SAM domain of Samd7,11 subfamily of Polycomb group; SAM (sterile alpha motif) domain is a protein-protein interaction domain. Phylogenetic analysis suggests that proteins of this subfamily are most closely related to SAM-Ph1,2,3 subfamily of Polycomb group. They are predicted transcriptional repressors in photoreceptor cells and pinealocytes of vertebrates. SAM domain containing protein 11 is also known as Mr-s (major retinal SAM) protein. In mouse, it is predominantly expressed in developing retinal photoreceptors and in adult pineal gland. The SAM domain is involved in homooligomerization of whole proteins (it was shown based on immunoprecipitation assay and mutagenesis), however its repression activity is not due to SAM/SAM interactions but to the C-terminal region.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958774295 676 INKWTVDDVCNFVGGLSGCGEYARVFREQGIDGETLPLLTEEHLLNTMGLKLGPALKIRAQVAKRLGR 743
Cdd:cd09579     1 IRKWTVDDVCSFIGSLPGCAEYAQVFREHSIDGETLPLLTEEHLLNTMGLKLGPALKIRSQVAKRLGR 68

SAM domain of Samd7,11 subfamily of Polycomb group; SAM (sterile alpha motif) domain is a protein-protein interaction domain. Phylogenetic analysis suggests that proteins of this subfamily are most closely related to SAM-Ph1,2,3 subfamily of Polycomb group. They are predicted transcriptional repressors in photoreceptor cells and pinealocytes of vertebrates. SAM domain containing protein 11 is also known as Mr-s (major retinal SAM) protein. In mouse, it is predominantly expressed in developing retinal photoreceptors and in adult pineal gland. The SAM domain is involved in homooligomerization of whole proteins (it was shown based on immunoprecipitation assay and mutagenesis), however its repression activity is not due to SAM/SAM interactions but to the C-terminal region.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958774295 676 INKWTVDDVCNFVGGLSGCGEYARVFREQGIDGETLPLLTEEHLLNTMGLKLGPALKIRAQVAKRLGR 743
Cdd:cd09579     1 IRKWTVDDVCSFIGSLPGCAEYAQVFREHSIDGETLPLLTEEHLLNTMGLKLGPALKIRSQVAKRLGR 68

SAND domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958774295  114 PCIEVECGDNRALLYVRKLCQGSKGPSIRHRGEWLTPNEFQFVSGRETAKDWKRSIRHKGKSLKTLMSKGIL 185
Cdd:smart00258   1 SELPVTCGTVKGILYKKKFKCGISVKCIQYEDKWFTPKEFEIEGGKGKSKDWKRSIRCGGSSLRTLMENGTL 72

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958774295 678 KWTVDDVCNFVGGLsGCGEYARVFREQGIDGETLPLLTEEHLLNTMGLKLGPALKI 733
Cdd:pfam00536   2 GWSVEDVGEWLESI-GLGQYIDSFRAGYIDGDALLQLTEDDLLKLGVTLLGHRKKI 56

SAM domain of Samd7,11 subfamily of Polycomb group; SAM (sterile alpha motif) domain is a protein-protein interaction domain. Phylogenetic analysis suggests that proteins of this subfamily are most closely related to SAM-Ph1,2,3 subfamily of Polycomb group. They are predicted transcriptional repressors in photoreceptor cells and pinealocytes of vertebrates. SAM domain containing protein 11 is also known as Mr-s (major retinal SAM) protein. In mouse, it is predominantly expressed in developing retinal photoreceptors and in adult pineal gland. The SAM domain is involved in homooligomerization of whole proteins (it was shown based on immunoprecipitation assay and mutagenesis), however its repression activity is not due to SAM/SAM interactions but to the C-terminal region.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958774295 676 INKWTVDDVCNFVGGLSGCGEYARVFREQGIDGETLPLLTEEHLLNTMGLKLGPALKIRAQVAKRLGR 743
Cdd:cd09579     1 IRKWTVDDVCSFIGSLPGCAEYAQVFREHSIDGETLPLLTEEHLLNTMGLKLGPALKIRSQVAKRLGR 68

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        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958774295 676 INKWTVDDVCNFVGGLSGCGEYARVFREQGIDGETLPLLTEEHLLNTMGLKLGPALKIRAQVAK 739
Cdd:cd09509     1 PSKWSVDDVAQFIKSLDGCAEYAEVFREQEIDGQALLLLTEDDLLKGMGLKLGPALKIYNHIVK 64

SAND domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958774295  114 PCIEVECGDNRALLYVRKLCQGSKGPSIRHRGEWLTPNEFQFVSGRETAKDWKRSIRHKGKSLKTLMSKGIL 185
Cdd:smart00258   1 SELPVTCGTVKGILYKKKFKCGISVKCIQYEDKWFTPKEFEIEGGKGKSKDWKRSIRCGGSSLRTLMENGTL 72

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958774295 678 KWTVDDVCNFVGGlSGCGEYARVFREQGIDGETLPLLTEEHLLNTMGLKLGPALKIRAQVAK 739
Cdd:cd09583     3 NWSVEDVVQYFKT-AGFPEEANAFKEQEIDGKSLLLLTRSDVLTGLSLKLGPALKIYEHVVK 63

SAM domain of Scm proteins of Polycomb group; SAM (sterile alpha motif) domain of Scm (Sex comb on midleg) subfamily of Polycomb group is a protein-protein interaction domain. Proteins of this subfamily are transcriptional repressors associated with PRC1 complex. This group includes invertebrate Scm protein and chordate Scm homolog 1 and Scm-like 1, 2, 3 proteins. Most have a SAM domain, two MBT repeats, and a DUF3588 domain, except Scm-like 4 proteins which do not have MBT repeats. Originally the Scm protein was described in Drosophila as a regulator required for proper spatial expression of homeotic genes. It plays a major role during early embryogenesis. SAM domains of Scm proteins can interact with each other, forming homooligomers, as well as with SAM domains of other proteins, in particular with SAM domains of Ph (polyhomeotic) proteins, forming heterooligomers. Homooligomers are similar to the ones formed by SAM Pointed domains of the TEL proteins. Such SAM/SAM oligomers apparently play a role in transcriptional repression through polymerization along the chromosome. Mammalian Scmh1 protein is known be indispensible member of PRC1 complex; it plays a regulatory role for the complex during meiotic prophase of male sperm cells, and is particularly involved in regulation of chromatin modification at the XY chromatin domain of the pachytene spermatocytes.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958774295 678 KWTVDDVCNFVGGL--SGCGEYARVFREQGIDGETLPLLTEEHLLNTMGLKLGPALKI 733
Cdd:cd09578     6 TWSVEDVVQFIKEAdpQALAPHVDLFRKHEIDGKALLLLNSDMMMKYMGLKLGPALKL 63

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958774295  678 KWTVDDVCNFVGGLsGCGEYARVFREQGIDGETLPLLTEEHLLNTMG-LKLGPALKI 733
Cdd:smart00454   3 QWSPESVADWLESI-GLEQYADNFRKNGIDGALLLLLTSEEDLKELGiTKLGHRKKI 58

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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1958774295 683 DVCNFVGGLsGCGEYARVFREQGIDGETLPLLTEEHLLNTMGLKLGPALKI 733
Cdd:cd09487     1 DVAEWLESL-GLEQYADLFRKNEIDGDALLLLTDEDLKELGITSPGHRKKI 50

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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958774295 678 KWTVDDVCNFVGGLSGCGEYARVFREQGIDGETLPLLTEEHLLNtMGLKLGPALKI 733
Cdd:cd09528     2 DWTKEHVKQWLIEDLIDKKYAEILYEEEVTGAVLKELTEEDLVD-MGLPHGPALLI 56

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958774295 679 WTVDDVCNFVGGLsGCGEYARVFREQGIDGETLPLLTEEHLLNTMGLK-LGPALKI 733
Cdd:cd09505     5 WSEEDVCTWLRSI-GLEQYVEVFRANNIDGKELLNLTKESLSKDLKIEsLGHRNKI 59

SAM domain of Shank1,2,3 family proteins; SAM (sterile alpha motif) domain of Shank1,2,3 family proteins is a protein-protein interaction domain. Shank1,2,3 proteins are scaffold proteins that are known to interact with a variety of cytoplasmic and membrane proteins. SAM domains of the Shank1,2,3 family are prone to homooligomerization. They are highly enriched in the postsynaptic density, acting as scaffolds to organize assembly of postsynaptic proteins. SAM domains of Shank3 proteins can form large sheets of helical fibers. Shank genes show distinct patterns of expression, in rat Shank1 mRNA is found almost exclusively in brain, Shank2 in brain, kidney and liver, and Shank3 in heart, brain and spleen.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1958774295 679 WTVDDVCNFVGGLsGCGEYARVFREQGIDGETLPLLTEEHL 719
Cdd:cd09506     5 WTVDDVGDWLESL-NLGEHRERFMDNEIDGSHLPNLDKEDL 44

Ste50p, sterile alpha motif; The fungal Ste50p SAM domain consists of five helices, which form a compact, globular fold. It is required for mediation of homodimerization and heterodimerization (and in some cases oligomerization) of the protein.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1958774295 674 EDINKWTVDDVCNFVGGLSGCGEYARVF---REQGIDGETLPLLT 715
Cdd:pfam09235   1 SGFNEWSTDEVCKWCKAELGLTEGDPLIlriRENKITGSTLSELT 45

SAM domain of MLTK subfamily; SAM (sterile alpha motif) domain of MLTK subfamily is a protein-protein interaction domain. Besides SAM domain, these proteins have N-terminal protein tyrosine kinase domain and leucine-zipper motif. Proteins of this group act as mitogen-activated protein triple kinase in a number of MAPK cascades. They can be activated by autophosphorylation in response to stress signals. MLTK-alpha is known to phosphorylate histone H3. In mammals, MLTKs participate in the activation of the JNK/SAPK, p38, ERK5 pathways, the transcriptional factor NF-kB, in the regulation of the cell cycle checkpoint, and in the induction of apoptosis in a hepatoma cell line. Some members of this subfamily are proto-oncogenes, thus MLTK-alpha is involved in neoplasmic cell transformation and/or skin cancer development in athymic nude mice. Based on in vivo coprecipitation experiments in mammalian cells, it has been demonstrated that MLTK proteins might form homodimers/oligomers via their SAM domains.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1958774295 674 EDINKWtVDDVCNFVGGLSGCGEYARVFREQGIDGETLPLLTEEHlLNTMGLK 726
Cdd:cd09529     5 EDVHFW-MQQLVRKGGHPSELSQYADLFKENHITGKRLLLLTEED-LRDMGIG 55

SAM domain of Samd14 subfamily; SAM (sterile alpha motif) domain of SamD14 (or FAM15A) subfamily is a putative protein-protein interaction domain. SAM is widespread domain in proteins involved in signal transduction and regulation. In many cases SAM mediates homodimerization/oligomerization. The exact function of proteins belonging to this subfamily is unknown.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1958774295 678 KWTVDDVCNFVGGLsGCGEYARVFREQGIDGETLpLLTEEHLLNTMGLK 726
Cdd:cd09530     2 SWDTEDVAEWIEGL-GFPQYRECFTTNFIDGRKL-ILVDASTLPRMGVT 48