PHD finger found in inhibitor of growth protein 1 (ING1); ING1 is an epigenetic regulator and a type II tumor suppressor that impacts cell growth, aging, apoptosis, and DNA repair, by affecting chromatin conformation and gene expression. It acts as a reader of the active chromatin mark, the trimethylation of histone H3 lysine 4 (H3K4me3). It binds and directs Growth arrest and DNA damage inducible protein 45 a (Gadd45a) to target sites, thus linking the histone code with DNA demethylation. It interacts with the proliferating cell nuclear antigen (PCNA) via the PCNA-interacting protein (PIP) domain in a UV-inducible manner. It also interacts with a PCNA-interacting protein, p15 (PAF). Moreover, ING1 associates with members of the 14-3-3 family, which is necessary for the cytoplasmic relocalization. Endogenous ING1 protein specifically interacts with the pro-apoptotic BCL2 family member BAX and colocalizes with BAX in a UV-inducible manner. It stabilizes the p53 tumor suppressor by inhibiting polyubiquitination of multi-monoubiquitinated forms via interaction with and colocalization of the herpesvirus-associated ubiquitin-specific protease (HAUSP)-deubiquitinase with p53. It is also involved in trichostatin A-induced apoptosis and caspase 3 signaling in p53-deficient glioblastoma cells. In addition, tyrosine kinase Src can bind phosphorylate ING1 and further regulates its activity. ING1 contains an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

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2QIC_A      12 TYCLCNQVSYGEMIGCDNDECPIEWFHFSCVGLNHKPKGKWYCPKCRGE 60
Cdd:cd15682  1 TYCLCNQVSYGEMIGCDNDECPIEWFHFSCVGLNHKPKGKWYCPKCRGE 49

PHD finger found in inhibitor of growth protein 1 (ING1); ING1 is an epigenetic regulator and a type II tumor suppressor that impacts cell growth, aging, apoptosis, and DNA repair, by affecting chromatin conformation and gene expression. It acts as a reader of the active chromatin mark, the trimethylation of histone H3 lysine 4 (H3K4me3). It binds and directs Growth arrest and DNA damage inducible protein 45 a (Gadd45a) to target sites, thus linking the histone code with DNA demethylation. It interacts with the proliferating cell nuclear antigen (PCNA) via the PCNA-interacting protein (PIP) domain in a UV-inducible manner. It also interacts with a PCNA-interacting protein, p15 (PAF). Moreover, ING1 associates with members of the 14-3-3 family, which is necessary for the cytoplasmic relocalization. Endogenous ING1 protein specifically interacts with the pro-apoptotic BCL2 family member BAX and colocalizes with BAX in a UV-inducible manner. It stabilizes the p53 tumor suppressor by inhibiting polyubiquitination of multi-monoubiquitinated forms via interaction with and colocalization of the herpesvirus-associated ubiquitin-specific protease (HAUSP)-deubiquitinase with p53. It is also involved in trichostatin A-induced apoptosis and caspase 3 signaling in p53-deficient glioblastoma cells. In addition, tyrosine kinase Src can bind phosphorylate ING1 and further regulates its activity. ING1 contains an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

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2QIC_A      12 TYCLCNQVSYGEMIGCDNDECPIEWFHFSCVGLNHKPKGKWYCPKCRGE 60
Cdd:cd15682  1 TYCLCNQVSYGEMIGCDNDECPIEWFHFSCVGLNHKPKGKWYCPKCRGE 49

PHD finger found in inhibitor of growth protein 2 (ING2); ING2, also termed inhibitor of growth 1-like protein (ING1Lp), or p32, or p33ING2, is one member of the inhibitor of growth (ING) family of type II tumor suppressors. It is a core component of a multi-factor chromatin-modifying complex containing the transcriptional co-repressor SIN3A and histone deacetylase 1 (HDAC1). It has been implicated in the control of cell cycle, in genome stability, and in muscle differentiation. ING2 independently interacts with H3K4me3 (Histone H3 trimethylated on lysine 4) and PtdIns(5)P, and modulates crosstalk between lysine methylation and lysine acetylation on histone proteins through association with chromatin in the presence of DNA damage. It collaborates with SnoN to mediate transforming growth factor (TGF)-beta-induced Smad-dependent transcription and cellular responses. It is upregulated in colon cancer and increases invasion by enhanced MMP13 expression. It also acts as a cofactor of p300 for p53 acetylation and plays a positive regulatory role during p53-mediated replicative senescence. ING2 contains an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

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2QIC_A      12 TYCLCNQVSYGEMIGCDNDECPIEWFHFSCVGLNHKPKGKWYCPKCRGE 60
Cdd:cd15683  1 TYCLCNQVSYGEMIGCDNEQCPIEWFHFSCVGLTYKPKGKWYCPKCRGD 49

PHD finger found in inhibitor of growth protein 3 (ING3) and similar proteins; ING3, also termed p47ING3, is one member of the inhibitor of growth (ING) family of type II tumor suppressors. It is ubiquitously expressed and has been implicated in transcription modulation, cell cycle control, and the induction of apoptosis. It is an important subunit of human NuA4 histone acetyltransferase complex, which regulates the acetylation of histones H2A and H4. Moreover, ING3 promotes ultraviolet (UV)-induced apoptosis through the Fas/caspase-8-dependent pathway in melanoma cells. It physically interacts with subunits of E3 ligase Skp1-Cullin-F-boxprotein complex (SCF complex) and is degraded by the SCF (F-box protein S-phase kinase-associated protein 2, Skp2)-mediated ubiquitin-proteasome system. It also acts as a suppression factor during tumorigenesis and progression of hepatocellular carcinoma (HCC). ING3 contains an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

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2QIC_A      13 YCLCNQVSYGEMIGCDNDECPIEWFHFSCVGLNHKPKGKWYCPKC 57
Cdd:cd15585  1 YCICNQVSYGEMVGCDNDDCPIEWFHYGCVGLTEAPKGKWYCPQC 45

PHD finger found in yeast orthologs of ING tumor suppressor family; The yeast orthologs of the plant homeodomain (PHD) finger-containing ING tumor suppressor family consists of chromatin modification-related protein YNG1 (Yng1p), YNG2 (Yng2p), and transcriptional regulatory protein PHO23 (Pho23p). Yng1p, also termed ING1 homolog 1, is one of the components of the NuA3 histone acetyltransferase (HAT) complex. Its PHD finger binding to H3 Trimethylated at K4 (H3K4me3) promotes NuA3 H3 HAT activity at K14 of H3 on chromatin. Yng2p, also termed ESA1-associated factor 4, or ING1 homolog 2, is a subunit of the NuA4 HAT complex. It plays a critical role in intra-S-phase DNA damage response. Pho23p is part of the Rpd3/Sin3 histone deacetylase (HDAC) complex. It is required for the normal function of Rpd3 in the silencing of rDNA, telomeric, and mating-type loci. Yng1p and Pho23p inhibit p53-dependent transcription. In contrast, Yng2p has the opposite effect. All family members contain an N-terminal ING histone-binding domain and a C-terminal PHD finger.

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2QIC_A      13 YCLCNQVSYGEMIGCDNDECPIEWFHFSCVGLNHKPKGKWYCPKC 57
Cdd:cd15587  1 YCYCRRVSFGEMVACDNPDCKIEWFHFECVGLTETPKGKWYCSDC 45

PHD finger found in inhibitor of growth protein 4 (ING4); ING4, also termed p29ING4, is one member of the inhibitor of growth (ING) family of type II tumor suppressors. It acts as an E3 ubiquitin ligase to induce ubiquitination of the p65 subunit of NF-kappaB and inhibit the transactivation of NF-kappaB target genes. It also induces apoptosis through a p53 dependent pathway, including increasing p53 acetylation, inhibiting Mdm2-mediated degradation of p53 and enhancing the expression of p53 responsive genes both at the transcriptional and post-translational levels. Moreover, ING4 can inhibit the translation of proto-oncogene MYC by interacting with AUF1. It also regulates other transcription factors, such as hypoxia-inducible factor (HIF). In addition, ING4 associates with histone acetyltransferase (HAT) complexes containing MOZ (monocytic leukemia zinc finger protein)/MORF (MOZ-related factor) and HBO1, and further directs the MOZ/MORF and HBO1 complexes to chromatin. ING4 contains an N-terminal ING histone-binding domain and a C-terminal plant homeodomain (PHD) finger.

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2QIC_A      12 TYCLCNQVSYGEMIGCDNDECPIEWFHFSCVGLNHKPKGKWYCPKC 57
Cdd:cd15684  1 TYCLCHQVSYGEMIGCDNPDCSIEWFHFACVGLTTKPRGKWFCPRC 46

PHD finger found in CXXC-type zinc finger protein 1 (Cfp1); Cfp1, also termed CpG-binding protein, or PHD finger and CXXC domain-containing protein 1 (PCCX1), is a specificity factor that binds to unmethylated CpGs and links H3K4me3 with CpG islands (CGIs). It integrates both promoter CpG content and gene activity for accurate trimethylation of histone H3 Lys 4 (H3K4me3) deposition in embryonic stem cells. Moreover, Cfp1 is an essential component of the SETD1 histone H3K4 methyltransferase complex and functions as a critical regulator of histone methylation, cytosine methylation, cellular differentiation, and vertebrate development. Cfp1 contains a plant homeodomain (PHD) finger, a CXXC domain, and a CpG binding protein zinc finger C-terminal domain. Its CXXC domain selectively binds to non-methylated CpG islands, following by a preference for a guanosine nucleotide.

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2QIC_A      13 YCLCNQVSYGE-MIGCDNDEcpiEWFHFSCVGLNHKPKG---KWYCPKC 57
Cdd:cd15553  1 YCICRSSDISRfMIGCDNCE---EWYHGDCINITEKEAKaikEWYCQQC 46

PHD finger 5 found in nuclear SET domain-containing protein 2 (NSD2); NSD2, also termed histone-lysine N-methyltransferase NSD2, or multiple myeloma SET domain-containing protein (MMSET), or protein trithorax-5 Wolf-Hirschhorn syndrome candidate 1 protein (WHSC1), is overexpressed frequently in the t(4;14) translocation in 15% to 20% of multiple myeloma. It plays important roles in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. It also enhances androgen receptor (AR)-mediated transcription. The principal chromatin-regulatory activity of NSD2 is dimethylation of histone H3 at lysine 36 (H3K36me2). NSD2 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, a high mobility group (HMG) box, five PHD (plant-homeodomain) zinc fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP, HMG, and PHD fingers mediate chromatin interaction and recognition of histone marks. This model corresponds to the fifth PHD finger.

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2QIC_A      22 GEMIGCDNDECpIEWFHFSCVGLNHKPKGKWYCP 55
Cdd:cd15660  9 GQLVLCDRKSC-TKAYHLSCLGLTKRPFGKWECP 41

PHD finger found in Saccharomyces cerevisiae extracellular matrix protein 5 (Ecm5p), Schizosaccharomyces pombe Lid2 complex component Lid2p, and similar proteins; The family includes Saccharomyces cerevisiae Ecm5p, Schizosaccharomyces pombe Lid2 complex component Lid2p, and similar proteins. Ecm5p is a JmjC domain-containing protein that directly removes histone lysine methylation via a hydroxylation reaction. It associates with the yeast Snt2p and Rpd3 deacetylase, which may play a role in regulating transcription in response to oxidative stress. Ecm5p promotes oxidative stress tolerance, while Snt2p ultimately decreases tolerance. Ecm5p contains an N-terminal ARID domain, a JmjC domain, and a C-terminal plant homeodomain (PHD) finger. Lid2p is a trimethyl H3K4 (H3K4me3) demethylase responsible for H3K4 hypomethylation in heterochromatin. It interacts with the histone lysine-9 methyltransferase, Clr4, through the Dos1/Clr8-Rik1 complex, and mediates H3K9 methylation and small RNA production. It also acts cooperatively with the histone modification enzymes Set1 and Lsd1 and plays an essential role in cross-talk between H3K4 and H3K9 methylation in euchromatin. Lid2p contains a JmjC domain, three PHD fingers and a JmjN domain. This model includes the second PHD finger of Lid2p.

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2QIC_A      13 YCLCNQVSYGEMIGCdndECPIEWFHFSCVG---LNHKPKGKWYCPKC 57
Cdd:cd15518  1 YCFCRQGEGGTMIEC---EICKEWYHVKCIKngrWKLDDDDKFVCPIC 45