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 2121234  272 YCDFCLGDSKINKKTGQPEELVSCSDCGRSGHPSCLQFTPVMMAAVKTYRWQCIEC 327
Cdd:cd15691   1 YCDFCLGDSKINKKTGQPEELVSCSDCGRSGHPSCLQFTPVMMAAVKTYRWQCIEC 56

Putative transcriptional repressor regulating G2/M transition [Transcription / Cell division and chromosome partitioning];

                        10        20        30
                ....*....|....*....|....*....|...
gi 2121234  201 ILEDRDKPYACDICGKRYKNRPGLSYHYAHSHL 233
Cdd:COG5189 391 IFSAKDKPYRCEVCDKRYKNLNGLKYHRKHSHD 423

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 2121234  272 YCDFCLGDSKINKKTGQPEELVSCSDCGRSGHPSCLQFTPVMMAAVKTYRWQCIEC 327
Cdd:cd15691   1 YCDFCLGDSKINKKTGQPEELVSCSDCGRSGHPSCLQFTPVMMAAVKTYRWQCIEC 56

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 2121234    330 CNICGTSENDDQLLFCDDCDRGYHMYCLTPSMS--EPPEGSWSCHLC 374
Cdd:pfam00628   2 CAVCGKSDDGGELVQCDGCDDWFHLACLGPPLDpaEIPSGEWLCPEC 48

Putative transcriptional repressor regulating G2/M transition [Transcription / Cell division and chromosome partitioning];

                        10        20        30
                ....*....|....*....|....*....|...
gi 2121234  201 ILEDRDKPYACDICGKRYKNRPGLSYHYAHSHL 233
Cdd:COG5189 391 IFSAKDKPYRCEVCDKRYKNLNGLKYHRKHSHD 423

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 2121234     272 YCDFClgdskinKKTGQPEELVSCSDCGRSGHPSCLQFTPVMmaAVKTYRWQCIEC 327
Cdd:smart00249   1 YCSVC-------GKPDDGGELLQCDGCDRWYHQTCLGPPLLE--EEPDGKWYCPKC 47

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 2121234  272 YCDFCLGDSKINKKTGQPEELVSCSDCGRSGHPSCLQFTPVMMAAVKTYRWQCIEC 327
Cdd:cd15691   1 YCDFCLGDSKINKKTGQPEELVSCSDCGRSGHPSCLQFTPVMMAAVKTYRWQCIEC 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 2121234  272 YCDFCLGDSKINKKTGQPEELVSCSDCGRSGHPSCLQFTPVMMAAVKTYRWQCIECK 328
Cdd:cd15692   1 YCDFCLGGSNMNKKSGRPEELVSCADCGRSGHPTCLQFTVNMTEAVKTYQWQCIECK 57

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 2121234  329 CCNICGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLC 374
Cdd:cd15530   1 SCSLCGTSENDDQLLFCDDCDRGYHMYCLSPPMSEPPEGSWSCHLC 46

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 2121234  269 PNNYCDFCLGDSKINKKtGQPEELVSCSDCGRSGHPSCLQFTPVMMAAVKTYRWQCIEC 327
Cdd:cd15618   1 PIPICSFCLGTAEKNRD-GKPEELLSCADCGNSGHPSCLKYSPELTERVKALRWQCIEC 58

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2121234  269 PNNYCDFCLGDSKINKKTgQPEELVSCSDCGRSGHPSCLQFTPVMMAAVKTYRWQCIECK 328
Cdd:cd15688   1 PIPICSFCLGTKEQNREK-KPEELISCADCGNSGHPSCLKFSPELTVRVKALRWQCIECK 59

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2121234  269 PNNYCDFCLGDSKINKKTgQPEELVSCSDCGRSGHPSCLQFTPVMMAAVKTYRWQCIECK 328
Cdd:cd15689   1 PIPICSFCLGTKESNREK-KPEELLSCADCGSSGHPSCLKFCPELTANVKALRWQCIECK 59

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 2121234  330 CNICGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLC 374
Cdd:cd15627   2 CRICRRKGDAEKMLLCDGCDRGHHMYCLRPPLKKVPEGDWFCPDC 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 2121234  330 CNICGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLC 374
Cdd:cd15604   2 CRMCSRGDEDDKLLLCDGCDDNYHTFCLLPPLPEPPKGIWRCPKC 46

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 2121234  330 CNICGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLC 374
Cdd:cd15543   2 CRKCGLSDHPEWILLCDRCDAGYHTACLRPPLMIIPDGNWFCPPC 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 2121234  330 CNICGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLC 374
Cdd:cd15510   2 CQACRQPGDDTKMLVCETCDKGYHTSCLRPVMSSIPKYGWKCKNC 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 2121234  330 CNICGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLC 374
Cdd:cd15628   2 CKVCRKKGEDDKLILCDECNQAFHLFCLRPALYEVPDGEWMCPAC 46

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 2121234  330 CNICGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLC 374
Cdd:cd15536   2 CEVCGRSDREDRLLLCDGCDAGYHMECLTPPLDEVPIEEWFCPEC 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
                  ....*....|....*....|....*....|....*....|....*..
gi 2121234    330 CNICGTSENDDQLLFCDDCDRGYHMYCLTPSMS--EPPEGSWSCHLC 374
Cdd:pfam00628   2 CAVCGKSDDGGELVQCDGCDDWFHLACLGPPLDpaEIPSGEWLCPEC 48

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 2121234  330 CNICGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLC 374
Cdd:cd15513   2 CEGCGKASDESRLLLCDDCDISYHTYCLDPPLQTVPKGGWKCKWC 46

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 2121234  329 CCNICGTSENDDQLLFCDDCDRGYHMYCLTPSMSE-PPEGSWSCHLC 374
Cdd:cd15525   1 ACHVCGGKQDPEKQLLCDECDMAYHLYCLDPPLTSlPDDDEWYCPDC 47

PHD finger 1 found in lysine-specific demethylase 5B (KDM5B); KDM5B (also termed Cancer/testis antigen 31 (CT31), Histone demethylase JARID1B, Jumonji/ARID domain-containing protein 1B (JARID1B), PLU-1, or retinoblastoma-binding protein 2 homolog 1 (RBP2-H1 or RBBP2H1A)) is a member of the JARID subfamily within the JmjC proteins. It has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of pregnant females and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis. KDM5B acts as a histone demethylase that catalyzes the removal of trimethylation of lysine 4 on histone H3 (H3K4me3), induced by polychlorinated biphenyls (PCBs). It also mediates demethylation of H3K4me2 and H3K4me1. Moreover, KDM5B functions as a negative regulator of hematopoietic stem cell (HSC) self-renewal and progenitor cell activity. KDM5B has also been shown to interact with the DNA binding transcription factors BF-1 and PAX9, as well as TIEG1/KLF10 (transforming growth factor-beta inducible early gene-1/Kruppel-like transcription factor 10), and possibly function as a transcriptional corepressor. KDM5B 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 2121234  330 CNICGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLC 374
Cdd:cd15603   2 CLVCGSGNDEDRLLLCDGCDDSYHTFCLIPPLHDVPKGDWRCPKC 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 2121234  330 CNICGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLC 374
Cdd:cd15544   2 CKVCRKKGDPDNMILCDGCDKAFHLYCLRPALREVPSGDWFCPAC 46

PHD finger 1 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 first PHD finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 2121234  333 CGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLC 374
Cdd:cd15531   2 CEVCQQGGEIILCDTCPRAYHLVCLDPELEKAPEGKWSCPHC 43

Putative transcriptional repressor regulating G2/M transition [Transcription / Cell division and chromosome partitioning];

                        10        20        30
                ....*....|....*....|....*....|...
gi 2121234  201 ILEDRDKPYACDICGKRYKNRPGLSYHYAHSHL 233
Cdd:COG5189 391 IFSAKDKPYRCEVCDKRYKNLNGLKYHRKHSHD 423

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 2121234  330 CNICGTSENddqLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLC 374
Cdd:cd15539   2 CAVCGDGGE---LLCCDGCPRAFHLACLVPPLTLIPSGTWRCSSC 43

PHD finger found in BRPF proteins, Jade proteins, protein AF-10, AF-17, and similar proteins; The family includes BRPF proteins, Jade proteins, protein AF-10 and AF-17. BRPF proteins are scaffold proteins that form monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complexes with other regulatory subunits, such as inhibitor of growth 5 (ING5) and Esa1-associated factor 6 ortholog (EAF6). BRPF proteins have multiple domains, including a canonical Cys4HisCys3 plant homeodomain (PHD) zinc finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, a bromodomain and a proline-tryptophan-tryptophan-proline (PWWP) domain. PHD and ePHD fingers both bind to lysine 4 of histone H3 (K4H3), bromodomains interact with acetylated lysines on N-terminal tails of histones and other proteins, and PWWP domains show histone-binding and chromatin association properties. Jade proteins are required for ING4 and ING5 to associate with histone acetyltransferase (HAT) HBO1 and EAF6, to form a HBO1 complex that has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. AF-10, also termed ALL1 (acute lymphoblastic leukemia)-fused gene from chromosome 10 protein, is a transcription factor that has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. AF-17, also termed ALL1-fused gene from chromosome 17 protein, is a putative transcription factor that may play a role in multiple signaling pathways. All Jade proteins, AF-10, and AF-17 contain a canonical PHD finger followed by a non-canonical ePHD finger. This model corresponds to the canonical PHD finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 2121234  329 CCNIC--GTSENDDQLLFCDDCDRGYHMYCLtpSMSEPPEGSWSCHLC 374
Cdd:cd15492   1 VCDVCldGESEDDNEIVFCDGCNVAVHQSCY--GIPLIPEGDWFCRKC 46

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 2121234  330 CNICGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGS-WSCHLC 374
Cdd:cd15617   2 CYVCGGKQDAHMQLLCDECNMAYHIYCLNPPLDKIPEDEdWYCPSC 47

PHD finger found in the transcriptional intermediary factor 1 (TIF1) family and similar proteins; The TIF1 family of transcriptional cofactors includes TIF1alpha (TRIM24), TIF1beta (TRIM28), TIF1gamma (TRIM33), and TIF1delta (TRIM66), which are characterized by an N-terminal RING-finger B-box coiled-coil (RBCC/TRIM) motif and plant homeodomain (PHD) finger followed by a bromodomain in the C-terminal region. TIF1 proteins couple chromatin modifications to transcriptional regulation, signaling, and tumor suppression. They exert a deacetylase-dependent silencing effect when tethered to a promoter region. TIF1alpha, TIF1beta, and TIF1delta can homodimerize and contain a PXVXL motif necessary and sufficient for heterochromatin protein 1(HP1) binding. TIF1alpha and TIF1beta bind nuclear receptors and Kruppel-associated boxes (KRAB) specifically and respectively. In contrast, TIF1delta appears to lack nuclear receptor- and KRAB-binding activity. Moreover, TIF1delta is specifically involved in heterochromatin-mediated gene silencing during postmeiotic phases of spermatogenesis. TIF1gamma is structurally closely related to TIF1alpha and TIF1beta, but has very little functional features in common with them. It does not interact with the KRAB silencing domain of KOX1 or the heterochromatinic proteins HP1alpha, beta, and gamma. It cannot bind to nuclear receptors (NRs). This family also includes Sp100/Sp140 family proteins, the nuclear body SP100 and SP140. Sp110 is a leukocyte-specific component of the nuclear body. It may function as a nuclear hormone receptor transcriptional coactivator that may play a role in inducing differentiation of myeloid cells. It is also involved in resisting intracellular pathogens and functions as an important drug target for preventing intracellular pathogen diseases, such as tuberculosis, hepatic veno-occlusive disease, and intracellular cancers. SP140 is an interferon inducible nuclear leukocyte-specific protein involved in primary biliary cirrhosis and a risk factor in chronic lymphocytic leukemia. It is also implicated in innate immune response to human immunodeficiency virus type 1 (HIV-1) by binding to the virus viral infectivity factor (Vif) protein. Both Sp110 and Sp140 contain a SAND domain, a plant homeodomain (PHD) finger, and a bromodomain (BRD).

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 2121234  332 ICGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLC 374
Cdd:cd15541   1 WCAVCQNGGELLCCDKCPRVFHLDCHIPPIPEFPSGEWSCSLC 43

PHD finger 1 found in metal-response element-binding transcription factor 2 (MTF2); MTF2, also termed metal regulatory transcription factor 2, or metal-response element DNA-binding protein M96, or polycomb-like protein 2 (PCL2), complexes with the polycomb repressive complex-2 (PRC2) in embryonic stem cells and regulates the transcriptional networks during embryonic stem cell self-renewal and differentiation. It recruits the PRC2 complex to the inactive X chromosome and target loci in embryonic stem cells. Moreover, MTF2 is required for PRC2-mediated Hox cluster repression. It activates the Cdkn2a gene and promotes cellular senescence, thus suppressing the catalytic activity of PRC2 locally. MTF2 consists of an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain. This model corresponds to the first PHD finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 2121234  330 CNIC--GTSENDDQLLFCDDCDRGYHMYCLTPSMSE---PPEGSWSCHLCL 375
Cdd:cd15578   2 CTVCqdGSSESPNEIVLCDKCGQGYHQLCHNPKIDSsvlDPDVPWLCRQCV 52

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
                ....*....|....*....|....*....|....*....|....*....
gi 2121234  330 CNICGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGS----WSCHLC 374
Cdd:cd15562   2 CGICKKSNDQHLLALCDTCKLYYHLGCLDPPLTRMPKKTknsgWQCSEC 50

PHD finger found in transcriptional intermediary factor 1 gamma (TIF1gamma); TIF1gamma, also termed tripartite motif-containing 33 (trim33), or ectodermin, or RFG7, or PTC7, is an E3-ubiquitin ligase that functions as a regulator of transforming growth factor beta (TGFbeta) signaling; it inhibits the Smad4-mediated TGFbeta response by interaction with Smad2/3 or ubiquitylation of Smad4. Moreover, TIF1gamma is an important regulator of transcription during hematopoiesis, as well as a key factor of tumorigenesis. Like other TIF1 family members, TIF1gamma also contains an intrinsic transcriptional silencing function. It can control erythroid cell fate by regulating transcription elongation. It can bind to the anaphase-promoting complex/cyclosome (APC/C) and promotes mitosis. TIF1gamma contains an N-terminal RBCC (RING finger, B-box zinc-fingers, coiled-coil), a plant homeodomain (PHD) finger, followed by a bromodomain in the C-terminal region.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 2121234  333 CGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLCLDL 377
Cdd:cd15624   2 CAVCQNGGDLLCCEKCPKVFHLTCHVPTLLSFPSGDWICTFCRDI 46

PHD finger found in transcriptional intermediary factor 1 delta (TIF1delta); TIF1delta, also termed tripartite motif-containing protein 66 (TRIM66), is a novel heterochromatin protein 1 (HP1)-interacting member of the transcriptional intermediary factor1 (TIF1) family expressed by elongating spermatids. Like other TIF1 proteins, TIF1delta displays a potent trichostatin A (TSA)-sensitive repression function; TSA is a specific inhibitor of histone deacetylases. Moreover, TIF1delta plays an important role in heterochromatin-mediated gene silencing during postmeiotic phases of spermatogenesis. It functions as a negative regulator of postmeiotic genes acting through HP1 isotype gamma (HP1gamma) complex formation and centromere association. TIF1delta contains an N-terminal RBCC (RING finger, B-box zinc-fingers, coiled-coil), a plant homeodomain (PHD) finger, followed by a bromodomain in the C-terminal region.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 2121234  331 NICGTSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGSWSCHLCLDL 377
Cdd:cd15625   3 DFCAVCLNGGELLCCDRCPKVFHLSCHVPALLSFPVGEWVCTLCRNL 49

PHD finger 2 found in histone-lysine N-methyltransferase 2A (KMT2A) and 2B (KMT2B); This family includes histone-lysine N-methyltransferase trithorax (Trx) like proteins, KMT2A (MLL1) and KMT2B (MLL2), which comprise the mammalian Trx branch of the COMPASS family, and are both essential for mammalian embryonic development. KMT2A regulates chromatin-mediated transcription through the catalysis of methylation of histone 3 lysine 4 (H3K4), and is frequently rearranged in acute leukemia. KMT2A functions as the catalytic subunit in the MLL1 complex. KMT2B is a second human homolog of Drosophila trithorax, located on chromosome 19 and functions as the catalytic subunit in the MLL2 complex. It plays a critical role in memory formation through mediating hippocampal H3K4 di- and trimethylation. It is also required for RNA polymerase II association and protection from DNA methylation at the MagohB CpG island promoter. Both KMT2A and KMT2B contain a CxxC (x for any residue) zinc finger domain, three plant homeodomain (PHD) fingers, an extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain. This model corresponds to the second PHD finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 2121234  330 CNICG-TSENDDQLLFCDDCDRGYHMYCLTPSMSEPPEGS---WSCHLC 374
Cdd:cd15507   2 CHVCGrKGQAQKQLLECEKCQRGYHVDCLGPSYPTKPTRKkktWICSKC 50

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 2121234  330 CNICGTSendDQLLFCDDCDRGYHMYCLTPSMSEP--PEGSWSCHLC 374
Cdd:cd15535   2 CSACGGY---GSFLCCDGCPRSFHFSCLDPPLEEDnlPDDEWFCNEC 45

BAH, or Bromo Adjacent Homology domain, plant-specific sub-family with unknown function. BAH domains are found in a variety of proteins playing roles in transcriptional silencing and the remodeling of chromatin. It is assumed that in most or all of these instances the BAH domain mediates protein-protein interactions.

                        10        20
                ....*....|....*....|....
gi 2121234  351 GYHMYCLTPSMSEPPEGSWSCHLC 374
Cdd:cd04718   1 GFHLCCLRPPLKEVPEGDWICPFC 24

PHD finger 1 found in PHD finger protein 12 (PHF12); 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 model corresponds to the first PHD finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 2121234  329 CCNICGTSENddqLLFCDDCDRGYHMYCLTPSMSEP--PEGSWSCHLC 374
Cdd:cd15533   1 YCDSCGEGGD---LLCCDRCPASFHLQCCNPPLDEEdlPPGEWLCHRC 45

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 2121234  330 CNICGTSENDD--QLLFCDDCDRGYHMYCLtpSMSEPPEGSWSCHLC 374
Cdd:cd15679   2 CDVCQSPDGEDgnEMVFCDKCNICVHQACY--GILKVPEGSWLCRTC 46

PHD finger found in bromodomain and PHD finger-containing (BRPF) proteins; The family of BRPF proteins includes BRPF1, BRD1/BRPF2, and BRPF3. They are scaffold proteins that form monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complexes with other regulatory subunits, such as inhibitor of growth 5 (ING5) and Esa1-associated factor 6 ortholog (EAF6). BRPF proteins have multiple domains, including a canonical Cys4HisCys3 plant homeodomain (PHD) zinc finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, a bromodomain and a proline-tryptophan-tryptophan-proline (PWWP) domain. PHD and ePHD fingers both bind to lysine 4 of histone H3 (K4H3), bromodomains interact with acetylated lysines on N-terminal tails of histones and other proteins, and PWWP domains show histone-binding and chromatin association properties. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 2121234  330 CNIC--GTSENDDQLLFCDDCDRGYHMYCLtpSMSEPPEGSWSCHLCL 375
Cdd:cd15572   4 CCICldGECQNSNVILFCDMCNLAVHQECY--GVPYIPEGQWLCRRCL 49

PHD finger 5 found in nuclear SET domain-containing protein 3 (NSD3); NSD3, also termed histone-lysine N-methyltransferase NSD3, or protein whistle, or WHSC1-like 1 isoform 9 with methyltransferase activity to lysine, or Wolf-Hirschhorn syndrome candidate 1-like protein 1 (WHSC1-like protein 1, or WHSC1L1), is a lysine methyltransferase encoded by gene NSD3, which is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD3 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, five plant-homeodomain (PHD) zinc fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD fingers are involved in protein-protein interactions. This model corresponds to the fifth PHD finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 2121234  327 CKCCNICGtsenddQLLFCD--DCDRGYHMYCLtpSMSEPPEGSWSC 371
Cdd:cd15661   2 CFQCGDGG------ELVMCDkkDCPKAYHLLCL--NLTQPPYGKWEC 40

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.

                        10        20        30
                ....*....|....*....|....*....|..
gi 2121234  345 CDDCDRGYHMYCLTPSMSEPPEG--SWSCHLC 374
Cdd:cd15497  17 CDECKVSYHLLCVDPPLTKKPNRgfVWSCAPC 48