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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 688611876 734 ISKWSVEEV----------------FREQAIDGETLPLLTEDHLLNNMGLKLGPALKIRSQVARRIGR 785
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 688611876 734 ISKWSVEEV----------------FREQAIDGETLPLLTEDHLLNNMGLKLGPALKIRSQVARRIGR 785
Cdd:cd09579    1 IRKWTVDDVcsfigslpgcaeyaqvFREHSIDGETLPLLTEEHLLNTMGLKLGPALKIRSQVAKRLGR 68

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
                  ....*....|....*....|....*....|....*.
gi 688611876  740 EEVFREQAIDGETLPLLTEDHLLNNMGLKLGPALKI 775
Cdd:pfam00536  21 IDSFRAGYIDGDALLQLTEDDLLKLGVTLLGHRKKI 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 688611876 734 ISKWSVEEV----------------FREQAIDGETLPLLTEDHLLNNMGLKLGPALKIRSQVARRIGR 785
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 688611876 734 ISKWSVEEV----------------FREQAIDGETLPLLTEDHLLNNMGLKLGPALKIRSQVAR 781
Cdd:cd09509    1 PSKWSVDDVaqfiksldgcaeyaevFREQEIDGQALLLLTEDDLLKGMGLKLGPALKIYNHIVK 64

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 688611876 734 ISKWSVEEV---------------FREQAIDGETLPLLTEDHLLNNMGLKLGPALKIRSQVAR 781
Cdd:cd09583    1 PSNWSVEDVvqyfktagfpeeanaFKEQEIDGKSLLLLTRSDVLTGLSLKLGPALKIYEHVVK 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 688611876 733 DISKWSVEEV------------------FREQAIDGETLPLLTEDHLLNNMGLKLGPALKIRSQVAR 781
Cdd:cd09578    3 DPSTWSVEDVvqfikeadpqalaphvdlFRKHEIDGKALLLLNSDMMMKYMGLKLGPALKLCYHIDK 69

SAM domain of Scm-like-4MBT1,2 proteins of Polycomb group; SAM (sterile alpha motif) domain of Scm-like-4MBT1,2 (Sex comb on midleg, Malignant Brain Tumor) subfamily proteins (also known as Sfmbt1,2 proteins) is a putative protein-protein interaction domain. Proteins of this subfamily are transcriptional regulators belonging to Polycomb group. The majority of them are multidomain proteins: in addition to the C-terminal SAM domain, they contain four MBT repeats and DUF5388 domain. The MBT repeats of the human sfmbt1 protein are responsible for association with the nuclear matrix and for selective binding of H3 histone N-terminal tails, while the exact function of the SAM domain is unclear.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 688611876 736 KWSVEEVFR---------------EQAIDGETLPLLTEDHLLNNMGLKLGPALKIRSQVAR 781
Cdd:cd09581   14 FWSVDDVVRfikstdcaplakifkDQEIDGQALLLLTLPTVQECMELKLGPAIKLCHHIER 74

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
                 ....*....|....*....|....*....|....*.
gi 688611876 740 EEVFREQAIDGETLPLLTEDHLLNNMGLKLGPALKI 775
Cdd:cd09487   15 ADLFRKNEIDGDALLLLTDEDLKELGITSPGHRKKI 50

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 688611876   735 SKWSVEEV---------------FREQAIDGETLPLLTEDHLLNNMG-LKLGPALKI 775
Cdd:smart00454   2 SQWSPESVadwlesigleqyadnFRKNGIDGALLLLLTSEEDLKELGiTKLGHRKKI 58

SAM domain of USH1G_HARP family; SAM (sterile alpha motif) domain of USH1G/HARP (Usher syndrome type-1G/ Harmonin-interacting Ankyrin Repeat-containing protein) family is a protein-protein interaction domain. Members of this family have an N-terminal ankyrin repeat region and a C-terminal SAM domain. In mammals these proteins can interact via the SAM domain with the PDZ domain of harmonin to form a scaffolding complex that facilitates signal transduction in epithelial and inner ear sensory cells. It was suggested that USH1G and HARP can be tissue specific partners of harmonin. Mutations in ush1g genes lead to Usher syndrome type 1G. This syndrome is the cause of deaf-blindness in humans.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 688611876 737 WSVEE---VFREQAIDGETLPLLTEDHLLnNMGLKLGPALKIRSQVARR 782
Cdd:cd09517   12 NHLEEylpVFEREKIDLEALMLLTDEDLQ-SLKLPLGPRRKLLNAIAKR 59