Inhibitor of growth (ING) domain of plant inhibitor of growth proteins; This subfamily is composed of mainly plant inhibitor of growth proteins such as Arabidopsis thaliana ING1 (AtING1 or PHD finger protein ING1) and ING2 (AtING2 or PHD finger protein ING2). They are histone-binding components that specifically recognizes H3 tails trimethylated on 'Lys-4' (H3K4me3), which mark transcription start sites of virtually all active genes. 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, 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257646078  17 ASTFPAELQRLLNTVRELDERSQSLINQTRQQTKYCLGLASQSSKKGNgnhynnggLDEEETIEKMRKEIESSQENALSL 96
Cdd:cd17015    1 VASLPAELQRNLSLIRDLDERSQALQDQVEQKCERCLEEPSQSSESAS--------SSDDTAAAALREEIESAQKDCLQL 72

                         90       100
                 ....*....|....*....|....*.
gi 257646078  97 CTEKVLLARQAYDLIDSHVKRLDEDL 122
Cdd:cd17015   73 ADEKVALAQQAYDLVDGHIQRLDKDL 98

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 257646078 207 TYCVCHQVSFGDMIACDNENVSLLSQHLIIYFLMYSCYDETFC 249
Cdd:cd15683    1 TYCLCNQVSYGEMIGCDNEQCPIEWFHFSCVGLTYKPKGKWYC 43

Inhibitor of growth (ING) domain of plant inhibitor of growth proteins; This subfamily is composed of mainly plant inhibitor of growth proteins such as Arabidopsis thaliana ING1 (AtING1 or PHD finger protein ING1) and ING2 (AtING2 or PHD finger protein ING2). They are histone-binding components that specifically recognizes H3 tails trimethylated on 'Lys-4' (H3K4me3), which mark transcription start sites of virtually all active genes. 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, 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257646078  17 ASTFPAELQRLLNTVRELDERSQSLINQTRQQTKYCLGLASQSSKKGNgnhynnggLDEEETIEKMRKEIESSQENALSL 96
Cdd:cd17015    1 VASLPAELQRNLSLIRDLDERSQALQDQVEQKCERCLEEPSQSSESAS--------SSDDTAAAALREEIESAQKDCLQL 72

                         90       100
                 ....*....|....*....|....*.
gi 257646078  97 CTEKVLLARQAYDLIDSHVKRLDEDL 122
Cdd:cd17015   73 ADEKVALAQQAYDLVDGHIQRLDKDL 98

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257646078  10 VDDYLEYASTFPAELQRLLNTVRELDERSQSLINQTRQQTKYCLGLASQSSkkgngnhynnggLDEEETIEKMRKEIESS 89
Cdd:COG5034    7 LNDITDHLANVPSETDIRFTELSEIDAKVCDIIKNLRQMISILKKIIDLDS------------QTYEEVEDGLLKEIREL 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257646078  90 QENALSLCTEKVLLARQAYDLIDSHVKRLDEDL-----NNFAEDLKQEGKI----PPDEPSVLPPLPIVPK--AEKRKSF 158
Cdd:COG5034   75 LLKAIYIQKEKSDLADRAEKLLRRHRKLLDDRIakrphEKVAARIENCHDAvsrlERNSYSSAARRSSGEHrsAASSQGS 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257646078 159 YGTP-------QPKKIDYRDRDWDRDRDFELMPPP-------------GSNRKDLMPIEEQpIDPNEPTYCVCHQVSFGD 218
Cdd:COG5034  155 RHTKlkkrkniHNLKRRSPELSSKREVSFTLESPSvpdtatrvkegnnGGSTKSRGVSSED-NSEGEELYCFCQQVSYGQ 233

                 ....*...
gi 257646078 219 MIACDNEN 226
Cdd:COG5034  234 MVACDNAN 241

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 257646078 207 TYCVCHQVSFGDMIACDNENVSLLSQHLIIYFLMYSCYDETFC 249
Cdd:cd15683    1 TYCLCNQVSYGEMIGCDNEQCPIEWFHFSCVGLTYKPKGKWYC 43

Inhibitor of growth (ING) domain of plant inhibitor of growth proteins; This subfamily is composed of mainly plant inhibitor of growth proteins such as Arabidopsis thaliana ING1 (AtING1 or PHD finger protein ING1) and ING2 (AtING2 or PHD finger protein ING2). They are histone-binding components that specifically recognizes H3 tails trimethylated on 'Lys-4' (H3K4me3), which mark transcription start sites of virtually all active genes. 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, 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257646078  17 ASTFPAELQRLLNTVRELDERSQSLINQTRQQTKYCLGLASQSSKKGNgnhynnggLDEEETIEKMRKEIESSQENALSL 96
Cdd:cd17015    1 VASLPAELQRNLSLIRDLDERSQALQDQVEQKCERCLEEPSQSSESAS--------SSDDTAAAALREEIESAQKDCLQL 72

                         90       100
                 ....*....|....*....|....*.
gi 257646078  97 CTEKVLLARQAYDLIDSHVKRLDEDL 122
Cdd:cd17015   73 ADEKVALAQQAYDLVDGHIQRLDKDL 98

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 257646078    9 YVDDYLEYASTFPAELQRLLNTVRELDERSQSLINQTRQQT-KYclgLASQSSkkgngnhynnggLDEEETIEKMRKeIE 87
Cdd:pfam12998   1 YLEDYLDDLENLPLELQRNFTELREIDAKVQELLKEIDSQIqKF---IKQNGS------------LTPNPKEEELSK-IQ 64

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 257646078   88 SSQENALSLCTEKVLLARQAYDLIDSHVKRLDEDL 122
Cdd:pfam12998  65 EELKKAQELQDEKIQLANQALELVDKHIRRLDLDL 99

Inhibitor of growth (ING) domain of inhibitor of growth protein ING4, ING5, and similar proteins; 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 Inhibitor of 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 leucine zipper-like (LZL) motif-containing ING domain, and a well-characterized C-terminal plant homeodomain (PHD)-type zinc-finger domain. 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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257646078  21 PAELQRLLNTVRELDERSQSLINQTRQQTKYCLGLASQsskkgngnhynnggLDEEETIEKMrKEIESSQENALSLCTEK 100
Cdd:cd16859    5 PLELQRNFSLMRELDARVQDLLAEIEKLLREYLKTVKS--------------LSKEERRELL-KEIQDLFAKAKELSEEK 69

                         90       100
                 ....*....|....*....|..
gi 257646078 101 VLLARQAYDLIDSHVKRLDEDL 122
Cdd:cd16859   70 VQLATQTYETVDKHIRRLDADL 91

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 257646078  14 LEYASTFPAELQRLLNTVRELDERSQSLINQT-RQQTKYCLGLASQSSkkgngnhynnggldeEETIEKMRkEIESSQEN 92
Cdd:cd16862    1 LDSIENLPFELQRNFQLMRDLDQRTEDLKVEIdKLATEYVSNARSLSS---------------EEKLKLLK-QIQEAYGK 64

                         90       100       110
                 ....*....|....*....|....*....|
gi 257646078  93 ALSLCTEKVLLARQAYDLIDSHVKRLDEDL 122
Cdd:cd16862   65 CKEFGDDKVQLAMQTYEMVDKHIRRLDTDL 94

Inhibitor of growth (ING) domain of inhibitor of growth protein 5 (ING5); ING5, also termed p28ING5, is a 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 Inhibitor of 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 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 257646078  20 FPAELQRLLNTVRELDERsqslinqTRQQTKYCLGLASQSSKKGNGnhynnggLDEEETIEKMRKeiessQENALSLCTE 99
Cdd:cd16863    6 LPCELQRNFQLMRDLDQR-------TEDKKAEIDKLASEYIANVKN-------LSPEQRVEHLKK-----IQSAYSKCKE 66

                         90       100
                 ....*....|....*....|....*..
gi 257646078 100 ----KVLLARQAYDLIDSHVKRLDEDL 122
Cdd:cd16863   67 ysddKVQLAMQTYEMVDKHIRRLDADL 93

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.

                         10        20
                 ....*....|....*....|...
gi 257646078 207 TYCVCHQVSFGDMIACDNENVSL 229
Cdd:cd15684    1 TYCLCHQVSYGEMIGCDNPDCSI 23

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
                 ....*....|....*...
gi 257646078 208 YCVCHQVSFGDMIACDNE 225
Cdd:cd15584    1 YCLCNQVSYGEMIGCDND 18

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 257646078 207 TYCVCHQVSFGDMIACDNENVSLLSQHLIIYFLMYSCYDETFC 249
Cdd:cd15683    1 TYCLCNQVSYGEMIGCDNEQCPIEWFHFSCVGLTYKPKGKWYC 43

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.

                         10
                 ....*....|....*..
gi 257646078 208 YCVCHQVSFGDMIACDN 224
Cdd:cd15587    1 YCYCRRVSFGEMVACDN 17