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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217360882 393 SRNPSAWTVEDVVWFVKDADPQALGPHVELFRKHEIDGNALLLLKSDMVMKYLGLKLGPALKLCYHIDKLKQ 464
Cdd:cd09578     1 SKDPSTWSVEDVVQFIKEADPQALAPHVDLFRKHEIDGKALLLLNSDMMMKYMGLKLGPALKLCYHIDKLKQ 72

RNA binding Region;

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 2217360882   1 MQSQRIPGRkrGRPSLHSTPmKMAVHNLYSASAGSLPaVKIPKKRGRKPGYKK 53
Cdd:pfam17208   1 GQRGRKPGR--GKPPGSTSA-PKKGSSPKNAPAKKEP-IKIPKKRGPKPGSKR 49

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217360882 393 SRNPSAWTVEDVVWFVKDADPQALGPHVELFRKHEIDGNALLLLKSDMVMKYLGLKLGPALKLCYHIDKLKQ 464
Cdd:cd09578     1 SKDPSTWSVEDVVQFIKEADPQALAPHVDLFRKHEIDGKALLLLNSDMMMKYMGLKLGPALKLCYHIDKLKQ 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217360882 397 SAWTVEDVVWFVKDADpqaLGPHVELFRKHEIDGNALLLLKSDMVMKYLGLKLGPALKLCYHIDKLK 463
Cdd:pfam00536   1 DGWSVEDVGEWLESIG---LGQYIDSFRAGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRLK 64

RNA binding Region;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2217360882   1 MQSQRIPGRkrGRPSLHSTPmKMAVHNLYSASAGSLPaVKIPKKRGRKPGYKK 53
Cdd:pfam17208   1 GQRGRKPGR--GKPPGSTSA-PKKGSSPKNAPAKKEP-IKIPKKRGPKPGSKR 49

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217360882 393 SRNPSAWTVEDVVWFVKDADPQALGPHVELFRKHEIDGNALLLLKSDMVMKYLGLKLGPALKLCYHIDKLKQ 464
Cdd:cd09578     1 SKDPSTWSVEDVVQFIKEADPQALAPHVDLFRKHEIDGKALLLLNSDMMMKYMGLKLGPALKLCYHIDKLKQ 72

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217360882 396 PSAWTVEDVVWFVKDADpqALGPHVELFRKHEIDGNALLLLKSDMVMKYLGLKLGPALKLCYHIDK 461
Cdd:cd09509     1 PSKWSVDDVAQFIKSLD--GCAEYAEVFREQEIDGQALLLLTEDDLLKGMGLKLGPALKIYNHIVK 64

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2217360882 395 NPSAWTVEDVVWFVKDADPQALGPhveLFRKHEIDGNALLLLKSDMVMKYLGLKLGPALKLCYHIDKLKQAKF 467
Cdd:cd09581    11 NPLFWSVDDVVRFIKSTDCAPLAK---IFKDQEIDGQALLLLTLPTVQECMELKLGPAIKLCHHIERVKVAFY 80

SAM domain of Scm-like-4MBT proteins of Polycomb group; SAM (sterile alpha motif) domain of Scm-like-4MBT (Sex comb on midleg like, Malignant Brain Tumor) subfamily proteins of the polycomb group is a putative protein-protein interaction domain. Additionally to the SAM domain, most of the proteins of this subfamily have 4 MBT repeats. In Drosophila SAM-Scm-like-4MBT protein (known as dSfmbt) is a member of Pho repressive complex (PhoRC). Additionally to dSfmbt, the PhoRC complex includes Pho or Pho-like proteins. This complex is responsible for HOX (Homeobox) gene silencing: Pho or Pho-like proteins bind DNA and dSmbt binds methylated histones. dSmbt can interact with mono- and di-methylated histones H3 and H4 (however this activity has been shown for the MBT repeats, while exact function of the SAM domain is unclear). Besides interaction with histones, dSmbt can interact with Scm (a member of PRC complex), but this interaction also seems to be SAM domain independent.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2217360882 396 PSAWTVEDVVWFVKDADpqaLGPHVELFRKHEIDGNALLLLKSDMVMKYLGLKLGPALKLCYHIDKLK 463
Cdd:cd09580     1 PSTWGVKDVSQFLREND---CGAYCECFCRQNIDGKRLLSLTKEQIMTLTGMKVGPSLKIYDLIQQLK 65

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217360882 397 SAWTVEDVVWFVKDADpqaLGPHVELFRKHEIDGNALLLLKSDMVMKYLGLKLGPALKLCYHIDKLK 463
Cdd:pfam00536   1 DGWSVEDVGEWLESIG---LGQYIDSFRAGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRLK 64

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        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360882  396 PSAWTVEDVVWFVKDADpqaLGPHVELFRKHEIDGNALLLLKSDMVMKYLG-LKLGPALKLCYHIDKLKQ 464
Cdd:smart00454   1 VSQWSPESVADWLESIG---LEQYADNFRKNGIDGALLLLLTSEEDLKELGiTKLGHRKKILKAIQKLKE 67

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217360882 396 PSAWTVEDVV-WFVKdadpQALGPHVELFRKHEIDGNALLLLKSDMVMKYLGLK-LGPALKLCYHIDKLKQAKF 467
Cdd:cd09505     2 LQDWSEEDVCtWLRS----IGLEQYVEVFRANNIDGKELLNLTKESLSKDLKIEsLGHRNKILRKIEELKMKSD 71

SAM domain of STIM-1,2-like proteins; SAM (sterile alpha motif) domain of STIM-1,2-like (Stromal interaction molecule) proteins is a putative protein-protein interaction domain. STIM1 and STIM2 human proteins are type I transmembrane proteins. The N-terminal part of them includes "hidden" EF-hand and SAM domains. This region is responsible for sensing changes in store-operated and basal cytoplasmic Ca2+ levels and initiates oligomerization. "Hidden" EF hand and SAM domains have a stable intramolecular association, and the SAM domain is a component that regulates stability within STIM proteins. Destabilization of the EF-SAM association during Ca2+ depletion leads to partial unfolding and aggregation (homooligomerization), thus activating the store-operated Ca2+ entry. Immunoprecipitation analysis indicates that STIM1 and STIM2 can form co-precipitable oligomeric associations in vivo. It was suggested that STIM1 and STIM2 are involved in opposite regulation of store operated channels in plasma membrane.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2217360882 399 WTVEDVV-WFVKDAD-PQalgpHVELFRKHEIDGNALLLL---KSDMVMKYLGLK 448
Cdd:cd09504     5 WTVEDTVeWLVNSVElPQ----YVEAFKENGVDGSALPRLavnNPSFLTSVLGIK 55

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217360882 398 AWTVEDV-VW----FVKDADPQALGPHVELFRKHEIDGNALLLLkSDMVMKYLGLK-LGPALKLCYHIDKLK 463
Cdd:cd09529     1 AWTEEDVhFWmqqlVRKGGHPSELSQYADLFKENHITGKRLLLL-TEEDLRDMGIGsKGHIIHLKSAIEKLT 71

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        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2217360882 414 QALGPHVELFRKHEIDGNALLLLkSDMVMKYLGLKLGPALKLCYHIDKLKQA 465
Cdd:cd09517    12 NHLEEYLPVFEREKIDLEALMLL-TDEDLQSLKLPLGPRRKLLNAIAKRKQA 62