Sterile alpha motif (SAM)/Pointed domain of Tel/Yan protein; SAM Pointed domain of Tel (Translocation, Ets, Leukemia)/Yan subfamily of ETS transcriptional repressors is a protein-protein interaction domain. SAM Pointed domains of this type of regulators can interact with each other, forming head-to-tail homodimers or homooligomers, and/or interact with SAM Pointed domains of another subfamily of ETS factors forming heterodimers. The oligomeric form is able to block transcription of target genes and is involved in MAPK signaling. They participate in regulation of different processes during embryoniv development including hematopoietic differentiation and eye development. Tel/Yan transcriptional factors are frequent targets of chromosomal translocations resulting in fusions of SAM domain with new neighboring genes. Such chimeric proteins were found in different tumors. Members of this subfamily are potential targets for cancer therapy.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 82654200  56 LQPIYWSRDDVAQWLKWAENEFSLRPIESNTFEMNGKALLLLTKEDFRYRSPHSGDVLYELLQHILKQ 123
Cdd:cd08535   1 LQPRQWSREDVLQWLRWAENEFSLPPIDSNTFEMNGKALCLLTKEDFRYRCPHAGDVLYNLLQHLLKQ 68

Sterile alpha motif (SAM)/Pointed domain of Tel/Yan protein; SAM Pointed domain of Tel (Translocation, Ets, Leukemia)/Yan subfamily of ETS transcriptional repressors is a protein-protein interaction domain. SAM Pointed domains of this type of regulators can interact with each other, forming head-to-tail homodimers or homooligomers, and/or interact with SAM Pointed domains of another subfamily of ETS factors forming heterodimers. The oligomeric form is able to block transcription of target genes and is involved in MAPK signaling. They participate in regulation of different processes during embryoniv development including hematopoietic differentiation and eye development. Tel/Yan transcriptional factors are frequent targets of chromosomal translocations resulting in fusions of SAM domain with new neighboring genes. Such chimeric proteins were found in different tumors. Members of this subfamily are potential targets for cancer therapy.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 82654200  56 LQPIYWSRDDVAQWLKWAENEFSLRPIESNTFEMNGKALLLLTKEDFRYRSPHSGDVLYELLQHILKQ 123
Cdd:cd08535   1 LQPRQWSREDVLQWLRWAENEFSLPPIDSNTFEMNGKALCLLTKEDFRYRCPHAGDVLYNLLQHLLKQ 68

SAM / Pointed domain; A subfamily of the SAM domain

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82654200     38 PRALRMEEDSIHLPAHlrlqPIYWSRDDVAQWLKWAENEFSLRPIESNTFEMNGKALLLLTKEDFRYRSPHSGDVLYELL 117
Cdd:smart00251   1 PPNFEKEQKRLGIPAD----PQLWTEDHVLEWLEWAVKEFSLSPIDFSKFDMSGKELCSMSKEEFLERAPFGGDILWSHL 76

                   ....*.
gi 82654200    118 QHILKQ 123
Cdd:smart00251  77 QILRKA 82

Sterile alpha motif (SAM)/Pointed domain of Tel/Yan protein; SAM Pointed domain of Tel (Translocation, Ets, Leukemia)/Yan subfamily of ETS transcriptional repressors is a protein-protein interaction domain. SAM Pointed domains of this type of regulators can interact with each other, forming head-to-tail homodimers or homooligomers, and/or interact with SAM Pointed domains of another subfamily of ETS factors forming heterodimers. The oligomeric form is able to block transcription of target genes and is involved in MAPK signaling. They participate in regulation of different processes during embryoniv development including hematopoietic differentiation and eye development. Tel/Yan transcriptional factors are frequent targets of chromosomal translocations resulting in fusions of SAM domain with new neighboring genes. Such chimeric proteins were found in different tumors. Members of this subfamily are potential targets for cancer therapy.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 82654200  56 LQPIYWSRDDVAQWLKWAENEFSLRPIESNTFEMNGKALLLLTKEDFRYRSPHSGDVLYELLQHILKQ 123
Cdd:cd08535   1 LQPRQWSREDVLQWLRWAENEFSLPPIDSNTFEMNGKALCLLTKEDFRYRCPHAGDVLYNLLQHLLKQ 68

SAM / Pointed domain; A subfamily of the SAM domain

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 82654200     38 PRALRMEEDSIHLPAHlrlqPIYWSRDDVAQWLKWAENEFSLRPIESNTFEMNGKALLLLTKEDFRYRSPHSGDVLYELL 117
Cdd:smart00251   1 PPNFEKEQKRLGIPAD----PQLWTEDHVLEWLEWAVKEFSLSPIDFSKFDMSGKELCSMSKEEFLERAPFGGDILWSHL 76

                   ....*.
gi 82654200    118 QHILKQ 123
Cdd:smart00251  77 QILRKA 82

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 82654200  57 QPIYWSRDDVAQWLKWAENEFSLRPIESNTFEMNGKALLLLTKEDFRYRSPH-SGDVLYELLQHILK 122
Cdd:cd08203   1 DPLEWTPEHVQQWLSWVSKKFSLDPIDPDRFPMNGKELCALSKEDFRERAPSrGGDVLASHLALLRK 67

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 82654200  58 PIYWSRDDVAQWLKWAENEFSLRPIESNTFEMNGKALLLLTKEDFRYRSPHSGDVLYELLQHILK 122
Cdd:cd08536   2 PRSWSREHVRTWLRWVSARYQLEVVDLDKFLMNGKGLCLMSLEGFLYRVPVGGKLLYEDFQRRLA 66

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 82654200  58 PIYWSRDDVAQWLKWAENEFSLRPIESNTFE-MNGKALLLLTKEDF-RYRSPHSGDVLYELLqHILKQ 123
Cdd:cd08531   5 PLLWTREHVRQWVEWAIKEYSLKDVDVSRFDnIDGKELCRMTRDDFlRLTSAYNGDVLISHL-CYLRQ 71

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 82654200  58 PIYWSRDDVAQWLKWAENEFSLRPIESNTFEMNGKALLLLTKEDFRYRSPH-SGDVLY---ELL 117
Cdd:cd08534  19 PMEWTEDHVLHWLQWAVKEFGLTGINLSDWNITGRELCSLTQEEFLQRVPKdPGDIFWthlELL 82

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 82654200  38 PRALRMEEDSIHLPAhlrlQPIYWSRDDVAQWLKWAENEFSLRPIESNTFE-MNGKALLLLTKEDF-RYRSPHSGDVLYE 115
Cdd:cd08541   1 PPNMTTNERRVIVPA----DPTLWSQDHVRQWLEWAIKEYGLMEIDTSLFQnMDGKELCKMSKEDFlRLTSLYNTEVLLS 76

                ....*
gi 82654200 116 LLQHI 120
Cdd:cd08541  77 HLNYL 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 82654200  58 PIYWSRDDVAQWLKWAENEFSLRPIESNTFE-MNGKALLLLTKEDF-RYRSPHSGDVLYELLqHILKQR 124
Cdd:cd08540   5 PTLWSTDHVRQWLEWAVKEYGLPDVDVLLFQnIDGKELCKMTKEDFqRLTPSYNADILLSHL-HYLRET 72

SAM domain of sphingomyelin synthase related subfamily; SAM (sterile alpha motif) domain of SGMS-like (sphingomyelin synthase) subfamily is a potential protein-protein interaction domain. This group of proteins is related to sphingomyelin synthase 1, and contains an N-terminal SAM domain. The function of SGMS1-like proteins is unknown; they may play a role in sphingolipid metabolism.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 82654200  58 PIYWSRDDVAQWLKwaENEFS-LRPIESNTFEMNGKALLLLTKEDFR 103
Cdd:cd09515   1 VHEWTCEDVAKWLK--KEGFSkYVDLLCNKHRIDGKVLLSLTEEDLR 45

SAM domain of Polycomb group; SAM (sterile alpha motif) domain of Polycomb group is a protein-protein interaction domain. The Polycomb group includes transcriptional repressors which are involved in the regulation of some key regulatory genes during development in many organisms. They are best known for silencing Hox (Homeobox) genes. Polycomb proteins work together in large multimeric and chromatin-associated complexes. They organize chromatin of the target genes and maintain repressed states during many cell divisions. Polycomb proteins are classified based on their common function, but not on conserved domains and/or motifs; however many Polycomb proteins (members of PRC1 class complex) contain SAM domains which are more similar to each other inside of the Polycomb group than to SAM domains outside of it. Most information about structure and function of Polycomb SAM domains comes from studies of Ph (Polyhomeotic) and Scm (Sex comb on midleg) proteins. Polycomb SAM domains usually can be found at the C-terminus of the proteins. Some members of this group contain, in addition to the SAM domain, MTB repeats, Zn finger, and/or DUF3588 domains. Polycomb SAM domains can form homo- and/or heterooligomers through ML and EH surfaces. SAM/SAM oligomers apparently play a role in transcriptional repression through polymerization along the chromosome. Polycomb proteins are known to be highly expressed in some cells years before their cancer pathology; thus they are attractive markers for early cancer therapy.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 82654200  58 PIYWSRDDVAQWLKwaenEFSLRPIESNTF---EMNGKALLLLTKED 101
Cdd:cd09509   1 PSKWSVDDVAQFIK----SLDGCAEYAEVFreqEIDGQALLLLTEDD 43

SAM domain of Atherin/Atherin-like subfamily; SAM (sterile alpha motif) domain of SAM_Atherin and Atherin-like subfamily proteins is a putative protein-protein and/or protein-lipid interaction domain. In addition to the C-terminal SAM domain, the majority of proteins belonging to this group also have PHD (or Zn finger) domain. As potential members of the polycomb group, these proteins may be involved in regulation of some key regulatory genes during development. Atherin can be recruited by Ruk/CIN85 kinase-binding proteins via its SH3 domains thus participating in the signal transferring kinase cascades. Also, atherin was found associated with low density lipids (LDL) in atherosclerotic lesions in human. It was suggested that atherin plays an essential role in atherogenesis via immobilization of LDL in the arterial wall. SAM domains of atherins are predicted to form polymers. Inhibition of polymer formation could be a potential antiatherosclerotic therapy.

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                ....*....|....*....|....*....|....*....|....
gi 82654200  61 WSRDDVAQWLKwaENEFslrPIESNTF---EMNGKALLLLTKED 101
Cdd:cd09583   4 WSVEDVVQYFK--TAGF---PEEANAFkeqEIDGKSLLLLTRSD 42