protein (MOZ) and its factor (MORF); MOZ (also termed histone acetyltransferase KAT6A, YBF2/SAS3, SAS2 and TIP60protein 3 (MYST-3), 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 model corresponds to the first PHD finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1625649045  212 PIPICSFCLGTKESNREKKPEELLSCADCGSSGHPSCLKFCPELTTNVKALRWQCIEC 269
Cdd:cd15618      1 PIPICSFCLGTAEKNRDGKPEELLSCADCGNSGHPSCLKYSPELTERVKALRWQCIEC 58

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 1625649045  271 TCSACRVQGrNADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15527      1 TCSVCQDSG-NADNLLFCDACDKGFHMECHDPPLTRMPKGKWVCQIC 46

MYST family zinc finger domain; This zinc finger domain is found in the MYST family of histone acetyltransferases.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1625649045  426 RYPSVIEFGKYEIQTWYSSPYPQEYARLPKLYLCEFCLKYMKSKNILLRHSKKC 479
Cdd:pfam17772    2 KNIEKIQFGRYEIDTWYFSPYPEEYTNVDKLYVCEFCLKYMKSRKSYKRHRKKC 55

PHD finger 1 found in D4, zinc and double PHD fingers family 2 (DPF2); DPF2 (also termed zinc finger protein ubi-d4, apoptosis response zinc finger protein, BRG1-associated factor 45D (BAF45D), or protein requiem) is a transcription factor that is encoded by the ubiquitously expressed gene, ubi-d4, and may be involved in leukemia or other cancers with other genes connected with cancer. It recognizes acetylated histone H3 and suppresses the function of estrogen-related receptor alpha (ERRalpha) through histone deacetylase 1 (HDAC1). Moreover, DPF2 functions as a linker protein between the SWI/SNF complex and RelB/p52 NF-kappaB heterodimer and plays important roles in NF-kappaB transactivation via its non-canonical pathway. It is also required as a transcriptional coactivator in SWI/SNF complex-dependent activation of NF-kappaB RelA/p50 heterodimer. DPF2 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 subfamily also includes DPF3 from zebrafish. This model describes the first PHD finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1625649045  216 CSFCLGTKESNREK-KPEELLSCADCGSSGHPSCLKFCPELTTNVKALRWQCIEC 269
Cdd:cd15691      2 CDFCLGDSKINKKTgQPEELVSCSDCGRSGHPSCLQFTPVMMAAVKTYRWQCIEC 56

PHD finger 1 found in D4, zinc and double PHD fingers family 1 (DPF1); DPF1, also termed zinc finger protein neuro-d4, or BRG1-associated factor 45B (BAF45B), is encoded by a neuro specific gene, neuro-d4. It may be involved in the transcription regulation of neuro specific gene clusters. DPF1 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, 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. The family corresponds to the first PHD finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1625649045  212 PIPICSFCLGTkeSNREKKPEELLSCADCGSSGHPSCLKFCPELTTNVKALRWQCIECK 270
Cdd:cd15690      2 PNGYCDFCLGG--AKKTGCPEDLISCADCGRSGHPSCLQFTVNMTAAVRTYRWQCIECK 58

PHD finger found in bromodomain adjacent to zinc finger domain protein 2A (BAZ2A) and 2B (BAZ2B); BAZ2A, also termed transcription termination factor I-interacting protein 5 (TTF-I-interacting protein 5, or Tip5), or WALp3, is an epigenetic regulator. It has been implicated in epigenetic rRNA gene silencing, as the large subunit of the SNF2h-containing chromatin-remodeling complex NoRC that induces nucleosome sliding in an ATP- and histone H4 tail-dependent fashion. BAZ2A has also been shown to be broadly overexpressed in prostate cancer, to regulate numerous protein-coding genes and to cooperate with EZH2 (enhancer of zeste homolog 2) to maintain epigenetic silencing at genes repressed in prostate cancer metastasis. Its overexpression is tightly associated with a prostate cancer subtype displaying CpG island methylator phenotype (CIMP) in tumors and with prostate cancer recurrence in patients. BAZ2B, also termed WALp4, is a bromodomain-containing protein whose biological role is still elusive. It shows high sequence similarly with BAZ2A. Both BAZ2A and BAZ2B contain a TAM (TIP5/ARBP/MBD) domain, a DDT domain, four AT-hooks, BAZ 1 and BAZ 2 motifs, a WAKZ (WSTF/Acf1/KIAA0314/ZK783.4) motif, a plant homeodomain (PHD) finger, and a bromodomain. BAZ2B also harbors an extra Apolipophorin-III like domain in its N-terminal region.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1625649045  271 TCSACRvQGRNADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15545      1 SCQICR-SGDNEDQLLLCDGCDRGYHTYCFKPKMTNVPEGDWFCPEC 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 1625649045  272 CSACRvQGRNADNMLFCDSCDRGFHMECCDPPLSRM--PKGMWICQVCRPK 320
Cdd:pfam00628    2 CAVCG-KSDDGGELVQCDGCDDWFHLACLGPPLDPAeiPSGEWLCPECKPK 51

PHD finger found in Remodeling and spacing factor 1 (Rsf-1); Rsf-1, also termed HBV pX-associated protein 8, or Hepatitis B virus X-associated protein alpha (HBxAPalpha), or p325 subunit of RSF chromatin-remodeling complex, is a novel nuclear protein with histone chaperon function. It is a subunit of an ISWI chromatin remodeling complex, remodeling and spacing factor (RSF), and plays a role in mediating ATPase-dependent chromatin remodeling and conferring tumor aggressiveness in common carcinomas. As an ataxia-telangiectasia mutated (ATM)-dependent chromatin remodeler, Rsf-1 facilitates DNA damage checkpoints and homologous recombination repair. It regulates the mitotic spindle checkpoint and chromosome instability through the association with serine/threonine kinase BubR1 (BubR1) and Hepatitis B virus (HBV) X protein (HBx) in the chromatin fraction during mitosis. It also interacts with cyclin E1 and promotes tumor development. Rsf-1 contains a plant homeodomain (PHD) finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1625649045  272 CSACRvQGRNADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15543      2 CRKCG-LSDHPEWILLCDRCDAGYHTACLRPPLMIIPDGNWFCPPC 46

PHD finger found in bromodomain adjacent to zinc finger domain protein BAZ1A and BAZ1B; 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. 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. Both BAZ1A and BAZ1B contain 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 1625649045  272 CSACRVQGrNADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15544      2 CKVCRKKG-DPDNMILCDGCDKAFHLYCLRPALREVPSGDWFCPAC 46

PHD finger found in bromodomain adjacent to zinc finger domain protein 2A (BAZ2A); BAZ2A, also termed transcription termination factor I-interacting protein 5 (TTF-I-interacting protein 5, or Tip5), or WALp3, is an epigenetic regulator. It has been implicated in epigenetic rRNA gene silencing, as the large subunit of the SNF2h-containing chromatin-remodeling complex NoRC that induces nucleosome sliding in an ATP- and histone H4 tail-dependent fashion. BAZ2A has also been shown to be broadly overexpressed in prostate cancer, to regulate numerous protein-coding genes and to cooperate with EZH2 (enhancer of zeste homolog 2) to maintain epigenetic silencing at genes repressed in prostate cancer metastasis. Its overexpression is tightly associated with a prostate cancer subtype displaying CpG island methylator phenotype (CIMP) in tumors and with prostate cancer recurrence in patients. It contains a TAM (TIP5/ARBP/MBD) domain, a DDT domain, four AT-hooks, 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 1625649045  271 TCSACRvQGRNADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15629      1 TCLVCR-KGDNDEYLLLCDGCDRGCHMYCHRPKMLQVPEGDWFCPNC 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 1625649045   271 TCSACRvQGRNADNMLFCDSCDRGFHMECCDPPL-SRMPKGMWICQVC 317
Cdd:smart00249    1 YCSVCG-KPDDGGELLQCDGCDRWYHQTCLGPPLlEEEPDGKWYCPKC 47

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.

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                   ....*....|....*....|....*....|....*....|....*....
gi 1625649045  269 CKTCSacrvQGRNADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15515      2 CQVCG----RGDDEDKLLLCDGCDDSYHTFCLIPPLPDIPPGDWRCPKC 46

Domain in histone families 1 and 5;

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                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1625649045   113 RAIEGLEEPNGSSLKNIEKYLRSQSDLTSttnnPAFQQRLRLGAKRAVNNGRLLK 167
Cdd:smart00526   13 EAISALKERKGSSLQAIKKYIEANYKVLP----NNFRKLLKLALKRLVASGKLVQ 63

PHD finger 1 found in autoimmune regulator (AIRE); AIRE, also termed autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) protein, functions as a regulator of gene transcription in the thymus. It is essential for prevention of autoimmunity. AIRE plays a critical role in the induction of central tolerance. It promotes self-tolerance through tissue-specific antigen (TSA) expression. It also acts as an active regulator of chondrocyte differentiation. AIRE contains a homogeneously-staining region (HSR) or caspase-recruitment domain (CARD), a nuclear localization signal (NLS), a SAND (for Sp100, AIRE, nuclear phosphoprotein 41/75 or NucP41/75, and deformed epidermal auto regulatory factor 1 or Deaf1) domain, two plant homeodomain (PHD) fingers, and four LXXLL (where L stands for leucine) motifs. This model corresponds to the first PHD finger that recognizes the unmethylated tail of histone H3 and targets AIRE-dependent genes.

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                   ....*....|....*....|....*....|....*....|....*.
gi 1625649045  272 CSACRVQGrnadNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15539      2 CAVCGDGG----ELLCCDGCPRAFHLACLVPPLTLIPSGTWRCSSC 43

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.

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                   ....*....|....*....|....*....|....*....|....*
gi 1625649045  275 CRVQGR--NADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15536      2 CEVCGRsdREDRLLLCDGCDAGYHMECLTPPLDEVPIEEWFCPEC 46

PHD finger 1 found in Lysine-specific demethylase 5C (KDM5C) and 5D (KDM5D); The family includes KDM5C and KDM5D, both of which belong to the JARID subfamily within the JmjC proteins. KDM5C (also termed Histone demethylase JARID1C, Jumonji/ARID domain-containing protein 1C, SmcX, or Xe169) 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 (also termed Histocompatibility Y antigen (H-Y), Histone demethylase JARID1D, Jumonji/ARID domain-containing protein 1D, or SmcY) is a male-specific antigen that shows a demethylase activity specific for di- and tri-methylated histone H3K4 (H3K4me3 andH3K4me2), 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. Both KDM5C and KDM5D 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 plant homeodomain (PHD) fingers. This model corresponds to the first PHD finger.

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                   ....*....|....*....|....*....|....*....|....*....
gi 1625649045  269 CKTCSacrvQGRNADNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15604      2 CRMCS----RGDEDDKLLLCDGCDDNYHTFCLLPPLPEPPKGIWRCPKC 46

PHD finger 1 found in Saccharomyces cerevisiae 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 plant homeodomain (PHD) fingers, which are required for the methylation of histone H3 lysine 36 (H3K36) nucleosome recognition by Rpd3S. This model corresponds to the first PHD finger.

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                   ....*....|....*....|....*....|....*....|....*...
gi 1625649045  272 CSACRVQGRnadnMLFCDSCDRGFHMECCDPPLSR--MPKGMWICQVC 317
Cdd:cd15535      2 CSACGGYGS----FLCCDGCPRSFHFSCLDPPLEEdnLPDDEWFCNEC 45

PHD finger 2 found in Histone-lysine N-methyltransferase 2C (KMT2C); 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. KMT2C contains several plant homeodomain (PHD) fingers, two extended PHD (ePHD) fingers, Cys2HisCys5HisCys2His, an ATPase alpha beta signature, a high mobility group (HMG)-1 box, a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain and two FY (phenylalanine tyrosine)-rich domains. This model corresponds to the second PHD finger.

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                   ....*....|....*....|....*....|....*....|....*.
gi 1625649045  272 CSACRVQGRNaDNMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15594      2 CQTCRQPGDD-NKMLVCDTCDKGYHTFCLQPVMTTIPKNGWKCKNC 46

PHD finger 5 found in Histone-lysine N-methyltransferase 2C (KMT2C) and PHD finger 4 found in KMT2D; KMT2C, also termed myeloid/lymphoid or mixed-lineage leukemia protein 3 (MLL3), or homologous to ALR protein, is a histone H3 lysine 4 (H3K4) lysine methyltransferase that functions as a circadian factor contributing to genome-scale circadian transcription. It is a component of a large complex that acts as a coactivator of multiple transcription factors, including the bile acid (BA)-activated nuclear receptor, farnesoid X receptor (FXR), a critical player in BA homeostasis. The MLL3 complex is essential for p53 transactivation of small heterodimer partner (SHP). KMT2C is also a part of activating signal cointegrator-2 (ASC-2)-containing complex (ASCOM) that contains the transcriptional coactivator nuclear receptor coactivator 6 (NCOA6), KMT2C and its paralog MLL4. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named MLL4, a fourth human homolog of Drosophila trithorax, located on chromosome 12. It enzymatically generates trimethylated histone H3 Lysine 4 (H3K4me3). It plays an essential role in differentiating the human pluripotent embryonal carcinoma cell line NTERA-2 clone D1 (NT2/D1) stem cells by activating differentiation-specific genes, such as HOXA1-3 and NESTIN. KMT2D is also a part of ASCOM. Both KMT2C and KMT2D contain the catalytic domain SET, several plant homeodomain (PHD) fingers, 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 fifth PHD finger of KMT2C and the fourth PHD finger of KMT2D.

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                   ....*....|....*....|....*....|....*....|....*
gi 1625649045  275 CRVQGRNAD--NMLFCDSCDRGFHMECCDPPLSRMPKGMWICQVC 317
Cdd:cd15513      2 CEGCGKASDesRLLLCDDCDISYHTYCLDPPLQTVPKGGWKCKWC 46

PHD finger found in Arabidopsis thaliana pathogenesis-related homeodomain protein (PRHA) and similar proteins; PRHA is a homeodomain protein encoded by a single-copy Arabidopsis thaliana homeobox gene, prha. It shows the capacity to bind to TAATTG core sequence elements but requires additional adjacent bases for high-affinity binding. PRHA contains a plant homeodomain (PHD) finger, a homeodomain, peptide repeats and a putative leucine zipper dimerization domain.

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                   ....*....|....*....|....*....|....*....|....*....|..
gi 1625649045  272 CSACRVQGRNADN-MLFCDS-CDRGFHMECCDPPL--SRMPKG--MWICQVC 317
Cdd:cd15504      2 CAKCQSGEASPDNdILLCDGgCNRAYHQKCLEPPLltEDIPPEdeGWLCPLC 53

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.

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 1625649045  268 ECKTCSACRVQGRnadnMLFCDSCDRGFHMECCDPPLSRMPKGM----WICQVC 317
Cdd:cd15562      1 SCGICKKSNDQHL----LALCDTCKLYYHLGCLDPPLTRMPKKTknsgWQCSEC 50

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.

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                   ....*....|....*....|....*....|....*....|...
gi 1625649045  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.

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                   ....*....|....*....|....*....|....*....|....*..
gi 1625649045  274 ACRVQG--RNADNMLFCDSCDRGFHMECCDPPLSRMPKG-MWICQVC 317
Cdd:cd15525      1 ACHVCGgkQDPEKQLLCDECDMAYHLYCLDPPLTSLPDDdEWYCPDC 47

PHD finger 2 found in class II Chromodomain-Helicase-DNA binding (CHD) proteins; Class II CHD proteins includes chromodomain-helicase-DNA-binding protein CHD3, CHD4, and CHD5, which are nuclear and ubiquitously expressed chromatin remodelling ATPases generally associated with histone deacetylases (HDACs). They are involved in DNA Double Strand Break (DSB) signaling, DSB repair and/or p53-dependent pathways such as apoptosis and senescence, as well as in the maintenance of genomic stability, and/or cancer prevention. They function as subunits of the Nucleosome Remodelling and Deacetylase (NuRD) complex, which is generally associated with gene repression, heterochromatin formation, and overall chromatin compaction. In contrast to the class I CHD enzymes (CHD1 and CHD2), class II CHD proteins lack identifiable DNA-binding domains, but possess a C-terminal coiled-coil region. Moreover, in addition to the tandem chromodomains and a helicase domain, they all harbor tandem plant homeodomain (PHD) zinc fingers involved in the recognition of methylated histone tails. This model corresponds to the second PHD finger.