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 213627700 134 VPADPTLWSTDHVRQWLEWAIKEYGLPDVDVLLFQNIDGKELCKMTKEDFHRLTPSYNADILLSHLHYLRERGAS 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 213627700 134 VPADPTLWSTDHVRQWLEWAIKEYGLPDVDVLLFQNIDGKELCKMTKEDFHRLTPSYNADILLSHLHYLRERGAS 208
Cdd:cd08540    1 VPADPTLWSTDHVRQWLEWAVKEYGLPDVDVLLFQNIDGKELCKMTKEDFQRLTPSYNADILLSHLHYLRETPLP 75

Ets-domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213627700  289 QLWQFLLELLSDSSNSNCITWE-GTNGEFKMTDPDEVARRWGERKSKPNMNYDKLSRALRYYYDKNIMTKVHGKRYAYKF 367
Cdd:pfam00178   1 QLWQFLLDLLTDPEYSDIIKWTdKEEGEFRLVDPEAVARLWGKRKGNPKMTYEKLSRALRYYYKKGILEKVPGKRLTYRF 80

SAM / Pointed domain; A subfamily of the SAM domain

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213627700   122 PPNMTTNERRVIVPADPTLWSTDHVRQWLEWAIKEYGLPDVDvLLFQNIDGKELCKMTKEDFHRLTPsYNADILLSHLHY 201
Cdd:smart00251   1 PPNFEKEQKRLGIPADPQLWTEDHVLEWLEWAVKEFSLSPID-FSKFDMSGKELCSMSKEEFLERAP-FGGDILWSHLQI 78

                   ...
gi 213627700   202 LRE 204
Cdd:smart00251  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 213627700 134 VPADPTLWSTDHVRQWLEWAIKEYGLPDVDVLLFQNIDGKELCKMTKEDFHRLTPSYNADILLSHLHYLRERGAS 208
Cdd:cd08540    1 VPADPTLWSTDHVRQWLEWAVKEYGLPDVDVLLFQNIDGKELCKMTKEDFQRLTPSYNADILLSHLHYLRETPLP 75

erythroblast transformation specific domain; variation of the helix-turn-helix motif

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213627700   287 QIQLWQFLLELLSDSSNSNCITWEGTN-GEFKMTDPDEVARRWGERKSKPNMNYDKLSRALRYYYDKNIMTKVHGKRYAY 365
Cdd:smart00413   1 GIQLWQFLLDLLLDPENSDIIKWTDRDeGEFKLVDPEEVARLWGQRKNKPNMNYEKLSRALRYYYKKNILEKVPGKRLVY 80

                   ....*
gi 213627700   366 KFDFH 370
Cdd:smart00413  81 KFVKN 85

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 213627700 134 VPADPTLWSTDHVRQWLEWAIKEYGLPDVDVLLFQNIDGKELCKMTKEDFHRLTPSYNADILLSHLHYLRE 204
Cdd:cd08531    1 VPADPLLWTREHVRQWVEWAIKEYSLKDVDVSRFDNIDGKELCRMTRDDFLRLTSAYNGDVLISHLCYLRQ 71

SAM / Pointed domain; A subfamily of the SAM domain

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 213627700   122 PPNMTTNERRVIVPADPTLWSTDHVRQWLEWAIKEYGLPDVDvLLFQNIDGKELCKMTKEDFHRLTPsYNADILLSHLHY 201
Cdd:smart00251   1 PPNFEKEQKRLGIPADPQLWTEDHVLEWLEWAVKEFSLSPID-FSKFDMSGKELCSMSKEEFLERAP-FGGDILWSHLQI 78

                   ...
gi 213627700   202 LRE 204
Cdd:smart00251  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 213627700 131 RVIVPADPTLWSTDHVRQWLEWAIKEYGLPDVDVLLFqNIDGKELCKMTKEDFHRLTPSYNADILLSHLHYLRE 204
Cdd:cd08534   12 RLKIPYDPMEWTEDHVLHWLQWAVKEFGLTGINLSDW-NITGRELCSLTQEEFLQRVPKDPGDIFWTHLELLRK 84

Sterile alpha motif (SAM)/Pointed domain of ETS-1,2 family; SAM Pointed domain of ETS-1,2 family of transcriptional activators is a protein-protein interaction domain. It carries a kinase docking site and mediates interaction between ETS transcriptional activators and protein kinases. This group of transcriptional factors is involved in the Ras/MAP kinase signaling pathway. MAP kinases phosphorylate the transcription factors. Phosphorylated factors then recruit coactivators and enhance transactivation. Members of this group play a role in regulation of different embryonic developmental processes. ETS-1,2 transcriptional activators are proto-oncogenes involved in malignant transformation and tumor progression. They are potential molecular targets for selective cancer therapy.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 213627700 135 PADPTLWSTDHVRQWLEWAIKEYGLPDVDVLLFQnIDGKELCKMTKEDFHRLTPSYNADILLSHLHYLR 203
Cdd:cd08533    1 PKDPRQWSETQVAYWLDWAANEFSLEGVNLSNFC-MSGRDMCALGKEAFLSLAPPFVGDILWEHLDILQ 68

Sterile alpha motif (SAM)/Pointed domain of ETS-2; SAM Pointed domain of ETS-2 subfamily of ETS transcriptional regulators is a protein-protein interaction domain. It contains a docking site for Cdk10 (cyclin-dependent kinase 10), a member of the Cdc2 kinase family. The interaction between ETS-2 and Cdk10 kinase inhibits ETS-2 transactivation activity in mammals. ETS-2 is also regulated by ERK2 MAP kinase. ETS-2, which is phosphorylated by ERK2, can interact with coactivators and enhance transactivation. ETS-2 transcriptional activators are involved in embryonic development and cell cycle control. The Ets-2 gene is a proto-oncogene. It is overexpressed in breast and prostate cancer cells and its overexpression is necessary for transformation of such cells. Members of ETS-2 subfamily are potential molecular targets for selective cancer therapy.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 213627700 126 TTNERRVIVPADPTLWSTDHVRQWLEWAIKEYGLPDVDVLLFqNIDGKELCKMTKEDFHRLTPSYNADILLSHL 199
Cdd:cd08543    7 SKEQRRLGIPKNPWLWTEQQVCQWLLWATNEFSLVNVNFQQF-LMNGQELCNLGKERFLELAPDFVGDILWEHL 79

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 213627700 137 DPTLWSTDHVRQWLEWAIKEYGLPDVDVLLFQnIDGKELCKMTKEDF 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 213627700 138 PTLWSTDHVRQWLEWAIKEYGLpDVDVLLFQ--NIDGKELCKMTKEDF 183
Cdd:cd08538   13 PEYWTKRHVWEWLQFCCDQYKL-DANCISFChfNISGLQLCSMTQEEF 59

SAM domain of Samd9/Samd9L subfamily; SAM (sterile alpha motif) domain of Samd9/Samd9L subfamily is a putative protein-protein interaction domain. SAM is a widespread domain in signaling proteins. Samd9 is a tumor suppressor gene. It is involved in death signaling of malignant glioblastoma. Samd9 suppression blocks cancer cell death induced by HVJ-E or IFN-beta treatment. Deleterious mutations in Samd9 lead to normophosphatemic familial tumoral calcinosis, a cutaneous disorder characterized by cutaneous calcification or ossification.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 213627700 141 WSTDHVRQWLEWAI--KEYglpdVDVLLFQNIDGKELCKMTKEDFHRLTPSYNADILLSHL 199
Cdd:cd09528    3 WTKEHVKQWLIEDLidKKY----AEILYEEEVTGAVLKELTEEDLVDMGLPHGPALLIIHS 59

SAM domain of WDSUB1 proteins; SAM (sterile alpha motif) domain of WDSUB1 subfamily proteins is a putative protein-protein interaction domain. Proteins of this group contain multiple domains: SAM, one or more WD40 repeats and U-box (derived version of the RING-finger domain). Apparently the WDSUB1 subfamily proteins participate in protein degradation through ubiquitination, since U-box domain are known as a member of E3 ubiquitin ligase family, while SAM and WD40 domains most probably are responsible for an E2 ubiquitin-conjugating enzyme binding and a target protein binding.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 213627700 141 WSTDHVRQWLewaiKEYGLPD-VDVLLFQNIDGKELCKMTKE 181
Cdd:cd09505    5 WSEEDVCTWL----RSIGLEQyVEVFRANNIDGKELLNLTKE 42