Inhibitor of growth (ING) domain of inhibitor of growth protein 2 (ING2); ING2, also termed inhibitor of growth 1-like protein (ING1Lp), or p32, or p33ING2, 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 leucine zipper-like (LZL) motif-containing ING domain, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504695   32 LECVESLPHDMQRNVSVLRELDNKYQETLKEIDDVYEKYKKEDDLNQKKRLQQLLQRALINSQELGDEKIQIVTQMLELV 111
Cdd:cd16861   1 LECVESLPLEIQRNVSLLREIDTKYQEALKEVDEVYEKYKKETDPSQKKRLQQQLQRALINSQELGDEKIQIVTQMLELV 80

                ....*...
gi 4504695  112 ENRARQME 119
Cdd:cd16861  81 ENRARQME 88

Inhibitor of growth (ING) domain of inhibitor of growth protein 2 (ING2); ING2, also termed inhibitor of growth 1-like protein (ING1Lp), or p32, or p33ING2, 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 leucine zipper-like (LZL) motif-containing ING domain, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504695   32 LECVESLPHDMQRNVSVLRELDNKYQETLKEIDDVYEKYKKEDDLNQKKRLQQLLQRALINSQELGDEKIQIVTQMLELV 111
Cdd:cd16861   1 LECVESLPLEIQRNVSLLREIDTKYQEALKEVDEVYEKYKKETDPSQKKRLQQQLQRALINSQELGDEKIQIVTQMLELV 80

                ....*...
gi 4504695  112 ENRARQME 119
Cdd:cd16861  81 ENRARQME 88

Inhibitor of growth proteins N-terminal histone-binding; Histones undergo numerous post-translational modifications, including acetylation and methylation, at residues which are then probable docking sites for various chromatin remodelling complexes. Inhibitor of growth proteins (INGs) specifically bind to residues that have been thus modified. INGs carry a well-characterized C-terminal PHD-type zinc-finger domain, binding with lysine 4-tri-methylated histone H3 (H3K4me3), as well as this N-terminal domain that binds unmodified H3 tails. Although these two regions can bind histones independently, together they increase the apparent association of the ING for the H3 tail.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504695     27 YVQDYLECVESLPHDMQRNVSVLRELDNKYQETLKEIDDVYEKYKK---EDDLNQKKRLQQLLQRALINSQELGDEKIQI 103
Cdd:pfam12998   1 YLEDYLDDLENLPLELQRNFTELREIDAKVQELLKEIDSQIQKFIKqngSLTPNPKEEELSKIQEELKKAQELQDEKIQL 80

                          90       100
                  ....*....|....*....|
gi 4504695    104 VTQMLELVENRARQMELHSQ 123
Cdd:pfam12998  81 ANQALELVDKHIRRLDLDLE 100

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 4504695     215 CLCNQV-SYGEMIGCDneQCPiEWFHFSCVSLTYK---PKGKWYCPKC 258
Cdd:smart00249   3 SVCGKPdDGGELLQCD--GCD-RWYHQTCLGPPLLeeePDGKWYCPKC 47

Inhibitor of growth (ING) domain of inhibitor of growth protein 2 (ING2); ING2, also termed inhibitor of growth 1-like protein (ING1Lp), or p32, or p33ING2, 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 leucine zipper-like (LZL) motif-containing ING domain, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504695   32 LECVESLPHDMQRNVSVLRELDNKYQETLKEIDDVYEKYKKEDDLNQKKRLQQLLQRALINSQELGDEKIQIVTQMLELV 111
Cdd:cd16861   1 LECVESLPLEIQRNVSLLREIDTKYQEALKEVDEVYEKYKKETDPSQKKRLQQQLQRALINSQELGDEKIQIVTQMLELV 80

                ....*...
gi 4504695  112 ENRARQME 119
Cdd:cd16861  81 ENRARQME 88

Inhibitor of growth (ING) domain of inhibitor of growth protein ING1, ING2, and similar proteins; 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 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 and phosphorylate ING1 and further regulates its activity. ING2, also termed inhibitor of growth 1-like protein (ING1Lp), or p32, or p33ING2, 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. Both ING1 and ING2 contain an N-terminal leucine zipper-like (LZL) motif-containing ING domain, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504695   32 LECVESLPHDMQRNVSVLRELDNKYQETLKEIDDVYEKYKKEDDLNQ-KKRLQQLLQRALINSQELGDEKIQIVTQMLEL 110
Cdd:cd16857   1 LDCVENLPGDVQRNLSLMRELDKRYQEILNELEELYEEYLREDDESHaKKRLLARIQKLLIRSQELGDEKLQIVSQILDL 80

                ....*....
gi 4504695  111 VENRARQME 119
Cdd:cd16857  81 IENRNRQLE 89

PHD finger found in inhibitor of growth protein 1 (ING1) and 2 (ING2); 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 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 and phosphorylate ING1 and further regulates its activity. ING2, also termed inhibitor of growth 1-like protein (ING1Lp), or p32, or p33ING2, belongs to 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. Both ING1 and ING2 contain an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 4504695  214 YCLCNQVSYGEMIGCDNEQCPIEWFHFSCVSLTYKPKGKWYCPKC 258
Cdd:cd15584   1 YCLCNQVSYGEMIGCDNDECPIEWFHFSCVGLTHKPKGKWYCPKC 45

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 4504695  213 TYCLCNQVSYGEMIGCDNEQCPIEWFHFSCVSLTYKPKGKWYCPKCRGD 261
Cdd:cd15682   1 TYCLCNQVSYGEMIGCDNDECPIEWFHFSCVGLNHKPKGKWYCPKCRGE 49

PHD finger found in inhibitor of growth protein 4 (ING4) and 5 (ING5); ING4, also termed p29ING4, and ING5, also termed p28ING5, belong to the inhibitor of growth (ING) family of type II tumor suppressors. ING4 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). ING5 is a Tip60 cofactor that acetylates p53 at K120 and subsequently activates the expression of p53-dependent apoptotic genes in response to DNA damage. Aberrant ING5 expression may contribute to pathogenesis, growth, and invasion of gastric carcinomas and colorectal cancer. ING5 can physically interact with p300 and p53 in vivo, and its overexpression induces apoptosis in colorectal cancer cells. It also associates with cyclin A1 (INCA1) and functions as a growth suppressor with suppressed expression in Acute Myeloid Leukemia (AML). Moreover, ING5 translocation from the nucleus to the cytoplasm might be a critical event for carcinogenesis and tumor progression in human head and neck squamous cell carcinoma. Both ING4 and ING5 contain an N-terminal ING histone-binding domain and a C-terminal plant homeodomain (PHD) finger. They associate with histone acetyltransferase (HAT) complexes containing MOZ (monocytic leukemia zinc finger protein)/MORF (MOZ-related factor) and HBO1, and further direct the MOZ/MORF and HBO1 complexes to chromatin.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 4504695  214 YCLCNQVSYGEMIGCDNEQCPIEWFHFSCVSLTYKPKGKWYCPKC 258
Cdd:cd15586   1 YCLCHQVSYGEMIGCDNPDCPIEWFHFACVGLTTKPKGKWFCPRC 45

PHD finger found in inhibitor of growth protein 5 (ING5); ING5, also termed p28ING5, is one member of the inhibitor of growth (ING) family of type II tumor suppressors. It acts as a Tip60 cofactor that acetylates p53 at K120 and subsequently activates the expression of p53-dependent apoptotic genes in response to DNA damage. Aberrant ING5 expression may contribute to pathogenesis, growth, and invasion of gastric carcinomas and colorectal cancer. ING5 can physically interact with p300 and p53 in vivo, and its overexpression induces apoptosis in colorectal cancer cells. It also associates with cyclin A1 (INCA1) and functions as a growth suppressor with suppressed expression in Acute Myeloid Leukemia (AML). Moreover, ING5 translocation from the nucleus to the cytoplasm might be a critical event for carcinogenesis and tumor progression in human head and neck squamous cell carcinoma. In addition, ING5 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. ING5 contains an N-terminal ING histone-binding domain and a C-terminal plant homeodomain (PHD) finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 4504695  213 TYCLCNQVSYGEMIGCDNEQCPIEWFHFSCVSLTYKPKGKWYCPKCRGD 261
Cdd:cd15685   1 TYCLCHQVSYGEMIGCDNPDCPIEWFHFACVDLTTKPKGKWFCPRCTQE 49

Chromatin remodeling protein, contains PhD zinc finger [Chromatin structure and dynamics];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504695   30 DYLECVESLPHDMQRNVSVLRELDNKYQETLKEI---DDVYEKYKKEDDLNQKKR---LQQLLQRALINSQELGDEKIQI 103
Cdd:COG5034   9 DITDHLANVPSETDIRFTELSEIDAKVCDIIKNLrqmISILKKIIDLDSQTYEEVedgLLKEIRELLLKAIYIQKEKSDL 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504695  104 VTQMLELVENRARQMELHSQCFQDPAESERASDKAKMDSSQPERSSRRPRRQRTSESRDLCHMANGI------------- 170
Cdd:COG5034  89 ADRAEKLLRRHRKLLDDRIAKRPHEKVAARIENCHDAVSRLERNSYSSAARRSSGEHRSAASSQGSRhtklkkrknihnl 168

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504695  171 -----EDCD--------DQPPKEKKSKSAKKKKRSKAKQEREASPVEfaIDPNEPTYCLCNQVSYGEMIGCDNEQCPIEW 237
Cdd:COG5034 169 krrspELSSkrevsftlESPSVPDTATRVKEGNNGGSTKSRGVSSED--NSEGEELYCFCQQVSYGQMVACDNANCKREW 246

                       250       260
                ....*....|....*....|..
gi 4504695  238 FHFSCVSLTYKPKGKWYCPKCR 259
Cdd:COG5034 247 FHLECVGLKEPPKGKWYCPECK 268

Inhibitor of growth (ING) domain family; The Inhibitor of growth (ING) family includes a group of tumor suppressors, ING1-5, which act as readers and writers of the histone epigenetic code, affecting DNA damage response, chromatin remodeling, cellular senescence, differentiation, cell cycle regulation, and apoptosis. They may have a general role in mediating the cellular response to genotoxic stress through binding to and regulating the activities of histone acetyltransferase (HAT) and histone deacetylase (HDAC) chromatin remodeling complexes. All ING proteins contain an N-terminal leucine zipper-like (LZL) motif-containing ING domain that binds unmodified H3 tails, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain, which binds lysine 4-tri-methylated histone H3 (H3K4me3). Although these two regions can bind histones independently, together they increase the apparent association of the ING domain for the H3 tail. The ING family also includes three yeast orthologs, 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. 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 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504695   35 VESLPHDMQRNVSVLRELDNKYQETLKEIDDVYEKYKKED---DLNQKKRLQQLLQRALINSQELGDEKIQIVTQMLELV 111
Cdd:cd16101   1 LSHLPFELRRLLTLIRELDEKKTELQKEIDELAKELLKSArieSHQQKRRLLDEIRQLYEKSIELSDEKVQLSSQAYELV 80

                ....*...
gi 4504695  112 ENRARQME 119
Cdd:cd16101  81 DNHIRKLD 88

Inhibitor of growth (ING) domain of inhibitor of growth protein 4 (ING4); ING4, also termed p29ING4, is a 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 leucine zipper-like (LZL) motif-containing ING domain, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504695   32 LECVESLPHDMQRNVSVLRELDNKYQETLKEIDDVYEKYKKE-DDLNQKKRLQQL--LQRALINSQELGDEKIQIVTQML 108
Cdd:cd16862   1 LDSIENLPFELQRNFQLMRDLDQRTEDLKVEIDKLATEYVSNaRSLSSEEKLKLLkqIQEAYGKCKEFGDDKVQLAMQTY 80

                        90
                ....*....|.
gi 4504695  109 ELVENRARQME 119
Cdd:cd16862  81 EMVDKHIRRLD 91

Inhibitor of growth (ING) domain of inhibitor of growth protein 3 (ING3), Yng2p and similar proteins; ING3, also termed p47ING3, is a 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). Yeast chromatin modification-related protein Yng2p, also termed ESA1-associated factor 4 or ING1 homolog 2, is a subunit of the NuA4 histone acetyltransferase (HAT) complex. It plays a critical role in intra-S-phase DNA damage response. Members of this family contain an N-terminal leucine zipper-like (LZL) motif-containing ING domain, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504695   35 VESLPHDMQRNVSVLRELDNKYQETLKEIDDVYEKYKKEDDLN-------QKKRLQQLLQRALINSQELGDEKIQIVTQM 107
Cdd:cd16858   1 LENLPSELRHLLTEIREKDLQVQELLDRIQQRDAKLFKHIKKNgsltpnpKEEELYEKIREDYDKALELADEKVELANRL 80

                ....*
gi 4504695  108 LELVE 112
Cdd:cd16858  81 LDLVD 85

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 4504695     215 CLCNQV-SYGEMIGCDneQCPiEWFHFSCVSLTYK---PKGKWYCPKC 258
Cdd:smart00249   3 SVCGKPdDGGELLQCD--GCD-RWYHQTCLGPPLLeeePDGKWYCPKC 47

PHD finger 5 found in nuclear receptor-binding SET domain-containing (NSD) proteins; The nuclear receptor binding SET domain (NSD) protein is a family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1, that are critical in maintaining chromatin integrity. Reducing NSD activity through specific lysine-HMTase inhibitors appears promising to help suppress cancer growth. NSD proteins have specific mono- and dimethylase activities for H3K36, and they play non-redundant roles during development. NSD1 plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. NSD2 is involved in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. NSD3 is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD proteins contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). This model corresponds to the fifth PHD finger.

                        10        20        30
                ....*....|....*....|....*....|....
gi 4504695  223 GEMIGCDNEQCPiEWFHFSCVSLTYKPKGKWYCP 256
Cdd:cd15568   9 GDLVLCDFKGCP-KVYHLSCLGLEKPPGGKWICP 41

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 4504695  214 YCLCNQVSYGE-MIGCDNeqCPiEWFHFSCVSLTYKPKG---KWYCPKC 258
Cdd:cd15553   1 YCICRSSDISRfMIGCDN--CE-EWYHGDCINITEKEAKaikEWYCQQC 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 4504695    215 CLCNQVSY-GEMIGCDneQCPiEWFHFSCVSLTY----KPKGKWYCPKCRGD 261
Cdd:pfam00628   3 AVCGKSDDgGELVQCD--GCD-DWFHLACLGPPLdpaeIPSGEWLCPECKPK 51

PHD finger found in Set1 complex component SPP1; Set1C component SPP1, also called COMPASS component Spp1, or Complex proteins associated with set1 protein Spp1, or Suppressor of PRP protein 1, is a component of the COMPASS complex that links histone methylation to initiation of meiotic recombination. It induces double-strand break (DSB) formation by tethering to recombinationally cold regions. SPP1 interacts with H3K4me3 and Mer2, a protein required for DSB formation, to promote recruitment of potential meiotic DSB sites to the chromosomal axis. SPP1 contains a PHD finger, a zinc binding motif.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 4504695  214 YCLCNQVSYGE-MIGCDneQCPiEWFHFSCVSLTYKPKG---KWYCPKC 258
Cdd:cd16039   1 YCICQKPDDGRwMIACD--GCD-EWYHFTCVNIPEADVElvdSFFCPPC 46

PHD finger 2 and 3 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 second and third PHD fingers.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 4504695  214 YCLCNQvSYGE---MIGCDNEQcpiEWFHFSCVSLTYKPKGK---WYCPKC 258
Cdd:cd15560   1 YCICRT-PYDEsqfYIGCDRCQ---DWFHGRCVGILQSEAEKideYVCPQC 47

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 4504695  214 YCLCNQVSYGEMIGCdnEQCPiEWFHFSCVSL---TYKPKG-----------KWYCPKC 258
Cdd:cd15606   1 YCICRKPFSGFMLQC--ELCK-DWFHSSCVPLpksSSQKKGgngsgqgakelKFLCPLC 56

Inhibitor of growth (ING) domain of yeast Pho23p and similar proteins; This family is composed of Saccharomyces cerevisiae transcriptional regulatory protein PHO23 (Pho23p), Schizosaccharomyces pombe chromatin modification-related protein png2 (also called ING1 homolog 2), and similar proteins. Pho23p is part of 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. Pho23p inhibits p53-dependent transcription. The related mammalian ING proteins act as readers and writers of the histone epigenetic code, affecting DNA damage response, chromatin remodeling, cellular senescence, differentiation, cell cycle regulation and apoptosis. They may have a general role in mediating the cellular response to genotoxic stress through binding to and regulating the activities of histone acetyltransferase (HAT) and histone deacetylase (HDAC) chromatin remodeling complexes. All ING proteins contain an N-terminal leucine zipper-like (LZL) motif-containing ING domain that binds unmodified H3 tails, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain, binding with lysine 4-tri-methylated histone H3 (H3K4me3). Although these two regions can bind histones independently, together they increase the apparent association of the ING for the H3 tail.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504695   35 VESLPHDMQRNVSVLRELDNKYQETLKEIDDVYEKYKKEDDLNQKK--------RLQQLLQRALINSqelgDEKIQIVTQ 106
Cdd:cd17016   1 IEALPLEVMRYFTLLKEVDAKCRNPEPELNDLIDEFLKNPVEEQDKlerrellsRLRKKLQEILPSL----DEKMHVASD 76

                ....*.
gi 4504695  107 MLELVE 112
Cdd:cd17016  77 ANDNLD 82

PHD finger found in PHD finger protein 3 (PHF3), and death-inducer obliterator variants Dido1, Dido2, and Dido3; PHF3 is a human homolog of yeast protein bypass of Ess1 (Bye1), a nuclear protein with a domain resembling the central domain in the transcription elongation factor TFIIS. It is ubiquitously expressed in normal tissues including brain, but its expression is significantly reduced or lost in glioblastomas. PHF3 contains an N-terminal plant homeodomain (PHD) finger, a central RNA polymerase II (Pol II)-binding TFIIS-like domain (TLD) domain, and a C-terminal Spen paralogue and orthologue C-terminal (SPOC) domain. This family also includes Dido gene encoding three alternative splicing variants (Dido1, 2, and 3), which have been implicated in a number of cellular processes such as apoptosis and chromosomal segregation, particularly in the hematopoietic system. Dido1 is important for maintaining embryonic stem (ES) cells and directly regulates the expression of pluripotency factors. It is the shortest isoform that contains only a highly conserved PHD finger responsible for the binding of histone H3 with a higher affinity for trimethylated lysine4 (H3K4me3). Gene Dido1 is a Bone morphogenetic protein (BMP) target gene and promotes BMP-induced melanoma progression. It also triggers apoptosis after nuclear translocation and caspase upregulation. Dido3 is the largest isoform and is ubiquitously expressed in all human tissues. It is dispensable for ES cell self-renewal and pluripotency, but is involved in the maintenance of stem cell genomic stability and tumorigenesis. Dido3 contains a PHD finger, a transcription elongation factor S-II subunit M (TFSIIM) domain, a SPOC module, and a long C-terminal region (CT) of unknown homology.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 4504695  214 YCLCNQV-SYGEMIGCDneQCPiEWFHFSCVSLTyKPKGK--------WYCPKC 258
Cdd:cd15552   1 YCICRKPhNNRFMICCD--RCE-EWFHGDCVGIT-EAQGKemeenieeYVCPKC 50