Sterile alpha motif (SAM)/Pointed domain of ERG transcription factor; SAM Pointed domain of ERG subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. It may participate in formation of homodimers or heterodimers with ETS-2, Fli-1, ER81, and Pu-1. However, dimeric forms are inactive and SAM Pointed domain is not essential for dimerization, since ER81 and Pu-1 do not have it. In mouse, a regulator of this type binds the ESET histone H3-specific methyltransferase (human homolog is SETDB1), which leads to modification of the local chromatin structure through histone methylation. ERG regulators are involved in endothelial cell differentiation, bone morphogenesis and neural crest development. The Erg gene is a proto-oncogene. It is a target of chromosomal translocations resulting in fusions with other neighboring genes. Chimeric proteins were found in solid tumors such as myeloid leukemia or Ewing's sarcoma. Members of this subfamily are potential targets for cancer therapy.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4758300  134 VPADPTLWSTDHVRQWLEWAVKEYGLPDVNILLFQNIDGKELCKMTKDDFQRLTPSYNADILLSHLHYLRETPLP 208
Cdd:cd08540   1 VPADPTLWSTDHVRQWLEWAVKEYGLPDVDVLLFQNIDGKELCKMTKEDFQRLTPSYNADILLSHLHYLRETPLP 75

Sterile alpha motif (SAM)/Pointed domain of ERG transcription factor; SAM Pointed domain of ERG subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. It may participate in formation of homodimers or heterodimers with ETS-2, Fli-1, ER81, and Pu-1. However, dimeric forms are inactive and SAM Pointed domain is not essential for dimerization, since ER81 and Pu-1 do not have it. In mouse, a regulator of this type binds the ESET histone H3-specific methyltransferase (human homolog is SETDB1), which leads to modification of the local chromatin structure through histone methylation. ERG regulators are involved in endothelial cell differentiation, bone morphogenesis and neural crest development. The Erg gene is a proto-oncogene. It is a target of chromosomal translocations resulting in fusions with other neighboring genes. Chimeric proteins were found in solid tumors such as myeloid leukemia or Ewing's sarcoma. Members of this subfamily are potential targets for cancer therapy.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4758300  134 VPADPTLWSTDHVRQWLEWAVKEYGLPDVNILLFQNIDGKELCKMTKDDFQRLTPSYNADILLSHLHYLRETPLP 208
Cdd:cd08540   1 VPADPTLWSTDHVRQWLEWAVKEYGLPDVDVLLFQNIDGKELCKMTKEDFQRLTPSYNADILLSHLHYLRETPLP 75

Ets-domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758300    295 QLWQFLLELLSDSSNSSCITWE-GTNGEFKMTDPDEVARRWGERKSKPNMNYDKLSRALRYYYDKNIMTKVHGKRYAYKF 373
Cdd:pfam00178   1 QLWQFLLDLLTDPEYSDIIKWTdKEEGEFRLVDPEAVARLWGKRKGNPKMTYEKLSRALRYYYKKGILEKVPGKRLTYRF 80

Sterile alpha motif (SAM)/Pointed domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758300    122 PPNMTTNERRVIVPADPTLWSTDHVRQWLEWAVKEYGLPDVNILLFqNIDGKELCKMTKDDFQRLTPsYNADILLSHLHY 201
Cdd:pfam02198   1 LPSFEKEQLRLWIPADPRLWTKDHVLEWLEWAVDEFDLSKIDFSQF-DMNGKALCSLGKEEFLQRAP-GPGDILWSHLQI 78

                  ...
gi 4758300    202 LRE 204
Cdd:pfam02198  79 LRK 81

Sterile alpha motif (SAM)/Pointed domain of ERG transcription factor; SAM Pointed domain of ERG subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. It may participate in formation of homodimers or heterodimers with ETS-2, Fli-1, ER81, and Pu-1. However, dimeric forms are inactive and SAM Pointed domain is not essential for dimerization, since ER81 and Pu-1 do not have it. In mouse, a regulator of this type binds the ESET histone H3-specific methyltransferase (human homolog is SETDB1), which leads to modification of the local chromatin structure through histone methylation. ERG regulators are involved in endothelial cell differentiation, bone morphogenesis and neural crest development. The Erg gene is a proto-oncogene. It is a target of chromosomal translocations resulting in fusions with other neighboring genes. Chimeric proteins were found in solid tumors such as myeloid leukemia or Ewing's sarcoma. Members of this subfamily are potential targets for cancer therapy.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4758300  134 VPADPTLWSTDHVRQWLEWAVKEYGLPDVNILLFQNIDGKELCKMTKDDFQRLTPSYNADILLSHLHYLRETPLP 208
Cdd:cd08540   1 VPADPTLWSTDHVRQWLEWAVKEYGLPDVDVLLFQNIDGKELCKMTKEDFQRLTPSYNADILLSHLHYLRETPLP 75

Sterile alpha motif (SAM)/Pointed domain of friend leukemia integration 1 transcription activator; SAM Pointed domain of FLI-1 (Friend Leukemia Integration) subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. The FLI-1 protein participates in regulation of cellular differentiation, proliferation, and survival. The Fli-1 gene was initially described in Friend virus-induced erythroleukemias as a site for virus integration. It is highly expressed in hematopoietic tissues and at lower level in lungs, heart, and ovaries. Fli-1 is a proto-oncogene implicated in Ewing's sarcoma and erythroleukemia. Members of this subfamily are potential targets for cancer therapy.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758300  122 PPNMTTNERRVIVPADPTLWSTDHVRQWLEWAVKEYGLPDVNILLFQNIDGKELCKMTKDDFQRLTPSYNADILLSHLHY 201
Cdd:cd08541   1 PPNMTTNERRVIVPADPTLWSQDHVRQWLEWAIKEYGLMEIDTSLFQNMDGKELCKMSKEDFLRLTSLYNTEVLLSHLNY 80

                ....
gi 4758300  202 LRET 205
Cdd:cd08541  81 LRES 84

Sterile alpha motif (SAM)/Pointed domain of ERG (Ets related gene) and FLI-1 (Friend leukemia integration 1) transcription factors; SAM Pointed domain of ERG/FLI-1 subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. The ERG and FLI regulators are involved in endothelial cell differentiation, bone morphogenesis and neural crest development. They are proto-oncogenes implicated in cancer development such as myeloid leukemia, Ewing's sarcoma and erythroleukemia. Members of this subfamily are potential targets for cancer therapy.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4758300  134 VPADPTLWSTDHVRQWLEWAVKEYGLPDVNILLFQNIDGKELCKMTKDDFQRLTPSYNADILLSHLHYLRETPLP 208
Cdd:cd08531   1 VPADPLLWTREHVRQWVEWAIKEYSLKDVDVSRFDNIDGKELCRMTRDDFLRLTSAYNGDVLISHLCYLRQTPLP 75

Sterile alpha motif (SAM)/Pointed domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758300    122 PPNMTTNERRVIVPADPTLWSTDHVRQWLEWAVKEYGLPDVNILLFqNIDGKELCKMTKDDFQRLTPsYNADILLSHLHY 201
Cdd:pfam02198   1 LPSFEKEQLRLWIPADPRLWTKDHVLEWLEWAVDEFDLSKIDFSQF-DMNGKALCSLGKEEFLQRAP-GPGDILWSHLQI 78

                  ...
gi 4758300    202 LRE 204
Cdd:pfam02198  79 LRK 81

Sterile alpha motif (SAM)/Pointed domain of GA-binding protein (GABP) alpha chain; SAM Pointed domain of GA-binding protein (GABP) alpha subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. This type of transcriptional regulators forms heterotetramers containing two alpha and two beta subunits. It interacts with GA repeats (purine rich repeats). GABP transcriptional factors control gene expression in cell cycle control, apoptosis, and cellular respiration. GABP participates in regulation of transmembrane receptors and key hormones especially in myeloid cells and at the neuromuscular junction.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4758300  131 RVIVPADPTLWSTDHVRQWLEWAVKEYGLPDVNILLFqNIDGKELCKMTKDDFQRLTPSYNADILLSHLHYLRET 205
Cdd:cd08534  12 RLKIPYDPMEWTEDHVLHWLQWAVKEFGLTGINLSDW-NITGRELCSLTQEEFLQRVPKDPGDIFWTHLELLRKC 85

Sterile alpha motif (SAM)/Pointed domain of prostate-derived ETS factor; SAM Pointed domain of PDEF-like (Prostate-Derived ETS Factor) subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. In human males this activator is highly expressed in the prostate gland and enhances androgen-mediated activation of the PSA promoter though interaction with the DNA binding domain of androgen receptor. PDEF may play a role in prostate cancer development as well as in goblet cell formation and mucus production in the epithelial lining of respiratory and intestinal tracts.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4758300  134 VPADPTLWSTDHVRQWLEWAVKEYGLPDVNILLFQnIDGKELCKMTKDDFQRLTPSyNADILLSHL 199
Cdd:cd08532  10 ISPDPYQWSTANVQAWLQWTEHQYRLPPNPPRCFQ-MNGKTLCALSEEDFVRRAPQ-GGDTLHAQL 73

Sterile alpha motif (SAM)/Pointed domain of ETS-1; SAM Pointed domain of ETS-1 subfamily of ETS transcriptional activators is a protein-protein interaction domain. The ETS-1 activator is regulated by phosphorylation. It contains a docking site for the ERK2 MAP (Mitogen Activated Protein) kinase, while the ERK2 phosphorylation site is located in the N-terminal disordered region upstream of the SAM Pointed domain. Mutations of the kinase docking site residues inhibit phosphorylation. ETS-1 activators play a role in a number of different physiological processes, and they are expressed during embryonic development, including blood vessel formation, hematopoietic, lymphoid, neuronal and osteogenic differentiation. The Ets-1 gene is a proto-oncogene involved in progression of different tumors (including breast cancer, meningioma, and prostate cancer). Members of this subfamily are potential molecular targets for selective cancer therapy.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4758300  126 TTNERRVIVPADPTLWSTDHVRQWLEWAVKEYGLPDVNILLFqNIDGKELCKMTKDDFQRLTPSYNADILLSHLHYLRE 204
Cdd:cd08542   7 TKEQQRLGIPKDPREWTETHVREWVMWAVNEFSLKGVDFQKF-CMSGAALCALGKECFLELAPDFVGDILWEHLEILQK 84

Sterile alpha motif (SAM)/Pointed domain of Mae protein homolog; Mae (Modulator of the Activity of ETS) subfamily represents a group of SAM Pointed monodomain proteins. SAM Pointed domain is a protein-protein interaction domain. It can interact with other SAM pointed domains forming head-to-tail heterodimers and also provides a kinase docking site. For example, in Drosophila Mae is required for facilitating phosphorylation of the Yan factor and for blocking phosphorylation of the ETS-2 regulator. Mae interacts with the SAM Pointed domains of Yan and ETS-2. Binding enhances access of the kinase to the Yan phosphorylation site by providing a kinase docking site, or inhibits phosphorylation of ETS-2 by blocking its docking site. This type of factors participates in regulation of kinase signaling particularly during embryogenesis.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 4758300  137 DPTLWSTDHVRQWLEWAVKEYGLPDVNILLFQnIDGKELCKMTKDDF 183
Cdd:cd08536   1 DPRSWSREHVRTWLRWVSARYQLEVVDLDKFL-MNGKGLCLMSLEGF 46

Sterile alpha motif (SAM)/Pointed domain of ESE-2 like ETS transcriptional regulators; SAM Pointed domain of ESE-2-like (Epithelium-Specific ETS) subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. It can act as a major transactivator by providing a potential docking site for co-activators. ESE-2 factors are involved in regulation of gene expression in a variety of epithelial (glandular and secretory) cells. ESE-2 mRNA was found in skin keratinocytes, salivary gland, mammary gland, stomach, prostate, and kidneys. The DNA binding consensus motif for ESE-2 consists of a GGA core and AT-rich flanks. The expression profiles of these factors are altered in epithelial cancers. Members of this subfamily are potential targets for cancer therapy.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 4758300  138 PTLWSTDHVRQWLEWAVKEYGLpDVNILLFQ--NIDGKELCKMTKDDF 183
Cdd:cd08538  13 PEYWTKRHVWEWLQFCCDQYKL-DANCISFChfNISGLQLCSMTQEEF 59

Sterile alpha motif (SAM)/Pointed domain of ESE-3 like ETS transcriptional regulators; SAM Pointed domain of ESE-3-like (Epithelium-Specific ETS) subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. It can act as a major transactivator by providing a potential docking site for co-activators. The ESE-3 transcriptional activator is involved in regulation of glandular epithelium differentiation through the MAP kinase signaling cascade. It is found to be expressed in glandular epithelium of prostate, pancreas, salivary gland, and trachea. Additionally, ESE-3 is differentially expressed during monocyte-derived dendritic cells development. DNA binding consensus motif for ESE-3 consists of purine-rich GGAA/T core sequence. The expression profiles of these factors are altered in epithelial cancers. Members of this subfamily are potential targets for cancer therapy.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4758300  138 PTLWSTDHVRQWLEWAVKEYGLpDVNILLFQN--IDGKELCKMTKDDFQRLTPSYNAdILLSHLHYLR 203
Cdd:cd08539   9 PQYWTKFQVWEWLQHLLDTNQL-DANCIPFQEfdINGEHLCSMSLQEFTRAAGTAGQ-LLYSNLQHLK 74