SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694016497 115 PPNMTTNERRVIVPADPTLWSTDHVRQWLEWAVKEYGLLDVDVLLFQNIDGKELCKMTKDDFQRLTPSYNADILLSHLHY 194
Cdd:cd08541    1 PPNMTTNERRVIVPADPTLWSQDHVRQWLEWAIKEYGLMEIDTSLFQNMDGKELCKMSKEDFLRLTSLYNTEVLLSHLNY 80

                 ....
gi 694016497 195 LRET 198
Cdd:cd08541   81 LRES 84

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 694016497 115 PPNMTTNERRVIVPADPTLWSTDHVRQWLEWAVKEYGLLDVDVLLFQNIDGKELCKMTKDDFQRLTPSYNADILLSHLHY 194
Cdd:cd08541    1 PPNMTTNERRVIVPADPTLWSQDHVRQWLEWAIKEYGLMEIDTSLFQNMDGKELCKMSKEDFLRLTSLYNTEVLLSHLNY 80

                 ....
gi 694016497 195 LRET 198
Cdd:cd08541   81 LRES 84

Ets-domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694016497  312 QLWQFLLELLSDSSNSNCITWE-GTNGEFKMTDPDEVARRWGERKSKPNMNYDKLSRALRYYYDKNIMTKVHGKRYAYKF 390
Cdd:pfam00178   1 QLWQFLLDLLTDPEYSDIIKWTdKEEGEFRLVDPEAVARLWGKRKGNPKMTYEKLSRALRYYYKKGILEKVPGKRLTYRF 80

SAM / Pointed domain; A subfamily of the SAM domain

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694016497   115 PPNMTTNERRVIVPADPTLWSTDHVRQWLEWAVKEYGLLDVDvLLFQNIDGKELCKMTKDDFQRLTPsYNADILLSHLHY 194
Cdd:smart00251   1 PPNFEKEQKRLGIPADPQLWTEDHVLEWLEWAVKEFSLSPID-FSKFDMSGKELCSMSKEEFLERAP-FGGDILWSHLQI 78

                   ...
gi 694016497   195 LRE 197
Cdd:smart00251  79 LRK 81

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 694016497 115 PPNMTTNERRVIVPADPTLWSTDHVRQWLEWAVKEYGLLDVDVLLFQNIDGKELCKMTKDDFQRLTPSYNADILLSHLHY 194
Cdd:cd08541    1 PPNMTTNERRVIVPADPTLWSQDHVRQWLEWAIKEYGLMEIDTSLFQNMDGKELCKMSKEDFLRLTSLYNTEVLLSHLNY 80

                 ....
gi 694016497 195 LRET 198
Cdd:cd08541   81 LRES 84

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694016497   310 QIQLWQFLLELLSDSSNSNCITWEGTN-GEFKMTDPDEVARRWGERKSKPNMNYDKLSRALRYYYDKNIMTKVHGKRYAY 388
Cdd:smart00413   1 GIQLWQFLLDLLLDPENSDIIKWTDRDeGEFKLVDPEEVARLWGQRKNKPNMNYEKLSRALRYYYKKNILEKVPGKRLVY 80

                   ....*
gi 694016497   389 KFDFH 393
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 694016497 127 VPADPTLWSTDHVRQWLEWAVKEYGLLDVDVLLFQNIDGKELCKMTKDDFQRLTPSYNADILLSHLHYLRETPLP 201
Cdd:cd08531    1 VPADPLLWTREHVRQWVEWAIKEYSLKDVDVSRFDNIDGKELCRMTRDDFLRLTSAYNGDVLISHLCYLRQTPLP 75

SAM / Pointed domain; A subfamily of the SAM domain

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694016497   115 PPNMTTNERRVIVPADPTLWSTDHVRQWLEWAVKEYGLLDVDvLLFQNIDGKELCKMTKDDFQRLTPsYNADILLSHLHY 194
Cdd:smart00251   1 PPNFEKEQKRLGIPADPQLWTEDHVLEWLEWAVKEFSLSPID-FSKFDMSGKELCSMSKEEFLERAP-FGGDILWSHLQI 78

                   ...
gi 694016497   195 LRE 197
Cdd:smart00251  79 LRK 81

Sterile alpha motif (SAM)/Pointed domain; Sterile alpha motif (SAM)/Pointed domain is found in about 40% of transcriptional regulators of ETS family (initially named for Erythroblastosis virus, E26-E Twenty Six). SAM Pointed domain containing proteins of this family additionally have a C-terminal ETS DNA-binding domain. In a few cases, SAM Pointed domain appears as a single domain protein. Members of this group are mostly involved in regulation of embryonic development and growth control in eukaryotes. SAM Pointed domains mediate protein-protein interactions. Depending on the subgroup, they can interact with other SAM Pointed domains forming homo or hetero dimers/oligomers and/or they can recruit a protein kinase to its target which can be a SAM Pointed domain containing protein itself or another protein that has no kinase docking site. Thus, SAM Pointed domains participate in transcriptional regulation and signal transduction. Some genes coding ETS family transcriptional regulators are proto-oncogenes. They are prone to chromosomal translocations resulting in gene fusions. Chimeric proteins with SAM Pointed domains were found in a number of different human tumors including myeloid leukemia, lymphoblastic leukemia, Ewing's sarcoma and primitive neuroectodermal tumor. Members of this family are potential targets for cancer therapy.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 694016497 130 DPTLWSTDHVRQWLEWAVKEYGLLDVDVLLFQnIDGKELCKMTKDDFQRLTPSYNADILLSHLHYLRE 197
Cdd:cd08203    1 DPLEWTPEHVQQWLSWVSKKFSLDPIDPDRFP-MNGKELCALSKEDFRERAPSRGGDVLASHLALLRK 67

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 694016497 119 TTNERRVIVPADPTLWSTDHVRQWLEWAVKEYGLLDVDVLLFqNIDGKELCKMTKDDFQRLTPSYNADILLSHLHYLRE 197
Cdd:cd08542    7 TKEQQRLGIPKDPREWTETHVREWVMWAVNEFSLKGVDFQKF-CMSGAALCALGKECFLELAPDFVGDILWEHLEILQK 84

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 694016497 119 TTNERRVIVPADPTLWSTDHVRQWLEWAVKEYGLLDVDVLLFqNIDGKELCKMTKDDFQRLTPSYNADILLSHL 192
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 694016497 130 DPTLWSTDHVRQWLEWAVKEYGLLDVDVLLFQnIDGKELCKMTKDDF 176
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 694016497 131 PTLWSTDHVRQWLEWAVKEYGlLDVDVLLFQ--NIDGKELCKMTKDDF 176
Cdd:cd08538   13 PEYWTKRHVWEWLQFCCDQYK-LDANCISFChfNISGLQLCSMTQEEF 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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 694016497 132 TLWSTDHVRQWLEWAVKEY-------GLLDVDVLLFQN--IDGKELCKMTKDDFQRLTPSYNAdILLSHLHYLR 196
Cdd:cd08539    2 RQWHEIHPQYWTKFQVWEWlqhlldtNQLDANCIPFQEfdINGEHLCSMSLQEFTRAAGTAGQ-LLYSNLQHLK 74