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 808355870   1044 CQVCRRKTGTERKLMCKQCSTVFHYGCHRPTIsralfEEEGFKEGWWCAKC 1094
Cdd:smart00249    2 CSVCGKPDDGGELLQCDGCDRWYHQTCLGPPL-----LEEEPDGKWYCPKC 47

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|.
gi 808355870   1044 CQVCRRKTGTERKLMCKQCSTVFHYGCHRPTIsralfEEEGFKEGWWCAKC 1094
Cdd:smart00249    2 CSVCGKPDDGGELLQCDGCDRWYHQTCLGPPL-----LEEEPDGKWYCPKC 47

PHD finger found in Schizosaccharomyces pombe SWM histone demethylase complex subunits Phf1 (Phf1p) and Phf2 (Phf2p); Phf1p and Phf2p are components of the SWM histone demethylase complex that specifically demethylates histone H3 at lysine 9 (H3K9me2), a specific tag for epigenetic transcriptional activation. They function as corepressors and play roles in regulating heterochromatin propagation and euchromatic transcription. Both Phf1p and Phf2p contain a plant homeodomain (PHD) finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 808355870 1044 CQVCRRKTGTERKLM--CKQCSTVFHYGCHRPTISRALFEEEGfkEGWWCAKC 1094
Cdd:cd15502     2 CIVCQRGHSPKSNRIvfCDGCNTPYHQLCHDPSIDDEVVEDPD--AEWFCKKC 52

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 808355870   1044 CQVCRRKTGTERKLMCKQCSTVFHYGCHRPTIsralfEEEGFKEGWWCAKC 1094
Cdd:smart00249    2 CSVCGKPDDGGELLQCDGCDRWYHQTCLGPPL-----LEEEPDGKWYCPKC 47

PHD finger found in Schizosaccharomyces pombe SWM histone demethylase complex subunits Phf1 (Phf1p) and Phf2 (Phf2p); Phf1p and Phf2p are components of the SWM histone demethylase complex that specifically demethylates histone H3 at lysine 9 (H3K9me2), a specific tag for epigenetic transcriptional activation. They function as corepressors and play roles in regulating heterochromatin propagation and euchromatic transcription. Both Phf1p and Phf2p contain a plant homeodomain (PHD) finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 808355870 1044 CQVCRRKTGTERKLM--CKQCSTVFHYGCHRPTISRALFEEEGfkEGWWCAKC 1094
Cdd:cd15502     2 CIVCQRGHSPKSNRIvfCDGCNTPYHQLCHDPSIDDEVVEDPD--AEWFCKKC 52

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        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 808355870 1044 CQVCRRKTGTERKLMCKQCSTVFHYGCHRPTISRalfeeegFKEG-WWCAKC 1094
Cdd:cd15628     2 CKVCRKKGEDDKLILCDECNQAFHLFCLRPALYE-------VPDGeWMCPAC 46

PHD finger found in ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1); UHRF1 (also termed inverted CCAAT box-binding protein of 90 kDa, nuclear protein 95, nuclear zinc finger protein Np95 (Np95), RING finger protein 106, transcription factor ICBP90, or E3 ubiquitin-protein ligase 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. UHRF1 contains an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET and RING finger associated (SRA) domain, and a C-terminal RING-finger domain. It specifically binds to hemimethylated DNA, double-stranded CpG dinucleotides, and recruits the maintenance methyltransferase DNMT1 to its hemimethylated DNA substrate through its SRA domain. UHRF1-dependent H3K23 ubiquitylation has an essential role in maintaining DNA methylation and replication. The tandem Tudor domain directs UHRF1 binding to the heterochromatin mark histone H3K9me3 and the PHD finger targets UHRF1 to unmodified histone H3 in euchromatic regions. The RING-finger domain exhibit both autocatalytic E3 ubiquitin (Ub) ligase activity and activity against histone H3 and DNMT1.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 808355870 1043 SCQVCRRKTGTERKLMCKQCSTVFHYGCHRPTISRALFEEEgfkegWWCAKC 1094
Cdd:cd15616     1 ACHVCGGKQDPDKQLMCDECDMAFHIYCLNPPLSSIPDDED-----WYCPEC 47

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        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 808355870 1043 SCQVCRRKTGTERKLMCKQCSTVFHYGCHRPTISRALFEEEgfkegWWCAKC 1094
Cdd:cd15525     1 ACHVCGGKQDPEKQLLCDECDMAYHLYCLDPPLTSLPDDDE-----WYCPDC 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        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 808355870 1044 CQVCRrktGTERKLMCKQCSTVFHYGCHRPTISralfeeEGFKEGWWCAKC 1094
Cdd:cd15541     2 CAVCQ---NGGELLCCDKCPRVFHLDCHIPPIP------EFPSGEWSCSLC 43

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        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 808355870 1043 SCQVCRRKTGTERKLMCKQCSTVFHYGCHRPTISRALFEEEgfkegWWCAKC 1094
Cdd:cd15617     1 SCYVCGGKQDAHMQLLCDECNMAYHIYCLNPPLDKIPEDED-----WYCPSC 47

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        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 808355870 1043 SCQVCRRKTGTERKLMCKQCSTVFHYGCHRPTIsralfeeEGFKEG-WWCAKC 1094
Cdd:cd15629     1 TCLVCRKGDNDEYLLLCDGCDRGCHMYCHRPKM-------LQVPEGdWFCPNC 46

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        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 808355870 1044 CQVCRRKTGTERKLMCKQCSTVFHYGCHRPTISRAlfeeegfKEG-WWCAKC 1094
Cdd:cd15527     2 CSVCQDSGNADNLLFCDACDKGFHMECHDPPLTRM-------PKGkWVCQIC 46

PHD finger found in integrator complex subunit 12 (Int12) and similar proteins; Int12, also termed IntS12, or PHD finger protein 22, is a component of integrator, a multi-protein mediator of small nuclear RNA processing. The integrator complex directly interacts with the C-terminal domain of RNA polymerase II (RNAPII) largest subunit and mediates the 3' end processing of small nuclear RNAs (snRNAs) U1 and U2. Different from other components of integrator, Int12 contains a PHD finger, which is not required for snRNA 3' end cleavage. Instead, Int12 harbors a small microdomain at its N-terminus which is necessary and sufficient for Int12 function; this microdomain facilitates Int12 binding to Int1 and promotes snRNA 3' end formation.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 808355870 1043 SCQVCRR--KTGTERKLMCKQCSTVFHYGCHRPTISRAlfEEEGFKEGWWCAKC 1094
Cdd:cd15501     1 SCVVCKQmdVTSGNQLVECQECHNLYHQECHKPPVTDK--DVNDPRLVWYCSRC 52

PHD finger 1 found in PHD finger protein 19 (PHF19); PHF19, also termed Polycomb-like protein 3 (PCL3), is a component of the polycomb repressive complex 2 (PRC2), which is the major H3K27 methyltransferase that regulates pluripotency, differentiation, and tumorigenesis through catalysis of histone H3 lysine 27 trimethylation (H3K27me3) on chromatin. PHF19 consists of an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain. It binds trimethylated histone H3 Lys36 (H3K36me3) through its Tudor domain and recruits the PRC2 complex and the H3K36me3 demethylase NO66 to embryonic stem cell genes during differentiation. Moreover, PHF19 and its upstream regulator, Akt, play roles in the phenotype switch of melanoma cells from proliferative to invasive states. This model corresponds to the first PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 808355870 1044 CQVCRRKTG--TERKLMCKQCSTVFHYGCHRPTISRAlfeEEGFKEGWWCAKC 1094
Cdd:cd15579     2 CNVCLGKSSgpLNEILICGKCGLGYHQQCHIPVVDSS---DDPPLTPWFCRRC 51

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        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 808355870 1044 CQVCRRKTGTERKLMCKQCSTVFHYGCHRPTISRALFEEegfkegWWCAKC 1094
Cdd:cd15536     2 CEVCGRSDREDRLLLCDGCDAGYHMECLTPPLDEVPIEE------WFCPEC 46